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Sample records for model human respiratory

  1. A Novel Parametric Model For The Human Respiratory System

    Directory of Open Access Journals (Sweden)

    Clara Mihaela IONESCU

    2003-12-01

    Full Text Available The purpose of this work is to present some recent results in an ongoing research project between Ghent University and Chess Medical Technology Company Belgium. The overall aim of the project is to provide a fast method for identification of the human respiratory system in order to allow for an instantaneously diagnosis of the patient by the medical staff. A novel parametric model of the human respiratory system as well as the obtained experimental results is presented in this paper. A prototype apparatus developed by the company, based on the forced oscillation technique is used to record experimental data from 4 patients in this paper. Signal processing is based on spectral analysis and is followed by the parametric identification of a non-linear mechanistic model. The parametric model is equivalent to the structure of a simple electrical RLC-circuit, containing a non-linear capacitor. These parameters have a useful and easy-to-interpret physical meaning for the medical staff members.

  2. Velocity profiles in idealized model of human respiratory tract

    Directory of Open Access Journals (Sweden)

    Jicha M.

    2013-04-01

    Full Text Available This article deals with numerical simulation focused on velocity profiles in idealized model of human upper airways during steady inspiration. Three r gimes of breathing were investigated: Resting condition, Deep breathing and Light activity which correspond to most common regimes used for experiments and simulations. Calculation was validated with experimental data given by Phase Doppler Anemometry performed on the model with same geometry. This comparison was made in multiple points which form one cross-section in trachea near first bifurcation of bronchial tree. Development of velocity profile in trachea during steady inspiration was discussed with respect for common phenomenon formed in trachea and for future research of transport of aerosol particles in human respiratory tract.

  3. A Mathematical Model of the Human Respiratory Control System

    Science.gov (United States)

    Milhorn, Howard T.; Benton, Richard; Ross, Richard; Guyton, Arthur C.

    1965-01-01

    The respiratory system exhibits the properties of a control system of the regulator type. Equations describing this biological control system have been derived. Transient and steady-state solutions for various CO2 and O2 step input disturbances were obtained utilizing a digital computer and are compared with experimental results. The effectiveness of the respiratory system as a regulator is investigated. Further extensions of the model are suggested. PMID:14284328

  4. Understanding Emerging Zoonotic Respiratory Viruses : Animal models for human influenza and coronavirus infections

    NARCIS (Netherlands)

    L.C.M. Wiersma (Lidewij)

    2016-01-01

    markdownabstractThe objective of the work presented in this thesis was to improve understanding of, and response to, emerging zoonotic respiratory viruses. To this end, various animal models were employed to represent respiratory viral infections in humans. The introduction serves to provide a backg

  5. Development of an ex vivo human-porcine respiratory model for preclinical studies.

    Science.gov (United States)

    Perinel, Sophie; Pourchez, Jérémie; Leclerc, Lara; Avet, John; Durand, Marc; Prévôt, Nathalie; Cottier, Michèle; Vergnon, Jean M

    2017-02-24

    Anatomical models to study aerosol delivery impose huge limitations and extrapolation to humans remains controversial. This study aimed to develop and validate an ex vivo human-like respiratory tract model easy to use and relevant to compare to in vivo human data. A human plastinated head is connected to an ex vivo porcine pulmonary tract ventilated artificially by passive expansion. A physiological study measures "pleural" depressions, tidal volumes, and minute ventilation for the respiratory rates chosen (10, 15, and 20 per minute) with three inspiratory/expiratory ratios (1/1, 1/2, and 1/3). Scintigraphy with (81m)Krypton assesses the homogeneity of the ventilation. Forty different experiments were set for validation, with 36 (90%) ventilating successfully. At a respiratory rate of 15/minute with inspiratory/expiratory ratio of 1/2, the tidal volume average was 824 mL (standard deviation, 207 mL). The scintigraphy performed on 16 ex vivo models (44.4%), showed homogenous ventilation with great similarity to human physiological studies. Ratio of the peripheral to central count rates were equally correlated with human data published in the literature. This new model, combining research feasibility and human physiology likeness, provides a realistic approach to human inhalation and therefore can be an interesting tool in aerosol regional deposition studies.

  6. Development of an ex vivo human-porcine respiratory model for preclinical studies

    Science.gov (United States)

    Perinel, Sophie; Pourchez, Jérémie; Leclerc, Lara; Avet, John; Durand, Marc; Prévôt, Nathalie; Cottier, Michèle; Vergnon, Jean M.

    2017-01-01

    Anatomical models to study aerosol delivery impose huge limitations and extrapolation to humans remains controversial. This study aimed to develop and validate an ex vivo human-like respiratory tract model easy to use and relevant to compare to in vivo human data. A human plastinated head is connected to an ex vivo porcine pulmonary tract ventilated artificially by passive expansion. A physiological study measures “pleural” depressions, tidal volumes, and minute ventilation for the respiratory rates chosen (10, 15, and 20 per minute) with three inspiratory/expiratory ratios (1/1, 1/2, and 1/3). Scintigraphy with 81mKrypton assesses the homogeneity of the ventilation. Forty different experiments were set for validation, with 36 (90%) ventilating successfully. At a respiratory rate of 15/minute with inspiratory/expiratory ratio of 1/2, the tidal volume average was 824 mL (standard deviation, 207 mL). The scintigraphy performed on 16 ex vivo models (44.4%), showed homogenous ventilation with great similarity to human physiological studies. Ratio of the peripheral to central count rates were equally correlated with human data published in the literature. This new model, combining research feasibility and human physiology likeness, provides a realistic approach to human inhalation and therefore can be an interesting tool in aerosol regional deposition studies. PMID:28233793

  7. STABILITY AND BIFURCATION OF A HUMAN RESPIRATORY SYSTEM MODEL WITH TIME DELAY

    Institute of Scientific and Technical Information of China (English)

    沈启宏; 魏俊杰

    2004-01-01

    The stability and bifurcation of the trivial solution in the two-dimensional differential equation of a model describing human respiratory system with time delay were investigated. Formulas about the stability of bifurcating periodic solution and the direction of Hopf bifurcation were exhibited by applying the normal form theory and the center manifold theorem. Furthermore, numerical simulation was carried out.

  8. Studying human respiratory disease in animals--role of induced and naturally occurring models.

    Science.gov (United States)

    Williams, Kurt; Roman, Jesse

    2016-01-01

    Respiratory disorders like asthma, emphysema, and pulmonary fibrosis affect millions of Americans and many more worldwide. Despite advancements in medical research that have led to improved understanding of the pathophysiology of these conditions and sometimes to new therapeutic interventions, these disorders are for the most part chronic and progressive; current interventions are not curative and do not halt disease progression. A major obstacle to further advancements relates to the absence of animal models that exactly resemble the human condition, which delays the elucidation of relevant mechanisms of action, the unveiling of biomarkers of disease progression, and identification of new targets for intervention in patients. There are currently many induced animal models of human respiratory disease available for study, and even though they mimic features of human disease, discoveries in these models have not always translated into safe and effective treatments in humans. A major obstacle relates to the genetic, anatomical, and functional variations amongst species, which represents the major challenge to overcome when searching for appropriate models of respiratory disease. Nevertheless, rodents, in particular mice, have become the most common species used for experimentation, due to their relatively low cost, size, and adequate understanding of murine genetics, among other advantages. Less well known is the fact that domestic animals also suffer from respiratory illnesses similar to those found in humans. Asthma, bronchitis, pneumonia, and pulmonary fibrosis are among the many disorders occurring naturally in dogs, cats, and horses, among other species. These models might better resemble the human condition and are emphasized here, but further investigations are needed to determine their relevance.

  9. Feasibility of a 3D human airway epithelial model to study respiratory absorption.

    Science.gov (United States)

    Reus, Astrid A; Maas, Wilfred J M; Jansen, Harm T; Constant, Samuel; Staal, Yvonne C M; van Triel, Jos J; Kuper, C Frieke

    2014-03-01

    The respiratory route is an important portal for human exposure to a large variety of substances. Consequently, there is an urgent need for realistic in vitro strategies for evaluation of the absorption of airborne substances with regard to safety and efficacy assessment. The present study investigated feasibility of a 3D human airway epithelial model to study respiratory absorption, in particular to differentiate between low and high absorption of substances. Bronchial epithelial models (MucilAir™), cultured at the air-liquid interface, were exposed to eight radiolabeled model substances via the apical epithelial surface. Absorption was evaluated by measuring radioactivity in the apical compartment, the epithelial cells and the basolateral culture medium. Antipyrine, caffeine, naproxen and propranolol were highly transported across the epithelial cell layer (>5%), whereas atenolol, mannitol, PEG-400 and insulin were limitedly transported (absorption. The intra-experimental reproducibility of the results was considered adequate based on an average coefficient of variation (CV) of 15%. The inter-experimental reproducibility of highly absorbed compounds was in a similar range (CV of 15%), but this value was considerably higher for those compounds that were limitedly absorbed. No statistical significant differences between different donors and experiments were observed. The present study provides a simple method transposable in any lab, which can be used to rank the absorption of chemicals and pharmaceuticals, and is ready for further validation with respect to reproducibility and capacity of the method to predict respiratory transport in humans.

  10. Using a human cardiovascular-respiratory model to characterize cardiac tamponade and pulsus paradoxus

    Science.gov (United States)

    Ramachandran, Deepa; Luo, Chuan; Ma, Tony S; Clark, John W

    2009-01-01

    Background Cardiac tamponade is a condition whereby fluid accumulation in the pericardial sac surrounding the heart causes elevation and equilibration of pericardial and cardiac chamber pressures, reduced cardiac output, changes in hemodynamics, partial chamber collapse, pulsus paradoxus, and arterio-venous acid-base disparity. Our large-scale model of the human cardiovascular-respiratory system (H-CRS) is employed to study mechanisms underlying cardiac tamponade and pulsus paradoxus. The model integrates hemodynamics, whole-body gas exchange, and autonomic nervous system control to simulate pressure, volume, and blood flow. Methods We integrate a new pericardial model into our previously developed H-CRS model based on a fit to patient pressure data. Virtual experiments are designed to simulate pericardial effusion and study mechanisms of pulsus paradoxus, focusing particularly on the role of the interventricular septum. Model differential equations programmed in C are solved using a 5th-order Runge-Kutta numerical integration scheme. MATLAB is employed for waveform analysis. Results The H-CRS model simulates hemodynamic and respiratory changes associated with tamponade clinically. Our model predicts effects of effusion-generated pericardial constraint on chamber and septal mechanics, such as altered right atrial filling, delayed leftward septal motion, and prolonged left ventricular pre-ejection period, causing atrioventricular interaction and ventricular desynchronization. We demonstrate pericardial constraint to markedly accentuate normal ventricular interactions associated with respiratory effort, which we show to be the distinct mechanisms of pulsus paradoxus, namely, series and parallel ventricular interaction. Series ventricular interaction represents respiratory variation in right ventricular stroke volume carried over to the left ventricle via the pulmonary vasculature, whereas parallel interaction (via the septum and pericardium) is a result of

  11. Computational fluid dynamics modeling of Bacillus anthracis spore deposition in rabbit and human respiratory airways

    Energy Technology Data Exchange (ETDEWEB)

    Kabilan, S.; Suffield, S. R.; Recknagle, K. P.; Jacob, R. E.; Einstein, D. R.; Kuprat, A. P.; Carson, J. P.; Colby, S. M.; Saunders, J. H.; Hines, S. A.; Teeguarden, J. G.; Straub, T. M.; Moe, M.; Taft, S. C.; Corley, R. A.

    2016-09-01

    Three-dimensional computational fluid dynamics and Lagrangian particle deposition models were developed to compare the deposition of aerosolized Bacillus anthracis spores in the respiratory airways of a human with that of the rabbit, a species commonly used in the study of anthrax disease. The respiratory airway geometries for each species were derived respectively from computed tomography (CT) and µCT images. Both models encompassed airways that extended from the external nose to the lung with a total of 272 outlets in the human model and 2878 outlets in the rabbit model. All simulations of spore deposition were conducted under transient, inhalation–exhalation breathing conditions using average species-specific minute volumes. Two different exposure scenarios were modeled in the rabbit based upon experimental inhalation studies. For comparison, human simulations were conducted at the highest exposure concentration used during the rabbit experimental exposures. Results demonstrated that regional spore deposition patterns were sensitive to airway geometry and ventilation profiles. Due to the complex airway geometries in the rabbit nose, higher spore deposition efficiency was predicted in the nasal sinus compared to the human at the same air concentration of anthrax spores. In contrast, higher spore deposition was predicted in the lower conducting airways of the human compared to the rabbit lung due to differences in airway branching pattern. This information can be used to refine published and ongoing biokinetic models of inhalation anthrax spore exposures, which currently estimate deposited spore concentrations based solely upon exposure concentrations and inhaled doses that do not factor in species-specific anatomy and physiology for deposition.

  12. Computational Fluid Dynamics Modeling of Bacillus anthracis Spore Deposition in Rabbit and Human Respiratory Airways

    Energy Technology Data Exchange (ETDEWEB)

    Kabilan, Senthil; Suffield, Sarah R.; Recknagle, Kurtis P.; Jacob, Rick E.; Einstein, Daniel R.; Kuprat, Andrew P.; Carson, James P.; Colby, Sean M.; Saunders, James H.; Hines, Stephanie; Teeguarden, Justin G.; Straub, Tim M.; Moe, M.; Taft, Sarah; Corley, Richard A.

    2016-09-30

    Three-dimensional computational fluid dynamics and Lagrangian particle deposition models were developed to compare the deposition of aerosolized Bacillus anthracis spores in the respiratory airways of a human with that of the rabbit, a species commonly used in the study of anthrax disease. The respiratory airway geometries for each species were derived from computed tomography (CT) or µCT images. Both models encompassed airways that extended from the external nose to the lung with a total of 272 outlets in the human model and 2878 outlets in the rabbit model. All simulations of spore deposition were conducted under transient, inhalation-exhalation breathing conditions using average species-specific minute volumes. The highest exposure concentration was modeled in the rabbit based upon prior acute inhalation studies. For comparison, human simulation was also conducted at the same concentration. Results demonstrated that regional spore deposition patterns were sensitive to airway geometry and ventilation profiles. Due to the complex airway geometries in the rabbit nose, higher spore deposition efficiency was predicted in the upper conducting airways compared to the human at the same air concentration of anthrax spores. As a result, higher particle deposition was predicted in the conducting airways and deep lung of the human compared to the rabbit lung due to differences in airway branching pattern. This information can be used to refine published and ongoing biokinetic models of inhalation anthrax spore exposures, which currently estimate deposited spore concentrations based solely upon exposure concentrations and inhaled doses that do not factor in species-specific anatomy and physiology.

  13. Next Generation Respiratory Viral Vaccine System: Advanced and Emerging Bioengineered Human Lung Epithelia Model (HLEM) Organoid Technology

    Science.gov (United States)

    Goodwin, Thomas J.; Schneider, Sandra L.; MacIntosh, Victor; Gibbons, Thomas F.

    2010-01-01

    Acute respiratory infections, including pneumonia and influenza, are the S t" leading cause of United States and worldwide deaths. Newly emerging pathogens signaled the need for an advanced generation of vaccine technology.. Human bronchial-tracheal epithelial tissue was bioengineered to detect, identify, host and study the pathogenesis of acute respiratory viral disease. The 3-dimensional (3D) human lung epithelio-mesechymal tissue-like assemblies (HLEM TLAs) share characteristics with human respiratory epithelium: tight junctions, desmosomes, microvilli, functional markers villin, keratins and production of tissue mucin. Respiratory Syntial Virus (RSV) studies demonstrate viral growth kinetics and membrane bound glycoproteins up to day 20 post infection in the human lung-orgainoid infected cell system. Peak replication of RSV occurred on day 10 at 7 log10 particles forming units per ml/day. HLEM is an advanced virus vaccine model and biosentinel system for emergent viral infectious diseases to support DoD global surveillance and military readiness.

  14. The Revised International Commission on Radiological Protection (ICRP) dosimetric model for the human respiratory tract

    Energy Technology Data Exchange (ETDEWEB)

    Bair, W.J.

    1991-09-01

    The new respiratory tract model is based on the premise that the large differences in radiation sensitivity of respiratory tract tissues, and the wide range of doses they receive, argue for calculating specific tissue doses rather than average lung doses for radiation protection purposes. The new model is more complex than the current lung model because it describes deposition of inhaled radioactive material in the clearance from several tissues and regions of the respiratory tract and is applicable to the worldwide population of both workers and the public. 2 refs., 2 figs.

  15. The revised International Commission on Radiological Protection (ICRP) dosimetric model for the human respiratory tract

    Energy Technology Data Exchange (ETDEWEB)

    Bair, W.J.

    1992-05-01

    A task group has revised the dosimetric model of the respiratory tract used to calculate annual limits on intake of radionuclides. The revised model can be used to project respiratory tract doses for workers and members of the public from airborne radionuclides and to assess past exposures. Doses calculated for specific extrathoracic and thoracic tissues can be adjusted to account for differences in radiosensitivity and summed to yield two values of dose for the respiratory tract that are applicable to the ICRP tissue weighted dosimetry system.

  16. Study of airflow during respiratory cycle in semi-realistic model of human tracheobronchial tree

    Science.gov (United States)

    Elcner, Jakub; Zaremba, M.; Maly, M.; Jedelsky, J.; Lizal, F.; Jicha, M.

    2016-06-01

    This article deals with study of airflow under breathing process, which is characteristic by unsteady behavior. Simulations provided by computational fluid dynamics (CFD) was compared with experiments performed on similar geometry of human upper airways. This geometry was represented by mouth cavity of realistic shape connected to an idealized tracheobronchial tree up to fourth generation of branching. Commercial CFD software Star-CCM+ was used to calculate airflow inside investigated geometry and method of Reynolds averaging of Navier-Stokes equations was used for subscribing the turbulent behavior through model geometry. Conditions corresponding to resting state were considered. Comparisons with experiments were provided on several points through trachea and bronchial tree and results with respect to inspiratory and respiratory part of breathing cycle was discussed.

  17. Multi-Scale Computational Analyses of JP-8 Fuel Droplets and Vapors in Human Respiratory Airway Models

    Science.gov (United States)

    2007-10-31

    Deposition Clearance and Effects in the Lung 20, 294-309. Kleinstreuer, C., Zhang, Z., 2003. Laminar-to-turbulent fluid-particle flows in a human airway ...FA9550-04-1-0422 Vapors in Human Respiratory Airway Models 5b. GRANT NUMBER Sc. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Kleinstreuer...tracheobronchial airway models, transient 3- D as well as equivalent steady-state solutions have been obtained for the transport and deposition of

  18. Feasibility of a 3D human airway epithelial model to study respiratory absorption

    NARCIS (Netherlands)

    Reus, A.A.; Maas, W.J.M.; Jansen, H.T.; Constant, S.; Staal, Y.C.M.; Triel, J.J. van; Kuper, C.F.

    2014-01-01

    The respiratory route is an important portal for human exposure to a large variety of substances. Consequently, there is an urgent need for realistic in vitro strategies for evaluation of the absorption of airborne substances with regard to safety and efficacy assessment. The present study investiga

  19. A Computer Model for the Simulation of Nonspherical Particle Dynamics in the Human Respiratory Tract

    Directory of Open Access Journals (Sweden)

    Robert Sturm

    2012-01-01

    Full Text Available In the study presented here deposition of spheres and nonspherical particles with various aspect ratios (0.01–100 in the human respiratory tract was theoretically modeled. Shape of the nonspherical particles was considered by the application of the latest aerodynamic diameter concepts. Particle deposition was predicted by using a stochastic model of the lung geometry and simulating particle transport trajectories according to the random-walk algorithm. Concerning fibers total deposition is significantly enhanced with respect to that of spheres for μm-sized particles, whereby at normal breathing conditions peripheral lung compartments serve as primary deposition targets. In the case of oblate disks, total deposition becomes mostly remarkable for submicron particles, with the bronchioli and alveoli being targeted to a high extent. Enhancement of the aerodynamic diameter and/or flow rate generally causes a displacement of deposition maxima from peripheral to more proximal lung regions. From these findings, it can be concluded that these particle classes may represent tremendous occupational hazards, especially if they are attached with radioactive elements or heavy metals.

  20. COMPARATIVE COMPUTATIONAL MODELING OF AIRFLOWS AND VAPOR DOSIMETY IN THE RESPIRATORY TRACTS OF RAT, MONKEY, AND HUMAN

    Energy Technology Data Exchange (ETDEWEB)

    Corley, Richard A.; Kabilan, Senthil; Kuprat, Andrew P.; Carson, James P.; Minard, Kevin R.; Jacob, Rick E.; Timchalk, Charles; Glenny, Robb W.; Pipavath, Sudhaker; Cox, Timothy C.; Wallis, Chris; Larson, Richard; Fanucchi, M.; Postlewait, Ed; Einstein, Daniel R.

    2012-07-01

    Coupling computational fluid dynamics (CFD) with physiologically based pharmacokinetic (PBPK) models is useful for predicting site-specific dosimetry of airborne materials in the respiratory tract and elucidating the importance of species differences in anatomy, physiology, and breathing patterns. Historically, these models were limited to discrete regions of the respiratory system. CFD/PBPK models have now been developed for the rat, monkey, and human that encompass airways from the nose or mouth to the lung. A PBPK model previously developed to describe acrolein uptake in nasal tissues was adapted to the extended airway models as an example application. Model parameters for each anatomic region were obtained from the literature, measured directly, or estimated from published data. Airflow and site-specific acrolein uptake patterns were determined under steadystate inhalation conditions to provide direct comparisons with prior data and nasalonly simulations. Results confirmed that regional uptake was dependent upon airflow rates and acrolein concentrations with nasal extraction efficiencies predicted to be greatest in the rat, followed by the monkey, then the human. For human oral-breathing simulations, acrolein uptake rates in oropharyngeal and laryngeal tissues were comparable to nasal tissues following nasal breathing under the same exposure conditions. For both breathing modes, higher uptake rates were predicted for lower tracheo-bronchial tissues of humans than either the rat or monkey. These extended airway models provide a unique foundation for comparing dosimetry across a significantly more extensive range of conducting airways in the rat, monkey, and human than prior CFD models.

  1. An In vitro Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection

    NARCIS (Netherlands)

    Vissers, M.; Habets, M.N.; Ahout, I.M.L.; Jans, J.; Jonge, M.I. de; Diavatopoulos, D.A.; Ferwerda, G.

    2013-01-01

    Human respiratory syncytial virus (HRSV) infections present a broad spectrum of disease severity, ranging from mild infections to life-threatening bronchiolitis. An important part of the pathogenesis of severe disease is an enhanced immune response leading to immunopathology. Here, we describe a

  2. An In vitro Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection

    NARCIS (Netherlands)

    Vissers, M.; Habets, M.N.; Ahout, I.M.L.; Jans, J.; Jonge, M.I. de; Diavatopoulos, D.A.; Ferwerda, G.

    2013-01-01

    Human respiratory syncytial virus (HRSV) infections present a broad spectrum of disease severity, ranging from mild infections to life-threatening bronchiolitis. An important part of the pathogenesis of severe disease is an enhanced immune response leading to immunopathology. Here, we describe a pro

  3. Numerical simulation of micro-particle deposition in a realistic human upper respiratory tract model during transient breathing cycle

    Institute of Scientific and Technical Information of China (English)

    Jian hua Huang; Lian zhong Zhang

    2011-01-01

    An more reliable human upper respiratory tract model that consisted of an oropharynx and four generations of asymmetric tracheo-bronchial (TB) airways has been constructed to investigate the micro-particle deposition pattern and mass distribution in five lobes under steady inspiratory condition in former work by Huang and Zhang (2011 ).In the present work,transient airflow patterns and particle deposition during both inspiratory and expiratory processes were numerically simulated in the realistic human upper respiratory tract model with 14 cartilaginous rings (CRs) in the tracheal tube.The present model was validated under steady inspiratory flow rates by comparing current results with the theoretical models and published experimental data.The transient deposition fraction was found to strongly depend on breathing flow rate and particle diameter but slightly on turbulence intensity.Particles were mainly distributed in the high axial speed zones and traveled basically following the secondary flow.“Hot spots” of deposition were found in the lower portion of mouth cavity and posterior wall of pharynx/larynx during inspiration,but transferred to upper portion of mouth and interior wall of pharynx/larynx during expiration.The deposition fraction in the trachea during expiration was found to be much higher than that during inspiration because of the stronger secondary flow.

  4. Modeling the deposition of bioaerosols with variable size and shape in the human respiratory tract – A review

    Directory of Open Access Journals (Sweden)

    R. Sturm

    2012-10-01

    Full Text Available The behavior of bioaerosol particles with various size and shape in the human respiratory tract was simulated by using a probabilistic model of the lung and an almost realistic mathematical approach to particle deposition. Results obtained from the theoretical computations clearly show that biogenic particle deposition in different lung compartments does not only depend on physical particle properties, but also on breathing mode (nose or mouth breathing and inhalative flow rate (=tidal volume × breathing frequency/30. Whilst ultrafine (5 μm particles tend to accumulate in the extrathoracic region and the uppermost airways of the tracheobronchial tree, particles with intermediate size are characterized by higher penetration depth, leading to their possible accumulation in the lung alveoli. Due to their deposition in deep lung regions and insufficient clearance, some bioaerosol particles may induce severe lung diseases ranging from infections, allergies, and toxic reactions to cancer.

  5. Animal models for diseases of respiratory system

    Directory of Open Access Journals (Sweden)

    R. Adil

    2012-07-01

    Full Text Available Latest trends in understanding of respiratory diseases in human beings can be derived from thorough clinical studies of these diseases occurring in man, but conducting such studies in man is difficult in terms of experimental manipulation. In the last 2 decades, various types of experimental respiratory disease models has been developed and utilized by investigators, which have contributed a lot to the understanding of respiratory diseases in man, but only little investigation has been done on the naturally occurring pulmonary diseases of animals as potential models which could have added to our knowledge. There are certain selected examples of spontaneous pulmonary disease in animals that may serve as exploitable models for human chronic bronchitis, bronchiectasis, emphysema, interstitial lung disease, hypersensitivity pneumonitis, hyaline membrane disease, and bronchial asthma.

  6. A UWB Radar Signal Processing Platform for Real-Time Human Respiratory Feature Extraction Based on Four-Segment Linear Waveform Model.

    Science.gov (United States)

    Hsieh, Chi-Hsuan; Chiu, Yu-Fang; Shen, Yi-Hsiang; Chu, Ta-Shun; Huang, Yuan-Hao

    2016-02-01

    This paper presents an ultra-wideband (UWB) impulse-radio radar signal processing platform used to analyze human respiratory features. Conventional radar systems used in human detection only analyze human respiration rates or the response of a target. However, additional respiratory signal information is available that has not been explored using radar detection. The authors previously proposed a modified raised cosine waveform (MRCW) respiration model and an iterative correlation search algorithm that could acquire additional respiratory features such as the inspiration and expiration speeds, respiration intensity, and respiration holding ratio. To realize real-time respiratory feature extraction by using the proposed UWB signal processing platform, this paper proposes a new four-segment linear waveform (FSLW) respiration model. This model offers a superior fit to the measured respiration signal compared with the MRCW model and decreases the computational complexity of feature extraction. In addition, an early-terminated iterative correlation search algorithm is presented, substantially decreasing the computational complexity and yielding negligible performance degradation. These extracted features can be considered the compressed signals used to decrease the amount of data storage required for use in long-term medical monitoring systems and can also be used in clinical diagnosis. The proposed respiratory feature extraction algorithm was designed and implemented using the proposed UWB radar signal processing platform including a radar front-end chip and an FPGA chip. The proposed radar system can detect human respiration rates at 0.1 to 1 Hz and facilitates the real-time analysis of the respiratory features of each respiration period.

  7. Innovative characteristics of the new dosimetric model for the human respiratory tract studied by the ICRP appointed Task Group of Committee 2

    CERN Document Server

    Melandri, C; Tarroni, G

    1991-01-01

    In 1984, the ICRP appointed a Task Group of Committee 2 to review and revise, as necessary, the current lung dosimetric model. On the basis of the knowledge acquired during the past 20 years, the Task Group's approach has been to review, in depth, the morphology and physiology of the human respiratory tract, inspirability of aerosols and regional deposition of inhaled particles as functions of aerosol size and breathing parameters, clearance of deposited materials, nature and specific sites of damage to the respiratory system caused by inhaled radioactive substances. In the proposed model, clearance from the three regions of the respiratory tract (extrathoracic ET, fast-clearing thoracic T sub f and slow-clearing thoracic T sub s , comprising lymph nodes) is described in terms of competition between the mechanical processes moving particles, which do not depend on the substances, and those of absorption into the blood, determined solely by the material. A Task Group report will also include models for calcula...

  8. Computational Fluid and Particle Dynamics in the Human Respiratory System

    CERN Document Server

    Tu, Jiyuan; Ahmadi, Goodarz

    2013-01-01

    Traditional research methodologies in the human respiratory system have always been challenging due to their invasive nature. Recent advances in medical imaging and computational fluid dynamics (CFD) have accelerated this research. This book compiles and details recent advances in the modelling of the respiratory system for researchers, engineers, scientists, and health practitioners. It breaks down the complexities of this field and provides both students and scientists with an introduction and starting point to the physiology of the respiratory system, fluid dynamics and advanced CFD modeling tools. In addition to a brief introduction to the physics of the respiratory system and an overview of computational methods, the book contains best-practice guidelines for establishing high-quality computational models and simulations. Inspiration for new simulations can be gained through innovative case studies as well as hands-on practice using pre-made computational code. Last but not least, students and researcher...

  9. Electrical circuit models of the human respiratory system reflect small airway impairment measured by impulse oscillation (IOS).

    Science.gov (United States)

    Goldman, Michael D; Nazeran, Homer; Ramos, Carlos; Toon, Emily; Oates, Katrina; Bilton, Diana; Meraz, Erika; Hafezi, Nazila; Diong, Bill

    2010-01-01

    The use of the forced oscillatory input impedance parameter, frequency-dependence of Resistance (fdR), to assess small airway impairment (SAI) has not been widely accepted due to concern about the effects of "upper airway shunt" on oscillometric resistance and low frequency reactance. On the other hand, recent medical studies suggest that low frequency reactance is a very sensitive index of treatment intervention directed at small airways. The present study was undertaken to analyze and compare Impulse Oscillometry (IOS) resistance and reactance data with model-derived indices of small airway function from two models of the respiratory impedance, one with, and the other without an element for upper airway shunt capacitance. Fifty six patients with stable chronic obstructive lung disease of varying severity due to Cystic Fibrosis (CF) and 21 patients with asthma were evaluated by IOS testing. IOS data were input into the augmented RIC (aRIC) model with an upper airway shunt capacitance, and the extended RIC (eRIC) model, without a shunt capacitance element. Model-derived indices were compared between the two models for CF patients separately from asthma patients. We conclude that IOS indices of SAI are modeled equally well with or without upper airway shunt capacitance, and do not seem to be dependent on upper airway shunt capacitance.

  10. Animal model of Mycoplasma fermentans respiratory infection

    Directory of Open Access Journals (Sweden)

    Yáñez Antonio

    2013-01-01

    Full Text Available Abstract Background Mycoplasma fermentans has been associated with respiratory, genitourinary tract infections and rheumatoid diseases but its role as pathogen is controversial. The purpose of this study was to probe that Mycoplasma fermentans is able to produce respiratory tract infection and migrate to several organs on an experimental infection model in hamsters. One hundred and twenty six hamsters were divided in six groups (A-F of 21 hamsters each. Animals of groups A, B, C were intratracheally injected with one of the mycoplasma strains: Mycoplasma fermentans P 140 (wild strain, Mycoplasma fermentans PG 18 (type strain or Mycoplasma pneumoniae Eaton strain. Groups D, E, F were the negative, media, and sham controls. Fragments of trachea, lungs, kidney, heart, brain and spleen were cultured and used for the histopathological study. U frequency test was used to compare recovery of mycoplasmas from organs. Results Mycoplasmas were detected by culture and PCR. The three mycoplasma strains induced an interstitial pneumonia; they also migrated to several organs and persisted there for at least 50 days. Mycoplasma fermentans P 140 induced a more severe damage in lungs than Mycoplasma fermentans PG 18. Mycoplasma pneumoniae produced severe damage in lungs and renal damage. Conclusions Mycoplasma fermentans induced a respiratory tract infection and persisted in different organs for several weeks in hamsters. This finding may help to explain the ability of Mycoplasma fermentans to induce pneumonia and chronic infectious diseases in humans.

  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...

  12. Modeling Respiratory Toxicity of Authentic Lunar Dust

    Science.gov (United States)

    Santana, Patricia A.; James, John T.; Lam, Chiu-Wing

    2010-01-01

    The lunar expeditions of the Apollo operations from the 60 s and early 70 s have generated awareness about lunar dust exposures and their implication towards future lunar explorations. Critical analyses on the reports from the Apollo crew members suggest that lunar dust is a mild respiratory and ocular irritant. Currently, NASA s space toxicology group is functioning with the Lunar Airborne Dust Toxicity Assessment Group (LADTAG) and the National Institute for Occupational Safety and Health (NIOSH) to investigate and examine toxic effects to the respiratory system of rats in order to establish permissible exposure levels (PELs) for human exposure to lunar dust. In collaboration with the space toxicology group, LADTAG and NIOSH the goal of the present research is to analyze dose-response curves from rat exposures seven and twenty-eight days after intrapharyngeal instillations, and model the response using BenchMark Dose Software (BMDS) from the Environmental Protection Agency (EPA). Via this analysis, the relative toxicities of three types of Apollo 14 lunar dust samples and two control dust samples, titanium dioxide (TiO2) and quartz will be determined. This will be executed for several toxicity endpoints such as cell counts and biochemical markers in bronchoaveolar lavage fluid (BALF) harvested from the rats.

  13. Human metapneumovirus: a new respiratory pathogen

    Indian Academy of Sciences (India)

    S Broor; P Bharaj; H S Chahar

    2008-11-01

    Human metapneumovirus is a recently recognized pathogen of acute respiratory tract infection (ARI) in children as well as elderly and immunocompromised adults. The virus belongs to the family Paramyxoviridae, sub family Pneumovirinae and genus Metapneumovirus. Through genetic analysis it has been characterized into two groups A and B which are further divided into four sub-lineages. The virus is difficult to grow in tissue culture and hence reverse transcriptase-polymerase chain reaction (RT-PCR) for N and L gene is the method of choice for diagnosis. The virus has been seen in all countries with seasonal distribution in winter months for temperate and spring/summer for tropical countries. F gene is the most conserved among different lineages and efforts are underway to design recombination vaccine using F gene.

  14. 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 respiratory support. hMPV is present in young...

  15. Numerical analysis of respiratory flow patterns within human upper airway

    Science.gov (United States)

    Wang, Ying; Liu, Yingxi; Sun, Xiuzhen; Yu, Shen; Gao, Fei

    2009-12-01

    A computational fluid dynamics (CFD) approach is used to study the respiratory airflow dynamics within a human upper airway. The airway model which consists of the airway from nasal cavity, pharynx, larynx and trachea to triple bifurcation is built based on the CT images of a healthy volunteer and the Weibel model. The flow characteristics of the whole upper airway are quantitatively described at any time level of respiratory cycle. Simulation results of respiratory flow show good agreement with the clinical measures, experimental and computational results in the literature. The air mainly passes through the floor of the nasal cavity in the common, middle and inferior nasal meatus. The higher airway resistance and wall shear stresses are distributed on the posterior nasal valve. Although the airways of pharynx, larynx and bronchi experience low shear stresses, it is notable that relatively high shear stresses are distributed on the wall of epiglottis and bronchial bifurcations. Besides, two-dimensional fluid-structure interaction models of normal and abnormal airways are built to discuss the flow-induced deformation in various anatomy models. The result shows that the wall deformation in normal airway is relatively small.

  16. [The environment and human respiratory system].

    Science.gov (United States)

    Nikodemowicz, Marian

    2008-01-01

    The process of gas exchange that is breathing is an important element of any person's relation with the environment. What decides about our health and life are the respiratory systems responsible for the breathing process and the quality of the air we breathe. On an average through a person's life 400 millions liters of air flows which carries pollution in the form of constant gases and liquid particles. Particles of about PM-2.5 size get into the deepest structures of the respiratory system from which they are being spread into the whole organism through circulation exerting thier toxic effect on all tissues and organs. The outdoor pollution diffuses but in certain local circumstances it increases. It was so in big ecological disasters such as in 1930 in the Mozy valley in Belgium, in 1948 in the Donory region in the USA and in 1952 smog pollution in London. On an average any human being spends indoors about 60-80% of his time. The increased concentration of pollution occurs indoors and there is a possibility of exposing oneself to ETS- Environmental Tobacco Smoke. The biggest concentration of inhaled pollution takes place when smoking tobacco. Pollution of air causes diseases of the respiratory system, cardiovascular system, tumours and others. Frequent occurrence of COPD in certain areas correlates with the level of air pollution and it significantly increases in tobacco smokers. The number and frequency of bronchial asthma and the need for hospitalization depends on air pollution. Lung cancer cases were rarely described in literature before the area of industrialization and wide spread custom of tobacco smoking. Now it is the most frequently occurred cancer in the whole world. There is an interdependence of the density of population, of the number of smoked cigarettes and of density of pollution with the number lung cancer cases. It is hoped that in the future, smoking habits will be eliminated, the use of crude oil and coal will be replaced by hydroelectric

  17. Application of the physiological and morphological parameters of the brazilian population sample to the mathematical model of the human respiratory tract; Aplicacao dos parametros fisiologicos e morfologicos de uma amostra da populacao brasileira no modelo matematico do trato respiratorio humano

    Energy Technology Data Exchange (ETDEWEB)

    Reis, Arlene Alves dos

    2005-07-01

    The Human Respiratory Tract Model proposed by the ICRP Publication 66 accounts for the morphology and physiology of the respiratory tract. The characteristics of air drawn into the lungs and exhaled are greatly influenced by the morphology of the respiratory tract, which causes numerous changes in pressure, flow rate, direction and humidity as air moves into and out of the lungs. Concerning the respiratory physiological parameters the breathing characteristics influence the volume, the inhalation rate of air and the portion that enters through the nose and the mouth. These characteristics are important to determine the fractional deposition. The model uses morphological and physiological parameters from the Caucasian man to establish deposition fractions in the respiratory tract regions. It is known that the morphology and physiology are influenced by environmental, occupational and economic conditions. The ICRP recommends, for a reliable evaluation of the regional deposition, the use of parameters from a local population when information is available. The main purpose of this study is to verify the influence in using the morphology and physiology parameters representative of a sample of the Brazilian population on the deposition model of the ICRP Publication 66. The morphological and physiological data were obtained from the literature. The software EXCEL for Windows (version 2000) was used in order to implement the deposition model and also to allow the changes in parameters of interest. Initially, the implemented model was checked using the parameters defined by the ICRP and the results of the fraction deposition in the respiratory tract compartments were compared. Finally, morphological and physiological parameters from Brazilian adult male were applied and the fractional deposition calculated. The results suggest a significant variation in fractional deposition when Brazilian parameters are applied in the model. (author)

  18. Dynamics of human respiratory system mycoflora

    Directory of Open Access Journals (Sweden)

    Anna Biedunkiewicz

    2014-08-01

    Full Text Available The study aimed at determing the prevalence of individual species of fungi in the respiratory systems of women and men, analysis of the dynamics of the fungi in individual sections of the respiratory system as concerns their quantity and identification of phenology of the isolated fungi coupled with an attempt at identifying their possible preferences for appearing during specific seasons of thc year. During 10 years of studies (1989- 1998. 29 species of fungi belonging: Candida, Geolrichum, Saccharomyces, Saccharomycopsis, Schizosaccharomyces, Torulopsis, Trichosporon and Aspergillus were isolated from the ontocenoses of the respiratory systems of patients at the Independent Public Center for Pulmonology and Oncology in Olsztyn. Candida albicans was a clearly dominating fungus. Individual species appeared individually, in twos or threes in a single patient, they were isolated more frequently in the spring and autumn, less frequently during the winter and summer. The largest number of fungi species were isolated from sputum (29 species, bronchoscopic material (23 species and pharyngeal swabs (15 species. Sacchoromycopsis capsularis and Trichosporon beigelii should be treated as new for the respiratory system. Biodiversity of fungi, their numbers and continous fluctuations in frequency indicate that the respiratory system ontocenose offers the optimum conditions for growth and development of the majority of the majority of yeasts - like fungi.

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

    African Journals Online (AJOL)

    DR. AMINU

    50% of all pneumonia and up to 90% of the reported cases of bronchiolitis in infancy. It is a common ..... Clinical recovery from RSV bronchiolitis may occur in the presence of ..... of respiratory infections in bone marrow transplant. Pneumonia ...

  20. Aerosol deposition in the human respiratory system. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Yu, C.P.

    1988-01-01

    Attempts were made to develop mathematical models for the deposition of aerosols in the human respiratory system. Expressions were obtained for the mean deposition efficiency for nasal inspiration, nasal expiration, and mouth inspiration. A determination was made of statistical properties associated with each deposition efficiency due to intersubject and intrasubject variabilities. Expressions were then derived for head deposition with combined nose and mouth breathing. In the lung, deposition is a result primarily of impaction, sedimentation, and diffusion. While there was no adequate model for impaction, several deposition formulae for sedimentation were derived as well as ones for diffusion. Studies were also made of the particle charge effect, as the electrostatic image force on a particle contributes to its deposition. There is, however, a threshold charge per particle below which the particle charge has no effect on deposition. Deposition data on ultrafine particles is scarce due to the difficulties in conducting proper experiments.

  1. Respiratory tract deposition of polydisperse aerosols in humans.

    Science.gov (United States)

    Diu, C K; Yu, C P

    1983-01-01

    Total and regional deposition of polydisperse aerosols in the human respiratory tract are studied theoretically. The size distribution of the aerosol is assumed to be lognormal. For a given mass median particle diameter, mass deposition fraction is found to vary with the geometric standard deviation of the aerosol. The departure of the deposition pattern in various regions of the respiratory system from that of a monodisperse aerosol is interpreted in terms of the average mobility effect and deposition limitation effect of the polydisperse aerosol together with the sequential filtering effect of the respiratory tract.

  2. Human Respiratory Responses during High Performance Flight

    Science.gov (United States)

    1987-11-01

    6SZ United Kingdom (c) Copyright (C) Controller BHSO London 1987 Sunwmiy The respiratory responses of experienced militar , pilots have been...40 Merrifield J T, Flick C A. In-flight oxygen measurement equipment. Air Standardization Co-ordinating Committee : Aerospace Medico ! & Life Support...Flugrad Reyjavik ITALY Aeronautica Militare Ufficic del Delegate Nazionale alTAGARD 3 Piarzale Adenauer 00 i 44 Roms/EUR LUXEMBOURG See

  3. Computational modeling of aerosol deposition in respiratory tract: a review.

    Science.gov (United States)

    Rostami, Ali A

    2009-02-01

    This review article is intended to serve as an overview of the current status of the computational tools and approaches available for predicting respiratory-tract dosimetry of inhaled particulate matter. There are two groups of computational models available, depending on the intended use. The whole-lung models are designed to provide deposition prediction for the whole lung, from the oronasal cavities to the pulmonary region. The whole-lung models are generally semi-empirical and hence provide more reliable results but within the range of parameters used for empirical correlations. The local deposition or computational fluid dynamics (CFD)-based models, on the other hand, utilize comprehensive theoretical and computational approaches but are often limited to upper respiratory tracts. They are based on theoretical principles and are applicable to a wider range of parameters, but less accurate. One of the difficulties with modeling of aerosol deposition in human lung is related to the complexity of the airways geometry and the limited morphometric data available. Another difficulty corresponds to simulation of the realistic physiological conditions of lung environment. Furthermore, complex physical and chemical phenomena associated with dense and multicomponent aerosols complicate the modeling tasks. All of these issues are addressed in this review. The progress made in each area in the last three decades and the challenges ahead are discussed along with some suggestions for future direction. The following subjects are covered in this review: introduction, aerosol deposition mechanisms, elements of a computational model, respiratory-tract geometry models, whole-lung models, CFD based models, cigarette smoke deposition models, and conclusion.

  4. Dynamic stability of locomotor respiratory coupling during cycling in humans.

    Science.gov (United States)

    Villard, Sébastien; Casties, Jean-François; Mottet, Denis

    2005-08-05

    We explored the locomotor respiratory coupling (LRC) during a 50-min constant-load submaximal cycling exercise. A 4-week recombinant human erythropoietin (r-HuEPO) treatment improved participants' aerobic capabilities, but did not elicit significant changes in LRC. The distributions of the respiratory frequency over pedalling frequency ratios were systematically bimodal, with a preferred use of 1/3 and 1/2, and a progressive shift of the higher mode from 1/3 towards 1/2 with exercise duration. These results are interpreted in the framework of the sine circle map as the result of coordination dynamics between the physiological subsystems involved in the breathing pedalling cooperation.

  5. Cardiac, respiratory, and locomotor coordination during walking in humans.

    Science.gov (United States)

    Niizeki, K; Kawahara, K; Miyamoto, Y

    1996-01-01

    Interactions between locomotor, respiratory, and cardiac rhythms were investigated in human subjects (n = 11) walking on a treadmill. Investigation of the phase relationship between heart rate and gait signals revealed that cardiac rhythms were entrained to locomotor rhythms when both frequencies were close to an integer ratio. Coherence spectra were estimated between heartbeat fluctuation, respiratory, and gait signals, and their magnitudes were evaluated. The results suggest that the respiratory-induced fluctuation in heartbeat would vary depending on the strength of the cardiolocomotor coupling. The synchronization tends to occur for one or two specific phases in an individual subject, but there was some variation among subjects. When the subjects voluntarily synchronized their cadence with the cardiac rhythm, the heart rate and blood pressure varied depending on the phase lag within a cardiac cycle. The coordination of locomotor and cardiac rhythms is discussed.

  6. Human torso phantom for imaging of heart with realistic modes of cardiac and respiratory motion

    Science.gov (United States)

    Boutchko, Rostyslav; Balakrishnan, Karthikayan; Gullberg, Grant T; O& #x27; Neil, James P

    2013-09-17

    A human torso phantom and its construction, wherein the phantom mimics respiratory and cardiac cycles in a human allowing acquisition of medical imaging data under conditions simulating patient cardiac and respiratory motion.

  7. Recent advances in theoretical models of respiratory mechanics

    Institute of Scientific and Technical Information of China (English)

    Bo Huo; Rui-Rong Fu

    2012-01-01

    As an important branch of biomedical engineering,respiratory mechanics helps to understand the physiology of the respiratory system and provides fundamental data for developing such clinical technologies as ventilators.To solve different clinical problems,researchers have developed numerous models at various scales that describe biological and mechanical properties of the respiratory system.During the past decade,benefiting from the continuous accumulation of clinical data and the dramatic progress of biomedical technologies (e.g.biomedical imaging),the theoretical modeling of respiratory mechanics has made remarkable progress regarding the macroscopic properties of the respiratory process,complexities of the respiratory system,gas exchange within the lungs,and the coupling interaction between lung and heart.The present paper reviews the advances in the above fields and proposes potential future projects.

  8. Propagation of respiratory viruses in human airway epithelia reveals persistent virus-specific signatures.

    Science.gov (United States)

    Essaidi-Laziosi, Manel; Brito, Francisco; Benaoudia, Sacha; Royston, Léna; Cagno, Valeria; Fernandes-Rocha, Mélanie; Piuz, Isabelle; Zdobnov, Evgeny; Huang, Song; Constant, Samuel; Boldi, Marc-Olivier; Kaiser, Laurent; Tapparel, Caroline

    2017-08-07

    Leading etiologies of acute illnesses, respiratory viruses typically cause self-limited diseases, though severe complications can occur in fragile patients. Rhinoviruses, respiratory enteroviruses, influenza virus, respiratory syncytial viruses and coronaviruses are highly prevalent respiratory pathogens, but due to the lack of reliable animal models, their differential pathogenesis remains poorly characterized. To compare infections by respiratory viruses isolated from clinical specimens using reconstituted human airway epithelia. Tissues were infected with rhinoviruses RV-A55, RV-A49, RV-B48, RV-C8 and RV-C15, respiratory enterovirus EV-D68, influenza virus H3N2, respiratory syncytial virus RSV-B and coronavirus HCoV-OC43. Replication kinetics, cell tropism, impact on tissue integrity and cytokine secretion were compared. Virus adaptation and tissue response were assessed through RNA-sequencing. Rhinoviruses, RSV-B and HCoV-OC43 infected ciliated cells and caused no major cell death while H3N2 and EV-D68 induced ciliated cell loss and tissue integrity disruption. H3N2 was also detected in rare goblet and basal cells. All viruses except RV-B48 and HCoV-OC43 altered cilia beating and MCC. H3N2 was the strongest cytokine-inducer and HCoV-OC43 the weakest. Persistent infection was observed in all cases. RNA-sequencing highlighted perturbation of tissue metabolism and induction of a transient but important immune response at 4-days post-infection. No majority mutations emerged in the viral population. Our results highlight the differential in vitro pathogenesis of respiratory viruses during the acute infection-phase and their ability to persist under immune tolerance. These data help to appreciate the range of disease severity observed in vivo and the occurrence of chronic respiratory infections in immunocompromised hosts. Copyright © 2017. Published by Elsevier Inc.

  9. Differential expression of the Middle East respiratory syndrome coronavirus receptor in the upper respiratory tracts of humans and dromedary camels

    NARCIS (Netherlands)

    W. Widagdo; V.S. Raj (Stalin); D. Schipper (Debby); K. Kolijn (Kimberley); G.J.H.L. Leenders (Geert); B.J. Bosch (Berend Jan); A. Bensaid (Albert); J. Segalés (Joaquim); W. Baumgärtner (Wolfgang); A.D.M.E. Osterhaus (Albert); M.P.G. Koopmans D.V.M. (Marion); J.M.A. van den Brand (Judith); B.L. Haagmans (Bart)

    2016-01-01

    textabstractMiddle East respiratory syndrome coronavirus (MERS-CoV) is not efficiently transmitted between humans, but it is highly prevalent in dromedary camels. Here we report that the MERS-CoV receptor-dipeptidyl peptidase 4 (DPP4)-is expressed in the upper respiratory tract epithelium of camels

  10. LOCAL AND GLOBAL HOPF BIFURCATIONS IN A DELAYED HUMAN RESPIRATORY SYSTEM

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    This paper considers a delayed human respiratory model. Firstly, the stability of the equilibrium of the model is investigated and the occurrence of a sequence of Hopf bifurcations of the model is proved. Secondly, the explicit algorithms which determine the direction of the Hopf bifurcations and the stability of the bifurcating periodic solutions are derived by applying the normal form method and the center manifold theory. Finally, the existence of the global periodic solutions is showed under some ass...

  11. ANIMAL MODELS FOR PROTEIN RESPIRATORY SENSITIZERS

    Science.gov (United States)

    Protein induced respiratory hypersensitivity, particularly atopic disease in general, and allergic asthma in particular, has increased dramatically over the last several decades in the U.S. and other industrialized nations as a result of ill-defined changes in living conditions i...

  12. Respiratory activity and growth of human skin derma fibroblasts.

    Science.gov (United States)

    Papa, F; Scacco, S; Vergari, R; Bucaria, V; Dioguardi, D; Papa, S

    1998-09-01

    A study has been made on the speed of growth and respiratory activity of fibroblast cultures from control derma, cheloid (hypertrophic) scar and stabilized scar taken from human skin. The speed of growth and the efficiency of plaque formation of fibroblasts from cheloid scar were greater in comparison with those of fibroblasts from stabilized scar and were stimulated by the addition to the culture medium of the exudate from post-traumatic ulcer. Measurement of the contents of cytochromes showed a decrease in the content of cytochromes b562 and c + c1 in the fibroblast culture from both cheloid and stabilized scar as compared to the fibroblast culture from control derma. Cytochrome aa3 content did not show significant difference among the three types of fibroblast cultures. The respiratory activities supported by pyruvate plus malate, succinate or ascorbate plus N,N,N',N'-tetramethyl-p-phenylenediamine did not show, however, significant difference among the three fibroblast cultures. These observations show that the speed of growth of skin fibroblasts does not depend on the overall respiratory capacity. The exudate stimulated the activity of cytochrome c oxidase in fibroblasts from control derma, and cheloid scar. This effect and the accompanying stimulation of fibroblast growth might be correlated with the balance of oxygen free radicals.

  13. Effect of Streptococcus pneumoniae on human respiratory epithelium in vitro.

    Science.gov (United States)

    Steinfort, C; Wilson, R; Mitchell, T; Feldman, C; Rutman, A; Todd, H; Sykes, D; Walker, J; Saunders, K; Andrew, P W

    1989-07-01

    A total of 11 of 15 Streptococcus pneumoniae culture filtrates and all five bacterial autolysates produced by cell death in the stationary phase caused slowed ciliary beating and disruption of the surface integrity of human respiratory epithelium in organ culture. This effect was inhibited by cholesterol and was heat labile and reduced by standing at room temperature but was stable at -40 degrees C. The activity was detected at the late stationary phase of culture and was associated with the presence of hemolytic activity. Gel filtration of a concentrated culture filtrate and autolysate both yielded a single fraction of approximately 50 kilodaltons which slowed ciliary beating and were the only fractions with hemolytic activity. Rabbit antiserum to pneumolysin, a sulfhydryl-activated hemolytic cytotoxin released by S. pneumoniae during autolysis, neutralized the effect of the culture filtrate on respiratory epithelium. Both native and recombinant pneumolysin caused ciliary slowing and epithelial disruption. Electron microscopy showed a toxic effect of pneumolysin on epithelial cells: cytoplasmic blebs, mitochondrial swelling, cellular extrusion, and cell death, but no change in ciliary ultrastructure. Recombinant pneumolysin (10 micrograms/ml) caused ciliary slowing in the absence of changes in cell ultrastructure. Release of pneumolysin in the respiratory tract during infection may perturb host defenses, allowing bacterial proliferation and spread.

  14. Electromagnetic respiratory effort harvester: human testing and metabolic cost analysis.

    Science.gov (United States)

    Shahhaidar, E; Padasdao, B; Romine, R; Stickley, C; Lubecke, O Boric

    2015-03-01

    Remote health monitoring is increasingly recognized as a valuable tool in chronic disease management. Continuous respiratory monitoring could be a powerful tool in managing chronic diseases, however it is infrequently performed because of obtrusiveness and inconvenience of the existing methods. The movements of the chest wall and abdominal area during normal breathing can be monitored and harvested to enable self-powered wearable biosensors for continuous remote monitoring. This paper presents human testing results of a light-weight (30 g), wearable respiratory effort energy harvesting sensor. The harvester output voltage, power, and its metabolic burden, are measured on twenty subjects in two resting and exercise conditions each lasting 5 min. The system includes two off-the-shelf miniature electromagnetic generators harvesting and sensing thoracic and abdominal movements. Modules can be placed in series to increase the output voltage for rectification purposes. Electromagnetic respiratory effort harvester/sensor system can produce up to 1.4 V, 6.44 mW, and harvests 30.4 mJ during a 5-min exercise stage. A statistical paired t-test analysis of the calculated EE confirmed there is no significant change ( P > 0.05 ) in the metabolic rate of subjects wearing the electromagnetic harvester and biosensor.

  15. Differential Mucin Expression by Respiratory Syncytial Virus and Human Metapneumovirus Infection in Human Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Ma. Del Rocío Baños-Lara

    2015-01-01

    Full Text Available Mucins (MUC constitute an important component of the inflammatory and innate immune response. However, the expression of these molecules by respiratory viral infections is still largely unknown. Respiratory syncytial virus (RSV and human metapneumovirus (hMPV are two close-related paramyxoviruses that can cause severe low respiratory tract disease in infants and young children worldwide. Currently, there is not vaccine available for neither virus. In this work, we explored the differential expression of MUC by RSV and hMPV in human epithelial cells. Our data indicate that the MUC expression by RSV and hMPV differs significantly, as we observed a stronger induction of MUC8, MUC15, MUC20, MUC21, and MUC22 by RSV infection while the expression of MUC1, MUC2, and MUC5B was dominated by the infection with hMPV. These results may contribute to the different immune response induced by these two respiratory viruses.

  16. Numerical stability analysis in respiratory control system models

    Directory of Open Access Journals (Sweden)

    Laszlo E. Kollar

    2005-04-01

    Full Text Available Stability of the unique equilibrium in two mathematical models (based on chemical balance dynamics of human respiration is examined using numerical methods. Due to the transport delays in the respiratory control system these models are governed by delay differential equations. First, a simplified two-state model with one delay is considered, then a five-state model with four delays (where the application of numerical methods is essential is investigated. In particular, software is developed to perform linearized stability analysis and simulations of the model equations. Furthermore, the Matlab package DDE-BIFTOOL v.~2.00 is employed to carry out numerical bifurcation analysis. Our main goal is to study the effects of transport delays on the stability of the model equations. Critical values of the transport delays (i.e., where Hopf bifurcations occur are determined, and stable periodic solutions are found as the delays pass their critical values. The numerical findings are in good agreement with analytic results obtained earlier for the two-state model.

  17. Reference respiratory waveforms by minimum jerk model analysis

    Energy Technology Data Exchange (ETDEWEB)

    Anetai, Yusuke, E-mail: anetai@radonc.med.osaka-u.ac.jp; Sumida, Iori; Takahashi, Yutaka; Yagi, Masashi; Mizuno, Hirokazu; Ogawa, Kazuhiko [Department of Radiation Oncology, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita-shi, Osaka 565-0871 (Japan); Ota, Seiichi [Department of Medical Technology, Osaka University Hospital, Yamadaoka 2-15, Suita-shi, Osaka 565-0871 (Japan)

    2015-09-15

    Purpose: CyberKnife{sup ®} robotic surgery system has the ability to deliver radiation to a tumor subject to respiratory movements using Synchrony{sup ®} mode with less than 2 mm tracking accuracy. However, rapid and rough motion tracking causes mechanical tracking errors and puts mechanical stress on the robotic joint, leading to unexpected radiation delivery errors. During clinical treatment, patient respiratory motions are much more complicated, suggesting the need for patient-specific modeling of respiratory motion. The purpose of this study was to propose a novel method that provides a reference respiratory wave to enable smooth tracking for each patient. Methods: The minimum jerk model, which mathematically derives smoothness by means of jerk, or the third derivative of position and the derivative of acceleration with respect to time that is proportional to the time rate of force changed was introduced to model a patient-specific respiratory motion wave to provide smooth motion tracking using CyberKnife{sup ®}. To verify that patient-specific minimum jerk respiratory waves were being tracked smoothly by Synchrony{sup ®} mode, a tracking laser projection from CyberKnife{sup ®} was optically analyzed every 0.1 s using a webcam and a calibrated grid on a motion phantom whose motion was in accordance with three pattern waves (cosine, typical free-breathing, and minimum jerk theoretical wave models) for the clinically relevant superior–inferior directions from six volunteers assessed on the same node of the same isocentric plan. Results: Tracking discrepancy from the center of the grid to the beam projection was evaluated. The minimum jerk theoretical wave reduced the maximum-peak amplitude of radial tracking discrepancy compared with that of the waveforms modeled by cosine and typical free-breathing model by 22% and 35%, respectively, and provided smooth tracking for radial direction. Motion tracking constancy as indicated by radial tracking discrepancy

  18. Perinatal Lamb Model of Respiratory Syncytial Virus (RSV) Infection

    Science.gov (United States)

    Derscheid, Rachel J.; Ackermann, Mark R.

    2012-01-01

    Respiratory syncytial virus (RSV) is the most frequent cause of bronchiolitis in infants and children worldwide. Many animal models are used to study RSV, but most studies investigate disease in adult animals which does not address the unique physiology and immunology that makes infants more susceptible. The perinatal (preterm and term) lamb is a useful model of infant RSV disease as lambs have similar pulmonary structure including airway branching, Clara and type II cells, submucosal glands and Duox/lactoperoxidase (LPO) oxidative system, and prenatal alveologenesis. Lambs can be born preterm (90% gestation) and survive for experimentation although both preterm and term lambs are susceptible to ovine, bovine and human strains of RSV and develop clinical symptoms including fever, tachypnea, and malaise as well as mild to moderate gross and histologic lesions including bronchiolitis with epithelial injury, neutrophil infiltration and syncytial cell formation. RSV disease in preterm lambs is more severe than in term lambs; disease is progressively less in adults and age-dependent susceptibility is a feature similar to humans. Innate and adaptive immune responses by perinatal lambs closely parallel those of infants. The model is used to test therapeutic regimens, risk factors such as maternal ethanol consumption, and formalin inactivated RSV vaccines. PMID:23202468

  19. Perinatal Lamb Model of Respiratory Syncytial Virus (RSV Infection

    Directory of Open Access Journals (Sweden)

    Mark R. Ackermann

    2012-10-01

    Full Text Available Respiratory syncytial virus (RSV is the most frequent cause of bronchiolitis in infants and children worldwide. Many animal models are used to study RSV, but most studies investigate disease in adult animals which does not address the unique physiology and immunology that makes infants more susceptible. The perinatal (preterm and term lamb is a useful model of infant RSV disease as lambs have similar pulmonary structure including airway branching, Clara and type II cells, submucosal glands and Duox/lactoperoxidase (LPO oxidative system, and prenatal alveologenesis. Lambs can be born preterm (90% gestation and survive for experimentation although both preterm and term lambs are susceptible to ovine, bovine and human strains of RSV and develop clinical symptoms including fever, tachypnea, and malaise as well as mild to moderate gross and histologic lesions including bronchiolitis with epithelial injury, neutrophil infiltration and syncytial cell formation. RSV disease in preterm lambs is more severe than in term lambs; disease is progressively less in adults and age-dependent susceptibility is a feature similar to humans. Innate and adaptive immune responses by perinatal lambs closely parallel those of infants. The model is used to test therapeutic regimens, risk factors such as maternal ethanol consumption, and formalin inactivated RSV vaccines.

  20. Interactions between cardiac, respiratory, and brain activity in humans

    Science.gov (United States)

    Musizza, Bojan; Stefanovska, Aneta

    2005-05-01

    The electrical activity of the heart (ECG), respiratory function and electric activity of the brain (EEG) were simultaneously recorded in conscious, healthy humans. Instantaneous frequencies of the heart beat, respiration and α-waves were then determined from 30-minutes recordings. The instantaneous cardiac frequency was defined as the inverse value of the time interval between two consecutive R-peaks. The instantaneous respiratory frequency was obtained from recordings of the excursions of thorax by application of the Hilbert transform. To obtain the instantaneous frequency of α-waves, the EEG signal recorded from the forehead was first analysed using the wavelet transform. Then the frequency band corresponding to α-waves was extracted and the Hilbert transform applied. Synchronization analysis was performed and the direction of coupling was ascertained, using pairs of instantaneous frequencies in each case. It is shown that the systems are weakly bidirectionally coupled. It was confirmed that, in conscious healthy humans, respiration drives cardiac activity. We also demonstrate from these analyses that α-activity drives both respiration and cardiac activity.

  1. Presence of Saccharomycopsis capsularis in the human respiratory system

    Directory of Open Access Journals (Sweden)

    Maria Dynowska

    2014-08-01

    Full Text Available The following paper represents a fragment of studies on the dynamics of microflora in the human respiratory system with a particular focus on new species developing in that ontocoenosis. Saccharomycopsis capsularus amounts to 6.7% of all the isolated fungi. The isolates were obtained from sputum (41.9%, bronchoscopic material (18.6% and the pharyngeal, nasal and oral swabs representing jointly 39.5% of the positive results. Almost twice as many isolates were obtained from women (66.3% as from men (33.7%. The fungi were most frequently found in the spring and autumn, more rarely in the winter, the rarest in the summer. Appearance of S. capsularis in the human body is, most probably, a consequence of its increased expansiveness in the external environment. So far it has been isolated from the soil, pollens of some tropical plants and from water reservoirs contaminated with municipal sewage.

  2. Research on an active and continuous monitoring system for human respiratory system

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Continuous and dynamic measurements of human respiratory parameters are very important for vital diseases of respiratory system during mechanical ventilation. This paper analyzed the structure and mechanical properties of the human respiratory system, and designed an active intervening monitoring micro system for it. The mobile mechanism of the micro system is soft and earthworm-like movement actuated by pneumatic rubber actuator, the measurement and therapy unit of the system is an extensible mechanism with sensors in the front. The micro monitoring system can move in respiratory tract and measure the respiratory parameters in bronchium continuously. Experiments had been done in swine's respiratory tract,the results proved that the micro robot system could measure the respiratory parameters in real-time successfully and its movement was smooth in swine's respiratory tract.

  3. Modeling neural mechanisms for genesis of respiratory rhythm and pattern. II. Network models of the central respiratory pattern generator.

    Science.gov (United States)

    Rybak, I A; Paton, J F; Schwaber, J S

    1997-04-01

    The present paper describes several models of the central respiratory pattern generator (CRPG) developed employing experimental data and current hypotheses for respiratory rhythmogenesis. Each CRPG model includes a network of respiratory neuron types (e.g., early inspiratory; ramp inspiratory; late inspiratory; decrementing expiratory; postinspiratory; stage II expiratory; stage II constant firing expiratory; preinspiratory) and simplified models of lung and pulmonary stretch receptors (PSR), which provide feedback to the respiratory network. The used models of single respiratory neurons were developed in the Hodgkin-Huxley style as described in the previous paper. The mechanism for termination of inspiration (the inspiratory off-switch) in all models operates via late-I neuron, which is considered to be the inspiratory off-switching neuron. Several two- and three-phase CRPG models have been developed using different accepted hypotheses of the mechanism for termination of expiration. The key elements in the two-phase models are the early-I and dec-E neurons. The expiratory off-switch mechanism in these models is based on the mutual inhibitory connections between early-I and dec-E and adaptive properties of the dec-E neuron. The difference between the two-phase models concerns the mechanism for ramp firing patterns of E2 neurons resulting either from the intrinsic neuronal properties of the E2 neuron or from disinhibition from the adapting dec-E neuron. The key element of the three-phase models is the pre-I neuron, which acts as the expiratory off-switching neuron. The three-phase models differ by the mechanisms used for termination of expiration and for the ramp firing patterns of E2 neurons. Additional CRPG models were developed employing a dual switching neuron that generates two bursts per respiratory cycle to terminate both inspiration and expiration. Although distinctly different each model generates a stable respiratory rhythm and shows physiologically

  4. Present and Future Human Thermal Bioclimatic Conditions and Impacts on Respiratory Admissions in Crete Island, Greece

    Science.gov (United States)

    Bleta, Anastasia; Nastos, Panagiotis

    2015-04-01

    The objective of this study is to assess and quantify the association between present and future human thermal bioclimatic conditions and daily counts of respiratory problems in Heraklion city, Crete Island, Greece. The bioclimatic conditions were analyzed in terms of the Physiologically Equivalent Temperature (PET) and Universal Thermal Climate Index (UTCI), which are two of the most popular human thermal indices based on the human energy balance. The PET and UTCI analysis was performed by the application of the bioclimate model, "RayMan", which is well-suited to calculate radiation fluxes and human biometeorological indices. Future changes in meteorological parameters such as air temperature, relative humidity, wind speed and cloudiness (used as input variables in the estimation of PET and UTCI) were derived by the simulations of the regional atmospheric climate model KNMI under SRES A1B, for the near (2021-2050) and far (2071-2100) future with respect to the reference period 1961-1990. Generalized linear models (GLM) with Poisson distribution were applied to the time series of daily numbers of outpatients (total, males and females) with respiratory problems against present and future bioclimatic changes, after controlling for possible confounders and adjustment for season and trends. The interpretation of the results of this analysis suggests a significant association between cold weather and increased respiratory admissions. For the near future, the projected increase of 1.6oC in PET may result in reducing the incidence of respiratory problemsby almost 3% against 7.5% in the far future, when PET is projected to increase by 4oC.

  5. A Bidirectional Coupling Procedure Applied to Multiscale Respiratory Modeling.

    Science.gov (United States)

    Kuprat, A P; Kabilan, S; Carson, J P; Corley, R A; Einstein, D R

    2013-07-01

    In this study, we present a novel multiscale computational framework for efficiently linking multiple lower-dimensional models describing the distal lung mechanics to imaging-based 3D computational fluid dynamics (CFD) models of the upper pulmonary airways in order to incorporate physiologically appropriate outlet boundary conditions. The framework is an extension of the Modified Newton's Method with nonlinear Krylov accelerator developed by Carlson and Miller [1, 2, 3]. Our extensions include the retention of subspace information over multiple timesteps, and a special correction at the end of a timestep that allows for corrections to be accepted with verified low residual with as little as a single residual evaluation per timestep on average. In the case of a single residual evaluation per timestep, the method has zero additional computational cost compared to uncoupled or unidirectionally coupled simulations. We expect these enhancements to be generally applicable to other multiscale coupling applications where timestepping occurs. In addition we have developed a "pressure-drop" residual which allows for stable coupling of flows between a 3D incompressible CFD application and another (lower-dimensional) fluid system. We expect this residual to also be useful for coupling non-respiratory incompressible fluid applications, such as multiscale simulations involving blood flow. The lower-dimensional models that are considered in this study are sets of simple ordinary differential equations (ODEs) representing the compliant mechanics of symmetric human pulmonary airway trees. To validate the method, we compare the predictions of hybrid CFD-ODE models against an ODE-only model of pulmonary airflow in an idealized geometry. Subsequently, we couple multiple sets of ODEs describing the distal lung to an imaging-based human lung geometry. Boundary conditions in these models consist of atmospheric pressure at the mouth and intrapleural pressure applied to the multiple sets

  6. A bidirectional coupling procedure applied to multiscale respiratory modeling

    Science.gov (United States)

    Kuprat, A. P.; Kabilan, S.; Carson, J. P.; Corley, R. A.; Einstein, D. R.

    2013-07-01

    In this study, we present a novel multiscale computational framework for efficiently linking multiple lower-dimensional models describing the distal lung mechanics to imaging-based 3D computational fluid dynamics (CFDs) models of the upper pulmonary airways in order to incorporate physiologically appropriate outlet boundary conditions. The framework is an extension of the modified Newton's method with nonlinear Krylov accelerator developed by Carlson and Miller [1], Miller [2] and Scott and Fenves [3]. Our extensions include the retention of subspace information over multiple timesteps, and a special correction at the end of a timestep that allows for corrections to be accepted with verified low residual with as little as a single residual evaluation per timestep on average. In the case of a single residual evaluation per timestep, the method has zero additional computational cost compared to uncoupled or unidirectionally coupled simulations. We expect these enhancements to be generally applicable to other multiscale coupling applications where timestepping occurs. In addition we have developed a "pressure-drop" residual which allows for stable coupling of flows between a 3D incompressible CFD application and another (lower-dimensional) fluid system. We expect this residual to also be useful for coupling non-respiratory incompressible fluid applications, such as multiscale simulations involving blood flow. The lower-dimensional models that are considered in this study are sets of simple ordinary differential equations (ODEs) representing the compliant mechanics of symmetric human pulmonary airway trees. To validate the method, we compare the predictions of hybrid CFD-ODE models against an ODE-only model of pulmonary airflow in an idealized geometry. Subsequently, we couple multiple sets of ODEs describing the distal lung to an imaging-based human lung geometry. Boundary conditions in these models consist of atmospheric pressure at the mouth and intrapleural

  7. The draft genome sequence of the ferret (Mustela putorius furo) facilitates study of human respiratory disease.

    Science.gov (United States)

    Peng, Xinxia; Alföldi, Jessica; Gori, Kevin; Eisfeld, Amie J; Tyler, Scott R; Tisoncik-Go, Jennifer; Brawand, David; Law, G Lynn; Skunca, Nives; Hatta, Masato; Gasper, David J; Kelly, Sara M; Chang, Jean; Thomas, Matthew J; Johnson, Jeremy; Berlin, Aaron M; Lara, Marcia; Russell, Pamela; Swofford, Ross; Turner-Maier, Jason; Young, Sarah; Hourlier, Thibaut; Aken, Bronwen; Searle, Steve; Sun, Xingshen; Yi, Yaling; Suresh, M; Tumpey, Terrence M; Siepel, Adam; Wisely, Samantha M; Dessimoz, Christophe; Kawaoka, Yoshihiro; Birren, Bruce W; Lindblad-Toh, Kerstin; Di Palma, Federica; Engelhardt, John F; Palermo, Robert E; Katze, Michael G

    2014-12-01

    The domestic ferret (Mustela putorius furo) is an important animal model for multiple human respiratory diseases. It is considered the 'gold standard' for modeling human influenza virus infection and transmission. Here we describe the 2.41 Gb draft genome assembly of the domestic ferret, constituting 2.28 Gb of sequence plus gaps. We annotated 19,910 protein-coding genes on this assembly using RNA-seq data from 21 ferret tissues. We characterized the ferret host response to two influenza virus infections by RNA-seq analysis of 42 ferret samples from influenza time-course data and showed distinct signatures in ferret trachea and lung tissues specific to 1918 or 2009 human pandemic influenza virus infections. Using microarray data from 16 ferret samples reflecting cystic fibrosis disease progression, we showed that transcriptional changes in the CFTR-knockout ferret lung reflect pathways of early disease that cannot be readily studied in human infants with cystic fibrosis disease.

  8. Complete Genome Sequence of Human Respiratory Syncytial Virus from Lanzhou, China

    OpenAIRE

    Zhu, Chuanfeng; Fu, Shengfang; Zhou, Xv; Yu, Li

    2017-01-01

    ABSTRACT A complete genome of human respiratory syncytial virus was sequenced and analyzed. Phylogenetic analysis showed that the full-length human respiratory syncytial virus (HRSV) genome sequence belongs to gene type NA1. We sequenced the genome in order to create the full-length cDNA infectious clone and develop vaccines against HRSV.

  9. Xenograft model for therapeutic drug testing in recurrent respiratory papillomatosis.

    Science.gov (United States)

    Ahn, Julie; Bishop, Justin A; Akpeng, Belinda; Pai, Sara I; Best, Simon R A

    2015-02-01

    Identifying effective treatment for papillomatosis is limited by a lack of animal models, and there is currently no preclinical model for testing potential therapeutic agents. We hypothesized that xenografting of papilloma may facilitate in vivo drug testing to identify novel treatment options. A biopsy of fresh tracheal papilloma was xenografted into a NOD-scid-IL2Rgamma(null) (NSG) mouse. The xenograft began growing after 5 weeks and was serially passaged over multiple generations. Each generation showed a consistent log-growth pattern, and in all xenografts, the presence of the human papillomavirus (HPV) genome was confirmed by polymerase chain reaction (PCR). Histopathologic analysis demonstrated that the squamous architecture of the original papilloma was maintained in each generation. In vivo drug testing with bevacizumab (5 mg/kg i.p. twice weekly for 3 weeks) showed a dramatic therapeutic response compared to saline control. We report here the first successful case of serial xenografting of a tracheal papilloma in vivo with a therapeutic response observed with drug testing. In severely immunocompromised mice, the HPV genome and squamous differentiation of the papilloma can be maintained for multiple generations. This is a feasible approach to identify therapeutic agents in the treatment of recurrent respiratory papillomatosis. © The Author(s) 2014.

  10. In vivo Measurement of Unattached Radon Progeny Deposited in the Human Respiratory Tract

    Energy Technology Data Exchange (ETDEWEB)

    Butterweck, G.; Vezzu, G.; Schuler, Ch.; Mueller, R.; Marsh, J.W.; Thrift, S.; Birchall, A

    2001-07-01

    Seven nose breathing and seven mouth breathing volunteers were exposed to atmospheres enriched with unattached radon progeny ({sup 218}Po, {sup 214}Pb and {sup 214}Bi). The activity of these radionuclides deposited in the respiratory track was measured in vivo after the exposures. The results of these measurements are in agreement with predictions calculated with the ICRP Publication 66 Human Respiratory Tract Model. Temporal analysis of the activity deposited in the heads of the volunteers leads to the conclusion that a significant amount of the deposited activity associated with particle diameters of about 1 nm is not subject to a fast transport to the gastrointestinal tract as generally reported for larger aerosol particles. (author)

  11. A respiratory model for uranium aluminide based on occupational data.

    Science.gov (United States)

    Leggett, R W; Eckerman, K F; Boice, J D

    2005-12-01

    As part of an epidemiological study, doses from intake of radionuclides were estimated for workers employed during a 52-year period at the Rocketdyne/Atomics International facility in California. The facility was involved in a variety of research programmes, including nuclear fuel fabrication, spent nuclear fuel decladding, and reactor operation and disassembly. Most of the documented intakes involved inhalation of enriched uranium (U), fission products, or plutonium (Pu). Highest doses were estimated for a group of workers exposed to airborne uranium aluminide (UAl(x)) during the fabrication of reactor fuel plates. Much of the exposure to UAl(x) occurred early in the fuel fabrication programme, before it was recognised that intake and lung retention were being underestimated from urinary data due to an unexpected delayed dissolution of the inhaled material. In workers who had been removed from exposure, the rate of urinary excretion of U increased for a few months, peaked, and then declined at a rate consistent with moderately soluble material. This pattern differs markedly from the monotonically decreasing absorption rates represented by the default absorption types in the Human Respiratory Tract Model (HRTM) of the International Commission on Radiological Protection (ICRP). This paper summarises the findings on the behaviour of UAl(x) in these workers and describes material-specific parameter values of the HRTM based on this information.

  12. A Wearable Capacitive Sensor for Monitoring Human Respiratory Rate

    Science.gov (United States)

    Kundu, Subrata Kumar; Kumagai, Shinya; Sasaki, Minoru

    2013-04-01

    Realizing an untethered, low-cost, and comfortably wearable respiratory rate sensor for long-term breathing monitoring application still remains a challenge. In this paper, a conductive-textile-based wearable respiratory rate sensing technique based on the capacitive sensing approach is proposed. The sensing unit consists of two conductive textile electrodes that can be easily fabricated, laminated, and integrated in garments. Respiration cycle is detected by measuring the capacitance of two electrodes placed on the inner anterior and posterior sides of a T-shirt at either the abdomen or chest position. A convenient wearable respiratory sensor setup with a capacitance-to-voltage converter has been devised. Respiratory rate as well as breathing mode can be accurately identified using the designed sensor. The sensor output provides significant information on respiratory flow. The effectiveness of the proposed system for different breathing patterns has been evaluated by experiments.

  13. 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.

  14. Complete Genome Sequences of Four Different Bordetella sp. Isolates Causing Human Respiratory Infections

    Science.gov (United States)

    Peng, Yanhui; Loparev, Vladimir; Batra, Dhwani; Bowden, Katherine E.; Cassiday, Pamela K.; Davis, Jamie K.; Johnson, Taccara; Juieng, Phalasy; Miner, Christine E.; Rowe, Lori; Sheth, Mili; Tondella, M. Lucia; Williams, Margaret M.

    2016-01-01

    Species of the genus Bordetella associate with various animal hosts, frequently causing respiratory disease. Bordetella pertussis is the primary agent of whooping cough and other Bordetella species can cause similar cough illness. Here, we report four complete genome sequences from isolates of different Bordetella species recovered from human respiratory infections.

  15. Absence of human metapneumovirus co-infection in cases of severe respiratory syncytial virus infection

    NARCIS (Netherlands)

    van Woensel, J B M; Bos, A P; Lutter, R; Rossen, J W A; Schuurman, R

    2006-01-01

    It has been suggested that co-infection of human metapneumovirus (hMPV) in severe respiratory syncytial (RSV) virus bronchiolitis is very common. To evaluate the epidemiology of hMPV co-infection in children with severe lower respiratory tract infection caused by RSV virus. This was an observational

  16. Anatomy and bronchoscopy of the porcine lung. A model for translational respiratory medicine.

    LENUS (Irish Health Repository)

    Judge, Eoin P

    2014-09-01

    The porcine model has contributed significantly to biomedical research over many decades. The similar size and anatomy of pig and human organs make this model particularly beneficial for translational research in areas such as medical device development, therapeutics and xenotransplantation. In recent years, a major limitation with the porcine model was overcome with the successful generation of gene-targeted pigs and the publication of the pig genome. As a result, the role of this model is likely to become even more important. For the respiratory medicine field, the similarities between pig and human lungs give the porcine model particular potential for advancing translational medicine. An increasing number of lung conditions are being studied and modeled in the pig. Genetically modified porcine models of cystic fibrosis have been generated that, unlike mouse models, develop lung disease similar to human cystic fibrosis. However, the scientific literature relating specifically to porcine lung anatomy and airway histology is limited and is largely restricted to veterinary literature and textbooks. Furthermore, methods for in vivo lung procedures in the pig are rarely described. The aims of this review are to collate the disparate literature on porcine lung anatomy, histology, and microbiology; to provide a comparison with the human lung; and to describe appropriate bronchoscopy procedures for the pig lungs to aid clinical researchers working in the area of translational respiratory medicine using the porcine model.

  17. Crawling with Virus: Translational Insights from a Neonatal Mouse Model on the Pathogenesis of Respiratory Syncytial Virus in Infants.

    Science.gov (United States)

    You, Dahui; Saravia, Jordy; Siefker, David; Shrestha, Bishwas; Cormier, Stephania A

    2015-10-07

    The infant immune response to respiratory syncytial virus (RSV) remains incompletely understood. Here we review the use of a neonatal mouse model of RSV infection to mimic severe infection in human infants. We describe numerous age-specific responses, organized by cell type, observed in RSV-infected neonatal mice and draw comparisons (when possible) to human infants.

  18. Iterative integral parameter identification of a respiratory mechanics model

    Directory of Open Access Journals (Sweden)

    Schranz Christoph

    2012-07-01

    Full Text Available Abstract Background Patient-specific respiratory mechanics models can support the evaluation of optimal lung protective ventilator settings during ventilation therapy. Clinical application requires that the individual’s model parameter values must be identified with information available at the bedside. Multiple linear regression or gradient-based parameter identification methods are highly sensitive to noise and initial parameter estimates. Thus, they are difficult to apply at the bedside to support therapeutic decisions. Methods An iterative integral parameter identification method is applied to a second order respiratory mechanics model. The method is compared to the commonly used regression methods and error-mapping approaches using simulated and clinical data. The clinical potential of the method was evaluated on data from 13 Acute Respiratory Distress Syndrome (ARDS patients. Results The iterative integral method converged to error minima 350 times faster than the Simplex Search Method using simulation data sets and 50 times faster using clinical data sets. Established regression methods reported erroneous results due to sensitivity to noise. In contrast, the iterative integral method was effective independent of initial parameter estimations, and converged successfully in each case tested. Conclusion These investigations reveal that the iterative integral method is beneficial with respect to computing time, operator independence and robustness, and thus applicable at the bedside for this clinical application.

  19. Seasonal and pandemic human influenza viruses attach better to human upper respiratory tract epithelium than avian influenza viruses.

    Science.gov (United States)

    van Riel, Debby; den Bakker, Michael A; Leijten, Lonneke M E; Chutinimitkul, Salin; Munster, Vincent J; de Wit, Emmie; Rimmelzwaan, Guus F; Fouchier, Ron A M; Osterhaus, Albert D M E; Kuiken, Thijs

    2010-04-01

    Influenza viruses vary markedly in their efficiency of human-to-human transmission. This variation has been speculated to be determined in part by the tropism of influenza virus for the human upper respiratory tract. To study this tropism, we determined the pattern of virus attachment by virus histochemistry of three human and three avian influenza viruses in human nasal septum, conchae, nasopharynx, paranasal sinuses, and larynx. We found that the human influenza viruses-two seasonal influenza viruses and pandemic H1N1 virus-attached abundantly to ciliated epithelial cells and goblet cells throughout the upper respiratory tract. In contrast, the avian influenza viruses, including the highly pathogenic H5N1 virus, attached only rarely to epithelial cells or goblet cells. Both human and avian viruses attached occasionally to cells of the submucosal glands. The pattern of virus attachment was similar among the different sites of the human upper respiratory tract for each virus tested. We conclude that influenza viruses that are transmitted efficiently among humans attach abundantly to human upper respiratory tract, whereas inefficiently transmitted influenza viruses attach rarely. These results suggest that the ability of an influenza virus to attach to human upper respiratory tract is a critical factor for efficient transmission in the human population.

  20. Mobilisation of toxic elements in the human respiratory system

    Energy Technology Data Exchange (ETDEWEB)

    Pinheiro, T. E-mail: murmur@itn1.itn.pt; Alves, L.C.; Palhano, M.J.; Bugalho de Almeida, A

    2001-07-01

    The fate of respired particles in the respiratory system is inferred through the chemical characterisation of individual particles at the tracheal and bronchial mucosas, and the accumulation of toxic elements in lung alveoli and lymph nodes. The particles and tissue elemental distributions were identified and characterised using micro-PIXE elemental mapping of thin frozen sections using the ITN Nuclear Microprobe facility. Significant particle deposits are found at the distal respiratory tract. Al, Si, Ti, V, Cr, Fe, Ni, Cu and Zn are elements detected at these accumulation areas. The elemental distributions in the different cellular environments of lymph nodes vary. The major compartments for Al, Si, Ti, Fe and Cr are the phagocytic cells and capsule of lymph nodes, while V and Ni are in the cortex and paracortex medullar areas which retain more than 70% of these two elements, suggesting high solubility of the latter in the cellular milieu. The elemental mobilisation from particles or deposits to surrounding tissues at the respiratory ducts evidences patterns of diffusion and removal that are different than those for elements in the respiratory tract. Mobilisation of elements such as V, Cr and Ni is more relevant at alveoli areas where gaseous exchange takes place. The apparent high solubility of V and Ni in the respiratory tract tissue points towards a deviation of the lymphatic system filtering efficiency for these elements when compared to others.

  1. Respiratory tract clearance model for dosimetry and bioassay of inhaled radionuclides

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, M.R.; Birchall, A. (National Radiological Protection Board, Chilton (UK)); Cuddihy, R.G. (Inhalation Toxicology Research Inst., Albuquerque, NM (USA)); James, A.C. (Pacific Northwest Lab., Richland, WA (USA)); Roy, M. (CEA Centre d' Etudes Nucleaires de Fontenay-aux-Roses, 92 (France). Inst. de Protection et de Surete Nucleaire)

    1990-07-01

    The ICRP Task Group on Respiratory Tract Models is developing a model to describe the retention and clearance of deposited radionuclides for dose-intake calculations and interpretation of bioassay data. Clearance from each region is treated as competition between mechanical transport, which moves particles to the gastro-intestinal tract and lymph nodes, and the translocation of material to blood. It is assumed that mechanical transport rates are the same for all materials, and that rates of translocation to blood are the same in all regions. Time-dependent clearance is represented by combinations of compartments. Representative values of parameters to describe mechanical transport from the human respiratory tract have been estimated, and guidance is given on the determination of translocation rates. It is emphasized that the current version of the model described here is still provisional. 30 refs.

  2. A joint computational respiratory neural network-biomechanical model for breathing and airway defensive behaviors

    Directory of Open Access Journals (Sweden)

    Russell eO'Connor

    2012-07-01

    Full Text Available Data-driven computational neural network models have been used to study mechanisms for generating the motor patterns for breathing and breathing related behaviors such as coughing. These models have commonly been evaluated in open loop conditions or with feedback of lung volume simply represented as a filtered version of phrenic motor output. Limitations of these approaches preclude assessment of the influence of mechanical properties of the musculoskeletal system and motivated development of a biomechanical model of the respiratory muscles, airway, and lungs using published measures from human subjects. Here we describe the model and some aspects of its behavior when linked to a computational brainstem respiratory network model for breathing and airway defensive behavior composed of discrete integrate and fire populations. The network incorporated multiple circuit paths and operations for tuning inspiratory drive suggested by prior work. Results from neuromechanical system simulations included generation of a eupneic-like breathing pattern and the observation that increased respiratory drive and operating volume result in higher peak flow rates during cough, even when the expiratory drive is unchanged, or when the expiratory abdominal pressure is unchanged. Sequential elimination of the model’s sources of inspiratory drive during cough also suggested a role for disinhibitory regulation via tonic expiratory neurons, a result that was subsequently supported by an analysis of in vivo data. Comparisons with antecedent models, discrepancies with experimental results, and some model limitations are noted.

  3. The Linear Model Research on Tibetan Six-Character Poetry's Respiratory Signal

    Science.gov (United States)

    Yonghong, Li; Yangrui, Yang; Lei, Guo; Hongzhi, Yu

    In this paper, we studied the Tibetan six-character pomes' respiratory signal during reading from the perspective of the physiological. Main contents include: 1) Selected 40 representative Tibetan six-character and four lines pomes from ldquo; The Love-songs of 6th Dalai Lama Tshang•yangGya•tsho ", and recorded speech sounds, voice and respiratory signals; 2) Designed a set of respiratory signal parameters for the study of poetry; 3) Extracted the relevant parameters of poetry respiratory signal by using the well-established respiratory signal processing platform; 4) Studied the type of breathing pattern, established the linear model of poetry respiratory signal.

  4. Human respiratory epithelial cells from nasal turbinate expressed stem cell genes even after serial passaging.

    Science.gov (United States)

    Ruszymah, B H I; Izham, B A Azrul; Heikal, M Y Mohd; Khor, S F; Fauzi, M B; Aminuddin, B S

    2011-12-01

    Current development in the field of tissue engineering led to the idea of repairing and regenerating the respiratory airway through in vitro reconstruction using autologous respiratory epithelial (RE). To ensure the capability of proliferation, the stem cell property of RE cells from the nasal turbinate should be evaluated. Respiratory epithelial cells from six human nasal turbinates were harvested and cultured in vitro. The gene expression of FZD-9 and BST-1 were expressed in passage 2 (P2) and passage 4 (P4). The levels of expression were not significant between both passages. The RE cells exhibit the stem cell properties, which remains even after serial passaging.

  5. Scalability of human models

    NARCIS (Netherlands)

    Rodarius, C.; Rooij, L. van; Lange, R. de

    2007-01-01

    The objective of this work was to create a scalable human occupant model that allows adaptation of human models with respect to size, weight and several mechanical parameters. Therefore, for the first time two scalable facet human models were developed in MADYMO. First, a scalable human male was

  6. Three-Dimensionally Engineered Normal Human Lung Tissue-Like Assemblies: Target Tissues for Human Respiratory Viral Infections

    Science.gov (United States)

    Goodwin, Thomas J.; McCarthy, M.; Lin, Y-H.; Deatly, A. M.

    2008-01-01

    In vitro three-dimensional (3D) human lung epithelio-mesenchymal tissue-like assemblies (3D hLEM TLAs) from this point forward referred to as TLAs were engineered in Rotating Wall Vessel (RWV) technology to mimic the characteristics of in vivo tissues thus providing a tool to study human respiratory viruses and host cell interactions. The TLAs were bioengineered onto collagen-coated cyclodextran microcarriers using primary human mesenchymal bronchial-tracheal cells (HBTC) as the foundation matrix and an adult human bronchial epithelial immortalized cell line (BEAS-2B) as the overlying component. The resulting TLAs share significant characteristics with in vivo human respiratory epithelium including polarization, tight junctions, desmosomes, and microvilli. The presence of tissue-like differentiation markers including villin, keratins, and specific lung epithelium markers, as well as the production of tissue mucin, further confirm these TLAs differentiated into tissues functionally similar to in vivo tissues. Increasing virus titers for human respiratory syncytial virus (wtRSVA2) and the detection of membrane bound glycoproteins over time confirm productive infection with the virus. Therefore, we assert TLAs mimic aspects of the human respiratory epithelium and provide a unique capability to study the interactions of respiratory viruses and their primary target tissue independent of the host s immune system.

  7. Three-Dimensionally Engineered Normal Human Broncho-epithelial Tissue-Like Assemblies: Target Tissues for Human Respiratory Viral Infections

    Science.gov (United States)

    Goodwin, T. J.; McCarthy, M.; Lin, Y-H

    2006-01-01

    In vitro three-dimensional (3D) human broncho-epithelial (HBE) tissue-like assemblies (3D HBE TLAs) from this point forward referred to as TLAs were engineered in Rotating Wall Vessel (RWV) technology to mimic the characteristics of in vivo tissues thus providing a tool to study human respiratory viruses and host cell interactions. The TLAs were bioengineered onto collagen-coated cyclodextran microcarriers using primary human mesenchymal bronchial-tracheal cells (HBTC) as the foundation matrix and an adult human bronchial epithelial immortalized cell line (BEAS-2B) as the overlying component. The resulting TLAs share significant characteristics with in vivo human respiratory epithelium including polarization, tight junctions, desmosomes, and microvilli. The presence of tissue-like differentiation markers including villin, keratins, and specific lung epithelium markers, as well as the production of tissue mucin, further confirm these TLAs differentiated into tissues functionally similar to in vivo tissues. Increasing virus titers for human respiratory syncytial virus (wtRSVA2) and parainfluenza virus type 3 (wtPIV3 JS) and the detection of membrane bound glycoproteins over time confirm productive infections with both viruses. Therefore, TLAs mimic aspects of the human respiratory epithelium and provide a unique capability to study the interactions of respiratory viruses and their primary target tissue independent of the host's immune system.

  8. Three-Dimensionally Engineered Normal Human Broncho-epithelial Tissue-Like Assemblies: Target Tissues for Human Respiratory Viral Infections

    Science.gov (United States)

    Goodwin, T. J.; McCarthy, M.; Lin, Y-H

    2006-01-01

    In vitro three-dimensional (3D) human broncho-epithelial (HBE) tissue-like assemblies (3D HBE TLAs) from this point forward referred to as TLAs were engineered in Rotating Wall Vessel (RWV) technology to mimic the characteristics of in vivo tissues thus providing a tool to study human respiratory viruses and host cell interactions. The TLAs were bioengineered onto collagen-coated cyclodextran microcarriers using primary human mesenchymal bronchial-tracheal cells (HBTC) as the foundation matrix and an adult human bronchial epithelial immortalized cell line (BEAS-2B) as the overlying component. The resulting TLAs share significant characteristics with in vivo human respiratory epithelium including polarization, tight junctions, desmosomes, and microvilli. The presence of tissue-like differentiation markers including villin, keratins, and specific lung epithelium markers, as well as the production of tissue mucin, further confirm these TLAs differentiated into tissues functionally similar to in vivo tissues. Increasing virus titers for human respiratory syncytial virus (wtRSVA2) and parainfluenza virus type 3 (wtPIV3 JS) and the detection of membrane bound glycoproteins over time confirm productive infections with both viruses. Therefore, TLAs mimic aspects of the human respiratory epithelium and provide a unique capability to study the interactions of respiratory viruses and their primary target tissue independent of the host's immune system.

  9. RAGE inhibits human respiratory syncytial virus syncytium formation by interfering with F-protein function

    OpenAIRE

    2013-01-01

    Human respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infection. Infection is critically dependent on the RSV fusion (F) protein, which mediates fusion between the viral envelope and airway epithelial cells. The F protein is also expressed on infected cells and is responsible for fusion of infected cells with adjacent cells, resulting in the formation of multinucleate syncytia. The receptor for advanced glycation end products (RAGE) is a pattern-recognitio...

  10. Respiratory modulation of human autonomic function on Earth.

    Science.gov (United States)

    Eckberg, Dwain L; Cooke, William H; Diedrich, André; Biaggioni, Italo; Buckey, Jay C; Pawelczyk, James A; Ertl, Andrew C; Cox, James F; Kuusela, Tom A; Tahvanainen, Kari U O; Mano, Tadaaki; Iwase, Satoshi; Baisch, Friedhelm J; Levine, Benjamin D; Adams-Huet, Beverley; Robertson, David; Blomqvist, C Gunnar

    2016-10-01

    We studied healthy supine astronauts on Earth with electrocardiogram, non-invasive arterial pressure, respiratory carbon dioxide concentrations, breathing depth and sympathetic nerve recordings. The null hypotheses were that heart beat interval fluctuations at usual breathing frequencies are baroreflex mediated, that they persist during apnoea, and that autonomic responses to apnoea result from changes of chemoreceptor, baroreceptor or lung stretch receptor inputs. R-R interval fluctuations at usual breathing frequencies are unlikely to be baroreflex mediated, and disappear during apnoea. The subjects' responses to apnoea could not be attributed to changes of central chemoreceptor activity (hypocapnia prevailed); altered arterial baroreceptor input (vagal baroreflex gain declined and muscle sympathetic nerve burst areas, frequencies and probabilities increased, even as arterial pressure climbed to new levels); or altered pulmonary stretch receptor activity (major breathing frequency and tidal volume changes did not alter vagal tone or sympathetic activity). Apnoea responses of healthy subjects may result from changes of central respiratory motoneurone activity. We studied eight healthy, supine astronauts on Earth, who followed a simple protocol: they breathed at fixed or random frequencies, hyperventilated and then stopped breathing, as a means to modulate and expose to view important, but obscure central neurophysiological mechanisms. Our recordings included the electrocardiogram, finger photoplethysmographic arterial pressure, tidal volume, respiratory carbon dioxide concentrations and peroneal nerve muscle sympathetic activity. Arterial pressure, vagal tone and muscle sympathetic outflow were comparable during spontaneous and controlled-frequency breathing. Compared with spontaneous, 0.1 and 0.05 Hz breathing, however, breathing at usual frequencies (∼0.25 Hz) lowered arterial baroreflex gain, and provoked smaller arterial pressure and R-R interval

  11. Fluid-structure interaction including volumetric coupling with homogenised subdomains for modeling respiratory mechanics.

    Science.gov (United States)

    Yoshihara, Lena; Roth, Christian J; Wall, Wolfgang A

    2017-04-01

    In this article, a novel approach is presented for combining standard fluid-structure interaction with additional volumetric constraints to model fluid flow into and from homogenised solid domains. The proposed algorithm is particularly interesting for investigations in the field of respiratory mechanics as it enables the mutual coupling of airflow in the conducting part and local tissue deformation in the respiratory part of the lung by means of a volume constraint. In combination with a classical monolithic fluid-structure interaction approach, a comprehensive model of the human lung can be established that will be useful to gain new insights into respiratory mechanics in health and disease. To illustrate the validity and versatility of the novel approach, three numerical examples including a patient-specific lung model are presented. The proposed algorithm proves its capability of computing clinically relevant airflow distribution and tissue strain data at a level of detail that is not yet achievable, neither with current imaging techniques nor with existing computational models. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  12. SRS-A leukotrienes decrease the activity of human respiratory cilia

    DEFF Research Database (Denmark)

    Bisgaard, H; Pedersen, M

    1987-01-01

    We have studied the effects of the slow reacting substance of anaphylaxis (SRS-A) constituents leukotrienes (LT) C4 and D4 on the ciliary activity of human respiratory cells. The ciliary beat frequency on human nasal cells harvested by cell scraping from the inferior turbinate was measured in a b...

  13. Human cell tropism and innate immune system interactions of human respiratory coronavirus EMC compared to those of severe acute respiratory syndrome coronavirus.

    Science.gov (United States)

    Zielecki, Florian; Weber, Michaela; Eickmann, Markus; Spiegelberg, Larissa; Zaki, Ali Moh; Matrosovich, Mikhail; Becker, Stephan; Weber, Friedemann

    2013-05-01

    Infections with human coronavirus EMC (HCoV-EMC) are associated with severe pneumonia. We demonstrate that HCoV-EMC resembles severe acute respiratory syndrome coronavirus (SARS-CoV) in productively infecting primary and continuous cells of the human airways and in preventing the induction of interferon regulatory factor 3 (IRF-3)-mediated antiviral alpha/beta interferon (IFN-α/β) responses. However, HCoV-EMC was markedly more sensitive to the antiviral state established by ectopic IFN. Thus, HCoV-EMC can utilize a broad range of human cell substrates and suppress IFN induction, but it does not reach the IFN resistance of SARS-CoV.

  14. Detection of Severe Respiratory Disease Epidemic Outbreaks by CUSUM-Based Overcrowd-Severe-Respiratory-Disease-Index Model

    Directory of Open Access Journals (Sweden)

    Carlos Polanco

    2013-01-01

    Full Text Available A severe respiratory disease epidemic outbreak correlates with a high demand of specific supplies and specialized personnel to hold it back in a wide region or set of regions; these supplies would be beds, storage areas, hemodynamic monitors, and mechanical ventilators, as well as physicians, respiratory technicians, and specialized nurses. We describe an online cumulative sum based model named Overcrowd-Severe-Respiratory-Disease-Index based on the Modified Overcrowd Index that simultaneously monitors and informs the demand of those supplies and personnel in a healthcare network generating early warnings of severe respiratory disease epidemic outbreaks through the interpretation of such variables. A post hoc historical archive is generated, helping physicians in charge to improve the transit and future allocation of supplies in the entire hospital network during the outbreak. The model was thoroughly verified in a virtual scenario, generating multiple epidemic outbreaks in a 6-year span for a 13-hospital network. When it was superimposed over the H1N1 influenza outbreak census (2008–2010 taken by the National Institute of Medical Sciences and Nutrition Salvador Zubiran in Mexico City, it showed that it is an effective algorithm to notify early warnings of severe respiratory disease epidemic outbreaks with a minimal rate of false alerts.

  15. Detection of severe respiratory disease epidemic outbreaks by CUSUM-based overcrowd-severe-respiratory-disease-index model.

    Science.gov (United States)

    Polanco, Carlos; Castañón-González, Jorge Alberto; Macías, Alejandro E; Samaniego, José Lino; Buhse, Thomas; Villanueva-Martínez, Sebastián

    2013-01-01

    A severe respiratory disease epidemic outbreak correlates with a high demand of specific supplies and specialized personnel to hold it back in a wide region or set of regions; these supplies would be beds, storage areas, hemodynamic monitors, and mechanical ventilators, as well as physicians, respiratory technicians, and specialized nurses. We describe an online cumulative sum based model named Overcrowd-Severe-Respiratory-Disease-Index based on the Modified Overcrowd Index that simultaneously monitors and informs the demand of those supplies and personnel in a healthcare network generating early warnings of severe respiratory disease epidemic outbreaks through the interpretation of such variables. A post hoc historical archive is generated, helping physicians in charge to improve the transit and future allocation of supplies in the entire hospital network during the outbreak. The model was thoroughly verified in a virtual scenario, generating multiple epidemic outbreaks in a 6-year span for a 13-hospital network. When it was superimposed over the H1N1 influenza outbreak census (2008-2010) taken by the National Institute of Medical Sciences and Nutrition Salvador Zubiran in Mexico City, it showed that it is an effective algorithm to notify early warnings of severe respiratory disease epidemic outbreaks with a minimal rate of false alerts.

  16. A study of IOS data using the aRIC+I(p) model of respiratory impedance.

    Science.gov (United States)

    Nguyen, T-U; Diong, B; Goldman, M

    2009-01-01

    Development of better methods to assess human lung function has been continuing since the existing standard lung function test of spirometry requires subjects to inhale and exhale with maximum effort, which may be troublesome especially for the elderly and young children, leading to unreliable results. Therefore, the method of forced oscillation, and the Impulse Oscillometry System (IOS) in particular, has been developed to lessen the effort of the patients while obtaining valid measurements. The applied pressure waves and the resulting airflow responses are recorded to provide information about the respiratory system's input impedance, which can be fit by electric circuit models to possibly serve as a means to detect and diagnose respiratory diseases. Presently, research continues to find a more accurate model that also provides reasonable component values. This paper proposes the augmented RIC+I(p)(aRIC+I(p)) model and compares it to five other well-known models (the RIC, extended RIC, augmented RIC, DuBois and Mead models) in fitting the IOS data from adult COPD patients and healthy subjects. While the aRIC+I(p) model yielded slightly higher fitting error than the Mead and DuBois models, it did not produce unphysiologically large values for any of its components, unlike the Mead and DuBois models. Hence, the aRIC+(p) model appears to be the most reasonable one for use, at this point in time, in studying IOS-based computer-aided detection and diagnosis of COPD.

  17. Significance of respirasomes for the assembly/stability of human respiratory chain complex I.

    Science.gov (United States)

    Schägger, Hermann; de Coo, René; Bauer, Matthias F; Hofmann, Sabine; Godinot, Catherine; Brandt, Ulrich

    2004-08-27

    We showed that the human respiratory chain is organized in supramolecular assemblies of respiratory chain complexes, the respirasomes. The mitochondrial complexes I (NADH dehydrogenase) and III (cytochrome c reductase) form a stable core respirasome to which complex IV (cytochrome c oxidase) can also bind. An analysis of the state of respirasomes in patients with an isolated deficiency of single complexes provided evidence that the formation of respirasomes is essential for the assembly/stability of complex I, the major entry point of respiratory chain substrates. Genetic alterations leading to a loss of complex III prevented respirasome formation and led to the secondary loss of complex I. Therefore, primary complex III assembly deficiencies presented as combined complex III/I defects. This dependence of complex I assembly/stability on respirasome formation has important implications for the diagnosis of mitochondrial respiratory chain disorders.

  18. Ultrafine Particles in Residential Indoors and Doses Deposited in the Human Respiratory System

    Directory of Open Access Journals (Sweden)

    Maurizio Manigrasso

    2015-09-01

    Full Text Available Indoor aerosol sources may significantly contribute to the daily dose of particles deposited into the human respiratory system. Therefore, it is important to characterize the aerosols deriving from the operations currently performed in an indoor environment and also to estimate the relevant particle respiratory doses. For this aim, aerosols from indoor combustive and non-combustive sources were characterized in terms of aerosol size distributions, and the relevant deposition doses were estimated as a function of time, particle diameter and deposition site in the respiratory system. Ultrafine particles almost entirely made up the doses estimated. The maximum contribution was due to particles deposited in the alveolar region between the 18th and the 21st airway generation. When cooking operations were performed, respiratory doses per unit time were about ten-fold higher than the relevant indoor background dose. Such doses were even higher than those associated with outdoor traffic aerosol.

  19. Cross-host evolution of severe acute respiratory syndrome coronavirus in palm civet and human

    Science.gov (United States)

    Song, Huai-Dong; Tu, Chang-Chun; Zhang, Guo-Wei; Wang, Sheng-Yue; Zheng, Kui; Lei, Lian-Cheng; Chen, Qiu-Xia; Gao, Yu-Wei; Zhou, Hui-Qiong; Xiang, Hua; Zheng, Hua-Jun; Chern, Shur-Wern Wang; Cheng, Feng; Pan, Chun-Ming; Xuan, Hua; Chen, Sai-Juan; Luo, Hui-Ming; Zhou, Duan-Hua; Liu, Yu-Fei; He, Jian-Feng; Qin, Peng-Zhe; Li, Ling-Hui; Ren, Yu-Qi; Liang, Wen-Jia; Yu, Ye-Dong; Anderson, Larry; Wang, Ming; Xu, Rui-Heng; Wu, Xin-Wei; Zheng, Huan-Ying; Chen, Jin-Ding; Liang, Guodong; Gao, Yang; Liao, Ming; Fang, Ling; Jiang, Li-Yun; Li, Hui; Chen, Fang; Di, Biao; He, Li-Juan; Lin, Jin-Yan; Tong, Suxiang; Kong, Xiangang; Du, Lin; Hao, Pei; Tang, Hua; Bernini, Andrea; Yu, Xiao-Jing; Spiga, Ottavia; Guo, Zong-Ming; Pan, Hai-Yan; He, Wei-Zhong; Manuguerra, Jean-Claude; Fontanet, Arnaud; Danchin, Antoine; Niccolai, Neri; Li, Yi-Xue; Wu, Chung-I; Zhao, Guo-Ping

    2005-01-01

    The genomic sequences of severe acute respiratory syndrome coronaviruses from human and palm civet of the 2003/2004 outbreak in the city of Guangzhou, China, were nearly identical. Phylogenetic analysis suggested an independent viral invasion from animal to human in this new episode. Combining all existing data but excluding singletons, we identified 202 single-nucleotide variations. Among them, 17 are polymorphic in palm civets only. The ratio of nonsynonymous/synonymous nucleotide substitution in palm civets collected 1 yr apart from different geographic locations is very high, suggesting a rapid evolving process of viral proteins in civet as well, much like their adaptation in the human host in the early 2002–2003 epidemic. Major genetic variations in some critical genes, particularly the Spike gene, seemed essential for the transition from animal-to-human transmission to human-to-human transmission, which eventually caused the first severe acute respiratory syndrome outbreak of 2002/2003. PMID:15695582

  20. A previously unknown reovirus of bat origin is associated with an acute respiratory disease in humans.

    Science.gov (United States)

    Chua, Kaw Bing; Crameri, Gary; Hyatt, Alex; Yu, Meng; Tompang, Mohd Rosli; Rosli, Juliana; McEachern, Jennifer; Crameri, Sandra; Kumarasamy, Verasingam; Eaton, Bryan T; Wang, Lin-Fa

    2007-07-03

    Respiratory infections constitute the most widespread human infectious disease, and a substantial proportion of them are caused by unknown etiological agents. Reoviruses (respiratory enteric orphan viruses) were first isolated from humans in the early 1950s and so named because they were not associated with any known disease. Here, we report a previously unknown reovirus (named "Melaka virus") isolated from a 39-year-old male patient in Melaka, Malaysia, who was suffering from high fever and acute respiratory disease at the time of virus isolation. Two of his family members developed similar symptoms approximately 1 week later and had serological evidence of infection with the same virus. Epidemiological tracing revealed that the family was exposed to a bat in the house approximately 1 week before the onset of the father's clinical symptoms. Genome sequence analysis indicated a close genetic relationship between Melaka virus and Pulau virus, a reovirus isolated in 1999 from fruit bats in Tioman Island, Malaysia. Screening of sera collected from human volunteers on the island revealed that 14 of 109 (13%) were positive for both Pulau and Melaka viruses. This is the first report of an orthoreovirus in association with acute human respiratory diseases. Melaka virus is serologically not related to the different types of mammalian reoviruses that were known to infect humans asymptomatically. These data indicate that bat-borne reoviruses can be transmitted to and cause clinical diseases in humans.

  1. Assessing pneumococcal meningitis association with viral respiratory infections and antibiotics: insights from statistical and mathematical models.

    Science.gov (United States)

    Opatowski, Lulla; Varon, Emmanuelle; Dupont, Claire; Temime, Laura; van der Werf, Sylvie; Gutmann, Laurent; Boëlle, Pierre-Yves; Watier, Laurence; Guillemot, Didier

    2013-08-01

    Pneumococcus is an important human pathogen, highly antibiotic resistant and a major cause of bacterial meningitis worldwide. Better prevention requires understanding the drivers of pneumococcal infection incidence and antibiotic susceptibility. Although respiratory viruses (including influenza) have been suggested to influence pneumococcal infections, the underlying mechanisms are still unknown, and viruses are rarely considered when studying pneumococcus epidemiology. Here, we propose a novel mathematical model to examine hypothetical relationships between Streptococcus pneumoniae meningitis incidence (SPMI), acute viral respiratory infections (AVRIs) and antibiotic exposure. French time series of SPMI, AVRI and penicillin consumption over 2001-2004 are analysed and used to assess four distinct virus-bacteria interaction submodels, ascribing the interaction on pneumococcus transmissibility and/or pathogenicity. The statistical analysis reveals strong associations between time series: SPMI increases shortly after AVRI incidence and decreases overall as the antibiotic-prescription rate rises. Model simulations require a combined impact of AVRI on both pneumococcal transmissibility (up to 1.3-fold increase at the population level) and pathogenicity (up to threefold increase) to reproduce the data accurately, along with diminished epidemic fitness of resistant pneumococcal strains causing meningitis (0.97 (0.96-0.97)). Overall, our findings suggest that AVRI and antibiotics strongly influence SPMI trends. Consequently, vaccination protecting against respiratory virus could have unexpected benefits to limit invasive pneumococcal infections.

  2. A 2-adic approach of the human respiratory tree

    CERN Document Server

    Bernicot, Frederic; Salort, Delphine

    2010-01-01

    We propose here a general framework to address the question of trace operators on a dyadic tree. This work is motivated by the modeling of the human bronchial tree which, thanks to its regularity, can be extrapolated in a natural way to an infinite resistive tree. The space of pressure fields at bifurcation nodes of this infinite tree can be endowed with a Sobolev space structure, with a semi-norm which measures the instantaneous rate of dissipated energy. We aim at describing the behaviour of finite energy pressure fields near the end. The core of the present approach is an identification of the set of ends with the ring Z_2 of 2-adic integers. Sobolev spaces over Z_2 can be defined in a very natural way by means of Fourier transform, which allows us to establish precised trace theorems which are formally quite similar to those in standard Sobolev spaces, with a Sobolev regularity which depends on the growth rate of resistances, i.e. on geometrical properties of the tree. Furthermore, we exhibit an explicit ...

  3. The respiratory tract deposition model proposed by the ICRP Task Group

    Energy Technology Data Exchange (ETDEWEB)

    James, A.C.; Briant, J.K. (Pacific Northwest Lab., Richland, WA (USA)); Stahlhofen, W.; Rudolf, G. (Gesellschaft fuer Strahlen- und Umweltforschung mbH Muenchen, Frankfurt am Main (Germany, F.R.). Abt. fuer Biophysikalische Strahlenforschung); Egan, M.J.; Nixon, W. (AEA Safety and Reliability, Culcheth (UK)); Gehr, P. (Bern Univ. (Switzerland). Anatomisches Inst.)

    1990-11-01

    The Task Group has developed a new model of the deposition of inhaled aerosols in each anatomical region of the respiratory tract. The model is used to evaluate the fraction of airborne activity that is deposited in respiratory regions having distinct retention characteristics and clearance pathways: the anterior nares, the extrathoracic airways of the naso- and oropharynx and larynx, the bronchi, the bronchioles, and the alveolated airways of the lung. Drawn from experimental data on total and regional deposition in human subjects, the model is based on extrapolation of these data by means of a detailed theoretical model of aerosol transport and deposition within the lung. The Task Group model applies to all practical conditions, and for aerosol particles and vapors from atomic size up to very coarse aerosols with an activity median aerodynamic diameter of 100 {mu}m. The model is designed to predict regional deposition in different subjects, including adults of either sex, children of various ages, and infants, and also to account for anatomical differences among Caucasian and non-Caucasian subjects. The Task Group model represents aerosol inhalability and regional deposition in different subjects by algebraic expressions of aerosol size, breathing rates, standard lung volumes, and scaling factors for airway dimensions. 35 refs., 13 figs., 2 tabs.

  4. Respiratory health in Latin America: number of specialists and human resources training.

    Science.gov (United States)

    Vázquez-García, Juan-Carlos; Salas-Hernández, Jorge; Pérez Padilla, Rogelio; Montes de Oca, María

    2014-01-01

    Latin America is made up of a number of developing countries. Demographic changes are occurring in the close to 600 million inhabitants, in whom a significant growth in population is combined with the progressive ageing of the population. This part of the world poses great challenges for general and respiratory health. Most of the countries have significant, or even greater, rates of chronic respiratory diseases or exposure to risk. Human resources in healthcare are not readily available, particularly in the area of respiratory disease specialists. Academic training centers are few and even non-existent in the majority of the countries. The detailed analysis of these conditions provides a basis for reflection on the main challenges and proposals for the management and training of better human resources in this specialist area. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

  5. Respiratory Failure Secondary to Human Metapneumovirus Requiring Extracorporeal Membrane Oxygenation in a 32-Month-Old Child

    Directory of Open Access Journals (Sweden)

    Abha Gupta

    2012-01-01

    Full Text Available Human metapneumovirus (HMPV is a common virus that can cause respiratory problems ranging from mild upper respiratory tract disease to respiratory failure requiring mechanical support. Here, we report a case of a 32-month-old male with a previous history of asthma, who developed respiratory failure two weeks after onset of cough and rhinorrhea and required extracorporeal membrane oxygenation (ECMO for 9 days after failing high-frequency oscillatory ventilation (HFOV. To our knowledge, this is the oldest reported pediatric patient with respiratory failure secondary to human metapneumovirus that did not respond to mechanical ventilation. This case highlights three critical points: the potentially fatal causative role of HMPV in respiratory failure in an older pediatric age group of immunocompetent hosts, the importance of early recognition of impending respiratory failure, and the timely utilization of ECMO.

  6. Human Metapneumovirus Infection is Associated with Severe Respiratory Disease in Preschool Children with History of Prematurity

    Science.gov (United States)

    Pancham, Krishna; Sami, Iman; Perez, Geovanny F.; Huseni, Shehlanoor; Kurdi, Bassem; Rose, Mary C.; Rodriguez-Martinez, Carlos E.; Nino, Gustavo

    2017-01-01

    Rationale Human metapneumovirus (HMPV) is a recently discovered respiratory pathogen of the family Paramyxoviridae, the same of Respiratory Syncytial Virus (RSV). Premature children are at high risk of severe RSV infections, but it is unclear whether HMPV infection is more severe in hospitalized children with history of severe prematurity. Methods We conducted a retrospective analysis of the clinical respiratory presentation of all PCR-confirmed HMPV infections in preschool age children (≤5 yrs.) with and without history of severe prematurity (<32 weeks gestation). Respiratory distress scores were developed to examine the clinical severity of HMPV infections. Demographic and clinical variables were obtained from reviewing electronic medical records (EMR). Results A total of 571 pre-school children were identified by PCR-confirmed viral respiratory tract infection during the study period. HMPV was identified as a causative organism in 63 cases (11%). Fifty–eight (n=58) preschool age children with HMPV infection were included in this study after excluding those with significant co-morbidities. Our data demonstrated that 32.7% of children admitted with HMPV had history of severe prematurity. Preschool children with history of prematurity had more severe HMPV disease as illustrated by longer hospitalizations, new or increased need for supplemental O2, and higher severity scores independently of age, ethnicity and history of asthma. Conclusion Our study suggests that HMPV infection causes significant disease burden among preschool children with history of prematurity leading to severe respiratory infections and increasing health care resource utilization due to prolonged hospitalizations. PMID:26117550

  7. Molecular evolution of the fusion protein (F) gene in human respiratory syncytial virus subgroup B.

    Science.gov (United States)

    Kimura, Hirokazu; Nagasawa, Koo; Kimura, Ryusuke; Tsukagoshi, Hiroyuki; Matsushima, Yuki; Fujita, Kiyotaka; Hirano, Eiko; Ishiwada, Naruhiko; Misaki, Takako; Oishi, Kazunori; Kuroda, Makoto; Ryo, Akihide

    2017-08-01

    In this study, we examined the molecular evolution of the fusion protein (F) gene in human respiratory syncytial virus subgroup B (HRSV-B). First, we performed time-scale evolution analyses using the Bayesian Markov chain Monte Carlo (MCMC) method. Next, we performed genetic distance, linear B-cell epitope prediction, N-glycosylation, positive/negative selection site, and Bayesian skyline plot analyses. We also constructed a structural model of the F protein and mapped the amino acid substitutions and the predicted B-cell epitopes. The MCMC-constructed phylogenetic tree indicated that the HRSV F gene diverged from the bovine respiratory syncytial virus gene approximately 580years ago and had a relatively low evolutionary rate (7.14×10(-4)substitutions/site/year). Furthermore, a common ancestor of HRSV-A and -B diverged approximately 290years ago, while HRSV-B diverged into three clusters for approximately 60years. The genetic similarity of the present strains was very high. Although a maximum of 11 amino acid substitutions were observed in the structural model of the F protein, only one strain possessed an amino acid substitution located within the palivizumab epitope. Four epitopes were predicted, although these did not correspond to the neutralization sites of the F protein including the palivizumab epitope. In addition, five N-glycosylation sites of the present HRSV-B strains were inferred. No positive selection sites were identified; however, many sites were found to be under negative selection. The effective population size of the gene has remained almost constant. On the basis of these results, it can be concluded that the HRSV-B F gene is highly conserved, as is the F protein of HRSV-A. Moreover, our prediction of B-cell epitopes does not show that the palivizumab reaction site may be recognized as an epitope during naturally occurring infections. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Central respiratory chemosensitivity and cerebrovascular CO2 reactivity: a rebreathing demonstration illustrating integrative human physiology.

    Science.gov (United States)

    MacKay, Christina M; Skow, Rachel J; Tymko, Michael M; Boulet, Lindsey M; Davenport, Margie H; Steinback, Craig D; Ainslie, Philip N; Lemieux, Chantelle C M; Day, Trevor A

    2016-03-01

    One of the most effective ways of engaging students of physiology and medicine is through laboratory demonstrations and case studies that combine 1) the use of equipment, 2) problem solving, 3) visual representations, and 4) manipulation and interpretation of data. Depending on the measurements made and the type of test, laboratory demonstrations have the added benefit of being able to show multiple organ system integration. Many research techniques can also serve as effective demonstrations of integrative human physiology. The "Duffin" hyperoxic rebreathing test is often used in research settings as a test of central respiratory chemosensitivity and cerebrovascular reactivity to CO2. We aimed to demonstrate the utility of the hyperoxic rebreathing test for both respiratory and cerebrovascular responses to increases in CO2 and illustrate the integration of the respiratory and cerebrovascular systems. In the present article, methods such as spirometry, respiratory gas analysis, and transcranial Doppler ultrasound are described, and raw data traces can be adopted for discussion in a tutorial setting. If educators have these instruments available, instructions on how to carry out the test are provided so students can collect their own data. In either case, data analysis and quantification are discussed, including principles of linear regression, calculation of slope, the coefficient of determination (R(2)), and differences between plotting absolute versus normalized data. Using the hyperoxic rebreathing test as a demonstration of the complex interaction and integration between the respiratory and cerebrovascular systems provides senior undergraduate, graduate, and medical students with an advanced understanding of the integrative nature of human physiology.

  9. TRANSPORT AND DEPOSITION OF NANO-SIZE PARTICLES IN THE UPPER HUMAN RESPIRATORY AIRWAYS

    Science.gov (United States)

    TRANSPORT AND DEPOSITION OF NANO-SIZE PARTICLES IN THE UPPER HUMAN RESPIRATORY AIRWAYS. Zhe Zhang*, Huawei Shi, Clement Kleinstreuer, Department of Mechanical and Aerospace Engineering, North Carolina State University, Raleigh, NC 27695-7910; Chong S. Kim, National Health and En...

  10. Severe respiratory failure due to co-infection with human metapneumovirus and Streptococcus pneumoniae

    Directory of Open Access Journals (Sweden)

    Masafumi Seki

    2014-01-01

    Full Text Available A 64-year-old male patient was admitted with respiratory failure, although chest X-rays revealed only mild bronchiolitis. Streptococcus pneumoniae, which usually presents as massive lobular pneumonia, was isolated from sputum, however, pan-pathogen screening using a next-generation sequencer also detected human metapneumovirus genome fragments.

  11. High-throughput Gene Expression Analysis In Pigs As Model For Respiratory Infections

    DEFF Research Database (Denmark)

    Skovgaard, Kerstin; Brogaard, Louise; Schou, Kirstine Klitgaard

    Influenza A virus infections have great impact on human health and welfare and significant resources are linked to influenza epidemics due to excess hospitalizations and lost productivity. Up to 15% of the human population is affected when Influenza spreads around the world in seasonal epidemics...... to be an obvious large animal model for respiratory infections. This study aimed at providing a better understanding of the involvement of circulating non-coding RNA and innate immune factors in porcine blood leukocytes during influenza virus infection. By employing the pig as a model we were able to perform...... pleuropneumoniae causes pneumonia in pigs, a disease which is associated with high morbidity and mortality, as well as impaired animal welfare. The rapidly evolving pneumonia is characterized by large areas of lung necrosis resulting from the combined effect of tissue damage caused by the bacteria, and a strong...

  12. Experimental models of the respiratory distress syndrome : lavage and oleic acid

    NARCIS (Netherlands)

    R.M. van der Heijde (Roos); H.P. Grotjohan (Hans)

    1992-01-01

    textabstractSo far the existing animal models have a lack of long lasting stability. Hardly any attention was paid to standardization of the induction of respiratory distress. We aimed at models in which the individual animals have a comparable respiratory distress for several hours to obtain the op

  13. Multi-Scale Human Respiratory System Simulations to Study Health Effects of Aging, Disease, and Inhaled Substances

    Science.gov (United States)

    Kunz, Robert; Haworth, Daniel; Dogan, Gulkiz; Kriete, Andres

    2006-11-01

    Three-dimensional, unsteady simulations of multiphase flow, gas exchange, and particle/aerosol deposition in the human lung are reported. Surface data for human tracheo-bronchial trees are derived from CT scans, and are used to generate three- dimensional CFD meshes for the first several generations of branching. One-dimensional meshes for the remaining generations down to the respiratory units are generated using branching algorithms based on those that have been proposed in the literature, and a zero-dimensional respiratory unit (pulmonary acinus) model is attached at the end of each terminal bronchiole. The process is automated to facilitate rapid model generation. The model is exercised through multiple breathing cycles to compute the spatial and temporal variations in flow, gas exchange, and particle/aerosol deposition. The depth of the 3D/1D transition (at branching generation n) is a key parameter, and can be varied. High-fidelity models (large n) are run on massively parallel distributed-memory clusters, and are used to generate physical insight and to calibrate/validate the 1D and 0D models. Suitably validated lower-order models (small n) can be run on single-processor PC’s with run times that allow model-based clinical intervention for individual patients.

  14. Proton stoichiometry associated with human neutrophil respiratory-burst reactions.

    Science.gov (United States)

    Gabig, T G; Lefker, B A; Ossanna, P J; Weiss, S J

    1984-11-10

    Control of the intraphagosomal pH in neutrophils may be of importance in creating a microbicidal environment by regulating the activity of the O2-.-generating NADPH oxidase and the lysosomal enzymes discharged into this compartment. In this study, we examined the proton stoichiometry associated with the primary enzymatic reaction underlying the respiratory burst. A preparation of the neutrophil-derived, membrane oxidase consumed NADPH and generated O2-. with a stoichiometry of 1 NADPH:2 O2-. When the enzymatically produced O2-. was prevented from undergoing dismutation, net protons were released in an approximate 1:2 stoichiometry with O2-. generated. In contrast, when O2-. was allowed to dismutate to H2O2, net protons were consumed in a 1:1 stoichiometry with the accumulated H2O2. Thus, the delta pH associated with the NADPH oxidase-dependent production of O2-. was dictated by the fate of the generated radical. The consumption of the oxidase-generated H2O2 by the lysosomal enzyme myeloperoxidase resulted in the formation of HOCl which was trapped in the presence of taurine as the N-chloro derivative. The ratio of chlorinated product formed to H+ consumed was 1:1. The implications of these results are discussed in terms of the known intraphagosomal pH changes that occur following neutrophil stimulation. We conclude that the O2-.-generating oxidase plays a dual role in the phagosome by simultaneously creating an oxidizing environment that optimizes pH-dependent microbicidal processes.

  15. Specific Dietary Oligosaccharides Increase Th1 Responses in a Mouse Respiratory Syncytial Virus Infection Model

    NARCIS (Netherlands)

    Schijf, Marcel A.; Kruijsen, Debby; Bastiaans, Jacqueline; Coenjaerts, Frank E. J.; Garssen, Johan; van Bleek, Grada M.; van't Land, Belinda

    2012-01-01

    Breast feeding reduces the risk of developing severe respiratory syncytial virus (RSV) infections in infants. In addition to maternal antibodies, other immune-modulating factors in human milk contribute to this protection. Specific dietary prebiotic oligosaccharides, similar to oligosaccharides pres

  16. Heat and water rate transfer processes in the human respiratory tract at various altitudes.

    Science.gov (United States)

    Kandjov, I M

    2001-02-01

    The process of the respiratory air conditioning as a process of heat and mass exchange at the interface inspired air-airways surface was studied. Using a model of airways (Olson et al., 1970) where the segments of the respiratory tract are like cylinders with a fixed length and diameter, the corresponding heat transfer equations, in the paper are founded basic rate exchange parameters-convective heat transfer coefficient h(c)(W m(-2) degrees C(-1)) and evaporative heat transfer coefficient h(e)(W m(-2)hPa(-1)). The rate transfer parameters assumed as sources with known heat power are connected to airflow rate in different airways segments. Relationships expressing warming rate of inspired air due to convection, warming rate of inspired air due to evaporation, water diffused in the inspired air from the airways wall, i.e. a system of air conditioning parameters, was composed. The altitude dynamics of the relations is studied. Every rate conditioning parameter is an increasing function of altitude. The process of diffusion in the peripheral bronchial generations as a basic transfer process is analysed. The following phenomenon is in effect: the diffusion coefficient increases with altitude and causes a compensation of simultaneous decreasing of O(2)and CO(2)densities in atmospheric air. Due to this compensation, the diffusion in the peripheral generations with altitude is approximately constant. The elements of the human anatomy optimality as well as the established dynamics are discussed and assumed. The square form of the airways after the trachea expressed in terms of transfer supposes (in view of maximum contact surface), that a maximum heat and water exchange is achieved, i.e. high degree of air condition at fixed environmental parameters and respiration regime.

  17. Marked induction of matrix metalloproteinase-10 by respiratory syncytial virus infection in human nasal epithelial cells.

    Science.gov (United States)

    Hirakawa, Satoshi; Kojima, Takashi; Obata, Kazufumi; Okabayashi, Tamaki; Yokota, Shin-Ichi; Nomura, Kazuaki; Obonai, Toshimasa; Fuchimoto, Jun; Himi, Tetsuo; Tsutsumi, Hiroyuki; Sawada, Norimasa

    2013-12-01

    Respiratory syncytial virus (RSV) is an important pathogen of bronchiolitis, asthma, and severe lower respiratory tract disease in infants and young children. Matrix metalloproteinases (MMPs) play key roles in viral infection, inflammation and remodeling of the airway. However, the roles and regulation of MMPs in human nasal epithelial cells (HNECs) after RSV infection remain unclear. To investigate the regulation of MMP induced after RSV infection in HNECs, an RSV-infected model of HNECs in vitro was used. It was found that mRNA of MMP-10 was markedly increased in HNECs after RSV infection, together with induction of mRNAs of MMP-1, -7, -9, and -19. The amount of MMP-10 released from HNECs was also increased in a time-dependent manner after RSV infection as was that of chemokine RANTES. The upregulation of MMP-10 in HNECs after RSV infection was prevented by inhibitors of NF-κB and pan-PKC with inhibition of RSV replication, whereas it was prevented by inhibitors of JAK/STAT, MAPK, and EGF receptors without inhibition of RSV replication. In lung tissue of an infant with severe RSV infection in which a few RSV antibody-positive macrophages were observed, MMP-10 was expressed at the apical side of the bronchial epithelial cells and alveolar epithelial cells. In conclusion, MMP-10 induced by RSV infection in HNECs is regulated via distinct signal transduction pathways with or without relation to RSV replication. MMP-10 may play an important role in the pathogenesis of RSV diseases and it has the potential to be a novel marker and therapeutic target for RSV infection.

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

    DEFF Research Database (Denmark)

    von Linstow, M-L; Eugen-Olsen, J; Koch, A;

    2006-01-01

    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...... of the five children shedding RNA in faeces had diarrhoea and children shedding RNA in sweat were either less than five weeks of age or had a chronic lung disease. RSV and hMPV RNA was shed in nasal secretions for a median of 11.5 and 5.0 days respectively (p = 0.001). More than 75% of the family members...... 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....

  19. The impact of PM2.5 on the human respiratory system.

    Science.gov (United States)

    Xing, Yu-Fei; Xu, Yue-Hua; Shi, Min-Hua; Lian, Yi-Xin

    2016-01-01

    Recently, many researchers paid more attentions to the association between air pollution and respiratory system disease. In the past few years, levels of smog have increased throughout China resulting in the deterioration of air quality, raising worldwide concerns. PM2.5 (particles less than 2.5 micrometers in diameter) can penetrate deeply into the lung, irritate and corrode the alveolar wall, and consequently impair lung function. Hence it is important to investigate the impact of PM2.5 on the respiratory system and then to help China combat the current air pollution problems. In this review, we will discuss PM2.5 damage on human respiratory system from epidemiological, experimental and mechanism studies. At last, we recommend to the population to limit exposure to air pollution and call to the authorities to create an index of pollution related to health.

  20. Reflex influence of carotid baroreceptor inactivation on respiratory resistance in humans

    Directory of Open Access Journals (Sweden)

    Klawe JJ

    2009-12-01

    Full Text Available Abstract Our previous study demonstrated that selective carotid baroreceptors activation decreases airway resistance. The aim of the present study was to evaluate the effect of carotid baroreceptor inactivation on the reflex change of respiratory resistance. Twenty healthy men aged between 20 and 25 were included in the study. Selective inactivation of carotid baroreceptors was induced by generating a positive pressure of 40 mmHg for 5 s in two capsules placed bilaterally on the neck over the bifurcation of the carotid arteries. The oscillatory method (Siregnost FD5, Siemens was used to measure continuously respiratory resistance. Inactivation of carotid baroreceptors produced a short increase in respiratory resistance by 0.39 ± 0.01(SE mbar/l/s, i.e., 21.7% above the resting level. We conclude that in humans, carotid baroreceptors might have a background contribution to bronchodilator tone. This observation seems to be important for clinical situations of impairment of baroreflex function.

  1. [Effects of airborne fine particulate matter on human respiratory symptoms and pulmonary function].

    Science.gov (United States)

    Gao, Zhi-Yi; Li, Peng-Kun; Zhao, Jin-Zhuo; Jiang, Rong-Fang; Yang, Bin-Jie; Zhang, Min-Hua; Song, Wei-Min

    2010-10-01

    to explore effects of airborne fine particulate matter exposure on human respiratory symptoms and pulmonary function. one hundred and seven field traffic policemen were recruited as airborne fine particulate matter high-exposure group and one hundred and one male residents as common exposure group. The individual sampler was used to measure fine particulate matter exposure levels of the two groups. To obtain personal information, especially respiratory symptoms such as cough, sputum, etc. a questionnaire survey was used. The pulmonary ventilation function was detected: forced expiratory vital capacity (FVC), the first 1 second forced expiratory volume (FEV1.0), FVC/FEV1.0% and peak flow values (PEF), and the difference of fine particulate matter exposure level and respiratory function of the two groups was compared. 24 h individual average fine particulate matter exposure concentration of traffic police and residents were respectively (115.4 ± 46.17) microg/m(3) and (74.94 ± 40.09) microg/m(3), the traffic police PM2.5 exposure levels were significantly higher than the residents. In the incidence of respiratory symptoms, compared with high-exposure group and common exposure group, coughing, expectoration, throat unwell, asthma, short of breath and nose discomfort, traffic police group was higher than residents group (P matter exposure, may impact respiratory health and impair pulmonary function.

  2. Influence of lower body negative pressure release on soleus H reflex, respiratory sensations and reflexes in human subjects.

    Science.gov (United States)

    Anand, Ashima; Raj, Hans; Gupta, Uday A; Srivastava, Niraj

    2010-09-30

    Using a physiological model of acutely increasing venous return into the lungs, i.e. by applying and then releasing lower body negative pressure (LBNP) to mimic the natural stimulus of juxtapulmonary capillary (J) or pulmonary C fibre receptors, produced an immediate and significant reduction in the amplitude of the Hoffman (H) reflex by 81±4% (P=0.001) in a majority of subjects 70% (n=5). Accompanying this was a notable change in the respiratory pattern with tidal volume (V(T)) increasing in all subjects from (mean) 0.462±.038 to 0.777±.061l/min (P=0.001) and the respiratory rate (F(R)) in 40% from 14±1 to 24±0.8 breaths/min. A feeling of pressure in throat, upper chest was reported by all and a shortness of breath-by 70% of the subjects. These were similar in nature to the respiratory sensations felt with threshold doses of intravenous lobeline, a well-established chemical stimulant of J receptors. All effects lasted for 15-20s and within a minute the parameters resumed their earlier control values. In animals, respiratory augmentation and locomotion inhibition are well-established reflexes of J receptors - this simultaneous though transitory reduction in H reflex amplitude reflecting change in the excitability of the motoneurone pool and appearance of respiratory effects, is the first demonstration in human subjects of the two reflexes appearing in response to a sudden increase in pulmonary blood flow that mimics the natural stimulus of these receptors. Copyright 2010 Elsevier B.V. All rights reserved.

  3. The significance of Candida in the human respiratory tract: our evolving understanding.

    Science.gov (United States)

    Pendleton, Kathryn M; Huffnagle, Gary B; Dickson, Robert P

    2017-04-01

    Candida is an opportunistic pathogen and the most commonly isolated fungal genus in humans. Though Candida is often detected in respiratory specimens from humans with and without lung disease, its significance remains undetermined. While historically considered a commensal organism with low virulence potential, the status of Candida as an innocent bystander has recently been called into question by both clinical observations and animal experimentation. We here review what is currently known and yet to be determined about the clinical, microbiological and pathophysiological significance of the detection of Candida spp. in the human respiratory tract. Published by Oxford University Press on behalf of FEMS 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  4. 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.

  5. Seasonal behavior of radon decay products in indoor air and resulting radiation dose to human respiratory tract

    Directory of Open Access Journals (Sweden)

    A.M.A. Mostafa

    2015-01-01

    Full Text Available Most of radiation hazard of indoor radon is largely due to the radon progenies, which are inhaled and deposited in the human respiratory tract. It is essential to evaluate aerodynamic characteristics of the radon progenies, which are either attached or unattached to aerosol particles, because the dose is strongly dependent on the location of deposition in respiratory tract and hence on the aerodynamic characteristics of the aerosol particles. This paper presents the seasonal behavior of radon decay products in indoor air under domestic conditions at Nagoya University, Japan. A low pressure cascade impactor as an instrument for classifying aerosol sizes and imaging plate as a radiation detector have been employed to characterize the activity size distribution of short-lived radon decay products. In parallel, radon and its progenies concentrations were measured. Taking into account the progeny characteristics, the inhalation dose in the different seasons was also estimated based on a lung dose model with the structure that is related to the ICRP66 respiratory tract model. The result evident that, the highest dose 0.22 mSvy−1 was observed during the winter where the highest value of equilibrium equivalent concentration of radon (EEC and lowest value of the activity median aerodynamic diameter (AMAD were found in this season; whereas, the dose in spring appeared to be lowest 0.02 mSvy−1.

  6. Detection of human bocavirus and human metapneumovirus by real-time PCR from patients with respiratory symptoms in Southern Brazil

    Directory of Open Access Journals (Sweden)

    Diogo André Pilger

    2011-02-01

    Full Text Available The introduction of newer molecular methods has led to the discovery of new respiratory viruses, such as human metapneumovirus (hMPV and human bocavirus (hBoV, in respiratory tract specimens. We have studied the occurrence of hMPV and hBoV in the Porto Alegre (PA metropolitan area, one of the southernmost cities of Brazil, evaluating children with suspected lower respiratory tract infection from May 2007-June 2008. A real-time polymerase chain reaction method was used for amplification and detection of hMPV and hBoV and to evaluate coinfections with respiratory syncytial virus (RSV, influenza A and B, parainfluenza 1, 2 and 3, human rhinovirus and human adenovirus. Of the 455 nasopharyngeal aspirates tested, hMPV was detected in 14.5% of samples and hBoV in 13.2%. A unique causative viral agent was identified in 46.2% samples and the coinfection rate was 43.7%. For hBoV, 98.3% of all positive samples were from patients with mixed infections. Similarly, 84.8% of all hMPV-positive results were also observed in mixed infections. Both hBoV and hMPV usually appeared with RSV. In summary, this is the first confirmation that hMPV and hBoV circulate in PA; this provides evidence of frequent involvement of both viruses in children with clinical signs of acute viral respiratory tract infection, although they mainly appeared as coinfection agents.

  7. Distance to human populations influences epidemiology of respiratory disease in desert tortoises

    Science.gov (United States)

    Berry, Kristin H.; Ashley A. Coble (formerly Emerson), no longer USGS; Yee, Julie L.; Mack, Jeremy S.; Perry, William M.; Anderson, Kemp M.; Brown, Mary B.

    2014-01-01

    We explored variables likely to affect health of Agassiz's desert tortoises (Gopherus agassizii) in a 1,183-km2 study area in the central Mojave Desert of California between 2005 and 2008. We evaluated 1,004 tortoises for prevalence and spatial distribution of 2 pathogens, Mycoplasma agassizii and M. testudineum, that cause upper respiratory tract disease. We defined tortoises as test-positive if they were positive by culture and/or DNA identification or positive or suspect for specific antibody for either of the two pathogens. We used covariates of habitat (vegetation, elevation, slope, and aspect), tortoise size and sex, distance from another test-positive tortoise, and anthropogenic variables (distances to roads, agricultural areas, playas, urban areas, and centroids of human-populated census blocks). We used both logistic regression models and regression trees to evaluate the 2 species of Mycoplasma separately. The prevalence of test-positive tortoises was low: 1.49% (15/1,004) for M. agassizii and 2.89% (29/1,004) for M. testudineum. The spatial distributions of test-positive tortoises for the 2 Mycoplasma species showed little overlap; only 2 tortoises were test-positive for both diseases. However, the spatial distributions did not differ statistically between the 2 species. We consistently found higher prevalence of test-positive tortoises with shorter distances to centroids of human-populated census blocks. The relationship between distance to human-populated census blocks and tortoises that are test-positive for M. agassizii and potentially M. testudineum may be related to release or escape of captive tortoises because the prevalence of M. agassizii in captive tortoises is high. Our findings have application to other species of chelonians where both domestic captive and wild populations exist. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  8. Human iPS cell-derived astrocyte transplants preserve respiratory function after spinal cord injury.

    Science.gov (United States)

    Li, Ke; Javed, Elham; Scura, Daniel; Hala, Tamara J; Seetharam, Suneil; Falnikar, Aditi; Richard, Jean-Philippe; Chorath, Ashley; Maragakis, Nicholas J; Wright, Megan C; Lepore, Angelo C

    2015-09-01

    Transplantation-based replacement of lost and/or dysfunctional astrocytes is a promising therapy for spinal cord injury (SCI) that has not been extensively explored, despite the integral roles played by astrocytes in the central nervous system (CNS). Induced pluripotent stem (iPS) cells are a clinically-relevant source of pluripotent cells that both avoid ethical issues of embryonic stem cells and allow for homogeneous derivation of mature cell types in large quantities, potentially in an autologous fashion. Despite their promise, the iPS cell field is in its infancy with respect to evaluating in vivo graft integration and therapeutic efficacy in SCI models. Astrocytes express the major glutamate transporter, GLT1, which is responsible for the vast majority of glutamate uptake in spinal cord. Following SCI, compromised GLT1 expression/function can increase susceptibility to excitotoxicity. We therefore evaluated intraspinal transplantation of human iPS cell-derived astrocytes (hIPSAs) following cervical contusion SCI as a novel strategy for reconstituting GLT1 expression and for protecting diaphragmatic respiratory neural circuitry. Transplant-derived cells showed robust long-term survival post-injection and efficiently differentiated into astrocytes in injured spinal cord of both immunesuppressed mice and rats. However, the majority of transplant-derived astrocytes did not express high levels of GLT1, particularly at early times post-injection. To enhance their ability to modulate extracellular glutamate levels, we engineered hIPSAs with lentivirus to constitutively express GLT1. Overexpression significantly increased GLT1 protein and functional GLT1-mediated glutamate uptake levels in hIPSAs both in vitro and in vivo post-transplantation. Compared to human fibroblast control and unmodified hIPSA transplantation, GLT1-overexpressing hIPSAs reduced (1) lesion size within the injured cervical spinal cord, (2) morphological denervation by respiratory phrenic motor

  9. Respiratory dysfunction and proinflammatory chemokines in the pneumonia virus of mice (PVM) model of viral bronchiolitis.

    Science.gov (United States)

    Bonville, Cynthia A; Bennett, Nicholas J; Koehnlein, Melissa; Haines, Deborah M; Ellis, John A; DelVecchio, Alfred M; Rosenberg, Helene F; Domachowske, Joseph B

    2006-05-25

    We explore relationships linking clinical symptoms, respiratory dysfunction, and local production of proinflammatory chemokines in the pneumonia virus of mice (PVM) model of viral bronchiolitis. With a reduced inoculum of this natural rodent pathogen, we observe virus clearance by day 9, while clinical symptoms and respiratory dysfunction persist through days 14 and 17 postinoculation, respectively. Via microarray and ELISA, we identify expression profiles of proinflammatory mediators MIP-1alpha, MCP-1, and MIP-2 that correlate with persistent respiratory dysfunction. MIP-1alpha is localized in bronchial epithelium, which is also the major site of PVM replication. Interferon-gamma was detected in lung tissue, but at levels that do not correlate with respiratory dysfunction. Taken together, we present a modification of our pneumovirus infection model that results in improved survival and data that stand in support of a connection between local production of specific mediators and persistent respiratory dysfunction in the setting of acute viral bronchiolitis.

  10. Differential expression of the MERS-coronavirus receptor in the upper respiratory tract of humans and dromedary camels

    NARCIS (Netherlands)

    Widagdo, W; Raj, V Stalin; Schipper, Debby; Kolijn, Kimberley; van Leenders, Geert J L H; Bosch, Berend J; Bensaid, Albert; Segalés, Joaquim; Baumgärtner, Wolfgang; Osterhaus, Albert D M E; Koopmans, Marion P; van den Brand, Judith M A; Haagmans, Bart L

    2016-01-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) is not efficiently transmitted between humans, but it is highly prevalent in dromedary camels. Here we report that the MERS-CoV receptor - dipeptidyl peptidase 4 (DPP4) - is expressed in the upper respiratory tract epithelium of camels but not

  11. Study of mitochondrial respiratory defects on reprogramming to human induced pluripotent stem cells

    Science.gov (United States)

    Hung, Sandy S.C.; Van Bergen, Nicole J.; Jackson, Stacey; Liang, Helena; Mackey, David A.; Hernández, Damián; Lim, Shiang Y.; Hewitt, Alex W.; Trounce, Ian; Pébay, Alice; Wong, Raymond C.B.

    2016-01-01

    Reprogramming of somatic cells into a pluripotent state is known to be accompanied by extensive restructuring of mitochondria and switch in metabolic requirements. Here we utilized Leber's hereditary optic neuropathy (LHON) as a mitochondrial disease model to study the effects of homoplasmic mtDNA mutations and subsequent oxidative phosphorylation (OXPHOS) defects in reprogramming. We obtained fibroblasts from a total of 6 LHON patients and control subjects, and showed a significant defect in complex I respiration in LHON fibroblasts by high-resolution respiratory analysis. Using episomal vector reprogramming, our results indicated that human induced pluripotent stem cell (hiPSC) generation is feasible in LHON fibroblasts. In particular, LHON-specific OXPHOS defects in fibroblasts only caused a mild reduction and did not significantly affect reprogramming efficiency, suggesting that hiPSC reprogramming can tolerate a certain degree of OXPHOS defects. Our results highlighted the induction of genes involved in mitochondrial biogenesis (TFAM, NRF1), mitochondrial fusion (MFN1, MFN2) and glycine production (GCAT) during reprogramming. However, LHON-associated OXPHOS defects did not alter the kinetics or expression levels of these genes during reprogramming. Together, our study provides new insights into the effects of mtDNA mutation and OXPHOS defects in reprogramming and genes associated with various aspects of mitochondrial biology. PMID:27127184

  12. DNA strand breaks in human nasal respiratory epithelium are induced upon exposure to urban pollution

    Energy Technology Data Exchange (ETDEWEB)

    Calderon-Garciduenas, L.; Osnaya-Brizuela, N.; Ramirez-Martinez, L. [Instituto Nacional de Pediatria, Mexico City (Mexico)] [and others

    1996-02-01

    All organisms have the ability to respond and adapt to a myriad of environmental insults. The human respiratory epithelium, when exposed to oxidant gases in photochemical smog, is at risk of DNA damage and requires efficient cellular adaptative responses to resist the environmentally induced cell damage. Ozone and its reaction products induce in vitro and in vivo DNA single strand breaks (SSBs) in respiratory epithelial cells and alveolar macrophages. To determine if exposure to a polluted atmosphere with ozone as the main criteria pollutant of 19 children and 13 adult males who lived in a low-polluted Pacific port, 69 males and 16 children who were permanent residents of Southwest Metropolitan Mexico City (SWMMC), and 22 young males newly arrived to SWMMC and followed for 12 weeks. Respiratory symptoms, nasal cytology and histopathology, cell viabilities, and single-cell gel electrophoresis were investigated. Atmospheric pollutant data were obtained from a fixed-site monitoring station. SWMMC volunteers spent >7 hr/day outdoors and all had upper respiratory symptoms. A significant difference in the numbers of DNA-damaged nasal cells was observed between control and chronically exposed subjects, both in children (p<0.00001) and in adults (p>0.01). SSBs in newly arrived subjects quickly increased upon arrival to the city, from 39.8 {+-}8.34% in the first week to 67.29 {+-}2.35 by week 2. Thereafter, the number of cells with SSBs remained stable in spite of the continuous increase in cumulative ozone, suggesting a threshold for cumulative DNA nasal damage. Exposure to a polluted urban atmosphere induces SSBs in human nasal respiratory epithelium, and nasal SSBs could serve as a biomarker of ozone exposure. Further, because DNA strand breaks are a threat to cell viability and genome integrity and appear to be a critical lesion responsible for p53 induction, nasal SSBs should be evaluated in ozone-exposed individuals. 43 refs., 5 figs., 4 tabs.

  13. Transcription of human respiratory syncytial virus genome RNA in vitro: requirement of cellular factor(s).

    OpenAIRE

    Barik, S

    1992-01-01

    Extracts made from human respiratory syncytial virus (RSV)-infected Hep-2 cells synthesized mRNAs encoded by all known viral genes. In contrast, RSV ribonucleoproteins purified from infected cells failed to transcribe in vitro; transcription was restored by addition of a cytoplasmic extract of uninfected Hep-2 cells, demonstrating that a cellular factor(s) has a role in RSV gene expression. Quantitation of the individual gene mRNAs transcribed in vitro revealed polarity of transcription of th...

  14. Mitochondrial respiratory capacity and content are normal in young insulin-resistant obese humans.

    Science.gov (United States)

    Fisher-Wellman, Kelsey H; Weber, Todd M; Cathey, Brook L; Brophy, Patricia M; Gilliam, Laura A A; Kane, Constance L; Maples, Jill M; Gavin, Timothy P; Houmard, Joseph A; Neufer, P Darrell

    2014-01-01

    Considerable debate exists about whether alterations in mitochondrial respiratory capacity and/or content play a causal role in the development of insulin resistance during obesity. The current study was undertaken to determine whether such alterations are present during the initial stages of insulin resistance in humans. Young (∼23 years) insulin-sensitive lean and insulin-resistant obese men and women were studied. Insulin resistance was confirmed through an intravenous glucose tolerance test. Measures of mitochondrial respiratory capacity and content as well as H(2)O(2) emitting potential and the cellular redox environment were performed in permeabilized myofibers and primary myotubes prepared from vastus lateralis muscle biopsy specimens. No differences in mitochondrial respiratory function or content were observed between lean and obese subjects, despite elevations in H(2)O(2) emission rates and reductions in cellular glutathione. These findings were apparent in permeabilized myofibers as well as in primary myotubes. The results suggest that reductions in mitochondrial respiratory capacity and content are not required for the initial manifestation of peripheral insulin resistance.

  15. Respiratory mechanics in an infant with perinatal lethal hypophosphatasia treated with human recombinant enzyme replacement therapy.

    Science.gov (United States)

    Rodriguez, Elena; Bober, Michael B; Davey, Lauren; Zamora, Arlene; Li Puma, Annelise B; Chidekel, Aaron; Shaffer, Thomas H

    2012-09-01

    Hypophosphatasia is a rare autosomal recessive disorder caused by deficient activity of tissue nonspecific alkaline phosphatase (TNSALP) and characterized by defective bone mineralization. In the perinatal lethal form, respiratory complications due to rachitic deformities of the thoracic cage and associated hypoplastic lungs are present. ENB-0040 is a bone-targeted human recombinant TNSALP fusion protein that aims to restore skeletal mineralization. The goal of this study was to characterize pulmonary and thoracic cage mechanics in an infant with the perinatal lethal form of hypophosphatasia under enzyme replacement therapy. Pulmonary function testing was performed on a preterm, 8-week-old patient with hypophosphatasia who was mechanically ventilated since birth because of severe chest wall insufficiency. The measurements consisted of respiratory impulse oscillation measurements (resistance and reactance), ventilatory mechanics (compliance and resistance), and thoracoabdominal motion (TAM) analysis. At baseline, chest wall compliance was 50% of normal, and the TAM indicated predominantly abdominal displacement. After 12 weeks of treatment, a consistent decrease in ventilator requirements and improvement in lung function and chest wall mechanics were observed and correlated with thoracic cage radiologic findings. Measurable changes in chest wall dynamics and respiratory mechanics using noninvasive technology were useful for respiratory management and therapeutic guidance of ENB-0040 treatment in this patient.

  16. Modeling the Early Events of Severe Acute Respiratory Syndrome Coronavirus Infection In Vitro

    Science.gov (United States)

    Yen, Yu-Ting; Liao, Fang; Hsiao, Cheng-Hsiang; Kao, Chuan-Liang; Chen, Yee-Chun; Wu-Hsieh, Betty A.

    2006-01-01

    The clinical picture of severe acute respiratory syndrome (SARS) is characterized by pulmonary inflammation and respiratory failure, resembling that of acute respiratory distress syndrome. However, the events that lead to the recruitment of leukocytes are poorly understood. To study the cellular response in the acute phase of SARS coronavirus (SARS-CoV)-host cell interaction, we investigated the induction of chemokines, adhesion molecules, and DC-SIGN (dendritic cell-specific ICAM-3-grabbing nonintegrin) by SARS-CoV. Immunohistochemistry revealed neutrophil, macrophage, and CD8 T-cell infiltration in the lung autopsy of a SARS patient who died during the acute phase of illness. Additionally, pneumocytes and macrophages in the patient's lung expressed P-selectin and DC-SIGN. In in vitro study, we showed that the A549 and THP-1 cell lines were susceptible to SARS-CoV. A549 cells produced CCL2/monocyte chemoattractant protein 1 (MCP-1) and CXCL8/interleukin-8 (IL-8) after interaction with SARS-CoV and expressed P-selectin and VCAM-1. Moreover, SARS-CoV induced THP-1 cells to express CCL2/MCP-1, CXCL8/IL-8, CCL3/MIP-1α, CXCL10/IP-10, CCL4/MIP-1β, and CCL5/RANTES, which attracted neutrophils, monocytes, and activated T cells in a chemotaxis assay. We also demonstrated that DC-SIGN was inducible in THP-1 as well as A549 cells after SARS-CoV infection. Our in vitro experiments modeling infection in humans together with the study of a lung biopsy of a patient who died during the early phase of infection demonstrated that SARS-CoV, through a dynamic interaction with lung epithelial cells and monocytic cells, creates an environment conducive for immune cell migration and accumulation that eventually leads to lung injury. PMID:16501078

  17. Human Coronavirus in the 2014 Winter Season as a Cause of Lower Respiratory Tract Infection.

    Science.gov (United States)

    Kim, Kyu Yeun; Han, Song Yi; Kim, Ho Seong; Cheong, Hyang Min; Kim, Sung Soon; Kim, Dong Soo

    2017-01-01

    During the late autumn to winter season (October to December) in the Republic of Korea, respiratory syncytial virus (RSV) is the most common pathogen causing lower respiratory tract infections (LRTIs). Interestingly, in 2014, human coronavirus (HCoV) caused not only upper respiratory infections but also LRTIs more commonly than in other years. Therefore, we sought to determine the epidemiology, clinical characteristics, outcomes, and severity of illnesses associated with HCoV infections at a single center in Korea. We retrospectively identified patients with positive HCoV respiratory specimens between October 2014 and December 2014 who were admitted to Severance Children's Hospital at Yonsei University Medical Center for LRTI. Charts of the patients with HCoV infection were reviewed and compared with RSV infection. During the study period, HCoV was the third most common respiratory virus and accounted for 13.7% of infections. Coinfection was detected in 43.8% of children with HCoV. Interestingly, one patient had both HCoV-OC43 and HCoV-NL63. Mild pneumonia was most common (60.4%) with HCoV, and when combined with RSV, resulted in bronchiolitis. Two patients required care in the intensive care unit. However, compared with that of RSV infection, the disease course HCoV was short. Infections caused by HCoVs are common, and can cause LRTIs. During an epidemic season, clinicians should be given special consideration thereto. When combined with other medical conditions, such as neurologic or cardiologic diseases, intensive care unit (ICU) care may be necessary.

  18. Protection of human upper respiratory tract cell lines against sulphur mustard toxicity by hexamethylenetetramine (HMT).

    Science.gov (United States)

    Andrew, D J; Lindsay, C D

    1998-07-01

    1. Sulphur mustard ('mustard gas', HD) is a highly toxic chemical warfare agent which affects the skin and respiratory tract. The primary targets of inhaled HD are the epithelia of the upper respiratory tract. Hexamethylenetetramine (HMT) has been shown to protect human lung cells against HD toxicity and has also been shown to be effective in vivo against the chemical warfare agent phosgene. The ability of HMT to protect against the toxicity of HD was investigated in the human upper respiratory tract cell lines BEAS-2B and RPMI 2650. 2. HD was highly toxic to both cell lines, with LC50 values of 15-30 microM. HMT, at a concentration of 10 mM, was shown to protect the cell lines against the toxic effects of 20 microM and 40 microM HD. Results demonstrated that it was necessary for HMT to be in situ at the time of exposure to HD for effective cytoprotection. No protection was seen when cells were treated with HMT following exposure to HD, or where HMT was removed prior to HD exposure. 3. Results suggest that HMT may be effective prophylaxis for exposure to HD by inhalation.

  19. Carnitine Palmitoyltransferase 1B 531K Allele Carriers Sustain a Higher Respiratory Quotient after Aerobic Exercise, but β3-Adrenoceptor 64R Allele Does Not Affect Lipolysis: A Human Model

    Science.gov (United States)

    Gómez-Gómez, Eduardo; Ríos-Martínez, Martín Efrén; Castro-Rodríguez, Elena Margarita; Del-Toro-Equíhua, Mario; Ramírez-Flores, Mario; Delgado-Enciso, Ivan; Pérez-Huitimea, Ana Lilia; Baltazar-Rodríguez, Luz Margarita; Velasco-Pineda, Gilberto; Muñiz-Murguía, Jesús

    2014-01-01

    Carnitine palmitoyltransferase IB (CPT1B) and adrenoceptor beta-3 (ADRB3) are critical regulators of fat metabolism. CPT1B transports free acyl groups into mitochondria for oxidation, and ADRB3 triggers lipolysis in adipocytes, and their respective polymorphisms E531K and W64R have been identified as indicators of obesity in population studies. It is therefore important to understand the effects of these mutations on ADRB3 and CPT1B function in adipose and skeletal muscle tissue, respectively. This study aimed to analyze the rate of lipolysis of plasma indicators (glycerol, free fatty acids, and beta hydroxybutyrate) and fat oxidation (through the non-protein respiratory quotient). These parameters were measured in 37 participants during 30 min of aerobic exercise at approximately 62% of maximal oxygen uptake, followed by 30 min of recovery. During recovery, mean respiratory quotient values were higher in K allele carriers than in non-carriers, indicating low post-exercise fatty acid oxidation rates. No significant differences in lipolysis or lipid oxidation were observed between R and W allele carriers of ADRB3 at any time during the aerobic load. The substitution of glutamic acid at position 531 by lysine in the CPT1B protein decreases the mitochondrial beta-oxidation pathway, which increases the non-protein respiratory quotient value during recovery from exercise. This may contribute to weight gain or reduced weight-loss following exercise. PMID:24905907

  20. Carnitine palmitoyltransferase 1B 531K allele carriers sustain a higher respiratory quotient after aerobic exercise, but β3-adrenoceptor 64R allele does not affect lipolysis: a human model.

    Directory of Open Access Journals (Sweden)

    Eduardo Gómez-Gómez

    Full Text Available Carnitine palmitoyltransferase IB (CPT1B and adrenoceptor beta-3 (ADRB3 are critical regulators of fat metabolism. CPT1B transports free acyl groups into mitochondria for oxidation, and ADRB3 triggers lipolysis in adipocytes, and their respective polymorphisms E531K and W64R have been identified as indicators of obesity in population studies. It is therefore important to understand the effects of these mutations on ADRB3 and CPT1B function in adipose and skeletal muscle tissue, respectively. This study aimed to analyze the rate of lipolysis of plasma indicators (glycerol, free fatty acids, and beta hydroxybutyrate and fat oxidation (through the non-protein respiratory quotient. These parameters were measured in 37 participants during 30 min of aerobic exercise at approximately 62% of maximal oxygen uptake, followed by 30 min of recovery. During recovery, mean respiratory quotient values were higher in K allele carriers than in non-carriers, indicating low post-exercise fatty acid oxidation rates. No significant differences in lipolysis or lipid oxidation were observed between R and W allele carriers of ADRB3 at any time during the aerobic load. The substitution of glutamic acid at position 531 by lysine in the CPT1B protein decreases the mitochondrial beta-oxidation pathway, which increases the non-protein respiratory quotient value during recovery from exercise. This may contribute to weight gain or reduced weight-loss following exercise.

  1. Time-varying respiratory system elastance: a physiological model for patients who are spontaneously breathing.

    Directory of Open Access Journals (Sweden)

    Yeong Shiong Chiew

    Full Text Available BACKGROUND: Respiratory mechanics models can aid in optimising patient-specific mechanical ventilation (MV, but the applications are limited to fully sedated MV patients who have little or no spontaneously breathing efforts. This research presents a time-varying elastance (E(drs model that can be used in spontaneously breathing patients to determine their respiratory mechanics. METHODS: A time-varying respiratory elastance model is developed with a negative elastic component (E(demand, to describe the driving pressure generated during a patient initiated breathing cycle. Data from 22 patients who are partially mechanically ventilated using Pressure Support (PS and Neurally Adjusted Ventilatory Assist (NAVA are used to investigate the physiology relevance of the time-varying elastance model and its clinical potential. E(drs of every breathing cycle for each patient at different ventilation modes are presented for comparison. RESULTS: At the start of every breathing cycle initiated by patient, E(drs is 25 cmH2Os/l and thus can be used as an acute respiratory distress syndrome (ARDS severity indicator. CONCLUSION: The E(drs model captures unique dynamic respiratory mechanics for spontaneously breathing patients with respiratory failure. The model is fully general and is applicable to both fully controlled and partially assisted MV modes.

  2. Circulating strains of human respiratory syncytial virus in central and south America.

    Directory of Open Access Journals (Sweden)

    Merly Sovero

    Full Text Available Human respiratory syncytial virus (HRSV is a major cause of viral lower respiratory tract infections among infants and young children. HRSV strains vary genetically and antigenically and have been classified into two broad subgroups, A and B (HRSV-A and HRSV-B, respectively. To date, little is known about the circulating strains of HRSV in Latin America. We have evaluated the genetic diversity of 96 HRSV strains by sequencing a variable region of the G protein gene of isolates collected from 2007 to 2009 in Central and South America. Our results show the presence of the two antigenic subgroups of HRSV during this period with the majority belonging to the genotype HRSV-A2.

  3. Computational human body models

    NARCIS (Netherlands)

    Wismans, J.S.H.M.; Happee, R.; Dommelen, J.A.W. van

    2005-01-01

    Computational human body models are widely used for automotive crashsafety research and design and as such have significantly contributed to a reduction of traffic injuries and fatalities. Currently crash simulations are mainly performed using models based on crash-dummies. However crash dummies dif

  4. Computational human body models

    NARCIS (Netherlands)

    Wismans, J.S.H.M.; Happee, R.; Dommelen, J.A.W. van

    2005-01-01

    Computational human body models are widely used for automotive crashsafety research and design and as such have significantly contributed to a reduction of traffic injuries and fatalities. Currently crash simulations are mainly performed using models based on crash-dummies. However crash dummies

  5. Comparison of severe pneumonia caused by Human metapneumovirus and respiratory syncytial virus in hospitalized children

    Directory of Open Access Journals (Sweden)

    Yuqing Wang

    2014-01-01

    Full Text Available Objectives: The objective of this study is to compare the incidence and clinical characteristics of severe pneumonia caused by Human metapneumovirus (hMPV to respiratory syncytial virus (RSV infection in children. Patients and Methods: A total of 151 children hospitalized with severe pneumonia, were tested for hMPV using reverse-transcription polymerase chain reaction. At the same time, samples were tested for RSV and other common respiratory viruses. Medical records, including clinical, laboratory data, and chest radiography findings, were reviewed for all children. Results: Of the 151 samples, 88 (58.3% were positive for respiratory viruses. Of the 88 positive, there were 6 (4.0% with hMPV, 66 (43.7% with RSV, 13 (8.6% with influenza A, 2 (1.3% with parainfluenza virus III, 1 (0.7% with parainfluenza virus I, 1 (0.7% with adenovirus and 1 (0.7% with influenza B. hMPV-infected patients were significantly older than RSV-infected patients (P < 0.001. Children with hMPV pneumonia had fever more frequently (P = 0.03. Two hMPV-positive patients (33.3% required admission to an intensive care unit, and two patients (33.3% required mechanical ventilation. The duration of illness was 18.33 ± 7.09 days. These characteristics of hMPV infections were similar to patients with RSV infections. Conclusion: Human metapneumovirus is an infrequent viral pathogen causing severe pneumonia in children. Children with hMPV were older than those with RSV. The disease caused by hMPV was similar in presentation and severity to RSV, with a minority of children requiring additional respiratory support.

  6. Total liquid ventilation provides superior respiratory support to conventional mechanical ventilation in a large animal model of severe respiratory failure.

    Science.gov (United States)

    Pohlmann, Joshua R; Brant, David O; Daul, Morgan A; Reoma, Junewai L; Kim, Anne C; Osterholzer, Kathryn R; Johnson, Kent J; Bartlett, Robert H; Cook, Keith E; Hirschl, Ronald B

    2011-01-01

    Total liquid ventilation (TLV) has the potential to provide respiratory support superior to conventional mechanical ventilation (CMV) in the acute respiratory distress syndrome (ARDS). However, laboratory studies are limited to trials in small animals for no longer than 4 hours. The objective of this study was to compare TLV and CMV in a large animal model of ARDS for 24 hours. Ten sheep weighing 53 ± 4 (SD) kg were anesthetized and ventilated with 100% oxygen. Oleic acid was injected into the pulmonary circulation until PaO2:FiO2 ≤ 60 mm Hg, followed by transition to a protective CMV protocol (n = 5) or TLV (n = 5) for 24 hours. Pathophysiology was recorded, and the lungs were harvested for histological analysis. Animals treated with CMV became progressively hypoxic and hypercarbic despite maximum ventilatory support. Sheep treated with TLV maintained normal blood gases with statistically greater PO2 (p < 10(-9)) and lower PCO2 (p < 10(-3)) than the CMV group. Survival at 24 hours in the TLV and CMV groups were 100% and 40%, respectively (p < 0.05). Thus, TLV provided gas exchange superior to CMV in this laboratory model of severe ARDS.

  7. Recombinant subgroup B human respiratory syncytial virus expressing enhanced green fluorescent protein efficiently replicates in primary human cells and is virulent in cotton rats

    NARCIS (Netherlands)

    K. Lemon (Ken); D.T. Nguyen (Tien); M. Ludlow (Martin); L.J. Rennick (Linda); S. Yüksel (Selma); G. van Amerongen (Geert); S. McQuaid (Stephen); B.K. Rima (Bert); R.L. de Swart (Rik); W.P. Duprex (Paul)

    2015-01-01

    textabstractHuman respiratory syncytial virus (HRSV) is the most important viral cause of severe respiratory tract disease in infants. Two subgroups (A and B) have been identified, which cocirculate during, or alternate between, yearly epidemics and cause indistinguishable disease. Existing in vitro

  8. A human lung xenograft mouse model of Nipah virus infection.

    Directory of Open Access Journals (Sweden)

    Gustavo Valbuena

    2014-04-01

    Full Text Available Nipah virus (NiV is a member of the genus Henipavirus (family Paramyxoviridae that causes severe and often lethal respiratory illness and encephalitis in humans with high mortality rates (up to 92%. NiV can cause Acute Lung Injury (ALI in humans, and human-to-human transmission has been observed in recent outbreaks of NiV. While the exact route of transmission to humans is not known, we have previously shown that NiV can efficiently infect human respiratory epithelial cells. The molecular mechanisms of NiV-associated ALI in the human respiratory tract are unknown. Thus, there is an urgent need for models of henipavirus infection of the human respiratory tract to study the pathogenesis and understand the host responses. Here, we describe a novel human lung xenograft model in mice to study the pathogenesis of NiV. Following transplantation, human fetal lung xenografts rapidly graft and develop mature structures of adult lungs including cartilage, vascular vessels, ciliated pseudostratified columnar epithelium, and primitive "air" spaces filled with mucus and lined by cuboidal to flat epithelium. Following infection, NiV grows to high titers (10(7 TCID50/gram lung tissue as early as 3 days post infection (pi. NiV targets both the endothelium as well as respiratory epithelium in the human lung tissues, and results in syncytia formation. NiV infection in the human lung results in the production of several cytokines and chemokines including IL-6, IP-10, eotaxin, G-CSF and GM-CSF on days 5 and 7 pi. In conclusion, this study demonstrates that NiV can replicate to high titers in a novel in vivo model of the human respiratory tract, resulting in a robust inflammatory response, which is known to be associated with ALI. This model will facilitate progress in the fundamental understanding of henipavirus pathogenesis and virus-host interactions; it will also provide biologically relevant models for other respiratory viruses.

  9. A study of IOS data using two mead-related models of respiratory impedance.

    Science.gov (United States)

    Nguyen, T-U; Diong, B; Nazeran, H; Goldman, M

    2007-01-01

    This paper introduces two new respiratory system models, the Mead-Cw model and the Mead-Cl model, which are 6-component models that are intermediate in complexity between the well-known 7-component Mead model and the recently proposed 5-component augmented RIC model (derived from the Mead model by eliminating both Cw and Cl). Their modeling errors were compared to the RIC, extended RIC, augmented RIC and Mead models, for component values estimated from IOS data. The two new models yielded lower errors than all the other models, except for the Mead model. However, the Mead-Cl model and the Mead-Cw model also yielded unreasonably large values for Cw and Cl, respectively, which are known disadvantages of the Mead model. Hence the augmented RIC model appears to be the most useful at present for IOS-based computer-aided detection and diagnosis of respiratory disorders.

  10. An attraction-repulsion point process model for respiratory syncytial virus infections.

    Science.gov (United States)

    Goldstein, Joshua; Haran, Murali; Simeonov, Ivan; Fricks, John; Chiaromonte, Francesca

    2015-06-01

    How is the progression of a virus influenced by properties intrinsic to individual cells? We address this question by studying the susceptibility of cells infected with two strains of the human respiratory syncytial virus (RSV-A and RSV-B) in an in vitro experiment. Spatial patterns of infected cells give us insight into how local conditions influence susceptibility to the virus. We observe a complicated attraction and repulsion behavior, a tendency for infected cells to lump together or remain apart. We develop a new spatial point process model to describe this behavior. Inference on spatial point processes is difficult because the likelihood functions of these models contain intractable normalizing constants; we adapt an MCMC algorithm called double Metropolis-Hastings to overcome this computational challenge. Our methods are computationally efficient even for large point patterns consisting of over 10,000 points. We illustrate the application of our model and inferential approach to simulated data examples and fit our model to various RSV experiments. Because our model parameters are easy to interpret, we are able to draw meaningful scientific conclusions from the fitted models.

  11. Glycomic analysis of human respiratory tract tissues and correlation with influenza virus infection.

    Directory of Open Access Journals (Sweden)

    Trevenan Walther

    2013-03-01

    Full Text Available The first step in influenza infection of the human respiratory tract is binding of the virus to sialic (Sia acid terminated receptors. The binding of different strains of virus for the receptor is determined by the α linkage of the sialic acid to galactose and the adjacent glycan structure. In this study the N- and O-glycan composition of the human lung, bronchus and nasopharynx was characterized by mass spectrometry. Analysis showed that there was a wide spectrum of both Sia α2-3 and α2-6 glycans in the lung and bronchus. This glycan structural data was then utilized in combination with binding data from 4 of the published glycan arrays to assess whether these current glycan arrays were able to predict replication of human, avian and swine viruses in human ex vivo respiratory tract tissues. The most comprehensive array from the Consortium for Functional Glycomics contained the greatest diversity of sialylated glycans, but was not predictive of productive replication in the bronchus and lung. Our findings indicate that more comprehensive but focused arrays need to be developed to investigate influenza virus binding in an assessment of newly emerging influenza viruses.

  12. Multi-Organ Damage in Human Dipeptidyl Peptidase 4 Transgenic Mice Infected with Middle East Respiratory Syndrome-Coronavirus.

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    Guangyu Zhao

    Full Text Available The Middle East Respiratory Syndrome Coronavirus (MERS-CoV causes severe acute respiratory failure and considerable extrapumonary organ dysfuction with substantial high mortality. For the limited number of autopsy reports, small animal models are urgently needed to study the mechanisms of MERS-CoV infection and pathogenesis of the disease and to evaluate the efficacy of therapeutics against MERS-CoV infection. In this study, we developed a transgenic mouse model globally expressing codon-optimized human dipeptidyl peptidase 4 (hDPP4, the receptor for MERS-CoV. After intranasal inoculation with MERS-CoV, the mice rapidly developed severe pneumonia and multi-organ damage, with viral replication being detected in the lungs on day 5 and in the lungs, kidneys and brains on day 9 post-infection. In addition, the mice exhibited systemic inflammation with mild to severe pneumonia accompanied by the injury of liver, kidney and spleen with neutrophil and macrophage infiltration. Importantly, the mice exhibited symptoms of paralysis with high viral burden and viral positive neurons on day 9. Taken together, this study characterizes the tropism of MERS-CoV upon infection. Importantly, this hDPP4-expressing transgenic mouse model will be applicable for studying the pathogenesis of MERS-CoV infection and investigating the efficacy of vaccines and antiviral agents designed to combat MERS-CoV infection.

  13. Human migraine models

    DEFF Research Database (Denmark)

    Iversen, Helle Klingenberg

    2001-01-01

    The need for experimental models is obvious. In animal models it is possible to study vascular responses, neurogenic inflammation, c-fos expression etc. However, the pathophysiology of migraine remains unsolved, why results from animal studies not directly can be related to the migraine attack......, which is a human experience. A set-up for investigations of experimental headache and migraine in humans, has been evaluated and headache mechanisms explored by using nitroglycerin and other headache-inducing agents. Nitric oxide (NO) or other parts of the NO activated cascade seems to be responsible...

  14. Human Pharyngeal Microbiome May Play A Protective Role in Respiratory Tract Infections

    Institute of Scientific and Technical Information of China (English)

    Zhancheng Gao; Yu Kang; Jun Yu; Lufeng Ren

    2014-01-01

    The human pharyngeal microbiome, which resides at the juncture of digestive and respi-ratory tracts, may have an active role in the prevention of respiratory tract infections, similar to the actions of the intestinal microbiome against enteric infections. Recent studies have demonstrated that the pharyngeal microbiome comprises an abundance of bacterial species that interacts with the local epithelial and immune cells, and together, they form a unique micro-ecological system. Most of the microbial species in microbiomes are obligate symbionts constantly adapting to their unique surroundings. Indigenous commensal species are capable of both maintaining dominance and evoking host immune responses to eliminate invading species. Temporary damage to the pha-ryngeal microbiome due to the impaired local epithelia is also considered an important predisposing risk factor for infections. Therefore, reinforcement of microbiome homeostasis to prevent invasion of infection-prone species would provide a novel treatment strategy in addition to antibiotic treat-ment and vaccination. Hence continued research efforts on evaluating probiotic treatment and developing appropriate procedures are necessary to both prevent and treat respiratory infections.

  15. Premature infants have impaired airway antiviral IFNγ responses to human metapneumovirus compared to respiratory syncytial virus

    Science.gov (United States)

    Pancham, Krishna; Perez, Geovanny F.; Huseni, Shehlanoor; Jain, Amisha; Kurdi, Bassem; Rodriguez-Martinez, Carlos E.; Preciado, Diego; Rose, Mary C.; Nino, Gustavo

    2017-01-01

    BACKGROUND It is unknown why human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) cause severe respiratory infection in children, particularly in premature infants. Our aim was to investigate if there are defective airway antiviral responses to these viruses in young children with history of prematurity. METHODS Nasal airway secretions were collected from 140 children ≤3 y old without detectable virus (n = 80) or with PCR-confirmed HMPV or RSV infection (n = 60). Nasal protein levels of IFNγ, CCL5/RANTES, IL-10, IL-4, and IL-17 were determined using a multiplex magnetic bead immunoassay. RESULTS Full-term children with HMPV and RSV infection had increased levels of nasal airway IFNγ, CCL5, and IL-10 along with an elevation in Th1 (IFNγ)/Th2 (IL-4) ratios, which is expected during antiviral responses. In contrast, HMPV-infected premature children (< 32 wk gestation) did not exhibit increased Th1/Th2 ratios or elevated nasal airway secretion of IFNγ, CCL5, and IL-10 relative to uninfected controls. CONCLUSION Our study is the first to demonstrate that premature infants have defective IFNγ, CCL5/RANTES, and IL-10 airway responses during HMPV infection and provides novel insights about the potential reason why HMPV causes severe respiratory disease in children with history of prematurity. PMID:26086642

  16. Molecular Analysis of Human Metapneumovirus Detected in Patients with Lower Respiratory Tract Infection in Upper Egypt

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    Mona S. Embarek Mohamed

    2014-01-01

    Full Text Available Introduction. Since 2001, when Human metapneumovirus (HMPV was isolated in the Netherlands, the virus has been detected in several continents. Although reports have confirmed the prevalence of HMPV worldwide, data from Egypt remain limited. HMPV plays an important role in respiratory tract infections in individuals of all ages particularly in children. This study was aimed at estimating the prevalence of HMPV in patients with community-acquired lower respiratory infection in Upper Egypt and characterizing the circulating Egyptian HMPV strains for the first time. Materials and Methods. From 2005 to 2008, respiratory samples from 520 patients were analyzed for the presence of HMPV by real-time RT-PCR. Molecular and phylogenetic analyses were performed on partial fusion gene sequences of HMPV-positive patients. Results. HMPV-positive patients were detected in 2007-2008. The overall infection rate was 4%, while 57% of the patients were children. Sequence analysis demonstrated circulation of subgroup B viruses with predominance of lineage B2. Nucleotide sequence identity within lineage B1 was 98.8%–99.7% and higher than that in lineage B2 (94.3%–100%. Three new amino acid substitutions (T223N, R229K, and D280N of lineage B2 were observed. Conclusion. HMPV is a major viral pathogen in the Egyptian population especially in children. During 2007-2008, predominantly HMPV B2 circulated in Upper Egypt.

  17. Functional and histopathological identification of the respiratory failure in a DMSXL transgenic mouse model of myotonic dystrophy

    OpenAIRE

    Petrica-Adrian Panaite; Thierry Kuntzer; Geneviève Gourdon; Johannes Alexander Lobrinus; Ibtissam Barakat-Walter

    2013-01-01

    SUMMARY Acute and chronic respiratory failure is one of the major and potentially life-threatening features in individuals with myotonic dystrophy type 1 (DM1). Despite several clinical demonstrations showing respiratory problems in DM1 patients, the mechanisms are still not completely understood. This study was designed to investigate whether the DMSXL transgenic mouse model for DM1 exhibits respiratory disorders and, if so, to identify the pathological changes underlying these respiratory p...

  18. Human intermittent hypoxia-induced respiratory plasticity is not caused by inflammation.

    Science.gov (United States)

    Beaudin, Andrew E; Waltz, Xavier; Pun, Matiram; Wynne-Edwards, Katherine E; Ahmed, Sofia B; Anderson, Todd J; Hanly, Patrick J; Poulin, Marc J

    2015-10-01

    Ventilatory instability, reflected by enhanced acute hypoxic (AHVR) and hypercapnic (AHCVR) ventilatory responses is a fundamental component of obstructive sleep apnoea (OSA) pathogenesis. Intermittent hypoxia-induced inflammation is postulated to promote AHVR enhancement in OSA, although the role of inflammation in intermittent hypoxia-induced respiratory changes in humans has not been examined. Thus, this study assessed the role of inflammation in intermittent hypoxia-induced respiratory plasticity in healthy humans.In a double-blind, placebo-controlled, randomised crossover study design, 12 males were exposed to 6 h of intermittent hypoxia on three occasions. Prior to intermittent hypoxia exposures, participants ingested (for 4  days) either placebo or the nonsteroidal anti-inflammatory drugs indomethacin (nonselective cyclooxygenase (COX) inhibitor) and celecoxib (selective COX-2 inhibitor). Pre- and post-intermittent hypoxia resting ventilation, AHVR, AHCVR and serum concentration of the pro-inflammatory cytokine tumour necrosis factor (TNF)-α were assessed.Pre-intermittent hypoxia resting ventilation, AHVR, AHCVR and TNF-α concentrations were similar across all three conditions (p≥0.093). Intermittent hypoxia increased resting ventilation and the AHVR similarly across all conditions (p=0.827), while the AHCVR was increased (p=0.003) and TNF-α was decreased (p=0.006) with only selective COX-2 inhibition.These findings indicate that inflammation does not contribute to human intermittent hypoxia-induced respiratory plasticity. Moreover, selective COX-2 inhibition augmented the AHCVR following intermittent hypoxia exposure, suggesting that selective COX-2 inhibition could exacerbate OSA severity by increasing ventilatory instability.

  19. All Known Human Rhinovirus Species Are Present in Sputum Specimens of Military Recruits During Respiratory Infection

    Directory of Open Access Journals (Sweden)

    Merja Roivainen

    2009-12-01

    Full Text Available Human rhinoviruses (HRV are known to cause common cold as well as more complicated respiratory infections. HRV species -A, -B and -C have all been associated with lower respiratory infections and exacerbations of asthma. However, the type distribution of strains connected to different kinds of lower respiratory conditions is not clearly known. We have analysed the presence of HRV in sputum specimens derived from military recruits with and without pre-diagnosed asthma at times of acute respiratory infection (CIAS Study, 2004-2005. The analysis was performed with HRV and HEV real-time RT-PCR assays. Subsequently we studied type distribution of HRV strains by genetic typing in the VP4/VP2 genomic region. In total 146 (38.8% specimens were HRV-positive and 36 (9.3% HEV-positive. No difference was found in HRV detection between the asthmatic vs. non-asthmatic patients. Most of the genetically typed strains, 18 (62.1%, belonged to HRV-A, while HRV-B strains constituted five (17.2% of the HRV-positive strains. HRV-C strain was typed four times from the HRV-positive cases and a HEV-D strain twice. We further typed six HEV positive strains in the partial VP1 region. Three of these belonged to HRV-A and three to HEV-D. HRV-A strains were discovered throughout the study period, while HRV-C strains originated from winter and spring specimens. Interestingly, four out of five typed HRV-B strains originated from the summer season specimens.

  20. Impairment of the baroreflex control of human respiratory resistance with age

    Directory of Open Access Journals (Sweden)

    Tafil-Klawe M

    2009-12-01

    Full Text Available Abstract Background The mechanism responsible for the central baroreflex resetting with age are an area of limited knowledge. We previously demonstrated that in subjects aged above 50 the airway resistance did not change in response to baroreceptor activation, whereas in younger volunteers the airway resistance significantly decreased. Objective The aim of the present study was to evaluate the effect of carotid baroreceptor inactivation on the reflex change of respiratory resistance, in the course of aging. Materials and methods 80 healthy men, divided in four groups: aged 20-30 (Group I, 31-40 (Group II, 41-50 (Group III, and 51-60 (Group IV were included in the study. The selective inactivation of carotid baroreceptors was induced by generating a positive pressure of 40 mmHg for 5 s in two capsules placed bilaterally on the neck over the bifurcation of the carotid arteries. The oscillatory method (Siregnost FD5, Siemens was used to measure continuously respiratory resistance. Results Inactivation of carotid baroreceptors produced a short increase in respiratory resistance by 0.38 ± 0.01SE mbar/l/s, i.e., 21.7% above the resting level in Group I and by 0.25 ± 0.01 mbar/l/s in Group II. In the two older groups (III and IV respiratory resistance did not change in response to baroreceptors inactivation. Conclusions In humans aged above 40, carotid baroreceptors do not contribute to bronchodilator tone, which causes imbalance between the activities of upper airway and chest wall inspiratory muscles leading to a collapsing effect on the upper airway.

  1. S-CMC-Lys-dependent stimulation of electrogenic glutathione secretion by human respiratory epithelium.

    Science.gov (United States)

    Guizzardi, F; Rodighiero, S; Binelli, A; Saino, S; Bononi, E; Dossena, S; Garavaglia, M L; Bazzini, C; Bottà, G; Conese, M; Daffonchio, L; Novellini, R; Paulmichl, M; Meyer, G

    2006-01-01

    Glutathione (GSH) is one of the most important defense mechanisms against oxidative stress in the respiratory epithelial lining fluid. Considering that GSH secretion in respiratory cells has been postulated to be at least partially electrogenic, and that the mucoregulator S-carbocysteine lysine salt monohydrate (S-CMC-Lys) can cause an activation of epithelial Cl(-) conductance, the purpose of this study was to verify whether S-CMC-Lys is able to stimulate GSH secretion. Experiments have been performed by patch-clamp technique, by high-performance liquid chromatography (HPLC) assay, and by Western blot analysis on cultured lines of human respiratory cells (WI-26VA4 and CFT1-C2). In whole-cell configuration, after cell exposure to 100 microM S-CMC-Lys, a current due to an outward GSH flux was observed, which was inhibitable by 5-nitro-2-(3-phenylpropylamino)-benzoate and glibenclamide. This current was not observed in CFT1-C2 cells, where a functional cystic fibrosis transmembrane conductance regulator (CFTR) is lacking. Inside-out patch-clamp experiments (GSH on the cytoplasm side, Cl(-) on the extracellular side) showed the activity of a channel, which was able to conduct current in both directions: the single channel conductance was 2-4 pS, and the open probability (P(o)) was low and voltage-independent. After preincubation with 100 microM S-CMC-Lys, there was an increase in P(o), in the number of active channels present in each patch, and in the relative permeability to GSH vs Cl(-). Outwardly directed efflux of GSH could also be increased by protein kinase A, adenosine 5'-triphosphate, and cyclic adenosine monophosphate (cAMP) added to the cytoplasmic side (whole-cell configuration). The increased secretion of GSH observed in the presence of S-CMC-Lys or 8-bromoadenosine-3',5'-cyclic monophosphate was also confirmed by HPLC assay of GSH on a confluent monolayer of respiratory cells. Western blot analysis confirmed the presence of CFTR in WI-26VA4 cells. This

  2. A Conjugate Fluid-Porous Approach for Simulating Airflow in Realistic Geometric Representations of the Human Respiratory System.

    Science.gov (United States)

    DeGroot, Christopher T; Straatman, Anthony G

    2016-03-01

    Simulation of flow in the human lung is of great practical interest as a means to study the detailed flow patterns within the airways for many physiological applications. While computational simulation techniques are quite mature, lung simulations are particularly complicated due to the vast separation of length scales between upper airways and alveoli. Many past studies have presented numerical results for truncated airway trees, however, there are significant difficulties in connecting such results with respiratory airway models. This article presents a new modeling paradigm for flow in the full lung, based on a conjugate fluid-porous formulation where the upper airway is considered as a fluid region with the remainder of the lung being considered as a coupled porous region. Results are presented for a realistic lung geometry obtained from computed tomography (CT) images, which show the method's potential as being more efficient and practical than attempting to directly simulate flow in the full lung.

  3. A Defective Interfering Influenza RNA Inhibits Infectious Influenza Virus Replication in Human Respiratory Tract Cells: A Potential New Human Antiviral

    Directory of Open Access Journals (Sweden)

    Claire M. Smith

    2016-08-01

    Full Text Available Defective interfering (DI viruses arise during the replication of influenza A virus and contain a non-infective version of the genome that is able to interfere with the production of infectious virus. In this study we hypothesise that a cloned DI influenza A virus RNA may prevent infection of human respiratory epithelial cells with infection by influenza A. The DI RNA (244/PR8 was derived by a natural deletion process from segment 1 of influenza A/PR/8/34 (H1N1; it comprises 395 nucleotides and is packaged in the DI virion in place of a full-length genome segment 1. Given intranasally, 244/PR8 DI virus protects mice and ferrets from clinical influenza caused by a number of different influenza A subtypes and interferes with production of infectious influenza A virus in cells in culture. However, evidence that DI influenza viruses are active in cells of the human respiratory tract is lacking. Here we show that 244/PR8 DI RNA is replicated by an influenza A challenge virus in human lung diploid fibroblasts, bronchial epithelial cells, and primary nasal basal cells, and that the yield of challenge virus is significantly reduced in a dose-dependent manner indicating that DI influenza virus has potential as a human antiviral.

  4. A finite state model for respiratory motion analysis in image guided radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Wu Huanmei [College of Computer and Information Science, Northeastern University, Boston, MA 02115 (United States); Sharp, Gregory C [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114 (United States); Salzberg, Betty [College of Computer and Information Science, Northeastern University, Boston, MA 02115 (United States); Kaeli, David [Department of Electrical and Computer Engineering, Northeastern University, Boston, MA 02115 (United States); Shirato, Hiroki [Department of Radiation Medicine, Hokkaido University School of Medicine, Sapporo (Japan); Jiang, Steve B [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114 (United States)

    2004-12-07

    Effective image guided radiation treatment of a moving tumour requires adequate information on respiratory motion characteristics. For margin expansion, beam tracking and respiratory gating, the tumour motion must be quantified for pretreatment planning and monitored on-line. We propose a finite state model for respiratory motion analysis that captures our natural understanding of breathing stages. In this model, a regular breathing cycle is represented by three line segments, exhale, end-of-exhale and inhale, while abnormal breathing is represented by an irregular breathing state. In addition, we describe an on-line implementation of this model in one dimension. We found this model can accurately characterize a wide variety of patient breathing patterns. This model was used to describe the respiratory motion for 23 patients with peak-to-peak motion greater than 7 mm. The average root mean square error over all patients was less than 1 mm and no patient has an error worse than 1.5 mm. Our model provides a convenient tool to quantify respiratory motion characteristics, such as patterns of frequency changes and amplitude changes, and can be applied to internal or external motion, including internal tumour position, abdominal surface, diaphragm, spirometry and other surrogates.

  5. [Amphibians as a model system for the investigation of respiratory control development].

    Science.gov (United States)

    Belzile, Olivier; Simard, Edith; Gulemetova, Roumiana; Bairam, Aida; Kinkead, Richard

    2004-10-01

    Recent medical advances have made it possible for babies to survive premature birth at increasingly earlier developmental stages. This population requires costly and sophisticated medical care to address the problems associated with immaturity of the respiratory system. In addition to pulmonary complications, respiratory instability and apnea reflecting immaturity of the respiratory control system are major causes of hospitalization and morbidity in this highly vulnerable population. These medical concerns, combined with the curiosity of physiologists, have contributed to the expansion of research in respiratory neurobiology. While most researchers working in this field commonly use rodents as an animal model, recent research using in vitro brainstem preparation from bullfrogs (Rana catesbeiana) have revealed the technical advantages of this animal model, and shown that the basic principles underlying respiratory control and its ontogeny are very similar between these two groups of vertebrates. The present review highlights the recent advances in the area of research with a focus on intermittent (episodic) breathing and the role of serotonergic and GABAergic modulation of respiratory activity during development.

  6. Prevalence of Human Papillomavirus (HPV) in upper respiratory tract mucosa in a group of pre-school children

    OpenAIRE

    Jaroslaw Szydłowski; Katarzyna Jonczyk-Potoczna; Beata Pucher; Beata Buraczyńska-Andrzejewska; Magdalena Prauzińska; Jagoda Kolasińska-Lipńska; Hanna Krauss; Jacek Piątek; Wioletta Żukiewicz-Sobczak

    2014-01-01

    [b]introduction[/b]. Human Papillomavirus (HPV) is a group of DNA viruses which is an etiological factor of many benign and malignant diseases of the upper respiratory tract mucosa, female genital tract and the skin. HPV infection is considered a sexually-transmitted infection, but can also be transmitted by non-sexual routes, including perinatal vertical transmission, physical contact, iatrogenic infection and autoinoculation. Recurrent Respiratory Papillomatosis (RRP) in children is connect...

  7. Chemical exposure-response relationship between air pollutants and reactive oxygen species in the human respiratory tract

    OpenAIRE

    Lakey, Pascale S. J.; Thomas Berkemeier; Haijie Tong; Arangio, Andrea M.; Kurt Lucas; Ulrich Pöschl; Manabu Shiraiwa

    2016-01-01

    Air pollution can cause oxidative stress and adverse health effects such as asthma and other respiratory diseases, but the underlying chemical processes are not well characterized. Here we present chemical exposure-response relations between ambient concentrations of air pollutants and the production rates and concentrations of reactive oxygen species (ROS) in the epithelial lining fluid (ELF) of the human respiratory tract. In highly polluted environments, fine particulate matter (PM2.5) con...

  8. Human Factors Model

    Science.gov (United States)

    1993-01-01

    Jack is an advanced human factors software package that provides a three dimensional model for predicting how a human will interact with a given system or environment. It can be used for a broad range of computer-aided design applications. Jack was developed by the computer Graphics Research Laboratory of the University of Pennsylvania with assistance from NASA's Johnson Space Center, Ames Research Center and the Army. It is the University's first commercial product. Jack is still used for academic purposes at the University of Pennsylvania. Commercial rights were given to Transom Technologies, Inc.

  9. Validation of statistical models for estimating hospitalization associated with influenza and other respiratory viruses.

    Directory of Open Access Journals (Sweden)

    Lin Yang

    Full Text Available BACKGROUND: Reliable estimates of disease burden associated with respiratory viruses are keys to deployment of preventive strategies such as vaccination and resource allocation. Such estimates are particularly needed in tropical and subtropical regions where some methods commonly used in temperate regions are not applicable. While a number of alternative approaches to assess the influenza associated disease burden have been recently reported, none of these models have been validated with virologically confirmed data. Even fewer methods have been developed for other common respiratory viruses such as respiratory syncytial virus (RSV, parainfluenza and adenovirus. METHODS AND FINDINGS: We had recently conducted a prospective population-based study of virologically confirmed hospitalization for acute respiratory illnesses in persons <18 years residing in Hong Kong Island. Here we used this dataset to validate two commonly used models for estimation of influenza disease burden, namely the rate difference model and Poisson regression model, and also explored the applicability of these models to estimate the disease burden of other respiratory viruses. The Poisson regression models with different link functions all yielded estimates well correlated with the virologically confirmed influenza associated hospitalization, especially in children older than two years. The disease burden estimates for RSV, parainfluenza and adenovirus were less reliable with wide confidence intervals. The rate difference model was not applicable to RSV, parainfluenza and adenovirus and grossly underestimated the true burden of influenza associated hospitalization. CONCLUSION: The Poisson regression model generally produced satisfactory estimates in calculating the disease burden of respiratory viruses in a subtropical region such as Hong Kong.

  10. Heme Oxygenase-1 Modulates Human Respiratory Syncytial Virus Replication and Lung Pathogenesis during Infection.

    Science.gov (United States)

    Espinoza, Janyra A; León, Miguel A; Céspedes, Pablo F; Gómez, Roberto S; Canedo-Marroquín, Gisela; Riquelme, Sebastían A; Salazar-Echegarai, Francisco J; Blancou, Phillipe; Simon, Thomas; Anegon, Ignacio; Lay, Margarita K; González, Pablo A; Riedel, Claudia A; Bueno, Susan M; Kalergis, Alexis M

    2017-07-01

    Human respiratory syncytial virus (hRSV) is the leading cause of severe lower respiratory tract infections in children. The development of novel prophylactic and therapeutic antiviral drugs against hRSV is imperative to control the burden of disease in the susceptible population. In this study, we examined the effects of inducing the activity of the host enzyme heme oxygenase-1 (HO-1) on hRSV replication and pathogenesis on lung inflammation induced by this virus. Our results show that after hRSV infection, HO-1 induction with metalloporphyrin cobalt protoporphyrin IX significantly reduces the loss of body weight due to hRSV-induced disease. Further, HO-1 induction also decreased viral replication and lung inflammation, as evidenced by a reduced neutrophil infiltration into the airways, with diminished cytokine and chemokine production and reduced T cell function. Concomitantly, upon cobalt protoporphyrin IX treatment, there is a significant upregulation in the production of IFN-α/β mRNAs in the lungs. Furthermore, similar antiviral and protective effects occur by inducing the expression of human HO-1 in MHC class II(+) cells in transgenic mice. Finally, in vitro data suggest that HO-1 induction can modulate the susceptibility of cells, especially the airway epithelial cells, to hRSV infection. Copyright © 2017 by The American Association of Immunologists, Inc.

  11. Human coronavirus EMC is not the same as severe acute respiratory syndrome coronavirus.

    Science.gov (United States)

    Perlman, Stanley; Zhao, Jincun

    2013-01-15

    A newly identified betacoronavirus, human coronavirus EMC (HCoV-EMC), has been isolated from several patients with respiratory and renal disease in the Middle East. While only a few infected patients have been identified, the mortality of the infection is greater than 50%. Like its better-known cousin severe acute respiratory syndrome coronavirus (SARS-CoV), HCoV-EMC appears to have originated from bats. In a recent article in mBio, Müller et al. described several important differences between the two viruses [M. A. Müller et al., mBio 3(6):e00515-12, 2012, doi:10.1128/mBio.00515-12]. Unlike SARS-CoV, HCoV-EMC can directly infect bat cells. As important, HCoV-EMC does not enter cells using the SARS-CoV receptor, human angiotensin-converting receptor-2 (hACE2). These results provide a strong incentive for identifying the host cell receptor used by HCoV-EMC. Identification of the receptor will provide insight into the pathogenesis of pulmonary and renal disease and may also suggest novel therapeutic interventions.

  12. A test of syndromic surveillance using a severe acute respiratory syndrome model.

    Science.gov (United States)

    Wallace, David J; Arquilla, Bonnie; Heffernan, Richard; Kramer, Martin; Anderson, Todd; Bernstein, David; Augenbraun, Michael

    2009-05-01

    We describe a field simulation that was conducted using volunteers to assess the ability of 3 hospitals in a network to manage a large influx of patients with a potentially communicable disease. This drill provided the opportunity to evaluate the ability of the New York City Department of Health and Mental Hygiene's (NYC-DOHMH) emergency department chief complaint syndromic surveillance system to detect a cluster of patients with febrile respiratory illness. The evaluation was a prospective simulation. The clinical picture was modeled on severe acute respiratory syndrome symptoms. Forty-four volunteers participated in the drill as mock patients. Records from 42 patients (95%) were successfully transmitted to the NYC-DOHMH. The electronic chief complaint for 24 (57%) of these patients indicated febrile or respiratory illness. The drill did not generate a statistical signal in the NYC-DOHMH SaTScan analysis. The 42 drill patients were classified in 8 hierarchical categories based on chief complaints: sepsis (2), cold (3), diarrhea (2), respiratory (20), fever/flu (4), vomit (3), and other (8). The number of respiratory visits, while elevated on the day of the drill, did not appear particularly unusual when compared with the 14-day baseline period used for spatial analyses. This drill with a cluster of patients with febrile respiratory illness failed to trigger a signal from the NYC-DOHMH emergency department chief complaint syndromic surveillance system. This highlighted several limitations and challenges to syndromic surveillance monitoring.

  13. Prophylactic antibody treatment and intramuscular immunization reduce infectious human rhinovirus 16 load in the lower respiratory tract of challenged cotton rats

    Directory of Open Access Journals (Sweden)

    Jorge C.G. Blanco

    2014-01-01

    Full Text Available Human rhinoviruses (HRV represent the single most important etiological agents of the common cold and are the most frequent cause of acute respiratory infections in humans. Currently the performance of available animal models for immunization studies using HRV challenge is very limited. The cotton rat (Sigmodon hispidus is a well-recognized model for the study of human respiratory viral infections. In this work we show that, without requiring any genetic modification of either the host or the virus, intranasal infection of cotton rats with HRV16 resulted in measurable isolation of infective virus, lower respiratory tract pathology, mucus production, and expression of interferon-activated genes. Intramuscular immunization with live HRV16 generated robust protective immunity that correlated with high serum levels of neutralizing antibodies. In addition, cotton rats treated prophylactically with hyperimmune anti-HRV16 serum were protected against HRV16 intranasal challenge. Finally, protection by immunization was efficiently transferred from mothers to newborn animals resulting in a substantial reduction of infectious virus loads in the lung following intranasal challenge. Overall, our results demonstrate that the cotton rat provides valuable additional model development options for testing vaccines and prophylactic therapies against rhinovirus infection.

  14. Use of ex vivo and in vitro cultures of the human respiratory tract to study the tropism and host responses of highly pathogenic avian influenza A (H5N1) and other influenza viruses.

    Science.gov (United States)

    Chan, Renee W Y; Chan, Michael C W; Nicholls, John M; Malik Peiris, J S

    2013-12-05

    The tropism of influenza viruses for the human respiratory tract is a key determinant of host-range, and consequently, of pathogenesis and transmission. Insights can be obtained from clinical and autopsy studies of human disease and relevant animal models. Ex vivo cultures of the human respiratory tract and in vitro cultures of primary human cells can provide complementary information provided they are physiologically comparable in relevant characteristics to human tissues in vivo, e.g. virus receptor distribution, state of differentiation. We review different experimental models for their physiological relevance and summarize available data using these cultures in relation to highly pathogenic avian influenza H5N1, in comparison where relevant, with other influenza viruses. Transformed continuous cell-lines often differ in important ways to the corresponding tissues in vivo. The state of differentiation of primary human cells (respiratory epithelium, macrophages) can markedly affect virus tropism and host responses. Ex vivo cultures of human respiratory tissues provide a close resemblance to tissues in vivo and may be used to risk assess animal viruses for pandemic threat. Physiological factors (age, inflammation) can markedly affect virus receptor expression and virus tropism. Taken together with data from clinical studies on infected humans and relevant animal models, data from ex vivo and in vitro cultures of human tissues and cells can provide insights into virus transmission and pathogenesis and may provide understanding that leads to novel therapeutic interventions.

  15. The effects of salbutamol in an experimental model with acute respiratory distress syndrome

    Institute of Scientific and Technical Information of China (English)

    Sema Yilmaz; Diner Yildizdas; Kenan Daglioglu; Arbil Acikalin; Can Acipayam; Ibrahim Bayram; Derya Gumurdulu; Atila Tanyeli

    2012-01-01

    Objective: To investigate salbutamol effects on histopathologic features of acute respiratory distress syndrome (ARDS). Methods: ARDS was designed in Wistar albino male rats, 250-300 g in weight, by intratracheal instillation of physiological saline solution. Anesthezied and tracheotomized rats with ARDS were pressure-controlled ventilated. At the end of the 210 minutes, two hours past and nebulized salbutamol inhalation was tried. All rats were assigned to two groups: Group 1 (n=10) control group, given no treatment, group 2 (n=10) received salbutamol. Nebulized salbutamol inhalation was given in the dosage of 0, 15 mg/kg/dose. Rats were continued to be on ventilator through the experiment. After the last inhalation, two hours past and their both lungs were excised for histopathological examination. Results: Rat-model ARDS had similar histopathological appearance occuring during the acute phase of the acute respiratory distress syndrome in humans. A statistical difference was seen between control and salbutamol group (P=0.002) for HM. The margination of leukocytes was decreased in salbutamol group. The difference was significant (P<0.042). Hemorrhage and interstitial/intraalveolar edema were much lower in 0.15 mg/dose nebulized salbutamol group than that of control group. There was a significant difference statistically between two groups (P<0.001). Conclusions: Inhaled salbutamol therapy for ARDS is may be associated with the improvement of inflamation. Besides known effects of salbutamol, the reducing of infiltration of polymorphonuclear neutrophil leukocytes, interstitial/intraalveolar edema, perivascular and/or intraalveolar hemorrhage and hyaline membrane formation should be emphasized.

  16. Noninvasive evaluation of respiratory muscles in pre-clinical model of Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Daniela M. Oliveira

    2016-04-01

    Full Text Available Abstract Since respiratory insufficiency is the main cause of death in patients affected by Duchenne Muscular Dystrophy (DMD, the present study aims at establishing a new non-invasive method to evaluate the clinical parameters of respiratory conditions of experimental models affected by DMD. With this purpose in mind, we evaluated the cardiorespiratory clinical conditions, the changes in the intercostal muscles, the diaphragmatic mobility, and the respiratory cycles in Golden Retriever Muscular Dystrophy (GRMD employing ultrasonography (US. A control group consisting of dogs of the same race, but not affected by muscular dystrophy, were used in this study. The results showed that inspiration, expiration and plateau movements (diaphragm mobility were lower in the affected group. Plateau phase in the affected group was practically non-existent and showed that the diaphragm remained in constant motion. Respiratory rate reached 15.5 per minute for affected group and 26.93 per minute for the control group. Expiration and inspiration movements of intercostal muscles reached 8.99mm and 8.79mm, respectively, for control group and 7.42mm and 7.40mm, respectively, for affected group. Methodology used in the present analysis proved to be viable for the follow-up and evaluation of the respiratory model in GRMD and may be adapted to other muscular dystrophy experimental models.

  17. The Respiratory Impedance in an Asymmetric Model of the Lung Structure

    Directory of Open Access Journals (Sweden)

    Robin De Keyser

    2011-01-01

    Full Text Available This paper presents a model of the respiratory tree as a recurrent, but asymmetric, structure. The intrinsic properties posed by such a system lead to a multi-fractal structure, i.e. a non-integer order model of the total impedance. The fractional order behavior of the asymmetric tree simulated as a dynamic system is assessed by means of Bode plots, on a wide range of frequencies. The results indicate than in a specific frequency range, both the symmetric
    and asymmetric representation of the respiratory tree lead to similar values in the impedance.

  18. Lamb Model of Respiratory Syncytial Virus–Associated Lung Disease: Insights to Pathogenesis and Novel Treatments

    Science.gov (United States)

    Ackermann, Mark R.

    2014-01-01

    Preterm birth is a risk factor for respiratory syncytial virus (RSV) bronchiolitis and hospitalization. The pathogenesis underlying this is not fully understood, and in vivo studies are needed to better clarify essential cellular features and molecular mechanisms. Such studies include analysis of lung tissue from affected human infants and various animal models. The preterm and newborn lamb lung has developmental, structural, cellular, physiologic, and immunologic features similar to that of human infants. Also, the lamb lung is susceptible to various strains of RSV that infect infants and cause similar bronchiolar lesions. Studies in lambs suggest that viral replication in airways (especially bronchioles) is extensive by 4 days after infection, along with bronchiolitis characterized by degeneration and necrosis of epithelial cells, syncytial cell formation, neutrophil infiltration, epithelial cell hypertrophy and hyperplasia, and innate and adaptive immune responses. RSV bronchiolitis greatly affects airflow and gaseous exchange. RSV disease severity is increased in preterm lambs compared with full-term lambs; similar to human infants. The lamb is conducive to experimental assessment of novel, mechanistic therapeutic interventions such as delivery of vascular endothelial growth factor and enhancement of airway epithelial oxidative responses, Club (Clara) cell protein 10, and synthesized compounds such as nanobodies. In contrast, exposure of the fetal ovine lung in vivo to ethanol, a risk factor for preterm birth, reduces pulmonary alveolar development and surfactant protein A expression. Because the formalin-inactivated RSV vaccination enhances some inflammatory responses to RSV infection in lambs, this model has the potential to assess mechanisms of formalin-inactivated RSV enhanced disease as well as newly developed vaccines. PMID:24936027

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

    Directory of Open Access Journals (Sweden)

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

    Science.gov (United States)

    Malasao, Rungnapa; Okamoto, Michiko; Chaimongkol, Natthawan; Imamura, Tadatsugu; Tohma, Kentaro; Dapat, Isolde; Dapat, Clyde; Suzuki, Akira; Saito, Mayuko; Saito, Mariko; Tamaki, Raita; Pedrera-Rico, Gay Anne Granada; Aniceto, Rapunzel; Quicho, Reynaldo Frederick Negosa; Segubre-Mercado, Edelwisa; Lupisan, Socorro; Oshitani, Hitoshi

    2015-01-01

    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. PMID:26540236

  1. An adaptive breath sampler for use with human subjects with an impaired respiratory function.

    Science.gov (United States)

    Basanta, M; Koimtzis, T; Singh, D; Wilson, I; Thomas, C L P

    2007-02-01

    An adaptive sampler for collecting 2.5 dm(3) samples of exhaled air from human subjects with an impaired respiratory function is described. Pressure in the upper respiratory tract is continuously monitored and the data used to control an automated system to collect select portions of the expired breathing cycle onto a mixed bed Tenax(trade mark) and Carbotrap(trade mark) adsorbent trap for analysis by GC-MS. The sampling approach is intended for use in metabolomic profiling of volatiles in human breath at concentrations greater than microg m(-3). The importance of experimental reproducibility in metabolomic data is emphasised and consequently a high purity air supply is used to maintain a stable exogenous volatile organic compound profile at concentrations in the range 5 to 30 microg m(-3). The results of a 90 day stability study showed that exogenous VOCs were maintained at significantly lower levels (40 times lower for isopropyl alcohol) and with significantly higher reproducibility (80 times lower standard deviation for isopropyl alcohol) than would have been be the case if ambient air had been used. The sampling system was evaluated with healthy controls alongside subjects with chronic obstructive pulmonary disease. Subjects were able to breathe normally with control subjects observed to breathe at a rate of 9 to 17 breaths per minute, compared to 16 to 30 breaths per minute for subjects with COPD. This study presents, for the first time, observations and estimates of intra-subject breath sample reproducibility from human subjects. These reproducibility studies indicated that VOCs in exhaled breath exhibit a variety of dynamic behaviours, with some species recovered with a RSD <30%, while other species were observed to have significantly more variable concentrations, 30 to 130% RSD. The approach was also demonstrated to reliably differentiate the differences in the VOC profiles between alveolar and dead space air.

  2. Inverse Modeling of Respiratory System during Noninvasive Ventilation by Maximum Likelihood Estimation

    Directory of Open Access Journals (Sweden)

    Esra Saatci

    2010-01-01

    Full Text Available We propose a procedure to estimate the model parameters of presented nonlinear Resistance-Capacitance (RC and the widely used linear Resistance-Inductance-Capacitance (RIC models of the respiratory system by Maximum Likelihood Estimator (MLE. The measurement noise is assumed to be Generalized Gaussian Distributed (GGD, and the variance and the shape factor of the measurement noise are estimated by MLE and Kurtosis method, respectively. The performance of the MLE algorithm is also demonstrated by the Cramer-Rao Lower Bound (CRLB with artificially produced respiratory signals. Airway flow, mask pressure, and lung volume are measured from patients with Chronic Obstructive Pulmonary Disease (COPD under the noninvasive ventilation and from healthy subjects. Simulations show that respiratory signals from healthy subjects are better represented by the RIC model compared to the nonlinear RC model. On the other hand, the Patient group respiratory signals are fitted to the nonlinear RC model with lower measurement noise variance, better converged measurement noise shape factor, and model parameter tracks. Also, it is observed that for the Patient group the shape factor of the measurement noise converges to values between 1 and 2 whereas for the Control group shape factor values are estimated in the super-Gaussian area.

  3. Respiratory and oral vaccination improves protection conferred by the live vaccine strain against pneumonic tularemia in the rabbit model.

    Science.gov (United States)

    Stinson, Elizabeth; Smith, Le'Kneitah P; Cole, Kelly Stefano; Barry, Eileen M; Reed, Douglas S

    2016-10-01

    Tularemia is a severe, zoonotic disease caused by a gram-negative bacterium, Francisella tularensis We have previously shown that rabbits are a good model of human pneumonic tularemia when exposed to aerosols containing a virulent, type A strain, SCHU S4. We further demonstrated that the live vaccine strain (LVS), an attenuated type B strain, extended time to death when given by scarification. Oral or aerosol vaccination has been previously shown in humans to offer superior protection to parenteral vaccination against respiratory tularemia challenge. Both oral and aerosol vaccination with LVS were well tolerated in the rabbit with only minimal fever and no weight loss after inoculation. Plasma antibody titers against F. tularensis were higher in rabbits that were vaccinated by either oral or aerosol routes compared to scarification. Thirty days after vaccination, all rabbits were challenged with aerosolized SCHU S4. LVS given by scarification extended time to death compared to mock-vaccinated controls. One orally vaccinated rabbit did survive aerosol challenge, however, only aerosol vaccination extended time to death significantly compared to scarification. These results further demonstrate the utility of the rabbit model of pneumonic tularemia in replicating what has been reported in humans and macaques as well as demonstrating the utility of vaccination by oral and respiratory routes against an aerosol tularemia challenge.

  4. Searching for animal models and potential target species for emerging pathogens: Experience gained from Middle East respiratory syndrome (MERS coronavirus

    Directory of Open Access Journals (Sweden)

    Júlia Vergara-Alert

    2017-06-01

    Full Text Available Emerging and re-emerging pathogens represent a substantial threat to public health, as demonstrated with numerous outbreaks over the past years, including the 2013–2016 outbreak of Ebola virus in western Africa. Coronaviruses are also a threat for humans, as evidenced in 2002/2003 with infection by the severe acute respiratory syndrome coronavirus (SARS-CoV, which caused more than 8000 human infections with 10% fatality rate in 37 countries. Ten years later, a novel human coronavirus (Middle East respiratory syndrome coronavirus, MERS-CoV, associated with severe pneumonia, arose in the Kingdom of Saudi Arabia. Until December 2016, MERS has accounted for more than 1800 cases and 35% fatality rate. Finding an animal model of disease is key to develop vaccines or antivirals against such emerging pathogens and to understand its pathogenesis. Knowledge of the potential role of domestic livestock and other animal species in the transmission of pathogens is of importance to understand the epidemiology of the disease. Little is known about MERS-CoV animal host range. In this paper, experimental data on potential hosts for MERS-CoV is reviewed. Advantages and limitations of different animal models are evaluated in relation to viral pathogenesis and transmission studies. Finally, the relevance of potential new target species is discussed.

  5. RAGE inhibits human respiratory syncytial virus syncytium formation by interfering with F-protein function.

    Science.gov (United States)

    Tian, Jane; Huang, Kelly; Krishnan, Subramaniam; Svabek, Catherine; Rowe, Daniel C; Brewah, Yambasu; Sanjuan, Miguel; Patera, Andriani C; Kolbeck, Roland; Herbst, Ronald; Sims, Gary P

    2013-08-01

    Human respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infection. Infection is critically dependent on the RSV fusion (F) protein, which mediates fusion between the viral envelope and airway epithelial cells. The F protein is also expressed on infected cells and is responsible for fusion of infected cells with adjacent cells, resulting in the formation of multinucleate syncytia. The receptor for advanced glycation end products (RAGE) is a pattern-recognition receptor that is constitutively highly expressed by type I alveolar epithelial cells. Here, we report that RAGE protected HEK cells from RSV-induced cell death and reduced viral titres in vitro. RAGE appeared to interact directly with the F protein, but, rather than inhibiting RSV entry into host cells, virus replication and budding, membrane-expressed RAGE or soluble RAGE blocked F-protein-mediated syncytium formation and sloughing. These data indicate that RAGE may contribute to protecting the lower airways from RSV by inhibiting the formation of syncytia, viral spread, epithelial damage and airway obstruction.

  6. Biophysical characterization of G protein ectodomain of group B human respiratory syncytial virus from E. coli.

    Science.gov (United States)

    Khan, Wajihul Hasan; Srungaram, V L N Raghuram; Islam, Asimul; Beg, Ilyas; Haider, Md Shakir H; Ahmad, Faizan; Broor, Shobha; Parveen, Shama

    2016-07-03

    Human respiratory syncytial virus (hRSV) is an important pathogen of acute respiratory tract infection. The G protein of hRSV is a transmembrane glycoprotein that is a neutralizing antigen and is thus a vaccine candidate. In this study, synthetic codon optimized ectodomain G protein [G(ΔTM)] of BA genotype of group B hRSV was cloned, expressed, and characterized using biophysical techniques. The molar absorption coefficient and mean residue ellipticity at 222 nm ([θ]222) of G (ΔTM) was found to be 7950 M(-1) cm(-1) and -19701.7 deg cm(2) dmol(-1) respectively. It was concluded that G(ΔTM) mainly consist of α-helix (74.9%) with some amount of β-sheet (4%). The protein was stable up to 85°C without any transition curve. However, heat-induced denaturation of G(ΔTM) resulted in total loss of β-sheet whereas not much change was observed in the α-helix part of the secondary structure. It was concluded that G(ΔTM) is an α-helical protein and it is highly stable at high temperature, but could be easily denatured using high concentrations of GdmCl/urea or acidic condition. This is the first investigation of cloning, expression, and characterization of G(ΔTM) of BA viruses from India. Structural characterization of G protein will assist in drug designing and vaccine development for hRSV.

  7. Testing Human Skin and Respiratory Sensitizers—What Is Good Enough?

    Directory of Open Access Journals (Sweden)

    Anki Malmborg

    2017-01-01

    Full Text Available Alternative methods for accurate in vitro assessment of skin and respiratory sensitizers are urgently needed. Sensitization is a complex biological process that cannot be evaluated accurately using single events or biomarkers, since the information content is too restricted in these measurements. On the contrary, if the tremendous information content harbored in DNA/mRNA could be mined, most complex biological processes could be elucidated. Genomic technologies available today, including transcriptional profiling and next generation sequencing, have the power to decipher sensitization, when used in the right context. Thus, a genomic test platform has been developed, denoted the Genomic Allergen Rapid Detection (GARD assay. Due to the high informational content of the GARD test, accurate predictions of both the skin and respiratory sensitizing capacity of chemicals, have been demonstrated. Based on a matured dendritic cell line, acting as a human-like reporter system, information about potency has also been acquired. Consequently, multiparametric diagnostic technologies are disruptive test principles that can change the way in which the next generation of alternative methods are designed.

  8. Effects of oxygen tension and pH on the respiratory burst of human neutrophils.

    Science.gov (United States)

    Gabig, T G; Bearman, S I; Babior, B M

    1979-06-01

    The respiratory burst of human neutrophils was measured under conditions of hypoxia and low pH. O2 -- production by neutrophils activated with opsonized zymosan fell slowly as the oxygen concentration declined to 1%, then dropped more sharply, reaching negligible levels at oxygen concentrations less than 0.25%. Production was half maximal at an oxygen concentration of 0.35% (equivalent to approximately 10-microM dissolved oxygen). O2- production by the cell-free O2- -forming system prepared from zymosan-activated neutrophils showed a similar dependence on oxygen concentration. A drop in pH caused decreases in both oxygen consumption and O2-- production by zymosan-treated neutrophils, values at PH 6.0 being 10%--20% of those observed at pH 7.5. Experiments with the cell-free O2-- -forming system suggested that this decline in respiratory burst activity at low pH was due to inefficient activation of the O2-- -forming enzyme under acidic conditions.

  9. Respiratory mechanics

    CERN Document Server

    Wilson, Theodore A

    2016-01-01

    This book thoroughly covers each subfield of respiratory mechanics: pulmonary mechanics, the respiratory pump, and flow. It presents the current understanding of the field and serves as a guide to the scientific literature from the golden age of respiratory mechanics, 1960 - 2010. Specific topics covered include the contributions of surface tension and tissue forces to lung recoil, the gravitational deformation of the lung, and the interdependence forces that act on pulmonary airways and blood vessels. The geometry and kinematics of the ribs is also covered in detail, as well as the respiratory action of the external and internal intercostal muscles, the mechanics of the diaphragm, and the quantitative compartmental models of the chest wall is also described. Additionally, flow in the airways is covered thoroughly, including the wave-speed and viscous expiratory flow-limiting mechanisms; convection, diffusion and the stationary front; and the distribution of ventilation. This is an ideal book for respiratory ...

  10. Human airway xenograft models of epithelial cell regeneration

    Directory of Open Access Journals (Sweden)

    Puchelle Edith

    2000-10-01

    Full Text Available Abstract Regeneration and restoration of the airway epithelium after mechanical, viral or bacterial injury have a determinant role in the evolution of numerous respiratory diseases such as chronic bronchitis, asthma and cystic fibrosis. The study in vivo of epithelial regeneration in animal models has shown that airway epithelial cells are able to dedifferentiate, spread, migrate over the denuded basement membrane and progressively redifferentiate to restore a functional respiratory epithelium after several weeks. Recently, human tracheal xenografts have been developed in immunodeficient severe combined immunodeficiency (SCID and nude mice. In this review we recall that human airway cells implanted in such conditioned host grafts can regenerate a well-differentiated and functional human epithelium; we stress the interest in these humanized mice in assaying candidate progenitor and stem cells of the human airway mucosa.

  11. Computational modeling as part of alternative testing strategies in the respiratory and cardiovascular systems: inhaled nanoparticle dose modeling based on representative aerosol measurements and corresponding toxicological analysis.

    Science.gov (United States)

    Pilou, Marika; Mavrofrydi, Olga; Housiadas, Christos; Eleftheriadis, Kostas; Papazafiri, Panagiota

    2015-05-01

    The objectives of modeling in this work were (a) the integration of two existing numerical models in order to connect external exposure to nanoparticles (NPs) with internal dose through inhalation, and (b) to use computational fluid-particle dynamics (CFPD) to analyze the behavior of NPs in the respiratory and the cardiovascular system. Regarding the first objective, a lung transport and deposition model was combined with a lung clearance/retention model to estimate NPs dose in the different regions of the human respiratory tract and some adjacent tissues. On the other hand, CFPD was used to estimate particle transport and deposition of particles in a physiologically based bifurcation created by the third and fourth lung generations (respiratory system), as well as to predict the fate of super-paramagnetic particles suspended in a liquid under the influence of an external magnetic field (cardiovascular system). All the above studies showed that, with proper refinement, the developed computational models and methodologies may serve as an alternative testing strategy, replacing transport/deposition experiments that are expensive both in time and resources and contribute to risk assessment.

  12. Genetic variation of human respiratory syncytial virus among children with fever and respiratory symptoms in Shanghai, China, from 2009 to 2012.

    Science.gov (United States)

    Liu, Jia; Mu, Yonglin; Dong, Wei; Yao, Fujia; Wang, Lili; Yan, Huajie; Lan, Ke; Zhang, Chiyu

    2014-10-01

    Human respiratory syncytial virus (HRSV) of genus Pneumovirus is one of the most common pathogens causing severe acute lower respiratory tract infection in infants and children. No information on the genotype distribution of HRSV is available in East China (e.g. Shanghai). From August 2009 to December 2012, 2407 nasopharyngeal swabs were collected from outpatient children with fever and respiratory symptoms in Shanghai. HRSV infection was determined using a multiplex RT-PCR assay. The second hypervariable region (HVR2) of G protein gene of HRSV was amplified and sequenced from HRSV positive samples. Genotypes were characterized by phylogenetic analyses. Of 2407 nasopharyngeal samples, 184 (7.6%) were tested as HRSV positive. From 160 positive subjects with sufficient nasopharyngeal samples, 69 HVR2 sequences were obtained by RT-PCR and sequencing. Three HRSV epidemic seasons were observed from August 2009 to December 2012, and an extreme outbreak of HRSV occurred in the 2009-2010 epidemic season. A genotype shift of predominant HRSV strains from B group in the 2009-2010 epidemic season to group A in the subsequent epidemic seasons was observed. Ten HRSV genotypes, including four group A genotypes NA1, NA3, NA4, and ON1, and six group B genotypes BA9, BA10, SAB4, CB1, BAc, and BA?, were detected in Shanghai. Seven genotypes (NA1, BA9-10, SAB4, CB1, BAc and BA?) were found in the 2009-2010 epidemic season. The co-circulation of multiple genotypes was associated with the extreme outbreak of HRSV among children with fever and respiratory symptoms in the 2009-2010 epidemic season.

  13. A novel swine model of ricin-induced acute respiratory distress syndrome

    Science.gov (United States)

    Katalan, Shahaf; Falach, Reut; Rosner, Amir; Goldvaser, Michael; Brosh-Nissimov, Tal; Dvir, Ayana; Mizrachi, Avi; Goren, Orr; Cohen, Barak; Gal, Yoav; Sapoznikov, Anita; Ehrlich, Sharon; Kronman, Chanoch

    2017-01-01

    ABSTRACT Pulmonary exposure to the plant toxin ricin leads to respiratory insufficiency and death. To date, in-depth study of acute respiratory distress syndrome (ARDS) following pulmonary exposure to toxins is hampered by the lack of an appropriate animal model. To this end, we established the pig as a large animal model for the comprehensive study of the multifarious clinical manifestations of pulmonary ricinosis. Here, we report for the first time, the monitoring of barometric whole body plethysmography for pulmonary function tests in non-anesthetized ricin-treated pigs. Up to 30 h post-exposure, as a result of progressing hypoxemia and to prevent carbon dioxide retention, animals exhibited a compensatory response of elevation in minute volume, attributed mainly to a large elevation in respiratory rate with minimal response in tidal volume. This response was followed by decompensation, manifested by a decrease in minute volume and severe hypoxemia, refractory to oxygen treatment. Radiological evaluation revealed evidence of early diffuse bilateral pulmonary infiltrates while hemodynamic parameters remained unchanged, excluding cardiac failure as an explanation for respiratory insufficiency. Ricin-intoxicated pigs suffered from increased lung permeability accompanied by cytokine storming. Histological studies revealed lung tissue insults that accumulated over time and led to diffuse alveolar damage. Charting the decline in PaO2/FiO2 ratio in a mechanically ventilated pig confirmed that ricin-induced respiratory damage complies with the accepted diagnostic criteria for ARDS. The establishment of this animal model of pulmonary ricinosis should help in the pursuit of efficient medical countermeasures specifically tailored to deal with the respiratory deficiencies stemming from ricin-induced ARDS. PMID:28067630

  14. A novel swine model of ricin-induced acute respiratory distress syndrome

    Directory of Open Access Journals (Sweden)

    Shahaf Katalan

    2017-02-01

    Full Text Available Pulmonary exposure to the plant toxin ricin leads to respiratory insufficiency and death. To date, in-depth study of acute respiratory distress syndrome (ARDS following pulmonary exposure to toxins is hampered by the lack of an appropriate animal model. To this end, we established the pig as a large animal model for the comprehensive study of the multifarious clinical manifestations of pulmonary ricinosis. Here, we report for the first time, the monitoring of barometric whole body plethysmography for pulmonary function tests in non-anesthetized ricin-treated pigs. Up to 30 h post-exposure, as a result of progressing hypoxemia and to prevent carbon dioxide retention, animals exhibited a compensatory response of elevation in minute volume, attributed mainly to a large elevation in respiratory rate with minimal response in tidal volume. This response was followed by decompensation, manifested by a decrease in minute volume and severe hypoxemia, refractory to oxygen treatment. Radiological evaluation revealed evidence of early diffuse bilateral pulmonary infiltrates while hemodynamic parameters remained unchanged, excluding cardiac failure as an explanation for respiratory insufficiency. Ricin-intoxicated pigs suffered from increased lung permeability accompanied by cytokine storming. Histological studies revealed lung tissue insults that accumulated over time and led to diffuse alveolar damage. Charting the decline in PaO2/FiO2 ratio in a mechanically ventilated pig confirmed that ricin-induced respiratory damage complies with the accepted diagnostic criteria for ARDS. The establishment of this animal model of pulmonary ricinosis should help in the pursuit of efficient medical countermeasures specifically tailored to deal with the respiratory deficiencies stemming from ricin-induced ARDS.

  15. Experimental evidence for phase synchronization transitions in human cardio-respiratory system

    CERN Document Server

    Bartsch, R; Kantelhardt, J W; Penzel, T; Bartsch, Ronny; Havlin, Shlomo; Kantelhardt, Jan W.; Penzel, Thomas

    2007-01-01

    Transitions in the dynamics of complex systems can be characterized by changes in the synchronization behavior of their components. Taking the human cardio-respiratory system as an example and using an automated procedure for screening the synchrograms of 112 healthy subjects we study the frequency and the distribution of synchronization episodes under different physiological conditions that occur during sleep. We find that phase synchronization between heartbeat and breathing is significantly enhanced during non-rapid-eye-movement (non-REM) sleep (deep sleep and light sleep) and reduced during REM sleep. Our results suggest that the synchronization is mainly due to a weak influence of the breathing oscillator upon the heartbeat oscillator, which is disturbed in the presence of long-term correlated noise, superimposed by the activity of higher brain regions during REM sleep.

  16. Online estimation of respiratory mechanics in non-invasive pressure support ventilation: a bench model study.

    Science.gov (United States)

    Mulqueeny, Qestra; Tassaux, Didier; Vignaux, Laurence; Jolliet, Philippe; Schindhelm, Klaus; Redmond, Stephen; Lovell, Nigel H

    2010-01-01

    An online algorithm for determining respiratory mechanics in patients using non-invasive ventilation (NIV) in pressure support mode was developed and embedded in a ventilator system. Based on multiple linear regression (MLR) of respiratory data, the algorithm was tested on a patient bench model under conditions with and without leak and simulating a variety of mechanics. Bland-Altman analysis indicates reliable measures of compliance across the clinical range of interest (± 11-18% limits of agreement). Resistance measures showed large quantitative errors (30-50%), however, it was still possible to qualitatively distinguish between normal and obstructive resistances. This outcome provides clinically significant information for ventilator titration and patient management.

  17. Construction of kidney phantom model with acoustic shadow by rib bones and respiratory organ motion

    Science.gov (United States)

    Lee, Dongjun; Koizumi, Norihiro; Tsukihara, Hiroyuki; Azuma, Takashi; Nomiya, Akira; Yoshinaka, Kiyoshi; Sugita, Naohiko; Homma, Yukio; Matsumoto, Yoichiro; Mitsuishi, Mamoru

    2017-03-01

    We have been studying the Non-Invasive Ultrasound Theragnostic System (NIUTS), which tracks and follows the affected area while irradiating High Intensity Focused Ultrasound (HIFU). In this report, we propose a phantom model that includes rib bones and respiratory motion.

  18. Population pharmacodynamic modeling and simulation of the respiratory effect of acetazolamide in decompensated COPD patients.

    Directory of Open Access Journals (Sweden)

    Nicholas Heming

    Full Text Available BACKGROUND: Chronic obstructive pulmonary disease (COPD patients may develop metabolic alkalosis during weaning from mechanical ventilation. Acetazolamide is one of the treatments used to reverse metabolic alkalosis. METHODS: 619 time-respiratory (minute ventilation, tidal volume and respiratory rate and 207 time-PaCO2 observations were obtained from 68 invasively ventilated COPD patients. We modeled respiratory responses to acetazolamide in mechanically ventilated COPD patients and then simulated the effect of increased amounts of the drug. RESULTS: The effect of acetazolamide on minute ventilation and PaCO2 levels was analyzed using a nonlinear mixed effect model. The effect of different ventilatory modes was assessed on the model. Only slightly increased minute ventilation without decreased PaCO2 levels were observed in response to 250 to 500 mg of acetazolamide administered twice daily. Simulations indicated that higher acetazolamide dosage (>1000 mg daily was required to significantly increase minute ventilation (P0.75 L min(-1 in 60% of the population. The model also predicts that 45% of patients would have a decrease of PaCO2>5 mmHg with doses of 1000 mg per day. CONCLUSIONS: Simulations suggest that COPD patients might benefit from the respiratory stimulant effect after the administration of higher doses of acetazolamide.

  19. A novel modelling approach to energy transport in a respiratory system.

    Science.gov (United States)

    Nithiarasu, Perumal; Sazonov, Igor

    2016-11-24

    In this paper, energy transport in a respiratory tract is modelled using the finite element method for the first time. The upper and lower respiratory tracts are approximated as a 1-dimensional domain with varying cross-sectional and surface areas, and the radial heat conduction in the tissue is approximated using the 1-dimensional cylindrical coordinate system. The governing equations are solved using 1-dimensional linear finite elements with convective and evaporative boundary conditions on the wall. The results obtained for the exhalation temperature of the respiratory system have been compared with the available animal experiments. The study of a full breathing cycle indicates that evaporation is the main mode of heat transfer, and convection plays almost negligible role in the energy transport. This is in-line with the results obtained from animal experiments. Copyright © 2016 John Wiley & Sons, Ltd.

  20. Metagenomics Study of Viral Pathogens in Undiagnosed Respiratory Specimens and Identification of Human Enteroviruses at a Thailand Hospital

    Science.gov (United States)

    Zhou, Yanfei; Fernandez, Stefan; Yoon, In-Kyu; Simasathien, Sriluck; Watanaveeradej, Veerachai; Yang, Yu; Marte-Salcedo, Omely A.; Shuck-Lee, Deidra J.; Thomas, Stephen J.; Hang, Jun; Jarman, Richard G.

    2016-01-01

    Numerous pathogens cause respiratory infections with similar symptoms. Routine diagnostics detect only a limited number of pathogens, leaving a gap in respiratory illness etiology surveillance. This study evaluated next-generation sequencing for unbiased pathogen identification. Respiratory samples collected in Thailand, Philippines, Bhutan, and Nepal, that were negative by several molecular and immunofluorescence assays, underwent viral cultivation. Samples which demonstrated cytopathic effect in culture (N = 121) were extracted and tested by Luminex xTAG respiratory viral panel (RVP) assay and deep sequencing by Roche 454 FLX Titanium system. Using RVP assay, 52 (43%) samples were positive for enterovirus or rhinovirus and another three were positive for respiratory syncytial virus B, parainfluenza 4, and adenovirus. Deep sequencing confirmed the Luminex assay results and identified additional viral pathogens. Human enteroviruses, including Enterovirus A type 71 and 12 types of Enterovirus B (EV-B) were identified from a hospital in Bangkok. Phylogenetic and recombination analysis showed high correlation of VP1 gene-based phylogeny with genome-wide phylogeny and the frequent genetic exchange among EV-B viruses. The high number and diversity of enteroviruses in the hospital in Bangkok suggests prevalent existence. The metagenomic approach used in our study enabled comprehensive diagnoses of respiratory viruses. PMID:27352877

  1. A dynamic population-based model for the development of work-related respiratory health effects among bakery workers

    NARCIS (Netherlands)

    Warren, N.; Meijster, T.; Heederik, D.; Tielemans, E.

    2009-01-01

    Objectives: This paper presents a dynamic population-based model for the development of sensitisation and respiratory symptoms in bakery workers. The model simulates a population of individual workers longitudinally and tracks the development of work-related sensitisation and respiratory symptoms in

  2. A dynamic population-based model for the development of work-related respiratory health effects among bakery workers.

    NARCIS (Netherlands)

    Warren, N.; Meijster, T.; Heederik, D.; Tielemans, E.

    2009-01-01

    OBJECTIVES: This paper presents a dynamic population-based model for the development of sensitisation and respiratory symptoms in bakery workers. The model simulates a population of individual workers longitudinally and tracks the development of work-related sensitisation and respiratory symptoms in

  3. Aerosol deposition doses in the human respiratory tree of electronic cigarette smokers.

    Science.gov (United States)

    Manigrasso, Maurizio; Buonanno, Giorgio; Fuoco, Fernanda Carmen; Stabile, Luca; Avino, Pasquale

    2015-01-01

    Aerosols from eight e-cigarettes at different nicotine levels and flavoring were characterized as particle number size distributions in the range 5.6-560 nm by FMPS and CPC. Results were used to provided osimetry estimates applying the MMPD model.Particle number concentrations varied between 3.26 x 10(9) and 4.09 x 10(9) part cm(-3) for e-liquids without nicotine and between 5.08 x 10(9) and 5.29 x 10(9) part cm(-3) for e-liquids with nicotine. No flavor effects were detected on particle concentration data. Particle size distributions were unimodal with modes between 107-165 nm and 165-255 nm, for number and volume metrics, respectively. Averagely, 6.25 x 10(10) particles were deposited in respiratory tree after a single puff. Highest deposition densities and mean layer thickness of e-cigarette liquid on the lung epithelium were estimated at lobar bronchi. Our study shows that e-cigarette aerosol is source of high particle dose in respiratory system, from 23%to 35% of the daily dose of a no-smoking individual.

  4. Osmolality and respiratory regulation in humans: respiratory compensation for hyperchloremic metabolic acidosis is absent after infusion of hypertonic saline in healthy volunteers.

    Science.gov (United States)

    Moen, Vibeke; Brudin, Lars; Rundgren, Mats; Irestedt, Lars

    2014-10-01

    Several animal studies show that changes in plasma osmolality may influence ventilation. Respiratory depression caused by increased plasma osmolality is interpreted as inhibition of water-dependent thermoregulation because conservation of body fluid predominates at the cost of increased core temperature. Respiratory alkalosis, on the other hand, is associated with a decrease in plasma osmolality and strong ion difference (SID) during human pregnancy. We investigated the hypothesis that osmolality would influence ventilation, so that increased osmolality will decrease ventilation and decreased osmolality will stimulate ventilation in both men and women. Our study participants were healthy volunteers of both sexes (ASA physical status I). Ten men (mean 28 years; range 20-40) and 9 women (mean 33 years; range 22-43) were included. All women participated in both the follicular and luteal phases of the menstrual cycle. Hyperosmolality was induced by IV infusion of hypertonic saline 3%, and hypoosmolality by drinking tap water. Arterial blood samples were collected for analysis of electrolytes, osmolality, and blood gases. Sensitivity to CO2 was determined by rebreathing tests performed before and after the fluid-loading procedures. Infusion of hypertonic saline caused hyperchloremic metabolic acidosis with decreased SID in all subjects. Analysis of pooled data showed absence of respiratory compensation. Baseline arterial PCO2 (PaCO2) mean (SD) 37.8 (2.9) mm Hg remained unaltered, with lowest PaCO2 37.8 (2.9) mm Hg after 100 minutes, P = 0.70, causing a decrease in pH from mean (SD) 7.42 (0.02) to 7.38 (0.02), P acidosis was also observed during water loading. Pooled results show that PaCO2 decreased from 38.2 (3.3) mm Hg at baseline to 35.7 (2.8) mm Hg after 80 minutes of drinking water, P = 0.002, and pH remained unaltered: pH 7.43 (0.02) at baseline to pH 7.42 (0.02), P = 0.14, mean difference (confidence interval) = pH -0.007 (-0.017 to 0.003). Our results indicate

  5. Comparative pathology of rhesus macaque and common marmoset animal models with Middle East respiratory syndrome coronavirus

    Science.gov (United States)

    Yu, Pin; Xu, Yanfeng; Deng, Wei; Bao, Linlin; Huang, Lan; Xu, Yuhuan; Yao, Yanfeng; Qin, Chuan

    2017-01-01

    Middle East respiratory syndrome (MERS), which is caused by a newly discovered coronavirus (CoV), has recently emerged. It causes severe viral pneumonia and is associated with a high fatality rate. However, the pathogenesis, comparative pathology and inflammatory cell response of rhesus macaques and common marmosets experimentally infected with MERS-CoV are unknown. We describe the histopathological, immunohistochemical, and ultrastructural findings from rhesus macaque and common marmoset animal models of MERS-CoV infection. The main histopathological findings in the lungs of rhesus macaques and common marmosets were varying degrees of pulmonary lesions, including pneumonia, pulmonary oedema, haemorrhage, degeneration and necrosis of the pneumocytes and bronchial epithelial cells, and inflammatory cell infiltration. The characteristic inflammatory cells in the lungs of rhesus macaques and common marmosets were eosinophils and neutrophils, respectively. Based on these observations, the lungs of rhesus macaques and common marmosets appeared to develop chronic and acute pneumonia, respectively. MERS-CoV antigens and viral RNA were identified in type I and II pneumocytes, alveolar macrophages and bronchial epithelial cells, and ultrastructural observations showed that viral protein was found in type II pneumocytes and inflammatory cells in both species. Correspondingly, the entry receptor DDP4 was found in type I and II pneumocytes, bronchial epithelial cells, and alveolar macrophages. The rhesus macaque and common marmoset animal models of MERS-CoV can be used as a tool to mimic the oncome of MERS-CoV infections in humans. These models can help to provide a better understanding of the pathogenic process of this virus and to develop effective medications and prophylactic treatments. PMID:28234937

  6. Morphological changes of carotid bodies in acute respiratory distress syndrome: a morphometric study in humans

    Directory of Open Access Journals (Sweden)

    Vinhaes E.N.G.

    2002-01-01

    Full Text Available Carotid bodies are chemoreceptors sensitive to a fall of partial oxygen pressure in blood (hypoxia. The morphological alterations of these organs in patients with chronic obstructive pulmonary disease (COPD and in people living at high altitude are well known. However, it is not known whether the histological profile of human carotid bodies is changed in acute clinical conditions such as acute respiratory distress syndrome (ARDS. The objective of the present study was to perform a quantitative analysis of the histology of carotid bodies collected from patients who died of ARDS. A morphometric study of carotid bodies collected during routine autopsies was carried out on three groups: patients that died of non-respiratory diseases (controls, N = 8, patients that presented COPD and died of its complications or associated diseases (N = 7, and patients that died of ARDS (N = 7. Morphometric measurements of the volume fraction of clusters of chief cells were performed in five fields on each slide at 40X magnification. The numerical proportion of the four main histological cell types (light, dark, progenitor and sustentacular cells was determined analyzing 10 fields on each slide at 400X magnification. The proportion of dark cells was 0.22 in ARDS patients, 0.12 in controls (P<0.001, and 0.08 in the COPD group. The proportion of light cells was 0.33 (ARDS, 0.44 (controls (P<0.001, and 0.36 (COPD. These findings suggest that chronic and acute hypoxia have different effects on the histology of glomic tissue.

  7. S-CMC-Lys protective effects on human respiratory cells during oxidative stress.

    Science.gov (United States)

    Garavaglia, Maria Lisa; Bononi, Elena; Dossena, Silvia; Mondini, Anna; Bazzini, Claudia; Lanata, Luigi; Balsamo, Rossella; Bagnasco, Michela; Conese, Massimo; Bottà, Guido; Paulmichl, Markus; Meyer, Giuliano

    2008-01-01

    The mucoactive drug S-carbocysteine lysine salt monohydrate (S-CMC-Lys) stimulates glutathione (GSH) efflux from respiratory cells. Since GSH is one of the most important redox regulatory mechanisms, the aim of this study was to evaluate the S-CMC-Lys effects on GSH efflux and intracellular concentration during an oxidative stress induced by the hydroxyl radical (xOH). Experiments were performed on cultured human respiratory WI-26VA4 cells by means of patch-clamp experiments in whole-cell configuration and of fluorimetric analyses at confocal microscope. xOH exposure induced an irreversible inhibition of the GSH and chloride currents that was prevented if the cells were incubated with S-CMC-Lys. In this instance, the currents were inhibited by the specific blocker CFTR(inh)-172. CFT1-C2 cells, which lack a functional CFTR channel, were not responsive to S-CMC-Lys, but the stimulatory effect of the drug was restored in LCFSN-infected CFT1 cells, functionally corrected to express CFTR. Fluorimetric measurements performed on the S-CMC-Lys-incubated cells revealed a significant increase of the GSH concentration that was completely hindered after oxidative stress and abolished by CFTR(inh)-172. The cellular content of reactive oxygen species was significantly lower in the S-CMC-Lys-treated cells either before or after xOH exposure. As a conclusion, S-CMC-Lys could exert a protective function during oxidative stress, therefore preventing or reducing the ROS-mediated inflammatory response. Copyright 2008 S. Karger AG, Basel.

  8. Hypoxia selectively inhibits respiratory burst activity and killing of Staphylococcus aureus in human neutrophils.

    Science.gov (United States)

    McGovern, Naomi N; Cowburn, Andrew S; Porter, Linsey; Walmsley, Sarah R; Summers, Charlotte; Thompson, Alfred A R; Anwar, Sadia; Willcocks, Lisa C; Whyte, Moira K B; Condliffe, Alison M; Chilvers, Edwin R

    2011-01-01

    Neutrophils play a central role in the innate immune response and a critical role in bacterial killing. Most studies of neutrophil function have been conducted under conditions of ambient oxygen, but inflamed sites where neutrophils operate may be extremely hypoxic. Previous studies indicate that neutrophils sense and respond to hypoxia via the ubiquitous prolyl hydroxylase/hypoxia-inducible factor pathway and that this can signal for enhanced survival. In the current study, human neutrophils were shown to upregulate hypoxia-inducible factor (HIF)-1α-dependent gene expression under hypoxic incubation conditions (3 kPa), with a consequent substantial delay in the onset of apoptosis. Despite this, polarization and chemotactic responsiveness to IL-8 and fMLP were entirely unaffected by hypoxia. Similarly, hypoxia did not diminish the ability of neutrophils to phagocytose serum-opsonized heat-killed streptococci. Of the secretory functions examined, IL-8 generation was preserved and elastase release was enhanced by hypoxia. Hypoxia did, however, cause a major reduction in respiratory burst activity induced both by the soluble agonist fMLP and by ingestion of opsonized zymosan, without affecting expression of the NADPH oxidase subunits. Critically, this reduction in respiratory burst activity under hypoxia was associated with a significant defect in the killing of Staphylococcus aureus. In contrast, killing of Escherichia coli, which is predominantly oxidase independent, was fully preserved under hypoxia. In conclusion, these studies suggest that although the NADPH oxidase-dependent bacterial killing mechanism may be compromised by hypoxia, neutrophils overall appear extremely well adapted to operate successfully under severely hypoxic conditions.

  9. The respiratory burst oxidase of human neutrophils. Further studies of the purified enzyme.

    Science.gov (United States)

    Glass, G A; DeLisle, D M; DeTogni, P; Gabig, T G; Magee, B H; Markert, M; Babior, B M

    1986-10-05

    A superoxide-forming oxidase from activated human neutrophil membranes was solubilized by two slightly different methods, then purified by "dye-affinity" chromatography. Kinetic studies of the purified preparations gave Vmax values of 5-10 mumol of O-2/min/mg of protein, and Km values for NADH and NADPH that were in reasonable agreement with values determined previously using particulate and crude solubilized preparations of the respiratory burst oxidase. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed prominent bands at 67, 48, and 32 kDa, together with some minor contaminants, whereas gel electrophoresis under non-denaturing conditions gave a single major band that when eluted and re-electrophoresed in the presence of sodium dodecyl sulfate showed bands at 67, 48, 32 kDa. We believe that all three bands represent oxidase components. The flavin content of the purified enzyme was 20.4 +/- 2.0 S.E. pmol of FAD/microgram of protein, whereas heme averaged 0.1 +/- 0.02 pmol/microgram and ubiquinone could not be detected. Assuming that the enzyme is composed of one 67-kDa subunit, one 48-kDa subunit, and one 32-kDa subunit (i.e. that its molecular mass is approximately 150 kDa), it can be calculated to have a turnover number of 700-1500 min-1, in agreement with a value reported previously for oxidase in a particulate O-2-forming system (Cross, A. R., Parkinson, J. F., and Jones, O. T. G. (1985) Biochem. J. 226, 881-884), and to contain the following quantities of redox carriers (mol/mol): FAD, 3.0; heme, 0.015; ubiquinone, less than 0.06. It remains to be determined whether this preparation represents the complete respiratory burst oxidase or is only the pyridine nucleotide dehydrogenating component of a more complex enzyme.

  10. Respiratory syncytial virus fusion protein promotes TLR-4-dependent neutrophil extracellular trap formation by human neutrophils.

    Directory of Open Access Journals (Sweden)

    Giselle A Funchal

    Full Text Available Acute viral bronchiolitis by Respiratory Syncytial Virus (RSV is the most common respiratory illness in children in the first year of life. RSV bronchiolitis generates large numbers of hospitalizations and an important burden to health systems. Neutrophils and their products are present in the airways of RSV-infected patients who developed increased lung disease. Neutrophil Extracellular Traps (NETs are formed by the release of granular and nuclear contents of neutrophils in the extracellular space in response to different stimuli and recent studies have proposed a role for NETs in viral infections. In this study, we show that RSV particles and RSV Fusion protein were both capable of inducing NET formation by human neutrophils. Moreover, we analyzed the mechanisms involved in RSV Fusion protein-induced NET formation. RSV F protein was able to induce NET release in a concentration-dependent fashion with both neutrophil elastase and myeloperoxidase expressed on DNA fibers and F protein-induced NETs was dismantled by DNase treatment, confirming that their backbone is chromatin. This viral protein caused the release of extracellular DNA dependent on TLR-4 activation, NADPH Oxidase-derived ROS production and ERK and p38 MAPK phosphorylation. Together, these results demonstrate a coordinated signaling pathway activated by F protein that led to NET production. The massive production of NETs in RSV infection could aggravate the inflammatory symptoms of the infection in young children and babies. We propose that targeting the binding of TLR-4 by F protein could potentially lead to novel therapeutic approaches to help control RSV-induced inflammatory consequences and pathology of viral bronchiolitis.

  11. 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

    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...... 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...

  12. El Bocavirus humano: un nuevo virus respiratorio Human bocavirus: a new respiratory virus

    Directory of Open Access Journals (Sweden)

    Carlos Aguirre Muñoz

    2006-01-01

    Full Text Available Las infecciones respiratorias agudas son una causa muy importante de morbilidad y mortalidad, especialmente en los niños y en los países en desarrollo. Con los métodos de laboratorio actuales, aproximadamente una tercera parte de estas infecciones se queda sin diagnóstico etiológico. Se acepta que los virus juegan un papel cardinal y que más de 200 virus, pertenecientes a seis familias virales están implicados en la génesis de este problema. La familia Parvoviridae se conoce desde mediados del siglo XX. El Parvovirus humano B19, identificado en 1980 y causante de enfermedades febriles y exantemáticas, fue considerado por muchos años como el único miembro de esta familia capaz de afectar a la especie humana. Sin embargo, un grupo de investigadores suecos comandado por Tobías Allander informó en agosto de 2005 el hallazgo de un nuevo Parvovirus, denominado provisionalmente Bocavirus humano, relacionado con infección respiratoria aguda en niños. En este artículo se resumen las características de este nuevo agente, se resalta la importancia de su hallazgo y de la técnica de investigación empleada. Respiratory tract infections are a leading cause of morbidity and mortality, mainly in children and also in developing countries. The aethiology of approximately 30% of these infections remains obscure, using current laboratory methods. It has been accepted that viruses play an important role and more than 200 viruses, belonging to 6 viral families are implied in the pathogenesis of this problem. Parvoviridae family has been known since the middle of the XX century. Human Parvovirus B19 was identified in 1980; it causes rashes and febrile diseases and it was considered for many years as the only member of this family able to affect humans. However, Dr. Tobias Allander and colleagues, at Karolinska Institut, have discovered a previously unknown parvovirus, called Human Bocavirus, that has been found to affect children, causing lower

  13. Identification of Burkholderia mallei and Burkholderia pseudomallei adhesins for human respiratory epithelial cells

    Directory of Open Access Journals (Sweden)

    Hogan Robert J

    2010-09-01

    Full Text Available Abstract Background Burkholderia pseudomallei and Burkholderia mallei cause the diseases melioidosis and glanders, respectively. A well-studied aspect of pathogenesis by these closely-related bacteria is their ability to invade and multiply within eukaryotic cells. In contrast, the means by which B. pseudomallei and B. mallei adhere to cells are poorly defined. The purpose of this study was to identify adherence factors expressed by these organisms. Results Comparative sequence analyses identified a gene product in the published genome of B. mallei strain ATCC23344 (locus # BMAA0649 that resembles the well-characterized Yersinia enterocolitica autotransporter adhesin YadA. The gene encoding this B. mallei protein, designated boaA, was expressed in Escherichia coli and shown to significantly increase adherence to human epithelial cell lines, specifically HEp2 (laryngeal cells and A549 (type II pneumocytes, as well as to cultures of normal human bronchial epithelium (NHBE. Consistent with these findings, disruption of the boaA gene in B. mallei ATCC23344 reduced adherence to all three cell types by ~50%. The genomes of the B. pseudomallei strains K96243 and DD503 were also found to contain boaA and inactivation of the gene in DD503 considerably decreased binding to monolayers of HEp2 and A549 cells and to NHBE cultures. A second YadA-like gene product highly similar to BoaA (65% identity was identified in the published genomic sequence of B. pseudomallei strain K96243 (locus # BPSL1705. The gene specifying this protein, termed boaB, appears to be B. pseudomallei-specific. Quantitative attachment assays demonstrated that recombinant E. coli expressing BoaB displayed greater binding to A549 pneumocytes, HEp2 cells and NHBE cultures. Moreover, a boaB mutant of B. pseudomallei DD503 showed decreased adherence to these respiratory cells. Additionally, a B. pseudomallei strain lacking expression of both boaA and boaB was impaired in its ability to

  14. Bilateral Entry and Release of Middle East Respiratory Syndrome Coronavirus Induces Profound Apoptosis of Human Bronchial Epithelial Cells

    Science.gov (United States)

    Tao, Xinrong; Hill, Terence E.; Morimoto, Chikao; Peters, Clarence J.; Ksiazek, Thomas G.

    2013-01-01

    The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) infects human bronchial epithelial Calu-3 cells. Unlike severe acute respiratory syndrome (SARS)-CoV, which exclusively infects and releases through the apical route, this virus can do so through either side of polarized Calu-3 cells. Infection results in profound apoptosis within 24 h irrespective of its production of titers that are lower than those of SARS-CoV. Together, our results provide new insights into the dissemination and pathogenesis of MERS-CoV and may indicate that the virus differs markedly from SARS-CoV. PMID:23824802

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

    Science.gov (United States)

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

    2015-08-01

    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.

  16. Human Respiratory Syncytial Virus: Role of Innate Immunity in Clearance and Disease Progression.

    Science.gov (United States)

    Farrag, Mohamed A; Almajhdi, Fahad N

    2016-01-01

    Human respiratory syncytial virus (HRSV) infections have worldwide records. The virus is responsible for bronchiolitis, pneumonia, and asthma in humans of different age groups. Premature infants, young children, and immunocompromised individuals are prone to severe HRSV infection that may lead to death. Based on worldwide estimations, millions of cases were reported in both developed and developing countries. In fact, HRSV symptoms develop mainly as a result of host immune response. Due to inability to establish long lasting adaptive immunity, HRSV infection is recurrent and hence impairs vaccine development. Once HRSV attached to the airway epithelia, interaction with the host innate immune components starts. HRSV interaction with pulmonary innate defenses is crucial in determining the disease outcome. Infection of alveolar epithelial cells triggers a cascade of events that lead to recruitment and activation of leukocyte populations. HRSV clearance is mediated by a number of innate leukocytes, including macrophages, natural killer cells, eosinophils, dendritic cells, and neutrophils. Regulation of these cells is mediated by cytokines, chemokines, and other immune mediators. Although the innate immune system helps to clear HRSV infection, it participates in disease progression such as bronchiolitis and asthma. Resolving the mechanisms by which HRSV induces pathogenesis, different possible interactions between the virus and immune components, and immune cells interplay are essential for developing new effective vaccines. Therefore, the current review focuses on how the pulmonary innate defenses mediate HRSV clearance and to what extent they participate in disease progression. In addition, immune responses associated with HRSV vaccines will be discussed.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  18. In Vitro and in Silico Tools To Assess Extent of Cellular Uptake and Lysosomal Sequestration of Respiratory Drugs in Human Alveolar Macrophages.

    Science.gov (United States)

    Ufuk, Ayşe; Assmus, Frauke; Francis, Laura; Plumb, Jonathan; Damian, Valeriu; Gertz, Michael; Houston, J Brian; Galetin, Aleksandra

    2017-04-03

    Accumulation of respiratory drugs in human alveolar macrophages (AMs) has not been extensively studied in vitro and in silico despite its potential impact on therapeutic efficacy and/or occurrence of phospholipidosis. The current study aims to characterize the accumulation and subcellular distribution of drugs with respiratory indication in human AMs and to develop an in silico mechanistic AM model to predict lysosomal accumulation of investigated drugs. The data set included 9 drugs previously investigated in rat AM cell line NR8383. Cell-to-unbound medium concentration ratio (Kp,cell) of all drugs (5 μM) was determined to assess the magnitude of intracellular accumulation. The extent of lysosomal sequestration in freshly isolated human AMs from multiple donors (n = 5) was investigated for clarithromycin and imipramine (positive control) using an indirect in vitro method (±20 mM ammonium chloride, NH4Cl). The AM cell parameters and drug physicochemical data were collated to develop an in silico mechanistic AM model. Three in silico models differing in their description of drug membrane partitioning were evaluated; model (1) relied on octanol-water partitioning of drugs, model (2) used in vitro data to account for this process, and model (3) predicted membrane partitioning by incorporating AM phospholipid fractions. In vitro Kp,cell ranged >200-fold for respiratory drugs, with the highest accumulation seen for clarithromycin. A good agreement in Kp,cell was observed between human AMs and NR8383 (2.45-fold bias), highlighting NR8383 as a potentially useful in vitro surrogate tool to characterize drug accumulation in AMs. The mean Kp,cell of clarithromycin (81, CV = 51%) and imipramine (963, CV = 54%) were reduced in the presence of NH4Cl by up to 67% and 81%, respectively, suggesting substantial contribution of lysosomal sequestration and intracellular binding in the accumulation of these drugs in human AMs. The in vitro data showed variability in drug

  19. [Hardware and software for EMG recording and analysis of respiratory muscles of human].

    Science.gov (United States)

    Solnushkin, S D; Chakhman, V N; Segizbaeva, M O; Pogodin, M A; Aleksandrov, V G

    2014-01-01

    This paper presents a new hardware and software system that allows to not only record the EMG of different groups of the respiratory muscles, but also hold its amplitude-frequency analysis, which allows to determine the change in the contribution to the work of breathing of a respiratory muscles and detect early signs of fatigue of the respiratory muscles. Presented complex can be used for functional diagnostics of breath in patients and healthy people and sportsmen.

  20. Multifractal heart rate dynamics in human cardiovascular model

    Science.gov (United States)

    Kotani, Kiyoshi; Takamasu, Kiyoshi; Safonov, Leonid; Yamamoto, Yoshiharu

    2003-05-01

    Human cardiovascular and/or cardio-respiratory systems are shown to exhibit both multifractal and synchronous dynamics, and we recently developed a nonlinear, physiologically plausible model for the synchronization between heartbeat and respiration (Kotani, et al. Phys. Rev. E 65: 051923, 2002). By using the same model, we now show the multifractality in the heart rate dynamics. We find that beat-to-beat monofractal noise (fractional Brownian motion) added to the brain stem cardiovascular areas results in significantly broader singularity spectra for heart rate through interactions between sympathetic and parasympathetic nervous systems. We conclude that the model proposed here would be useful in studying the complex cardiovascular and/or cardio- respiratory dynamics in humans.

  1. Characterization of human metapneumovirus from pediatric patients with acute respiratory infections in a 4-year period in Beijing, China

    Institute of Scientific and Technical Information of China (English)

    ZHU Ru-nan; QIAN Yuan; ZHAO Lin-qing; DENG Jie; SUN Yu; WANG Fang; LIAO Bin; LI Yan; HUANG Rong-yan

    2011-01-01

    Background Human metapneumovirus (hMPV) was discovered by scientists in the Netherlands as a novel respiratory virus in 2001 and had been found in children with acute respiratory tract infections (ARTI) in China. The objective of this study was to determine the importance of hMPV infection in children in Beijing and the genotypes of the circulating virus by the surveillance during a four-consecutive-year period.Methods Clinical specimens collected from children with ARTI from January 2006 to December 2009 were tested for hMPV by RT-PCR using primers targeting the matrix (M) gene, followed by genotyping of hMPV directly from positive samples by diplex PCR with primers for glycoprotein (G) genes. Sequence analysis was used for genotyping of those un-typable samples. Common respiratory viruses in these clinical specimens were tested by virus isolation and antigen detection, in addition to hMPV detection.Results Of 4730 tested specimens, 191 (4.0%) were positive for hMPV and 62.8% of 191 were identified as genotype A. The positive rate of hMPV from hospitalized patients was higher than that from outpatients each year. Most of hMPV positive children were under five years old. The peak of hMPV activity mostly occurred in late spring and overlapped with or followed that of respiratory syncytial virus (RSV) and followed by parainfluenza virus 3. Of hMPV infected cases,68.6% were lower respiratory tract infection, among which 79.4% were hospitalized, and upper respiratory tract infection was diagnosed for 31.4% of hMPV infected children. The 9.4% of hMPV positive samples were found to co-exist with other respiratory viruses.Conclusions hMPV was an important pathogen for ARTI in pediatric patients, especially those under five years old.Both genotypes A and B circulated simultaneously in Beijing.

  2. Chemical exposure-response relationship between air pollutants and reactive oxygen species in the human respiratory tract

    Science.gov (United States)

    Lakey, Pascale S. J.; Berkemeier, Thomas; Tong, Haijie; Arangio, Andrea M.; Lucas, Kurt; Pöschl, Ulrich; Shiraiwa, Manabu

    2016-09-01

    Air pollution can cause oxidative stress and adverse health effects such as asthma and other respiratory diseases, but the underlying chemical processes are not well characterized. Here we present chemical exposure-response relations between ambient concentrations of air pollutants and the production rates and concentrations of reactive oxygen species (ROS) in the epithelial lining fluid (ELF) of the human respiratory tract. In highly polluted environments, fine particulate matter (PM2.5) containing redox-active transition metals, quinones, and secondary organic aerosols can increase ROS concentrations in the ELF to levels characteristic for respiratory diseases. Ambient ozone readily saturates the ELF and can enhance oxidative stress by depleting antioxidants and surfactants. Chemical exposure-response relations provide a quantitative basis for assessing the relative importance of specific air pollutants in different regions of the world, showing that aerosol-induced epithelial ROS levels in polluted megacity air can be several orders of magnitude higher than in pristine rainforest air.

  3. Estimates of committed effective dose and annual limit on intake for radioactive dusts using the new ICRP respiratory tract model

    Energy Technology Data Exchange (ETDEWEB)

    O`Brien, R.S. [Australian Radiation Lab., Melbourne, VIC (Australia)

    1996-01-01

    This paper discusses some of the implications of using the new ICRP 66 respiratory tract model for calculation of the committed effective dose(CED), for a period of 50 years post-intake, together with the annual limit on intake(ALI), for radioactive dusts encountered in the uranium and mineral sand mining and processing industries. Some of the differences between the old ICRP 30 respiratory tract model and the LUDEP 1.1 computer code, which is based on the new ICRP 66 respiratory tract model, are discussed and a comparison of values obtained using both models is given. 4 figs; 8 tabs; 16 refs.

  4. Aerosol deposition in the respiratory tract of the rat. Experimental results and mathematical modelling.

    Science.gov (United States)

    Halík, J; Lenger, V; Kliment, V; Voboril, P

    1980-01-01

    The deposition fraction in the respiratory tract of rats were determined experimentally using aerosol 85Srl2 in saline. The dimensions of the particles [MMD 1.63 /+- /+- 0.47 micron, Sg = 1.29] were measured by two independent methods. Rats weighing 200 g were exposed for a period of 60 min [t] in the inhalation apparatus PIANO 3 with a generator according to Lauterbach. From the volume activity [A] of 3 - 11 Bq/litre air a depot of 35-129 kBq was formed in the animals. Spirometric values measured with a modified Jäger ergospirometer were: V = 178.8 /+- 42.9 ml, VT = = 1.18 /+- 0.24 ml. f = 163.1 /+- 28.1 cycles/min. The total amount inhaled [Q] was calculated [Q = V.A.t], the deposited amount [D] was measured by a whole body counter. THe mean deposition fraction was 0.570 /+- 0.052 and was not related either to exposure time or to aerosol activity. In view of the broad validity of the conclusions for aerosols of round-shaped particles, the mean deposition fraction was determined with the help of a mathematical model according to Landahl. The theoretical values amounted to 0.609 [from 0.522 to 0.686]. The good agreement between the mean deposition fractions estimated by two independent methods indicates that on the basis of the probability theory and dimensional analysis, the mathematical model can also be used in humans for simulation deposition as one of the basis foundations for a quantitative evaluation of inhalation risk from any kind of aerosol.

  5. Inducible expression of beta defensins by human respiratory epithelial cells exposed to Aspergillus fumigatus organisms

    Directory of Open Access Journals (Sweden)

    Tichanné-Seltzer Virginie

    2009-02-01

    defensin expression in primary culture of human respiratory cells exposed to A. fumigatus points to the biological significance of described phenomena. Conclusion Our findings provide evidence that respiratory epithelium might play an important role in the immune response during Aspergillus infection. Understanding the mechanisms of regulation of defensin expression may thus lead to new approaches that could enhance expression of antimicrobial peptides for potential therapeutic use during aspergillosis treatment.

  6. Model for the respiratory modulation of the heart beat-to-beat time interval series

    Science.gov (United States)

    Capurro, Alberto; Diambra, Luis; Malta, C. P.

    2005-09-01

    In this study we present a model for the respiratory modulation of the heart beat-to-beat interval series. The model consists of a set of differential equations used to simulate the membrane potential of a single rabbit sinoatrial node cell, excited with a periodic input signal with added correlated noise. This signal, which simulates the input from the autonomous nervous system to the sinoatrial node, was included in the pacemaker equations as a modulation of the iNaK current pump and the potassium current iK. We focus at modeling the heart beat-to-beat time interval series from normal subjects during meditation of the Kundalini Yoga and Chi techniques. The analysis of the experimental data indicates that while the embedding of pre-meditation and control cases have a roughly circular shape, it acquires a polygonal shape during meditation, triangular for the Kundalini Yoga data and quadrangular in the case of Chi data. The model was used to assess the waveshape of the respiratory signals needed to reproduce the trajectory of the experimental data in the phase space. The embedding of the Chi data could be reproduced using a periodic signal obtained by smoothing a square wave. In the case of Kundalini Yoga data, the embedding was reproduced with a periodic signal obtained by smoothing a triangular wave having a rising branch of longer duration than the decreasing branch. Our study provides an estimation of the respiratory signal using only the heart beat-to-beat time interval series.

  7. Residues in human respiratory syncytial virus P protein that are essential for its activity on RNA viral synthesis.

    Science.gov (United States)

    Asenjo, Ana; Mendieta, Jesús; Gómez-Puertas, Paulino; Villanueva, Nieves

    2008-03-01

    Human respiratory syncytial virus (HRSV) P protein, 241 amino acid long, is a structural homotetrameric phosphoprotein. Viral transcription and replication processes are dependent on functional P protein interactions inside viral ribonucleoprotein complexes (RNPs). Binding capacity to RNPs proteins and transcription and replication complementation analyses, using inactive P protein variants, have identified residues essential for functional interactions with itself, L, N and M2-1 proteins. P protein may establish some of these interactions as monomer, but efficient viral transcription and replication requires P protein oligomerization through the central region of the molecule. A structurally stable three-dimensional model has been generated in silico for this region (residues 98-158). Our analysis has indicated that P protein residues L135, D139, E140 and L142 are involved in homotetramerization. Additionally, the residues D136, S156, T160 and E179 appear to be essential for P protein activity on viral RNA synthesis and very high turnover phosphorylation at S143, T160 and T210 could regulate it. Thus, compounds targeted to those of these residues, located in the modeled three-dimensional structure, could have specific anti-HRSV effect.

  8. Joint PET-MR respiratory motion models for clinical PET motion correction

    Science.gov (United States)

    Manber, Richard; Thielemans, Kris; Hutton, Brian F.; Wan, Simon; McClelland, Jamie; Barnes, Anna; Arridge, Simon; Ourselin, Sébastien; Atkinson, David

    2016-09-01

    Patient motion due to respiration can lead to artefacts and blurring in positron emission tomography (PET) images, in addition to quantification errors. The integration of PET with magnetic resonance (MR) imaging in PET-MR scanners provides complementary clinical information, and allows the use of high spatial resolution and high contrast MR images to monitor and correct motion-corrupted PET data. In this paper we build on previous work to form a methodology for respiratory motion correction of PET data, and show it can improve PET image quality whilst having minimal impact on clinical PET-MR protocols. We introduce a joint PET-MR motion model, using only 1 min per PET bed position of simultaneously acquired PET and MR data to provide a respiratory motion correspondence model that captures inter-cycle and intra-cycle breathing variations. In the model setup, 2D multi-slice MR provides the dynamic imaging component, and PET data, via low spatial resolution framing and principal component analysis, provides the model surrogate. We evaluate different motion models (1D and 2D linear, and 1D and 2D polynomial) by computing model-fit and model-prediction errors on dynamic MR images on a data set of 45 patients. Finally we apply the motion model methodology to 5 clinical PET-MR oncology patient datasets. Qualitative PET reconstruction improvements and artefact reduction are assessed with visual analysis, and quantitative improvements are calculated using standardised uptake value (SUVpeak and SUVmax) changes in avid lesions. We demonstrate the capability of a joint PET-MR motion model to predict respiratory motion by showing significantly improved image quality of PET data acquired before the motion model data. The method can be used to incorporate motion into the reconstruction of any length of PET acquisition, with only 1 min of extra scan time, and with no external hardware required.

  9. Respiratory sensitization : Advances in assessing the risk of respiratory inflammation and irritation

    NARCIS (Netherlands)

    Vandebriel, R.; Callant Cransveld, C.; Crommelin, D.; Diamant, Z.; Glazenburg, B.; Joos, G.; Kuper, F.; Natsch, A.; Nijkamp, F.; Noteborn, H.; Pieters, R.; Roberts, D.; Roggen, E.; Rorije, E.; Seed, M.; Sewald, K.; Heuvel, R. van den; Engelen, J. van; Verstraelen, S.; Loveren, H. van

    2011-01-01

    Respiratory sensitization provides a case study for a new approach to chemical safety evaluation, as the prevalence of respiratory sensitization has increased considerably over the last decades, but animal and/or human experimental/predictive models are not currently available. Therefore, the goal

  10. Respiratory sensitization : Advances in assessing the risk of respiratory inflammation and irritation

    NARCIS (Netherlands)

    Vandebriel, R.; Callant Cransveld, C.; Crommelin, D.; Diamant, Z.; Glazenburg, B.; Joos, G.; Kuper, F.; Natsch, A.; Nijkamp, F.; Noteborn, H.; Pieters, R.; Roberts, D.; Roggen, E.; Rorije, E.; Seed, M.; Sewald, K.; Heuvel, R. van den; Engelen, J. van; Verstraelen, S.; Loveren, H. van

    2011-01-01

    Respiratory sensitization provides a case study for a new approach to chemical safety evaluation, as the prevalence of respiratory sensitization has increased considerably over the last decades, but animal and/or human experimental/predictive models are not currently available. Therefore, the goal o

  11. Endocytosis is required for exocytosis and priming of respiratory burst activity in human neutrophils.

    Science.gov (United States)

    Creed, T Michael; Tandon, Shweta; Ward, Richard A; McLeish, Kenneth R

    2017-06-21

    Neutrophil generation of reactive oxygen species (ROS) is enhanced by exposure to pro-inflammatory agents in a process termed priming. Priming is depending on exocytosis of neutrophil granules and p47(phox) phosphorylation-dependent translocation of cytosolic NADPH oxidase components. Clathrin-mediated endocytosis was recently reported to be necessary for priming, but the mechanism linking endocytosis to priming was not identified. The present study examined the hypothesis that endocytosis regulates neutrophil priming by controlling granule exocytosis. Clathrin-mediated endocytosis by isolated human neutrophils was inhibited by chlorpromazine, monodansylcadaverine, and sucrose. Exocytosis of granule subsets was measured as release of granule components by ELISA or chemiluminescence. ROS generation was measured as extracellular release of superoxide as reduction of ferrocytochrome c. p38 MAPK activation and p47(phox) phosphorylation were measured by immunoblot analysis. Statistical analysis was performed using a one-way ANOVA with the Tukey-Kramer multiple-comparison test. Inhibition of endocytosis prevented priming of superoxide release by TNFα and inhibited TNFα stimulation and priming of exocytosis of all four granule subsets. Inhibition of endocytosis did not reduce TNFα-stimulated p38 MAPK activation or p47(phox) phosphorylation. Inhibition of NADPH oxidase activity blocked TNFα stimulation of secretory vesicle and gelatinase granule exocytosis. Endocytosis is linked to priming of respiratory burst activity through ROS-mediated control of granule exocytosis.

  12. Secretion of respiratory syncytial virus inhibitors and antibody in human milk throughout lactation.

    Science.gov (United States)

    Toms, G L; Gardner, P S; Pullan, C R; Scott, M; Taylor, C

    1980-01-01

    Neutralising inhibitors to respiratory syncytial (RS) virus have been demonstrated in the whey of most samples of human milk tested. Although high titres were secreted in colostra of some mothers (1/10-1/2,560; median 1/40) inhibitor levels in milk collected after the first week of lactation were uniformly low (median 1/10). High neutralising titres correlated with high colostral levels of specific antiviral IgA but, unlike neutralising activity, IgA antiviral antibody persisted in the milk of only four of 18 mothers. Similarly, antiviral IgG and IgM antibodies were not generally detected after the first post-partum week. Differences in antibody secretion among mothers did not correlate with differences in total protein or total immunoglobulin secretion, and appeared to reflect maternal immune status. In one mother a marked rise in specific antiviral IgA and IgG secretions during the second and third months of lactation suggested a response to virus infection. The relevance of maternal immunity and colostral and milk antiviral antibody to protection of breast-fed babies from RS-virus bronchiolitis is discussed.

  13. Standardization of the antibody-dependent respiratory burst assay with human neutrophils and Plasmodium falciparum malaria.

    Science.gov (United States)

    Llewellyn, David; Miura, Kazutoyo; Fay, Michael P; Williams, Andrew R; Murungi, Linda M; Shi, Jianguo; Hodgson, Susanne H; Douglas, Alexander D; Osier, Faith H; Fairhurst, Rick M; Diakite, Mahamadou; Pleass, Richard J; Long, Carole A; Draper, Simon J

    2015-09-16

    The assessment of naturally-acquired and vaccine-induced immunity to blood-stage Plasmodium falciparum malaria is of long-standing interest. However, the field has suffered from a paucity of in vitro assays that reproducibly measure the anti-parasitic activity induced by antibodies in conjunction with immune cells. Here we optimize the antibody-dependent respiratory burst (ADRB) assay, which assesses the ability of antibodies to activate the release of reactive oxygen species from human neutrophils in response to P. falciparum blood-stage parasites. We focus particularly on assay parameters affecting serum preparation and concentration, and importantly assess reproducibility. Our standardized protocol involves testing each serum sample in singlicate with three independent neutrophil donors, and indexing responses against a standard positive control of pooled hyper-immune Kenyan sera. The protocol can be used to quickly screen large cohorts of samples from individuals enrolled in immuno-epidemiological studies or clinical vaccine trials, and requires only 6 μL of serum per sample. Using a cohort of 86 samples, we show that malaria-exposed individuals induce higher ADRB activity than malaria-naïve individuals. The development of the ADRB assay complements the use of cell-independent assays in blood-stage malaria, such as the assay of growth inhibitory activity, and provides an important standardized cell-based assay in the field.

  14. Human CD8(+) T Cells Target Multiple Epitopes in Respiratory Syncytial Virus Polymerase.

    Science.gov (United States)

    Burbulla, Daniel; Günther, Patrick S; Peper, Janet K; Jahn, Gerhard; Dennehy, Kevin M

    2016-06-01

    Respiratory syncytial virus (RSV) infection is a serious health problem in young children, immunocompromised patients, and the elderly. The development of novel prevention strategies, such as a vaccine to RSV, is a high priority. One strategy is to design a peptide-based vaccine that activates appropriate CD8(+) T-cell responses. However, this approach is limited by the low number of RSV peptide epitopes defined to date that activate CD8(+) T cells. We aimed to identify peptide epitopes that are presented by common human leukocyte antigen types (HLA-A*01, -A*02, and -B*07). We identify one novel HLA-A*02-restricted and two novel HLA-A*01-restricted peptide epitopes from RSV polymerase. Peptide-HLA multimer staining of specific T cells from healthy donor peripheral blood mononuclear cell, the memory phenotype of such peptide-specific T cells ex vivo, and functional IFNγ responses in short-term stimulation assays suggest that these peptides are recognized during RSV infection. Such peptides are candidates for inclusion into a peptide-based RSV vaccine designed to stimulate defined CD8(+) T-cell responses.

  15. Group B strains of human respiratory syncytial virus in Saudi Arabia: molecular and phylogenetic analysis.

    Science.gov (United States)

    Almajhdi, Fahad N; Farrag, Mohamed A; Amer, Haitham M

    2014-04-01

    The genetic variability and circulation pattern of human respiratory syncytial virus group B (HRSV-B) strains, identified in Riyadh during the winters of 2008 and 2009, were evaluated by partial sequencing of the attachment (G) protein gene. The second hypervariable region (HVR-2) of G gene was amplified by RT-PCR, sequenced and compared to representatives of different HRSV-B genotypes. Sequence and phylogenetic analysis revealed that all Saudi strains belonged to the genotype BA, which is characterized by 60-nucleotide duplication at HVR-2. Only strains of 2008 were clustered with subgroup BA-IV, while those isolated at 2009 were clustered among the most recent subgroups (particularly BA-X and CB-B). Amino acid sequence analysis demonstrated 18 amino acid substitutions in Saudi HRSV-B strains; among which five are specific for individual strains. Furthermore, two potential N-glycosylation sites at residues 230 and 296 were identified for all Saudi strains, and an additional site at amino acid 273 was found only in Riyadh 28/2008 strain. O-glycosylation was predicted in 42-43 sites, where the majority (no = 38) are highly conserved among Saudi strains. The average ratio between non-synonymous and synonymous mutations (ω) implied stabilizing selection pressure on G protein, with evidences of positive selection on certain Saudi strains. This report provides preliminary data on the circulation pattern and molecular characteristics of HRSV-B strains circulating in Saudi Arabia.

  16. Human metapneumovirus in patients hospitalized with acute respiratory infections: A meta-analysis.

    Science.gov (United States)

    Lefebvre, Annick; Manoha, Catherine; Bour, Jean-Baptiste; Abbas, Rachid; Fournel, Isabelle; Tiv, Michel; Pothier, Pierre; Astruc, Karine; Aho-Glélé, Ludwig Serge

    2016-08-01

    This meta-analysis aimed to estimate the prevalence of human metapneumovirus (hMPV) infections in patients hospitalized for acute respiratory infection (ARI) and to study factors associated with this prevalence. Medline and ScienceDirect databases were searched for prospective observational studies that screened hospitalized patients with ARI for hMPV by RT-PCR, with data available at December 27, 2014. The risk of bias was assessed regarding participation rate, definition of ARI, description of diagnostic technique, method of inclusion identical for all subjects, standardized and identical sampling method for all subjects, analysis performed according to the relevant subgroups, and presentation of data sources. Random-effect meta-analysis with arcsine transformation and meta-regressions was used. In the 75 articles included, the prevalence of hMPV among hospitalized ARI was 6.24% (95% CI 5.25-7.30). An effect of the duration of the inclusion period was observed (p=0.0114), with a higher prevalence of hMPV in studies conducted during periods of 7-11 months (10.56%, 95% CI 5.97-16.27) or complete years (7.55%, 95% CI 5.90-9.38) than in periods of 6 months or less (5.36%, 95% CI 4.29-6.54). A significant increase in the incidence with increasing distance from the equator was observed (p=0.0384). hMPV should be taken into account as a possible etiology in hospitalized ARI.

  17. Statistical modeling of 4D respiratory lung motion using diffeomorphic image registration.

    Science.gov (United States)

    Ehrhardt, Jan; Werner, René; Schmidt-Richberg, Alexander; Handels, Heinz

    2011-02-01

    Modeling of respiratory motion has become increasingly important in various applications of medical imaging (e.g., radiation therapy of lung cancer). Current modeling approaches are usually confined to intra-patient registration of 3D image data representing the individual patient's anatomy at different breathing phases. We propose an approach to generate a mean motion model of the lung based on thoracic 4D computed tomography (CT) data of different patients to extend the motion modeling capabilities. Our modeling process consists of three steps: an intra-subject registration to generate subject-specific motion models, the generation of an average shape and intensity atlas of the lung as anatomical reference frame, and the registration of the subject-specific motion models to the atlas in order to build a statistical 4D mean motion model (4D-MMM). Furthermore, we present methods to adapt the 4D mean motion model to a patient-specific lung geometry. In all steps, a symmetric diffeomorphic nonlinear intensity-based registration method was employed. The Log-Euclidean framework was used to compute statistics on the diffeomorphic transformations. The presented methods are then used to build a mean motion model of respiratory lung motion using thoracic 4D CT data sets of 17 patients. We evaluate the model by applying it for estimating respiratory motion of ten lung cancer patients. The prediction is evaluated with respect to landmark and tumor motion, and the quantitative analysis results in a mean target registration error (TRE) of 3.3 ±1.6 mm if lung dynamics are not impaired by large lung tumors or other lung disorders (e.g., emphysema). With regard to lung tumor motion, we show that prediction accuracy is independent of tumor size and tumor motion amplitude in the considered data set. However, tumors adhering to non-lung structures degrade local lung dynamics significantly and the model-based prediction accuracy is lower in these cases. The statistical respiratory

  18. Mathematical modeling and validation in physiology applications to the cardiovascular and respiratory systems

    CERN Document Server

    Bachar, Mostafa; Kappel, Franz

    2013-01-01

    This volume synthesizes theoretical and practical aspects of both the mathematical and life science viewpoints needed for modeling of the cardiovascular-respiratory system specifically and physiological systems generally.  Theoretical points include model design, model complexity and validation in the light of available data, as well as control theory approaches to feedback delay and Kalman filter applications to parameter identification. State of the art approaches using parameter sensitivity are discussed for enhancing model identifiability through joint analysis of model structure and data. Practical examples illustrate model development at various levels of complexity based on given physiological information. The sensitivity-based approaches for examining model identifiability are illustrated by means of specific modeling  examples. The themes presented address the current problem of patient-specific model adaptation in the clinical setting, where data is typically limited.

  19. Characterization of an animal model of severe sepsis associated with respiratory dysfunction

    Directory of Open Access Journals (Sweden)

    Luciano Cesar Pontes de Azevedo

    2007-01-01

    Full Text Available PURPOSE: Pathophysiological studies in humans regarding sepsis are difficult to perform due to ethical and methodological concerns. In this context, animal models of sepsis can be useful to better understand this condition and to test therapeutic strategies. The purpose of this study was to characterize a feasible and clinically relevant model of sepsis in pigs that could be useful for testing different therapeutic interventions. METHODS: 5 White Large pigs were anesthetized, arterial and pulmonary catheters were introduced, and sepsis was induced by fecal peritonitis. Several biochemical indicators of organ dysfunction and infectious parameters were measured. The pigs were monitored until death, when fragments of organs were removed for pathology. Three animals without peritonitis served as controls and were sacrificed 24 hours after surgery without developing significant changes in organ function. RESULTS: Septic pigs survived 17 hours on average (range, 16-18 h, and Escherichia coli was recovered from blood cultures. They developed a significant decrease in left ventricular work and a nonsignificant reduction in mixed venous oxygen saturation. Respiratory dysfunction was characterized by a decrease in the PaO2/FiO2 ratio and respiratory compliance. Pathology of the lungs revealed areas of pulmonary collapse, hemorrhage, pulmonary congestion, and discrete neutrophil infiltrate. CONCLUSIONS: Fecal peritonitis in pigs is a clinically relevant model of sepsis associated with acute lung injury without direct pulmonary insult. This model may prove to be useful for studying pathogenic aspects of secondary lung injury as well as for validating ventilatory or pharmacologic interventions.PROPOSTA: Estudos sobre sepse envolvendo sua fisiopatologia são difíceis de serem realizados devido a razões éticas e metodológicas. Neste sentido, modelos animais criam oportunidades de estudos para entender a fisiopatologia e testar estratégias terapêuticas. O

  20. Cynomolgus macaque as an animal model for severe acute respiratory syndrome.

    Directory of Open Access Journals (Sweden)

    James V Lawler

    2006-05-01

    Full Text Available The emergence of severe acute respiratory syndrome (SARS in 2002 and 2003 affected global health and caused major economic disruption. Adequate animal models are required to study the underlying pathogenesis of SARS-associated coronavirus (SARS-CoV infection and to develop effective vaccines and therapeutics. We report the first findings of measurable clinical disease in nonhuman primates (NHPs infected with SARS-CoV.In order to characterize clinically relevant parameters of SARS-CoV infection in NHPs, we infected cynomolgus macaques with SARS-CoV in three groups: Group I was infected in the nares and bronchus, group II in the nares and conjunctiva, and group III intravenously. Nonhuman primates in groups I and II developed mild to moderate symptomatic illness. All NHPs demonstrated evidence of viral replication and developed neutralizing antibodies. Chest radiographs from several animals in groups I and II revealed unifocal or multifocal pneumonia that peaked between days 8 and 10 postinfection. Clinical laboratory tests were not significantly changed. Overall, inoculation by a mucosal route produced more prominent disease than did intravenous inoculation. Half of the group I animals were infected with a recombinant infectious clone SARS-CoV derived from the SARS-CoV Urbani strain. This infectious clone produced disease indistinguishable from wild-type Urbani strain.SARS-CoV infection of cynomolgus macaques did not reproduce the severe illness seen in the majority of adult human cases of SARS; however, our results suggest similarities to the milder syndrome of SARS-CoV infection characteristically seen in young children.

  1. A model for the evaluation of respiratory therapy program admissions criteria.

    Science.gov (United States)

    Flanigan, K S

    1985-05-01

    Attrition in respiratory therapy programs is a waste of both human and economic resources and may be one cause of the current shortage of qualified personnel. Poor academic performance has been shown to be the leading cause of program attrition. The purposes of this study were to establish the predictive abilities of aptitude and performance measures for classroom and laboratory performance in a respiratory therapy program and to describe a methodology for the development of academic admissions criteria. The preprogram college cumulative grade point average (pPGPA), the preprogram science-mathematics grade point average (S-M GPA), the American College Test (ACT) composite, and four ACT subtest scores of 39 graduates of The Ohio State University Respiratory Therapy Division were compared to their program grade point average (PGPA). We applied a multiple regression analysis and derived regression equations. Multiple regression analysis demonstrated that the S-M GPA is the most significant predictor of program academic performance (P less than or equal to 0.05). The derived regression equation was applied to calculate the minimum S-M GPA for admission by using the standard error of the estimate (SEE) of the regression equation and the mean minimum acceptable PGPA at a 95% confidence interval. For those students who have met the minimum S-M GPA, we have experienced no academic attrition. Multiple regression analysis of student data and the derived regression equations may be used to determine program-specific admissions criteria.

  2. Evaluation of residual abdominal tumour motion in carbon ion gated treatments through respiratory motion modelling.

    Science.gov (United States)

    Meschini, Giorgia; Seregni, Matteo; Pella, Andrea; Ciocca, Mario; Fossati, Piero; Valvo, Francesca; Riboldi, Marco; Baroni, Guido

    2017-02-01

    At the Italian National Centre for Oncologic Hadrontherapy (CNAO) patients with upper-abdominal tumours are being treated with carbon ion therapy, adopting the respiratory gating technique in combination with layered rescanning and abdominal compression to mitigate organ motion. Since online imaging of the irradiated volume is not feasible, this study proposes a modelling approach for the estimation of residual motion of the target within the gating window. The model extracts a priori respiratory motion information from the planning 4DCT using deformable image registration (DIR), then combines such information with the external surrogate signal recorded during dose delivery. This provides estimation of a CT volume corresponding to any given respiratory phase measured during treatment. The method was applied for the retrospective estimation of tumour residual motion during irradiation, considering 16 patients treated at CNAO with the respiratory gating protocol. The estimated tumour displacement, calculated with respect to the reference end-exhale position, was always limited (average displacement is 0.32±0.65mm over all patients) and below the maximum motion defined in the treatment plan. This supports the hypothesis of target position reproducibility, which is the crucial assumption in the gating approach. We also demonstrated the use of the model as a simulation tool to establish a patient-specific relationship between residual motion and the width of the gating window. In conclusion, the implemented method yields an estimation of the repeatability of the internal anatomy configuration during gated treatments, which can be used for further studies concerning the dosimetric impact of the estimated residual organ motion.

  3. Modeling human color categorization

    NARCIS (Netherlands)

    van den Broek, Egon; Schouten, Th.E.; Kisters, P.M.F.

    2008-01-01

    A unique color space segmentation method is introduced. It is founded on features of human cognition, where 11 color categories are used in processing color. In two experiments, human subjects were asked to categorize color stimuli into these 11 color categories, which resulted in markers for a Colo

  4. Modeling human color categorization

    NARCIS (Netherlands)

    van den Broek, Egon; Schouten, Th.E.; Kisters, P.M.F.

    A unique color space segmentation method is introduced. It is founded on features of human cognition, where 11 color categories are used in processing color. In two experiments, human subjects were asked to categorize color stimuli into these 11 color categories, which resulted in markers for a

  5. A dynamic model of human physiology

    Science.gov (United States)

    Green, Melissa; Kaplan, Carolyn; Oran, Elaine; Boris, Jay

    2010-11-01

    To study the systems-level transport in the human body, we develop the Computational Man (CMAN): a set of one-dimensional unsteady elastic flow simulations created to model a variety of coupled physiological systems including the circulatory, respiratory, excretory, and lymphatic systems. The model systems are collapsed from three spatial dimensions and time to one spatial dimension and time by assuming axisymmetric vessel geometry and a parabolic velocity profile across the cylindrical vessels. To model the actions of a beating heart or expanding lungs, the flow is driven by user-defined changes to the equilibrium areas of the elastic vessels. The equations are then iteratively solved for pressure, area, and average velocity. The model is augmented with valves and contractions to resemble the biological structure of the different systems. CMAN will be used to track material transport throughout the human body for diagnostic and predictive purposes. Parameters will be adjustable to match those of individual patients. Validation of CMAN has used both higher-dimensional simulations of similar geometries and benchmark measurement from medical literature.

  6. Genome Sequences of Human Adenovirus 14 Isolates from Mild Respiratory Cases and a Fatal Pneumonia, Isolated during 2006-2007 Epidemics in North America

    Science.gov (United States)

    2010-01-01

    Hsiang Lin5, David Metzgar6 Abstract Background: Human adenovirus 14 (HAdV-14) is a recognized causative agent of epidemic febrile respiratory illness (FRI...Shih- Chuan 1st Road, Kaohsiung,80708, Taiwan. 6Department of Respiratory Diseases Research, Naval Health Research Center (NHRC), 140 Sylvester Rd San

  7. A community study of clinical traits and risk factors for human metapneumovirus and respiratory syncytial virus infection during the first year of life

    DEFF Research Database (Denmark)

    von Linstow, Marie-Louise; Høgh, Mette; Nordbø, Svein;

    2008-01-01

    Human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) are important respiratory pathogens with similar symptomatology. The aim of this prospective birth cohort study was to identify risk factors for an hMPV or RSV infection during the first year of life in unselected healthy children...

  8. Immunogenicity and efficacy of alphavirus-derived replicon vaccines for respiratory syncytial virus and human metapneumovirus in nonhuman primates.

    Science.gov (United States)

    Bates, John T; Pickens, Jennifer A; Schuster, Jennifer E; Johnson, Monika; Tollefson, Sharon J; Williams, John V; Davis, Nancy L; Johnston, Robert E; Schultz-Darken, Nancy; Slaughter, James C; Smith-House, Frances; Crowe, James E

    2016-02-10

    Human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) are major causes of illness among children, the elderly, and the immunocompromised. No vaccine has been licensed for protection against either of these viruses. We tested the ability of two Venezuelan equine encephalitis virus-based viral replicon particle (VEE-VRP) vaccines that express the hRSV or hMPV fusion (F) protein to confer protection against hRSV or hMPV in African green monkeys. Animals immunized with VEE-VRP vaccines developed RSV or MPV F-specific antibodies and serum neutralizing activity. Compared to control animals, immunized animals were better able to control viral load in the respiratory mucosa following challenge and had lower levels of viral genome in nasopharyngeal and bronchoalveolar lavage fluids. The high level of immunogenicity and protective efficacy induced by these vaccine candidates in nonhuman primates suggest that they hold promise for further development.

  9. 4D modeling and estimation of respiratory motion for radiation therapy

    CERN Document Server

    Lorenz, Cristian

    2013-01-01

    Respiratory motion causes an important uncertainty in radiotherapy planning of the thorax and upper abdomen. The main objective of radiation therapy is to eradicate or shrink tumor cells without damaging the surrounding tissue by delivering a high radiation dose to the tumor region and a dose as low as possible to healthy organ tissues. Meeting this demand remains a challenge especially in case of lung tumors due to breathing-induced tumor and organ motion where motion amplitudes can measure up to several centimeters. Therefore, modeling of respiratory motion has become increasingly important in radiation therapy. With 4D imaging techniques spatiotemporal image sequences can be acquired to investigate dynamic processes in the patient’s body. Furthermore, image registration enables the estimation of the breathing-induced motion and the description of the temporal change in position and shape of the structures of interest by establishing the correspondence between images acquired at different phases of the br...

  10. Functional and histopathological identification of the respiratory failure in a DMSXL transgenic mouse model of myotonic dystrophy.

    Science.gov (United States)

    Panaite, Petrica-Adrian; Kuntzer, Thierry; Gourdon, Geneviève; Lobrinus, Johannes Alexander; Barakat-Walter, Ibtissam

    2013-05-01

    Acute and chronic respiratory failure is one of the major and potentially life-threatening features in individuals with myotonic dystrophy type 1 (DM1). Despite several clinical demonstrations showing respiratory problems in DM1 patients, the mechanisms are still not completely understood. This study was designed to investigate whether the DMSXL transgenic mouse model for DM1 exhibits respiratory disorders and, if so, to identify the pathological changes underlying these respiratory problems. Using pressure plethysmography, we assessed the breathing function in control mice and DMSXL mice generated after large expansions of the CTG repeat in successive generations of DM1 transgenic mice. Statistical analysis of breathing function measurements revealed a significant decrease in the most relevant respiratory parameters in DMSXL mice, indicating impaired respiratory function. Histological and morphometric analysis showed pathological changes in diaphragmatic muscle of DMSXL mice, characterized by an increase in the percentage of type I muscle fibers, the presence of central nuclei, partial denervation of end-plates (EPs) and a significant reduction in their size, shape complexity and density of acetylcholine receptors, all of which reflect a possible breakdown in communication between the diaphragmatic muscles fibers and the nerve terminals. Diaphragm muscle abnormalities were accompanied by an accumulation of mutant DMPK RNA foci in muscle fiber nuclei. Moreover, in DMSXL mice, the unmyelinated phrenic afferents are significantly lower. Also in these mice, significant neuronopathy was not detected in either cervical phrenic motor neurons or brainstem respiratory neurons. Because EPs are involved in the transmission of action potentials and the unmyelinated phrenic afferents exert a modulating influence on the respiratory drive, the pathological alterations affecting these structures might underlie the respiratory impairment detected in DMSXL mice. Understanding

  11. Functional and histopathological identification of the respiratory failure in a DMSXL transgenic mouse model of myotonic dystrophy

    Directory of Open Access Journals (Sweden)

    Petrica-Adrian Panaite

    2013-05-01

    Acute and chronic respiratory failure is one of the major and potentially life-threatening features in individuals with myotonic dystrophy type 1 (DM1. Despite several clinical demonstrations showing respiratory problems in DM1 patients, the mechanisms are still not completely understood. This study was designed to investigate whether the DMSXL transgenic mouse model for DM1 exhibits respiratory disorders and, if so, to identify the pathological changes underlying these respiratory problems. Using pressure plethysmography, we assessed the breathing function in control mice and DMSXL mice generated after large expansions of the CTG repeat in successive generations of DM1 transgenic mice. Statistical analysis of breathing function measurements revealed a significant decrease in the most relevant respiratory parameters in DMSXL mice, indicating impaired respiratory function. Histological and morphometric analysis showed pathological changes in diaphragmatic muscle of DMSXL mice, characterized by an increase in the percentage of type I muscle fibers, the presence of central nuclei, partial denervation of end-plates (EPs and a significant reduction in their size, shape complexity and density of acetylcholine receptors, all of which reflect a possible breakdown in communication between the diaphragmatic muscles fibers and the nerve terminals. Diaphragm muscle abnormalities were accompanied by an accumulation of mutant DMPK RNA foci in muscle fiber nuclei. Moreover, in DMSXL mice, the unmyelinated phrenic afferents are significantly lower. Also in these mice, significant neuronopathy was not detected in either cervical phrenic motor neurons or brainstem respiratory neurons. Because EPs are involved in the transmission of action potentials and the unmyelinated phrenic afferents exert a modulating influence on the respiratory drive, the pathological alterations affecting these structures might underlie the respiratory impairment detected in DMSXL mice. Understanding

  12. Respiratory Effects of the Nociceptin/Orphanin FQ Peptide and Opioid Receptor Agonist, Cebranopadol, in Healthy Human Volunteers.

    Science.gov (United States)

    Dahan, Albert; Boom, Merel; Sarton, Elise; Hay, Justin; Groeneveld, Geert Jan; Neukirchen, Meike; Bothmer, John; Aarts, Leon; Olofsen, Erik

    2017-04-01

    Cebranopadol is a novel strong analgesic that coactivates the nociceptin/orphanin FQ receptor and classical opioid receptors. There are indications that activation of the nociceptin/orphanin FQ receptor is related to ceiling in respiratory depression. In this phase 1 clinical trial, we performed a pharmacokinetic-pharmacodynamic study to quantify cebranopadol's respiratory effects. Twelve healthy male volunteers received 600 μg oral cebranopadol as a single dose. The following main endpoints were obtained at regular time intervals for 10 to 11 h after drug intake: ventilation at an elevated clamped end-tidal pressure of carbon dioxide, pain threshold and tolerance to a transcutaneous electrical stimulus train, and plasma cebranopadol concentrations. The data were analyzed using sigmoid Emax (respiration) and power (antinociception) models. Cebranopadol displayed typical opioid-like effects including miosis, analgesia, and respiratory depression. The blood-effect-site equilibration half-life for respiratory depression and analgesia was 1.2 ± 0.4 h (median ± standard error of the estimate) and 8.1 ± 2.5 h, respectively. The effect-site concentration causing 50% respiratory depression was 62 ± 4 pg/ml; the effect-site concentration causing 25% increase in currents to obtain pain threshold and tolerance was 97 ± 29 pg/ml. The model estimate for minimum ventilation was greater than zero at 4.9 ± 0.7 l/min (95% CI, 3.5 to 6.6 l/min). At the dose tested, cebranopadol produced respiratory depression with an estimate for minimum ventilation greater than 0 l/min. This is a major advantage over full μ-opioid receptor agonists that will produce apnea at high concentrations. Further clinical studies are needed to assess whether such behavior persists at higher doses.

  13. Integrated Environmental Modelling: human decisions, human challenges

    Science.gov (United States)

    Glynn, Pierre D.

    2015-01-01

    Integrated Environmental Modelling (IEM) is an invaluable tool for understanding the complex, dynamic ecosystems that house our natural resources and control our environments. Human behaviour affects the ways in which the science of IEM is assembled and used for meaningful societal applications. In particular, human biases and heuristics reflect adaptation and experiential learning to issues with frequent, sharply distinguished, feedbacks. Unfortunately, human behaviour is not adapted to the more diffusely experienced problems that IEM typically seeks to address. Twelve biases are identified that affect IEM (and science in general). These biases are supported by personal observations and by the findings of behavioural scientists. A process for critical analysis is proposed that addresses some human challenges of IEM and solicits explicit description of (1) represented processes and information, (2) unrepresented processes and information, and (3) accounting for, and cognizance of, potential human biases. Several other suggestions are also made that generally complement maintaining attitudes of watchful humility, open-mindedness, honesty and transparent accountability. These suggestions include (1) creating a new area of study in the behavioural biogeosciences, (2) using structured processes for engaging the modelling and stakeholder communities in IEM, and (3) using ‘red teams’ to increase resilience of IEM constructs and use.

  14. Deposition of combustion aerosols in the human respiratory tract: comparison of theoretical predictions with experimental data considering nonspherical shape.

    Science.gov (United States)

    Hofmann, W; Morawska, L; Winkler-Heil, R; Moustafa, M

    2009-12-01

    Total deposition of petrol and diesel combustion aerosols and environmental tobacco smoke (ETS) particles in the human respiratory tract for nasal breathing conditions was computed for 14 nonsmoking volunteers, considering the specific pulmonary function parameters of each volunteer and the specific size distribution for each inhalation experiment. Theoretical predictions were 34.6% for petrol smoke, 24.0% for diesel smoke, and 18.5% for ETS particles. Compared to the experimental results, predicted deposition values were consistently smaller than the measured data (41.4% for petrol smoke, 29.6% for diesel smoke, and 36.2% for ETS particles). The apparent discrepancy between experimental data on total deposition and modeling results may be reconciled by considering the nonspherical shape of the test aerosols by diameter-dependent dynamic shape factors to account for differences between mobility-equivalent and volume-equivalent or thermodynamic diameters. While the application of dynamic shape factors is able to explain the observed differences for petrol and diesel combustion particles, additional mechanisms may be required for ETS particle deposition, such as the size reduction upon inspiration by evaporation of volatile compounds and/or condensation-induced restructuring, and, possibly, electrical charge effects.

  15. Prevalence of Human Papillomavirus (HPV in upper respiratory tract mucosa in a group of pre-school children

    Directory of Open Access Journals (Sweden)

    Jaroslaw Szydłowski

    2014-11-01

    Full Text Available [b]introduction[/b]. Human Papillomavirus (HPV is a group of DNA viruses which is an etiological factor of many benign and malignant diseases of the upper respiratory tract mucosa, female genital tract and the skin. HPV infection is considered a sexually-transmitted infection, but can also be transmitted by non-sexual routes, including perinatal vertical transmission, physical contact, iatrogenic infection and autoinoculation. Recurrent Respiratory Papillomatosis (RRP in children is connected with HPV infection transmitted vertically from mother to child during the passage of the foetus through an infected birth canal. [b]objective. [/b]The aim of this study was to establish the level of Human Papillomaviruses carrier state in upper respiratory tract mucosa in healthy pre-school children, and to identify potential risk factors for HPV infection. [b]materials and method[/b]. After obtaining consent from their parents, 97 pre-school children were examined – 51 girls and 46 boys between the ages of 3 – 5 years; average age – 4 years and 5 months. 68 children were urban dwellers and 29 came from a rural environment. A questionnaire with detailed history was taken including parents’ and child`s personal data, as well as perinatal risk factors in pregnancy. Socio-demographic information was also obtained, including the standard of living, and chosen environmental factors. Routine ENT examination was performed. Exfoliated oral squamous cells were collected from swabs and analysed for the presence of DNA papillomaviruses by polymerase chain reaction. [b]results.[/b] The presence of HPV in the respiratory tract in children was detected in 19.6% cases. ‘High oncogenic potential’ HPVs, such as HPV-16 and HPV-18, were not observed in squamous cell mucosa of the respiratory tract in the children. No significant differences were observed between the HPV carrier state in urban and rural inhabitants.

  16. Aspergillus culture filtrates and sputum sols from patients with pulmonary aspergillosis cause damage to human respiratory ciliated epithelium in vitro.

    Science.gov (United States)

    Amitani, R; Murayama, T; Nawada, R; Lee, W J; Niimi, A; Suzuki, K; Tanaka, E; Kuze, F

    1995-10-01

    Aspergillus species frequently colonize lower respiratory tracts and lungs with localized underlying conditions (healed tuberculous cavity, cystic fibrosis, bronchiectasis, etc.) even in subjects without systemic predisposing factors. We investigated the in vitro effects of culture filtrates of Aspergillus species and sputum sols from patients with pulmonary aspergillosis on ciliary beat frequency (CBF) and epithelial integrity of human respiratory ciliated epithelium. Culture filtrates of 25 clinically isolated fungi (16 Aspergillus fumigatus, three Aspergillus niger, one Aspergillus flavus, three Candida albicans, and two Cryptococcus neoformans) were obtained by culturing the fungi in Medium-199 at 37 degrees C for 7 days, and five sputum sols were obtained from patients with pulmonary aspergillosis infected by A. fumigatus. During 6 h experiments using a photometric technique, 14 out of 16 A. fumigatus culture filtrates caused progressive and significant reduction in CBF associated with marked epithelial disruption, whilst the culture filtrates of A. niger and A. flavus caused minor epithelial damage without slowing of CBF, and Medium-199 alone (Control) showed neither epithelial damage nor slowing of CBF. All of the sputum sols also caused significant slowing of CBF as well as epithelial disruption. Culture filtrates of C. albicans and Cr. neoformans had no effects on human respiratory epithelium. We conclude that Aspergillus species, especially A. fumigatus release a factor (or factors) which causes damage to respiratory epithelium and slows CBF, and that these factors may contribute to the colonization of the lower respiratory tracts by the Aspergillus species and may possibly contribute to the further proliferation and spread of the lesions in pulmonary aspergillosis.

  17. Biological effects of desert dust in respiratory epithelial cells and a murine model

    Science.gov (United States)

    Ghio, Andrew J.; Kummarapurugu, Suryanaren T.; Tong, Haiyan; Soukup, Joleen M.; Dailey, Lisa A.; Boykin, Elizabeth; Gilmour, M. Ian; Ingram, Peter; Roggli, Victor L.; Goldstein, Harland L.; Reynolds, Richard L.

    2014-01-01

    As a result of the challenge of recent dust storms to public health, we tested the postulate that desert dust collected in the southwestern United States imparts a biological effect in respiratory epithelial cells and an animal model. Two samples of surface sediment were collected from separate dust sources in northeastern Arizona. Analysis of the PM20 fraction demonstrated that the majority of both dust samples were quartz and clay minerals (total SiO2 of 52 and 57%). Using respiratory epithelial and monocytic cell lines, the two desert dusts increased oxidant generation, measured by Amplex Red fluorescence, along with carbon black (a control particle), silica, and NIST 1649 (an ambient air pollution particle). Cell oxidant generation was greatest following exposures to silica and the desert dusts. Similarly, changes in RNA for superoxide dismutase-1, heme oxygenase-1, and cyclooxygenase-2 were also greatest after silica and the desert dusts supporting an oxidative stress after cell exposure. Silica, desert dusts, and the ambient air pollution particle NIST 1649 demonstrated a capacity to activate the p38 and ERK1/2 pathways and release pro-inflammatory mediators. Mice, instilled with the same particles, showed the greatest lavage concentrations of pro-inflammatory mediators, neutrophils, and lung injury following silica and desert dusts. We conclude that, comparable to other particles, desert dusts have a capacity to (1) influence oxidative stress and release of pro-inflammatory mediators in respiratory epithelial cells and (2) provoke an inflammatory injury in the lower respiratory tract of an animal model. The biological effects of desert dusts approximated those of silica.

  18. A Previously Unknown Reovirus of Bat Origin Is Associated with an Acute Respiratory Disease in Humans

    National Research Council Canada - National Science Library

    Kaw Bing Chua; Gary Crameri; Alex Hyatt; Meng Yu; Mohd Rosli Tompang; Juliana Rosli; Jennifer McEachern; Sandra Crameri; Verasingam Kumarasamy; Bryan T. Eaton; Lin-Fa Wang

    2007-01-01

    .... Here, we report a previously unknown reovirus (named "Melaka virus") isolated from a 39-year-old male patient in Melaka, Malaysia, who was suffering from high fever and acute respiratory disease at the time of virus isolation...

  19. Cryopreserved, Xeno-Free Human Umbilical Cord Mesenchymal Stromal Cells Reduce Lung Injury Severity and Bacterial Burden in Rodent Escherichia coli-Induced Acute Respiratory Distress Syndrome.

    Science.gov (United States)

    Curley, Gerard F; Jerkic, Mirjana; Dixon, Steve; Hogan, Grace; Masterson, Claire; O'Toole, Daniel; Devaney, James; Laffey, John G

    2017-02-01

    Although mesenchymal stem/stromal cells represent a promising therapeutic strategy for acute respiratory distress syndrome, clinical translation faces challenges, including scarcity of bone marrow donors, and reliance on bovine serum during mesenchymal stem/stromal cell proliferation. We wished to compare mesenchymal stem/stromal cells from human umbilical cord, grown in xeno-free conditions, with mesenchymal stem/stromal cells from human bone marrow, in a rat model of Escherichia coli pneumonia. In addition, we wished to determine the potential for umbilical cord-mesenchymal stem/stromal cells to reduce E. coli-induced oxidant injury. Randomized animal study. University research laboratory. Male Sprague-Dawley rats. Acute respiratory distress syndrome was induced in rats by intratracheal instillation of E. coli (1.5-2 × 10 CFU/kg). "Series 1" compared the effects of freshly thawed cryopreserved umbilical cord-mesenchymal stem/stromal cells with bone marrow-mesenchymal stem/stromal cells on physiologic indices of lung injury, cellular infiltration, and E. coli colony counts in bronchoalveolar lavage. "Series 2" examined the effects of cryopreserved umbilical cord-mesenchymal stem/stromal cells on survival, as well as measures of injury, inflammation and oxidant stress, including production of reactive oxidative species, reactive oxidative species scavenging by superoxide dismutase-1 and superoxide dismutase-2. In "Series 1," animals subjected to E. coli pneumonia who received umbilical cord-mesenchymal stem/stromal cells had improvements in oxygenation, respiratory static compliance, and wet-to-dry ratios comparable to bone marrow-mesenchymal stem/stromal cell treatment. E. coli colony-forming units in bronchoalveolar lavage were reduced in both cell therapy groups, despite a reduction in bronchoalveolar lavage neutrophils. In series 2, umbilical cord-mesenchymal stem/stromal cells enhanced animal survival and decreased alveolar protein and proinflammatory

  20. Use of the human colorectal adenocarcinoma (Caco-2) cell line for isolating respiratory viruses from nasopharyngeal aspirates.

    Science.gov (United States)

    Chan, K H; Yan, M K; To, K K W; Lau, S K; Woo, P C; Cheng, V C C; Li, W S; Chan, J F W; Tse, H; Yuen, K Y

    2013-05-01

    The human colorectal adenocarcinoma-derived Caco-2 cell line was evaluated as a means isolating common respiratory viruses from nasopharyngeal aspirates for the diagnosis of respiratory diseases. One hundred eighty-nine direct immunofluorescence positive nasopharyngeal aspirates obtained from patients with various viral respiratory diseases were cultured in the presence of Caco-2 cells or the following conventional cell lines: LLC-MK2, MDCK, HEp-2, and A549. Caco-2 cell cultures effectively propagated the majority (84%) of the viruses present in nasopharyngeal aspirate samples compared with any positive cultures obtained using the panel cells (78%) or individual cell line MDCK (38%), HEp-2 (21%), LLC-MK2 (27%), or A549 (37%) cell lines. The differences against individual cell line were statistically significant (P = viruses which were not cultivated in conventional cell lines. By contrast, 80% (24/30) of viruses not cultivated in Caco-2 cells were isolated using the conventional panel. The findings indicated that Caco-2 cells were sensitive to a wide range of viruses and can be used to culture a broad range of respiratory viruses.

  1. Particle deposition in a child respiratory tract model: in vivo regional deposition of fine and ultrafine aerosols in baboons.

    Science.gov (United States)

    Albuquerque-Silva, Iolanda; Vecellio, Laurent; Durand, Marc; Avet, John; Le Pennec, Déborah; de Monte, Michèle; Montharu, Jérôme; Diot, Patrice; Cottier, Michèle; Dubois, Francis; Pourchez, Jérémie

    2014-01-01

    To relate exposure to adverse health effects, it is necessary to know where particles in the submicron range deposit in the respiratory tract. The possibly higher vulnerability of children requires specific inhalation studies. However, radio-aerosol deposition experiments involving children are rare because of ethical restrictions related to radiation exposure. Thus, an in vivo study was conducted using three baboons as a child respiratory tract model to assess regional deposition patterns (thoracic region vs. extrathoracic region) of radioactive polydisperse aerosols ([d16-d84], equal to [0.15 µm-0.5 µm], [0.25 µm-1 µm], or [1 µm-9 µm]). Results clearly demonstrated that aerosol deposition within the thoracic region and the extrathoraic region varied substantially according to particle size. High deposition in the extrathoracic region was observed for the [1 µm-9 µm] aerosol (72% ± 17%). The [0.15 µm-0.5 µm] aerosol was associated almost exclusively with thoracic region deposition (84% ± 4%). Airborne particles in the range of [0.25 µm-1 µm] showed an intermediate deposition pattern, with 49% ± 8% in the extrathoracic region and 51% ± 8% in the thoracic region. Finally, comparison of baboon and human inhalation experiments for the [1 µm-9 µm] aerosol showed similar regional deposition, leading to the conclusion that regional deposition is species-independent for this airborne particle sizes.

  2. Particle deposition in a child respiratory tract model: in vivo regional deposition of fine and ultrafine aerosols in baboons.

    Directory of Open Access Journals (Sweden)

    Iolanda Albuquerque-Silva

    Full Text Available To relate exposure to adverse health effects, it is necessary to know where particles in the submicron range deposit in the respiratory tract. The possibly higher vulnerability of children requires specific inhalation studies. However, radio-aerosol deposition experiments involving children are rare because of ethical restrictions related to radiation exposure. Thus, an in vivo study was conducted using three baboons as a child respiratory tract model to assess regional deposition patterns (thoracic region vs. extrathoracic region of radioactive polydisperse aerosols ([d16-d84], equal to [0.15 µm-0.5 µm], [0.25 µm-1 µm], or [1 µm-9 µm]. Results clearly demonstrated that aerosol deposition within the thoracic region and the extrathoraic region varied substantially according to particle size. High deposition in the extrathoracic region was observed for the [1 µm-9 µm] aerosol (72% ± 17%. The [0.15 µm-0.5 µm] aerosol was associated almost exclusively with thoracic region deposition (84% ± 4%. Airborne particles in the range of [0.25 µm-1 µm] showed an intermediate deposition pattern, with 49% ± 8% in the extrathoracic region and 51% ± 8% in the thoracic region. Finally, comparison of baboon and human inhalation experiments for the [1 µm-9 µm] aerosol showed similar regional deposition, leading to the conclusion that regional deposition is species-independent for this airborne particle sizes.

  3. Direct Visuo-Haptic 4D Volume Rendering Using Respiratory Motion Models.

    Science.gov (United States)

    Fortmeier, Dirk; Wilms, Matthias; Mastmeyer, Andre; Handels, Heinz

    2015-01-01

    This article presents methods for direct visuo-haptic 4D volume rendering of virtual patient models under respiratory motion. Breathing models are computed based on patient-specific 4D CT image data sequences. Virtual patient models are visualized in real-time by ray casting based rendering of a reference CT image warped by a time-variant displacement field, which is computed using the motion models at run-time. Furthermore, haptic interaction with the animated virtual patient models is provided by using the displacements computed at high rendering rates to translate the position of the haptic device into the space of the reference CT image. This concept is applied to virtual palpation and the haptic simulation of insertion of a virtual bendable needle. To this aim, different motion models that are applicable in real-time are presented and the methods are integrated into a needle puncture training simulation framework, which can be used for simulated biopsy or vessel puncture in the liver. To confirm real-time applicability, a performance analysis of the resulting framework is given. It is shown that the presented methods achieve mean update rates around 2,000 Hz for haptic simulation and interactive frame rates for volume rendering and thus are well suited for visuo-haptic rendering of virtual patients under respiratory motion.

  4. Middle East respiratory syndrome coronavirus quasispecies that include homologues of human isolates revealed through whole-genome analysis and virus cultured from dromedary camels in Saudi Arabia.

    Science.gov (United States)

    Briese, Thomas; Mishra, Nischay; Jain, Komal; Zalmout, Iyad S; Jabado, Omar J; Karesh, William B; Daszak, Peter; Mohammed, Osama B; Alagaili, Abdulaziz N; Lipkin, W Ian

    2014-04-29

    ABSTRACT Complete Middle East respiratory syndrome coronavirus (MERS-CoV) genome sequences were obtained from nasal swabs of dromedary camels sampled in the Kingdom of Saudi Arabia through direct analysis of nucleic acid extracts or following virus isolation in cell culture. Consensus dromedary MERS-CoV genome sequences were the same with either template source and identical to published human MERS-CoV sequences. However, in contrast to individual human cases, where only clonal genomic sequences are reported, detailed population analyses revealed the presence of more than one genomic variant in individual dromedaries. If humans are truly infected only with clonal virus populations, we must entertain a model for interspecies transmission of MERS-CoV wherein only specific genotypes are capable of passing bottleneck selection. IMPORTANCE In most cases of Middle East respiratory syndrome (MERS), the route for human infection with the causative agent, MERS coronavirus (MERS-CoV), is unknown. Antibodies to and viral nucleic acids of MERS-CoV have been found in dromedaries, suggesting the possibility that they may serve as a reservoir or vector for human infection. However, neither whole viral genomic sequence nor infectious virus has been isolated from dromedaries or other animals in Saudi Arabia. Here, we report recovery of MERS-CoV from nasal swabs of dromedaries, demonstrate that MERS-CoV whole-genome consensus sequences from dromedaries and humans are indistinguishable, and show that dromedaries can be simultaneously infected with more than one MERS-CoV. Together with data indicating widespread dromedary infection in the Kingdom of Saudi Arabia, these findings support the plausibility of a role for dromedaries in human infection.

  5. Analysis of impulse oscillometric measures of lung function and respiratory system model parameters in small airway-impaired and healthy children over a 2-year period

    Directory of Open Access Journals (Sweden)

    Nava Pat

    2011-03-01

    Full Text Available Abstract Background Is Impulse Oscillometry System (IOS a valuable tool to measure respiratory system function in Children? Asthma (A is the most prevalent chronic respiratory disease in children. Therefore, early and accurate assessment of respiratory function is of tremendous clinical interest in diagnosis, monitoring and treatment of respiratory conditions in this subpopulation. IOS has been successfully used to measure lung function in children with a high degree of sensitivity and specificity to small airway impairments (SAI and asthma. IOS measures of airway function and equivalent electrical circuit models of the human respiratory system have been developed to quantify the severity of these conditions. Previously, we have evaluated several known respiratory models based on the Mead's model and more parsimonious versions based on fitting IOS data known as extended RIC (eRIC and augmented RIC (aRIC models have emerged, which offer advantages over earlier models. Methods IOS data from twenty-six children were collected and compared during pre-bronchodilation (pre-B and post- bronchodilation (post-B conditions over a period of 2 years. Results and Discussion Are the IOS and model parameters capable of differentiating between healthy children and children with respiratory system distress? Children were classified into two main categories: Healthy (H and Small Airway-Impaired (SAI. The IOS measures and respiratory model parameters analyzed differed consistently between H and SAI children. SAI children showed smaller trend of "growth" and larger trend of bronchodilator responses than H children. The two model parameters: peripheral compliance (Cp and peripheral resistance (Rp tracked IOS indices of small airway function well. Cp was a more sensitive index than Rp. Both eRIC and aRIC Cps and the IOS Reactance Area, AX, (also known as the "Goldman Triangle" showed good correlations. Conclusions What are the most useful IOS and model parameters? In

  6. The microbiota of the respiratory tract: gatekeeper to respiratory health.

    Science.gov (United States)

    Man, Wing Ho; de Steenhuijsen Piters, Wouter A A; Bogaert, Debby

    2017-05-01

    The respiratory tract is a complex organ system that is responsible for the exchange of oxygen and carbon dioxide. The human respiratory tract spans from the nostrils to the lung alveoli and is inhabited by niche-specific communities of bacteria. The microbiota of the respiratory tract probably acts as a gatekeeper that provides resistance to colonization by respiratory pathogens. The respiratory microbiota might also be involved in the maturation and maintenance of homeostasis of respiratory physiology and immunity. The ecological and environmental factors that direct the development of microbial communities in the respiratory tract and how these communities affect respiratory health are the focus of current research. Concurrently, the functions of the microbiome of the upper and lower respiratory tract in the physiology of the human host are being studied in detail. In this Review, we will discuss the epidemiological, biological and functional evidence that support the physiological role of the respiratory microbiota in the maintenance of human health.

  7. Respiratory recovery following organophosphate poisoning in a rat model is suppressed by isolated hypoxia at the point of apnea.

    Science.gov (United States)

    Gaspari, Romolo J; Paydarfar, David

    2012-12-16

    Normal respiratory activity (eupnea) and gasping represent different types of respiratory activity, one of which is supported by oxygen (eupnea) and the other suppressed by oxygen (gasping). There is a loss of respiratory activity post-organophosphate (OP) poisoning that returns following treatment. It is not clear if post-OP respiratory activity represents eupnea or gasping. Depending on the type of respiratory activity, oxygenation during recovery from OP poisoning may have the potential to either support or suppress respiratory activity. We hypothesize that respiratory recovery following OP-induced central apnea represents a resumption of eupnea and is supported by oxygenation. We used an animal model of acute OP poisoning with detailed physiologic recordings. Animals were poisoned with dichlorvos and allowed to recover during a period of mechanical ventilation. Two experimental models were analyzed: (1) animals supported with 100% oxygen and (2) animals supported with a normoxic gas mixture titrated to a PaO(2) of 115 mmHg. Rats in this study demonstrated breathing that resumes spontaneously following OP-induced apnea with characteristics of both eupnea and gasping. The post-OP respiratory activity was suppressed by hypoxia, a characteristic of eupneic respiration and not gasping respiration. However, the respiratory rate during post-apneic breathing corresponded more closely to gasping. Analysis of phrenic nerve discharge activity was distinct from both eupnea and gasping, with peak inspiratory and post-inspiratory discharge activities significantly reduced compared to both eupnea and gasping. In summary, in this animal model post-apneic breathing distinct from eupnea and gasping that emerges following prolonged OP-induced central apnea is suppressed by hypoxia.

  8. Public health and budget impact of probiotics on common respiratory tract infections: a modelling study.

    Directory of Open Access Journals (Sweden)

    Irene Lenoir-Wijnkoop

    Full Text Available Two recent meta-analyses by the York Health Economics Consortium (YHEC and Cochrane demonstrated probiotic efficacy in reducing the duration and number of common respiratory tract infections (CRTI and associated antibiotic prescriptions. A health-economic analysis was undertaken to estimate the public health and budget consequences of a generalized probiotic consumption in France.A virtual age- and gender-standardized population was generated using a Markov microsimulation model. CRTI risk factors incorporated into this model were age, active/passive smoking and living in a community setting. Incidence rates and resource utilization were based on the 2011-2012 flu season and retrieved from the French GPs Sentinelles network. Results of both meta-analyses were independently applied to the French population to estimate CRTI events, assuming a generalized probiotic use compared to no probiotics during winter months: -0.77 days/CRTI episode (YHEC scenario or odds-ratio 0.58 for ≥1 CRTI episode (Cochrane scenario with vs. without probiotics. Economic perspectives were National Health System (NHS, society, family. Outcomes included cost savings related to the reduced numbers of CRTI episodes, days of illness, number of antibiotic courses, sick leave days, medical and indirect costs.For France, generalized probiotic use would save 2.4 million CRTI-days, 291,000 antibiotic courses and 581,000 sick leave days, based on YHEC data. Applying the Cochrane data, reductions were 6.6 million CRTI days, 473,000 antibiotic courses and 1.5 million sick days. From the NHS perspective, probiotics' economic impact was about €14.6 million saved according to YHEC and €37.7 million according to Cochrane. Higher savings were observed in children, active smokers and people with more frequent human contacts.Public health and budget impact of probiotics are substantial, whether they reduce CRTI episodes frequency or duration. Noteworthy, the 2011-12 winter CRTI

  9. Public Health and Budget Impact of Probiotics on Common Respiratory Tract Infections: A Modelling Study

    Science.gov (United States)

    Lenoir-Wijnkoop, Irene; Gerlier, Laetitia; Bresson, Jean-Louis; Le Pen, Claude; Berdeaux, Gilles

    2015-01-01

    Objectives Two recent meta-analyses by the York Health Economics Consortium (YHEC) and Cochrane demonstrated probiotic efficacy in reducing the duration and number of common respiratory tract infections (CRTI) and associated antibiotic prescriptions. A health-economic analysis was undertaken to estimate the public health and budget consequences of a generalized probiotic consumption in France. Methods A virtual age- and gender-standardized population was generated using a Markov microsimulation model. CRTI risk factors incorporated into this model were age, active/passive smoking and living in a community setting. Incidence rates and resource utilization were based on the 2011-2012 flu season and retrieved from the French GPs Sentinelles network. Results of both meta-analyses were independently applied to the French population to estimate CRTI events, assuming a generalized probiotic use compared to no probiotics during winter months: -0.77 days/CRTI episode (YHEC scenario) or odds-ratio 0.58 for ≥1 CRTI episode (Cochrane scenario) with vs. without probiotics. Economic perspectives were National Health System (NHS), society, family. Outcomes included cost savings related to the reduced numbers of CRTI episodes, days of illness, number of antibiotic courses, sick leave days, medical and indirect costs. Results For France, generalized probiotic use would save 2.4 million CRTI-days, 291,000 antibiotic courses and 581,000 sick leave days, based on YHEC data. Applying the Cochrane data, reductions were 6.6 million CRTI days, 473,000 antibiotic courses and 1.5 million sick days. From the NHS perspective, probiotics’ economic impact was about €14.6 million saved according to YHEC and €37.7 million according to Cochrane. Higher savings were observed in children, active smokers and people with more frequent human contacts. Conclusions Public health and budget impact of probiotics are substantial, whether they reduce CRTI episodes frequency or duration. Noteworthy

  10. Predictive modeling of respiratory tumor motion for real-time prediction of baseline shifts

    Science.gov (United States)

    Balasubramanian, A.; Shamsuddin, R.; Prabhakaran, B.; Sawant, A.

    2017-03-01

    Baseline shifts in respiratory patterns can result in significant spatiotemporal changes in patient anatomy (compared to that captured during simulation), in turn, causing geometric and dosimetric errors in the administration of thoracic and abdominal radiotherapy. We propose predictive modeling of the tumor motion trajectories for predicting a baseline shift ahead of its occurrence. The key idea is to use the features of the tumor motion trajectory over a 1 min window, and predict the occurrence of a baseline shift in the 5 s that immediately follow (lookahead window). In this study, we explored a preliminary trend-based analysis with multi-class annotations as well as a more focused binary classification analysis. In both analyses, a number of different inter-fraction and intra-fraction training strategies were studied, both offline as well as online, along with data sufficiency and skew compensation for class imbalances. The performance of different training strategies were compared across multiple machine learning classification algorithms, including nearest neighbor, Naïve Bayes, linear discriminant and ensemble Adaboost. The prediction performance is evaluated using metrics such as accuracy, precision, recall and the area under the curve (AUC) for repeater operating characteristics curve. The key results of the trend-based analysis indicate that (i) intra-fraction training strategies achieve highest prediction accuracies (90.5-91.4%) (ii) the predictive modeling yields lowest accuracies (50-60%) when the training data does not include any information from the test patient; (iii) the prediction latencies are as low as a few hundred milliseconds, and thus conducive for real-time prediction. The binary classification performance is promising, indicated by high AUCs (0.96-0.98). It also confirms the utility of prior data from previous patients, and also the necessity of training the classifier on some initial data from the new patient for reasonable

  11. ADMET Evaluation in Drug Discovery. Part 17: Development of Quantitative and Qualitative Prediction Models for Chemical-Induced Respiratory Toxicity.

    Science.gov (United States)

    Lei, Tailong; Chen, Fu; Liu, Hui; Sun, Huiyong; Kang, Yu; Li, Dan; Li, Youyong; Hou, Tingjun

    2017-07-03

    As a dangerous end point, respiratory toxicity can cause serious adverse health effects and even death. Meanwhile, it is a common and traditional issue in occupational and environmental protection. Pharmaceutical and chemical industries have a strong urge to develop precise and convenient computational tools to evaluate the respiratory toxicity of compounds as early as possible. Most of the reported theoretical models were developed based on the respiratory toxicity data sets with one single symptom, such as respiratory sensitization, and therefore these models may not afford reliable predictions for toxic compounds with other respiratory symptoms, such as pneumonia or rhinitis. Here, based on a diverse data set of mouse intraperitoneal respiratory toxicity characterized by multiple symptoms, a number of quantitative and qualitative predictions models with high reliability were developed by machine learning approaches. First, a four-tier dimension reduction strategy was employed to find an optimal set of 20 molecular descriptors for model building. Then, six machine learning approaches were used to develop the prediction models, including relevance vector machine (RVM), support vector machine (SVM), regularized random forest (RRF), extreme gradient boosting (XGBoost), naïve Bayes (NB), and linear discriminant analysis (LDA). Among all of the models, the SVM regression model shows the most accurate quantitative predictions for the test set (q(2)ext = 0.707), and the XGBoost classification model achieves the most accurate qualitative predictions for the test set (MCC of 0.644, AUC of 0.893, and global accuracy of 82.62%). The application domains were analyzed, and all of the tested compounds fall within the application domain coverage. We also examined the structural features of the compounds and important fragments with large prediction errors. In conclusion, the SVM regression model and the XGBoost classification model can be employed as accurate prediction tools

  12. Influence of the respiratory cycle structure on the flow field in human nasal cavity at a fixed level of breath depth

    Science.gov (United States)

    Bosykh, L. Yu.; Ganimedov, V. L.; Muchnaya, M. I.; Sadovskii, A. S.

    2016-10-01

    The evolution of air flow field in the human nasal cavity has studied during the respiratory cycle. Real tomographic scans of the adult without abnormalities in the upper airway have been used to construct the geometric model. Quiet breathing mode is selected: the duration of the respiratory cycle is 4.3 sec and the depth of breathing is 600 ml, which provides pulmonary ventilation at 8.4 liters of air per minute. The system of Navier - Stokes equations was used to describe the flow. Laminar flow regime was postulated. The Lagrange approach was used for calculation of submicron particles motion. The numerical solution was built on the basis of gas-dynamic solver FLUENT of software package ANSYS 12. Calculations were made for two cases in which the same value of the integral characteristic (the depth of breathing) was reached, but which had different kind of boundary conditions on the exit. In the first case, the velocity was assumed symmetrical with respect to inhalation - exhalation and was approximated by sinusoid. In the second case, the velocity as a function of time is determined by processing of the real person spirogram. For the both variants the flow fields were obtained and compared. Analysis of the results showed that in non-stationary case the use of symmetric boundary condition leads to an underestimation of respiratory effort for the implementation of the required depth of breathing. In cyclic flow the flow fields in acceleration and deceleration phases are, basically, the same as in the corresponding steady flow. At the same time taking into account of non-symmetry of respiratory cycle influences on deposition pattern of particles significantly.

  13. Development of a multiplex RT-PCR for simultaneous diagnosis of human metapneumovirus (HMPV) and human respiratory syncytial virus (HRSV) from clinical specimens.

    Science.gov (United States)

    Dayakar, Seetha; Pillai, Heera R; Thulasi, Vineetha P; Nair, Radhakrishnan R

    2016-12-01

    Human metapneumovirus (HMPV) and human respiratory syncytial virus (HRSV) are ubiquitous respiratory viral pathogens. They belong to the family Paramyxoviridae (subfamily Pneumovirinae) and is responsible for acute respiratory tract infections in children, elderly and immunocompromised patients. We designed and tested a multiplex reverse transcriptase polymerase chain reaction (mRT-PCR) as a cost-effective alternative to real-time PCR and cell culture based detection for HMPV and HRSV. The newly developed PCR was used to screen nasal/throat swab samples from 356 patients with suspected acute respiratory infection attending the Government Medical College, Thiruvananthapuram, Kerala, India. The method was compared with a commercially available kit employing real time PCR, for its sensitivity and specificity. 53 (14.9 %) samples were positive for at least one tested pathogen by mRT-PCR. All except one among the positive samples showed similar pathogen profile when tested using real time PCR. 8 (15.1 %) among these 53 were positive for HRSVA, 33 (62.3 %) positive for HRSVB and 12 (22.6 %) were positive for HMPV. 17 (32.7 %) samples showed co-infections in them. Sensitivity and specificity of the mRT-PCR was comparable to that of the commercial kit. Our findings indicate that this newly developed mRT-PCR can be used as a cost-effective alternative for laboratory diagnosis of HMPV/HRSV infection and will significantly reduce diagnostic costs for these viruses in clinical settings.

  14. Respiratory failure in a mouse model of myotonic dystrophy does not correlate with the CTG repeat length.

    OpenAIRE

    Panaite, P.A.; Kuntzer, T; Gourdon, G; Barakat-Walter, I.

    2013-01-01

    Myotonic dystrophy (DM1) is a multisystemic disease caused by an expansion of CTG repeats in the region of DMPK, the gene encoding DM protein kinase. The severity of muscle disability in DM1 correlates with the size of CTG expansion. As respiratory failure is one of the main causes of death in DM1, we investigated the correlation between respiratory impairment and size of the (CTG)n repeat in DM1 animal models. Using pressure plethysmography the respiratory function was assessed in control an...

  15. In Vivo 3D Analysis of Thoracic Kinematics: Changes in Size and Shape During Breathing and Their Implications for Respiratory Function in Recent Humans and Fossil Hominins.

    Science.gov (United States)

    Bastir, Markus; García-Martínez, Daniel; Torres-Tamayo, Nicole; Sanchis-Gimeno, Juan Alberto; O'Higgins, Paul; Utrilla, Cristina; Torres Sánchez, Isabel; García Río, Francisco

    2017-02-01

    The human ribcage expands and contracts during respiration as a result of the interaction between the morphology of the ribs, the costo-vertebral articulations and respiratory muscles. Variations in these factors are said to produce differences in the kinematics of the upper thorax and the lower thorax, but the extent and nature of any such differences and their functional implications have not yet been quantified. Applying geometric morphometrics we measured 402 three-dimensional (3D) landmarks and semilandmarks of 3D models built from computed tomographic scans of thoraces of 20 healthy adult subjects in maximal forced inspiration (FI) and expiration (FE). We addressed the hypothesis that upper and lower parts of the ribcage differ in kinematics and compared different models of functional compartmentalization. During inspiration the thorax superior to the level of the sixth ribs undergoes antero-posterior expansion that differs significantly from the medio-lateral expansion characteristic of the thorax below this level. This supports previous suggestions for dividing the thorax into a pulmonary and diaphragmatic part. While both compartments differed significantly in mean size and shape during FE and FI the size changes in the lower compartment were significantly larger. Additionally, for the same degree of kinematic shape change, the pulmonary thorax changes less in size than the diaphragmatic thorax. Therefore, variations in the form and function of the diaphragmatic thorax will have a strong impact on respiratory function. This has important implications for interpreting differences in thorax shape in terms of respiratory functional differences within and among recent humans and fossil hominins. Anat Rec, 300:255-264, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  16. Epidemic 2014 enterovirus D68 cross-reacts with human rhinovirus on a respiratory molecular diagnostic platform.

    Directory of Open Access Journals (Sweden)

    Shane C McAllister

    Full Text Available Enterovirus D68 (EV-D68 is an emerging virus known to cause sporadic disease and occasional epidemics of severe lower respiratory tract infection. However, the true prevalence of infection with EV-D68 is unknown, due in part to the lack of a rapid and specific nucleic acid amplification test as well as the infrequency with which respiratory samples are analyzed by enterovirus surveillance programs. During the 2014 EV-D68 epidemic in the United States, we noted an increased frequency of "low-positive" results for human rhinovirus (HRV detected in respiratory tract samples using the GenMark Diagnostics eSensor respiratory viral panel, a multiplex PCR assay able to detect 14 known respiratory viruses but not enteroviruses. We simultaneously noted markedly increased admissions to our Pediatric Intensive Care Unit for severe lower respiratory tract infections in patients both with and without a history of reactive airway disease. Accordingly, we hypothesized that these "low-positive" RVP results were due to EV-D68 rather than rhinovirus infection. Sequencing of the picornavirus 5' untranslated region (5'-UTR of 49 samples positive for HRV by the GenMark RVP revealed that 33 (67.3% were in fact EV-D68. Notably, the mean intensity of the HRV RVP result was significantly lower in the sequence-identified EV-D68 samples (20.3 nA compared to HRV (129.7 nA. Using a cut-off of 40 nA for the differentiation of EV-D68 from HRV resulted in 94% sensitivity and 88% specificity. The robust diagnostic characteristics of our data suggest that the cross-reactivity of EV-D68 and HRV on the GenMark Diagnostics eSensor RVP platform may be an important factor to consider in making accurate molecular diagnosis of EV-D68 at institutions utilizing this system or other molecular respiratory platforms that may also cross-react.

  17. Epidemic 2014 enterovirus D68 cross-reacts with human rhinovirus on a respiratory molecular diagnostic platform.

    Science.gov (United States)

    McAllister, Shane C; Schleiss, Mark R; Arbefeville, Sophie; Steiner, Marie E; Hanson, Ryan S; Pollock, Catherine; Ferrieri, Patricia

    2015-01-01

    Enterovirus D68 (EV-D68) is an emerging virus known to cause sporadic disease and occasional epidemics of severe lower respiratory tract infection. However, the true prevalence of infection with EV-D68 is unknown, due in part to the lack of a rapid and specific nucleic acid amplification test as well as the infrequency with which respiratory samples are analyzed by enterovirus surveillance programs. During the 2014 EV-D68 epidemic in the United States, we noted an increased frequency of "low-positive" results for human rhinovirus (HRV) detected in respiratory tract samples using the GenMark Diagnostics eSensor respiratory viral panel, a multiplex PCR assay able to detect 14 known respiratory viruses but not enteroviruses. We simultaneously noted markedly increased admissions to our Pediatric Intensive Care Unit for severe lower respiratory tract infections in patients both with and without a history of reactive airway disease. Accordingly, we hypothesized that these "low-positive" RVP results were due to EV-D68 rather than rhinovirus infection. Sequencing of the picornavirus 5' untranslated region (5'-UTR) of 49 samples positive for HRV by the GenMark RVP revealed that 33 (67.3%) were in fact EV-D68. Notably, the mean intensity of the HRV RVP result was significantly lower in the sequence-identified EV-D68 samples (20.3 nA) compared to HRV (129.7 nA). Using a cut-off of 40 nA for the differentiation of EV-D68 from HRV resulted in 94% sensitivity and 88% specificity. The robust diagnostic characteristics of our data suggest that the cross-reactivity of EV-D68 and HRV on the GenMark Diagnostics eSensor RVP platform may be an important factor to consider in making accurate molecular diagnosis of EV-D68 at institutions utilizing this system or other molecular respiratory platforms that may also cross-react.

  18. Acute encephalopathy with concurrent respiratory and metabolic disturbances in first known parenteral human administration of flunixin meglumine and acepromazine maleate.

    Science.gov (United States)

    Kamali, Michael F; Wilson, Anwar C; Acquisto, Nicole M; Spillane, Linda; Schneider, Sandra M

    2013-08-01

    Flunexin is a nonsteroidal anti-inflammatory drug approved for veterinary use in horses and cattle. Acepromazine is a phenothiazine derivative used in horses, dogs, and cats. Human exposure to these substances is rare. We report a case of a human injection of two equine medications, flunixin and acepromazine, which resulted in altered mental status, respiratory alkalosis, gastrointestinal bleeding, and elevation of liver transaminases in a 43-year-old woman who worked as a horse trainer. The patient intentionally self-injected these medications and subsequently presented to the Emergency Department with altered mental status and lethargy. The patient required hospitalization for metabolic abnormalities, including respiratory alkalosis, and suffered a gastrointestinal bleed requiring blood transfusion. The patient ultimately recovered with supportive measures. We believe this to be the first case of concomitant injection of flunixin and acepromazine in a human. This report explains a case of parenteral administration of two equine medications and the subsequent complications in a patient that presented to the Emergency Department. Human exposure to veterinary medications cannot be predicted by their effect in animals due to variations in absorption, distribution, and metabolism. Physicians should be aware that individuals who work with animals may have access to large quantities of veterinary medicine. This case also exemplifies the challenges that Emergency Physicians face on a daily basis, and generates additional consideration for overdoses and intoxications from medications that are not considered commonplace in humans. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Demonstration of carboxylesterase in cytology samples of human nasal respiratory epithelium

    Energy Technology Data Exchange (ETDEWEB)

    Rodgers, D.A.; Nikula, K.J.; Avila, K. [and others

    1995-12-01

    The epithelial lining of the nasal airways is a target for responses induced by a variety of toxicant exposures. The high metabolic capacity of this tissue has been suggested to play a role in both protection of the airways through detoxication of certain toxicants, as well as in activation of other compounds to more toxic metabolites. Specifically, nasal carboxylesterase (CE) has been shown to mediate the toxicity of inhaled esters and acrylates by converting them to more toxic acid and alcohol metabolites which can be cytotoxic and/or carcinogenic to the nasal mucosa. Due to difficulties in extrapolating rodent models to human, new paradigms using human cells and tissues are essential to understanding and evaluating the metabolic processes in human nasal epithelium.

  20. High-throughput gene expression analysis in pigs as model for respiratory infections

    DEFF Research Database (Denmark)

    Skovgaard, Kerstin; Brogaard, Louise; Schou, Kirstine Klitgaard

    Animal models are essential in understanding the mechanisms involved in human infectious disease and for the development of effective prevention and treatment strategies. It is increasingly realized that large animal models like the pig are exceptionally human like and serve as an excellent model...... highly controlled experimental infections and to study changes of symptoms, viral titer, and expression of microRNAs/mRNAs as the influenza infection progresses in time, generating information that would be difficult to obtain from human patients....

  1. Association of human leukocyte antigen class II alleles with severe Middle East respiratory syndrome-coronavirus infection.

    Science.gov (United States)

    Hajeer, Ali H; Balkhy, Hanan; Johani, Sameera; Yousef, Mohammed Z; Arabi, Yaseen

    2016-01-01

    Middle East Respiratory Syndrome (MERS) is a disease of the lower respiratory tract and is characterized by high mortality. It is caused by a beta coronavirus (CoV) referred to as MERS-CoV. Majority of MERS-CoV cases have been reported from Saudi Arabia. We investigated the human leukocyte antigen (HLA) Class II alleles in patients with severe MERS who were admitted in our Intensive Care Unit. A total of 23 Saudi patients with severe MERS-CoV infection were typed for HLA class II, results were compared with those of 161 healthy controls. Two HLA class II alleles were associated with the disease; HLA-DRB1*11:01 and DQB1*02:02, but not with the disease outcome. Our results suggest that the HLA-DRB1*11:01 and DQB1*02:02 may be associated with susceptibility to MERS.

  2. The development and validation of a digital peak respiratory pressure monitor and its characteristics in healthy human subjects.

    Science.gov (United States)

    Maruthy, K N; Vaz, M

    1999-04-01

    A digital peak respiratory pressure (DPRP) monitor for determining maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP) was developed using a pressure transducer and an analog to digital converter. It was calibrated using a mercury manometer. Human studies were conducted in healthy young adults in order to determine within-subject and inter-individual variability, as well as diurnal variations and gender differences in maximal respiratory pressures. The calibration studies for the instrument indicated that the instrument recorded accurate pressures, with little temporal drift. Within-subject variability was generally low while inter-individual variability was higher and significant. Gender differences were similar to those recorded in literature for other racial groups. The DPRP monitor described is inexpensive, accurate and portable, making it ideal for use at the patient's bedside.

  3. Dysrhythmias of the respiratory oscillator

    Science.gov (United States)

    Paydarfar, David; Buerkel, Daniel M.

    1995-03-01

    Breathing is regulated by a central neural oscillator that produces rhythmic output to the respiratory muscles. Pathological disturbances in rhythm (dysrhythmias) are observed in the breathing pattern of children and adults with neurological and cardiopulmonary diseases. The mechanisms responsible for genesis of respiratory dysrhythmias are poorly understood. The present studies take a novel approach to this problem. The basic postulate is that the rhythm of the respiratory oscillator can be altered by a variety of stimuli. When the oscillator recovers its rhythm after such perturbations, its phase may be reset relative to the original rhythm. The amount of phase resetting is dependent upon stimulus parameters and the level of respiratory drive. The long-range hypothesis is that respiratory dysrhythmias can be induced by stimuli that impinge upon or arise within the respiratory oscillator with certain combinations of strength and timing relative to the respiratory cycle. Animal studies were performed in anesthetized or decerebrate preparations. Neural respiratory rhythmicity is represented by phrenic nerve activity, allowing use of open-loop experimental conditions which avoid negative chemical feedback associated with changes in ventilation. In animal experiments, respiratory dysrhythmias can be induced by stimuli having specific combinations of strength and timing. Newborn animals readily exhibit spontaneous dysrhythmias which become more prominent at lower respiratory drives. In human subjects, swallowing was studied as a physiological perturbation of respiratory rhythm, causing a pattern of phase resetting that is characterized topologically as type 0. Computational studies of the Bonhoeffer-van der Pol (BvP) equations, whose qualitative behavior is representative of many excitable systems, supports a unified interpretation of these experimental findings. Rhythmicity is observed when the BvP model exhibits recurrent periods of excitation alternating with

  4. Optimal Determination of Respiratory Airflow Patterns Using a Nonlinear Multicompartment Model for a Lung Mechanics System

    Directory of Open Access Journals (Sweden)

    Hancao Li

    2012-01-01

    Full Text Available We develop optimal respiratory airflow patterns using a nonlinear multicompartment model for a lung mechanics system. Specifically, we use classical calculus of variations minimization techniques to derive an optimal airflow pattern for inspiratory and expiratory breathing cycles. The physiological interpretation of the optimality criteria used involves the minimization of work of breathing and lung volume acceleration for the inspiratory phase, and the minimization of the elastic potential energy and rapid airflow rate changes for the expiratory phase. Finally, we numerically integrate the resulting nonlinear two-point boundary value problems to determine the optimal airflow patterns over the inspiratory and expiratory breathing cycles.

  5. Optimal determination of respiratory airflow patterns using a nonlinear multicompartment model for a lung mechanics system.

    Science.gov (United States)

    Li, Hancao; Haddad, Wassim M

    2012-01-01

    We develop optimal respiratory airflow patterns using a nonlinear multicompartment model for a lung mechanics system. Specifically, we use classical calculus of variations minimization techniques to derive an optimal airflow pattern for inspiratory and expiratory breathing cycles. The physiological interpretation of the optimality criteria used involves the minimization of work of breathing and lung volume acceleration for the inspiratory phase, and the minimization of the elastic potential energy and rapid airflow rate changes for the expiratory phase. Finally, we numerically integrate the resulting nonlinear two-point boundary value problems to determine the optimal airflow patterns over the inspiratory and expiratory breathing cycles.

  6. Influences of parameter uncertainties within the ICRP 66 respiratory tract model: particle deposition.

    Science.gov (United States)

    Bolch, W E; Farfán, E B; Huh, C; Huston, T E; Bolch, W E

    2001-10-01

    Risk assessment associated with the inhalation of radioactive aerosols requires as an initial step the determination of particle deposition within the various anatomic regions of the respiratory tract. The model outlined in ICRP Publication 66 represents to date one of the most complete overall descriptions of not only particle deposition, but of particle clearance and local radiation dosimetry of lung tissues. In this study, a systematic review of the deposition component within the ICRP 66 respiratory tract model was conducted in which probability density functions were assigned to all input parameters. These distributions were subsequently incorporated within a computer code LUDUC (LUng Dose Uncertainty Code) in which Latin hypercube sampling techniques are used to generate multiple (e.g., 1,000) sets of input vectors (i.e., trials) for all of the model parameters needed to assess particle deposition within the extrathoracic (anterior and posterior), bronchial, bronchiolar, and alveolar-interstitial regions of the ICRP 66 respiratory tract model. Particle deposition values for the various trial simulations were shown to be well described by lognormal probability distributions. Geometric mean deposition fractions from LUDUC were found to be within approximately +/- 10% of the single-value estimates from the LUDEP computer code for each anatomic region and for particle diameters ranging from 0.001 to 50 microm. In all regions of the respiratory tract, LUDUC simulations for an adult male at light exertion show that uncertainties in particle deposition fractions are distributed only over a range of about a factor of approximately 2-4 for particle sizes between 0.005 to 0.2 microm. Below 0.005 microm, uncertainties increase only for deposition within the alveolar region. At particle sizes exceeding 1 microm, uncertainties in the deposition fraction within the extrathoracic regions are relatively small, but approach a factor of 20 for deposition in the bronchial

  7. 4D-CT motion estimation using deformable image registration and 5D respiratory motion modeling

    OpenAIRE

    2008-01-01

    Four-dimensional computed tomography (4D-CT) imaging technology has been developed for radiation therapy to provide tumor and organ images at the different breathing phases. In this work, a procedure is proposed for estimating and modeling the respiratory motion field from acquired 4D-CT imaging data and predicting tissue motion at the different breathing phases. The 4D-CT image data consist of series of multislice CT volume segments acquired in ciné mode. A modified optical flow deformable i...

  8. Respiratory failure in a mouse model of myotonic dystrophy does not correlate with the CTG repeat length.

    Science.gov (United States)

    Panaite, Petrica-Adrian; Kuntzer, Thierry; Gourdon, Geneviève; Barakat-Walter, Ibtissam

    2013-10-01

    Myotonic dystrophy (DM1) is a multisystemic disease caused by an expansion of CTG repeats in the region of DMPK, the gene encoding DM protein kinase. The severity of muscle disability in DM1 correlates with the size of CTG expansion. As respiratory failure is one of the main causes of death in DM1, we investigated the correlation between respiratory impairment and size of the (CTG)n repeat in DM1 animal models. Using pressure plethysmography the respiratory function was assessed in control and transgenic mice carrying either 600 (DM600) or >1300 CTG repeats (DMSXL). The statistical analysis of respiratory parameters revealed that both DM1 transgenic mice sub-lines show respiratory impairment compared to control mice. In addition, there is no significant difference in breathing functions between the DM600 and DMSXL mice. In conclusion, these results indicate that respiratory impairment is present in both transgenic mice sub-lines, but the severity of respiratory failure is not related to the size of the (CTG)n expansion.

  9. A patient-specific respiratory model of anatomical motion for radiation treatment planning

    CERN Document Server

    Zhang, Qinghui; Hertanto, Agung; Hu, Yu-Chi; Rosenzweig, Kenneth E; Ling, C Clifton; Mageras, Gig S

    2007-01-01

    Modeling of respiratory motion is important for a more accurate understanding and accounting of its effect on dose to cancers in the thorax and abdomen by radiotherapy. We have developed a model of respiration-induced organ motion in the thorax, without the commonly adopted assumption of repeatable breath cycles. The model describes the motion of a volume of interest within the patient, based on a reference 3-dimensional image (at end-expiration), and the diaphragm positions at different time points. The input data are respiration-correlated CT images of patients treated for nonsmall cell lung cancer, consisting of 3D images, including the diaphragm positions, at 10 phases of the respiratory cycle. A deformable image registration algorithm calculates the deformation field that maps each 3D image to the reference 3D image. A principle component analysis is performed to parameterize the 3D deformation field in terms of the diaphragm motion. We show that the first two principal components are adequate to accurat...

  10. Mathematical models of human behavior

    DEFF Research Database (Denmark)

    Møllgaard, Anders Edsberg

    data set, along with work on other behavioral data. The overall goal is to contribute to a quantitative understanding of human behavior using big data and mathematical models. Central to the thesis is the determination of the predictability of different human activities. Upper limits are derived......, thereby implying that interactions between spreading processes are driving forces of attention dynamics. Overall, the thesis contributes to a quantitative understanding of a wide range of different human behaviors by applying mathematical modeling to behavioral data. There can be no doubt......During the last 15 years there has been an explosion in human behavioral data caused by the emergence of cheap electronics and online platforms. This has spawned a whole new research field called computational social science, which has a quantitative approach to the study of human behavior. Most...

  11. 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.

  12. Cardio-respiratory development in bird embryos: new insights from a venerable animal model

    Directory of Open Access Journals (Sweden)

    Warren W. Burggren

    Full Text Available ABSTRACT The avian embryo is a time-honored animal model for understanding vertebrate development. A key area of extensive study using bird embryos centers on developmental phenotypic plasticity of the cardio-respiratory system and how its normal development can be affected by abiotic factors such as temperature and oxygen availability. Through the investigation of the plasticity of development, we gain a better understanding of both the regulation of the developmental process and the embryo's capacity for self-repair. Additionally, experiments with abiotic and biotic stressors during development have helped delineate not just critical windows for avian cardio-respiratory development, but the general characteristics (e.g., timing and dose-dependence of critical windows in all developing vertebrates. Avian embryos are useful in exploring fetal programming, in which early developmental experiences have implications (usually negative later in life. The ability to experimentally manipulate the avian embryo without the interference of maternal behavior or physiology makes it particularly useful in future studies of fetal programming. The bird embryo is also a key participant in studies of transgenerational epigenetics, whether by egg provisioning or effects on the germline that are transmitted to the F1 generation (or beyond. Finally, the avian embryo is heavily exploited in toxicology, in which both toxicological testing of potential consumer products as well as the consequences of exposure to anthropogenic pollutants are routinely carried out in the avian embryo. The avian embryo thus proves useful on numerous experimental fronts as an animal model that is concurrently both of adequate complexity and sufficient simplicity for probing vertebrate cardio-respiratory development.

  13. A natural human hand model

    NARCIS (Netherlands)

    Van Nierop, O.A.; Van der Helm, A.; Overbeeke, K.J.; Djajadiningrat, T.J.P.

    2007-01-01

    We present a skeletal linked model of the human hand that has natural motion. We show how this can be achieved by introducing a new biology-based joint axis that simulates natural joint motion and a set of constraints that reduce an estimated 150 possible motions to twelve. The model is based on obs

  14. Respiratory Tract Lung Geometry and Dosimetry Model for Male Sprague-Dawley Rats

    Energy Technology Data Exchange (ETDEWEB)

    Miller, Frederick J.; Asgharian, Bahman; Schroeter, Jeffry D.; Price, Owen; Corley, Richard A.; Einstein, Daniel R.; Jacob, Rick E.; Cox, Timothy C.; Kabilan, Senthil; Bentley, Timothy

    2015-07-24

    While inhalation toxicological studies of various compounds have been conducted using a number of different strains of rats, mechanistic dosimetry models have only had tracheobronchial (TB) structural data for Long-Evans rats, detailed morphometric data on the alveolar region of Sprague-Dawley rats and limited alveolar data on other strains. Based upon CT imaging data for two male Sprague-Dawley rats, a 15-generation, symmetric typical path model was developed for the TB region. Literature data for the alveolar region of Sprague-Dawley rats were analyzed to develop an eight-generation model, and the two regions were joined to provide a complete lower respiratory tract model for Sprague-Dawley rats. The resulting lung model was used to examine particle deposition in Sprague-Dawley rats and to compare these results with predicted deposition in Long-Evans rats. Relationships of various physiologic variables and lung volumes were either developed in this study or extracted from the literature to provide the necessary input data for examining particle deposition. While the lengths, diameters and branching angles of the TB airways differed between the two Sprague-Dawley rats, the predicted deposition patterns in the three major respiratory tract regions were very similar. Between Sprague-Dawley and Long-Evans rats, significant differences in TB and alveolar predicted deposition fractions were observed over a wide range of particle sizes, with TB deposition fractions being up to 3- to 4-fold greater in Sprague-Dawley rats and alveolar deposition being significantly greater in Long-Evans rats. Thus, strain-specific lung geometry models should be used for particle deposition calculations and interspecies dose comparisons.

  15. Non-typeable Haemophilus influenzae protects human airway epithelial cells from a subsequent respiratory syncytial virus challenge.

    Science.gov (United States)

    Hartwig, Stacey M; Ketterer, Margaret; Apicella, Michael A; Varga, Steven M

    2016-11-01

    Respiratory syncytial virus (RSV) and the common commensal and opportunistic pathogen, non-typeable Haemophilus influenzae (NTHi) both serve as a frequent cause of respiratory infection in children. Although it is well established that some respiratory viruses can increase host susceptibility to secondary bacterial infections, few studies have examined how commensal bacteria could influence a secondary viral response. Here, we examined the impact of NTHi exposure on a subsequent RSV infection of human bronchial epithelial cells (16HBE14o-). Co-culture of 16HBE14o- cells with NTHi resulted in inhibition of viral gene expression following RSV infection. 16HBE14o- cells co-cultured with heat-killed NTHi failed to protect against an RSV infection, indicating that protection requires live bacteria. However, NTHi did not inhibit influenza A virus replication, indicating that NTHi-mediated protection was RSV-specific. Our data demonstrates that prior exposure to a commensal bacterium such as NTHi can elicit protection against a subsequent RSV infection.

  16. Use of sensitive, broad-spectrum molecular assays and human airway epithelium cultures for detection of respiratory pathogens.

    Directory of Open Access Journals (Sweden)

    Krzysztof Pyrc

    Full Text Available Rapid and accurate detection and identification of viruses causing respiratory tract infections is important for patient care and disease control. Despite the fact that several assays are available, identification of an etiological agent is not possible in ~30% of patients suffering from respiratory tract diseases. Therefore, the aim of the current study was to develop a diagnostic set for the detection of respiratory viruses with sensitivity as low as 1-10 copies per reaction. Evaluation of the assay using a training clinical sample set showed that viral nucleic acids were identified in ~76% of cases. To improve assay performance and facilitate the identification of novel species or emerging strains, cultures of fully differentiated human airway epithelium were used to pre-amplify infectious viruses. This additional step resulted in the detection of pathogens in all samples tested. Based on these results it can be hypothesized that the lack of an etiological agent in some clinical samples, both reported previously and observed in the present study, may result not only from the presence of unknown viral species, but also from imperfections in the detection methods used.

  17. Use of Sensitive, Broad-Spectrum Molecular Assays and Human Airway Epithelium Cultures for Detection of Respiratory Pathogens

    Science.gov (United States)

    Wojcik, Krzysztof; Gawron, Katarzyna; Zeglen, Slawomir; Karolak, Wojciech; Wojarski, Jacek; Ochman, Marek; Hubalewska-Mazgaj, Magdalena; Bochenek, Grazyna; Sanak, Marek; Zembala, Marian; Szczeklik, Andrzej; Potempa, Jan

    2012-01-01

    Rapid and accurate detection and identification of viruses causing respiratory tract infections is important for patient care and disease control. Despite the fact that several assays are available, identification of an etiological agent is not possible in ∼30% of patients suffering from respiratory tract diseases. Therefore, the aim of the current study was to develop a diagnostic set for the detection of respiratory viruses with sensitivity as low as 1–10 copies per reaction. Evaluation of the assay using a training clinical sample set showed that viral nucleic acids were identified in ∼76% of cases. To improve assay performance and facilitate the identification of novel species or emerging strains, cultures of fully differentiated human airway epithelium were used to pre-amplify infectious viruses. This additional step resulted in the detection of pathogens in all samples tested. Based on these results it can be hypothesized that the lack of an etiological agent in some clinical samples, both reported previously and observed in the present study, may result not only from the presence of unknown viral species, but also from imperfections in the detection methods used. PMID:22403676

  18. Respiratory Health - Exposure Measurements and Modeling in the Fragrance and Flavour Industry.

    Directory of Open Access Journals (Sweden)

    Eric Angelini

    Full Text Available Although the flavor and fragrance industry is about 150 years old, the use of synthetic materials started more than 100 years ago, and the awareness of the respiratory hazard presented by some flavoring substances emerged only recently. In 2001, the US National Institute of Occupational Safety and Health (NIOSH identified for the first time inhalation exposure to flavoring substances in the workplace as a possible occupational hazard. As a consequence, manufacturers must comply with a variety of workplace safety requirements, and management has to ensure the improvement of health and safety of the employees exposed to hazardous volatile organic compounds. In this sensitive context, MANE opened its facilities to an intensive measuring campaign with the objective to better estimate the real level of hazardous respiratory exposure of workers. In this study, exposure to 27 hazardous volatile substances were measured during several types of handling operations (weighing-mixing, packaging, reconditioning-transferring, 430 measurement results were generated, and were exploited to propose an improved model derived from the well-known ECETOC-TRA model. The quantification of volatile substances in the working atmosphere involved three main steps: adsorption of the chemicals on a solid support, thermal desorption, followed by analysis by gas chromatography-mass spectrometry. Our approach was to examine experimental measures done in various manufacturing workplaces and to define correction factors to reflect more accurately working conditions and habits. Four correction factors were adjusted in the ECETOC-TRA to integrate important exposure variation factors: exposure duration, percentage of the substance in the composition, presence of collective protective equipment and wearing of personal protective equipment. Verification of the validity of the model is based on the comparison of the values obtained after adaptation of the ECETOC-TRA model, according to

  19. Respiratory Health – Exposure Measurements and Modeling in the Fragrance and Flavour Industry

    Science.gov (United States)

    Angelini, Eric; Camerini, Gerard; Diop, Malick; Roche, Patrice; Rodi, Thomas; Schippa, Christine; Thomas, Thierry

    2016-01-01

    Although the flavor and fragrance industry is about 150 years old, the use of synthetic materials started more than 100 years ago, and the awareness of the respiratory hazard presented by some flavoring substances emerged only recently. In 2001, the US National Institute of Occupational Safety and Health (NIOSH) identified for the first time inhalation exposure to flavoring substances in the workplace as a possible occupational hazard. As a consequence, manufacturers must comply with a variety of workplace safety requirements, and management has to ensure the improvement of health and safety of the employees exposed to hazardous volatile organic compounds. In this sensitive context, MANE opened its facilities to an intensive measuring campaign with the objective to better estimate the real level of hazardous respiratory exposure of workers. In this study, exposure to 27 hazardous volatile substances were measured during several types of handling operations (weighing-mixing, packaging, reconditioning-transferring), 430 measurement results were generated, and were exploited to propose an improved model derived from the well-known ECETOC-TRA model. The quantification of volatile substances in the working atmosphere involved three main steps: adsorption of the chemicals on a solid support, thermal desorption, followed by analysis by gas chromatography-mass spectrometry. Our approach was to examine experimental measures done in various manufacturing workplaces and to define correction factors to reflect more accurately working conditions and habits. Four correction factors were adjusted in the ECETOC-TRA to integrate important exposure variation factors: exposure duration, percentage of the substance in the composition, presence of collective protective equipment and wearing of personal protective equipment. Verification of the validity of the model is based on the comparison of the values obtained after adaptation of the ECETOC-TRA model, according to various exposure

  20. Respiratory Health - Exposure Measurements and Modeling in the Fragrance and Flavour Industry.

    Science.gov (United States)

    Angelini, Eric; Camerini, Gerard; Diop, Malick; Roche, Patrice; Rodi, Thomas; Schippa, Christine; Thomas, Thierry

    2016-01-01

    Although the flavor and fragrance industry is about 150 years old, the use of synthetic materials started more than 100 years ago, and the awareness of the respiratory hazard presented by some flavoring substances emerged only recently. In 2001, the US National Institute of Occupational Safety and Health (NIOSH) identified for the first time inhalation exposure to flavoring substances in the workplace as a possible occupational hazard. As a consequence, manufacturers must comply with a variety of workplace safety requirements, and management has to ensure the improvement of health and safety of the employees exposed to hazardous volatile organic compounds. In this sensitive context, MANE opened its facilities to an intensive measuring campaign with the objective to better estimate the real level of hazardous respiratory exposure of workers. In this study, exposure to 27 hazardous volatile substances were measured during several types of handling operations (weighing-mixing, packaging, reconditioning-transferring), 430 measurement results were generated, and were exploited to propose an improved model derived from the well-known ECETOC-TRA model. The quantification of volatile substances in the working atmosphere involved three main steps: adsorption of the chemicals on a solid support, thermal desorption, followed by analysis by gas chromatography-mass spectrometry. Our approach was to examine experimental measures done in various manufacturing workplaces and to define correction factors to reflect more accurately working conditions and habits. Four correction factors were adjusted in the ECETOC-TRA to integrate important exposure variation factors: exposure duration, percentage of the substance in the composition, presence of collective protective equipment and wearing of personal protective equipment. Verification of the validity of the model is based on the comparison of the values obtained after adaptation of the ECETOC-TRA model, according to various exposure

  1. Probiotics in respiratory virus infections.

    Science.gov (United States)

    Lehtoranta, L; Pitkäranta, A; Korpela, R

    2014-08-01

    Viral respiratory infections are the most common diseases in humans. A large range of etiologic agents challenge the development of efficient therapies. Research suggests that probiotics are able to decrease the risk or duration of respiratory infection symptoms. However, the antiviral mechanisms of probiotics are unclear. The purpose of this paper is to review the current knowledge on the effects of probiotics on respiratory virus infections and to provide insights on the possible antiviral mechanisms of probiotics. A PubMed and Scopus database search was performed up to January 2014 using appropriate search terms on probiotic and respiratory virus infections in cell models, in animal models, and in humans, and reviewed for their relevance. Altogether, thirty-three clinical trials were reviewed. The studies varied highly in study design, outcome measures, probiotics, dose, and matrices used. Twenty-eight trials reported that probiotics had beneficial effects in the outcome of respiratory tract infections (RTIs) and five showed no clear benefit. Only eight studies reported investigating viral etiology from the respiratory tract, and one of these reported a significant decrease in viral load. Based on experimental studies, probiotics may exert antiviral effects directly in probiotic-virus interaction or via stimulation of the immune system. Although probiotics seem to be beneficial in respiratory illnesses, the role of probiotics on specific viruses has not been investigated sufficiently. Due to the lack of confirmatory studies and varied data available, more randomized, double-blind, and placebo-controlled trials in different age populations investigating probiotic dose response, comparing probiotic strains/genera, and elucidating the antiviral effect mechanisms are necessary.

  2. Comparisons of calculated respiratory tract deposition of particles based on the NCRP/ITRI model and the new ICRP66 model

    Energy Technology Data Exchange (ETDEWEB)

    Yeh, Hsu-Chi; Phalen, R.F. [Univ. of California, Irvine, CA (United States); Chang, I. [Lovelace Inst., Albuquerque, NM (United States)] [and others

    1995-12-01

    The National Council on Radiation Protection and Measurements (NCRP) in the United States and the International Commission on Radiological Protection (ICRP) have been independently reviewing and revising respiratory tract dosimetry models for inhaled radioactive aerosols. The newly proposed NCRP respiratory tract dosimetry model represents a significant change in philosophy from the old ICRP Task Group model. The proposed NCRP model describes respiratory tract deposition, clearance, and dosimetry for radioactive substances inhaled by workers and the general public and is expected to be published soon. In support of the NCRP proposed model, ITRI staff members have been developing computer software. Although this software is still incomplete, the deposition portion has been completed and can be used to calculate inhaled particle deposition within the respiratory tract for particle sizes as small as radon and radon progeny ({approximately} 1 nm) to particles larger than 100 {mu}m. Recently, ICRP published their new dosimetric model for the respiratory tract, ICRP66. Based on ICRP66, the National Radiological Protection Board of the UK developed PC-based software, LUDEP, for calculating particle deposition and internal doses. The purpose of this report is to compare the calculated respiratory tract deposition of particles using the NCRP/ITRI model and the ICRP66 model, under the same particle size distribution and breathing conditions. In summary, the general trends of the deposition curves for the two models were similar.

  3. A Simulink model for the human circulatory system.

    Science.gov (United States)

    Wabel, P; Leonhardt, S

    1998-01-01

    This paper presents the mathematical simulation of the human circulatory system. The model is based on the former work of Coleman and co-workers and has been redesigned for simulation with the Matlab toolbox "Simulink". It includes the heart and the peripheral circulation, the respiratory system, the kidneys and the major neural and hormonal control mechanisms, which are necessary for maintaining homeostasis. The model contains more than 30 blocks with over 200 physiological variables, which can be accessed and plotted during the simulation.

  4. On the behavior of particles in the human respiratory tract. Ueber das Verhalten von Aerosolteilchen im menschlichen Atemtrakt

    Energy Technology Data Exchange (ETDEWEB)

    Stahlhofen, W.; Scheuch, G. (Gesellschaft fuer Strahlen- und Umweltforschung mbH Muenchen, Neuherberg (Germany, F.R.))

    1989-01-01

    The results of a series of inhalation experiments (nose- as well as mouth-breathing) are the basis for an estimation of particle behavior in the whole human respiratory tract and in certain regions as extrathoracic, tracheobronchial and alveolar region. Particle behavior depends on the breathing parameters and on particle diameter. Additionally the clearance function of the tracheobronchial tract is given. The clearance is shown to be slowed down for particles being smaller than six micrometers. This fact cannot be neglected in case dosis effect relations are calculated. The corresponding consequences are discussed. (orig.).

  5. Mathematical models of human behavior

    DEFF Research Database (Denmark)

    Møllgaard, Anders Edsberg

    During the last 15 years there has been an explosion in human behavioral data caused by the emergence of cheap electronics and online platforms. This has spawned a whole new research field called computational social science, which has a quantitative approach to the study of human behavior. Most...... studies have considered data sets with just one behavioral variable such as email communication. The Social Fabric interdisciplinary research project is an attempt to collect a more complete data set on human behavior by providing 1000 smartphones with pre-installed data collection software to students...... data set, along with work on other behavioral data. The overall goal is to contribute to a quantitative understanding of human behavior using big data and mathematical models. Central to the thesis is the determination of the predictability of different human activities. Upper limits are derived...

  6. Replication of avian, human and swine influenza viruses in porcine respiratory explants and association with sialic acid distribution

    Directory of Open Access Journals (Sweden)

    Nauwynck Hans J

    2010-02-01

    Full Text Available Abstract Background Throughout the history of human influenza pandemics, pigs have been considered the most likely "mixing vessel" for reassortment between human and avian influenza viruses (AIVs. However, the replication efficiencies of influenza viruses from various hosts, as well as the expression of sialic acid (Sia receptor variants in the entire porcine respiratory tract have never been studied in detail. Therefore, we established porcine nasal, tracheal, bronchial and lung explants, which cover the entire porcine respiratory tract with maximal similarity to the in vivo situation. Subsequently, we assessed virus yields of three porcine, two human and six AIVs in these explants. Since our results on virus replication were in disagreement with the previously reported presence of putative avian virus receptors in the trachea, we additionally studied the distribution of sialic acid receptors by means of lectin histochemistry. Human (Siaα2-6Gal and avian virus receptors (Siaα2-3Gal were identified with Sambucus Nigra and Maackia amurensis lectins respectively. Results Compared to swine and human influenza viruses, replication of the AIVs was limited in all cultures but most strikingly in nasal and tracheal explants. Results of virus titrations were confirmed by quantification of infected cells using immunohistochemistry. By lectin histochemistry we found moderate to abundant expression of the human-like virus receptors in all explant systems but minimal binding of the lectins that identify avian-like receptors, especially in the nasal, tracheal and bronchial epithelium. Conclusions The species barrier that restricts the transmission of influenza viruses from one host to another remains preserved in our porcine respiratory explants. Therefore this system offers a valuable alternative to study virus and/or host properties required for adaptation or reassortment of influenza viruses. Our results indicate that, based on the expression of Sia

  7. Evaluation of disease and viral biomarkers as triggers for therapeutic intervention in respiratory mousepox - an animal model of smallpox.

    Science.gov (United States)

    Parker, Scott; Chen, Nanhai G; Foster, Scott; Hartzler, Hollyce; Hembrador, Ed; Hruby, Dennis; Jordan, Robert; Lanier, Randall; Painter, George; Painter, Wesley; Sagartz, John E; Schriewer, Jill; Mark Buller, R

    2012-04-01

    The human population is currently faced with the potential use of natural or recombinant variola and monkeypox viruses as biological weapons. Furthermore, the emergence of human monkeypox in Africa and its expanding environs poses a significant natural threat. Such occurrences would require therapeutic and prophylactic intervention with antivirals to minimize morbidity and mortality of exposed populations. Two orally-bioavailable antivirals are currently in clinical trials; namely CMX001, an ether-lipid analog of cidofovir with activity at the DNA replication stage and ST-246, a novel viral egress inhibitor. Both of these drugs have previously been evaluated in the ectromelia/mousepox system; however, the trigger for intervention was not linked to a disease biomarker or a specific marker of virus replication. In this study we used lethal, intranasal, ectromelia virus infections of C57BL/6 and hairless SKH1 mice to model human disease and evaluate exanthematous rash (rash) as an indicator to initiate antiviral treatment. We show that significant protection can be provided to C57BL/6 mice by CMX001 or ST-246 when therapy is initiated on day 6 post infection or earlier. We also show that significant protection can be provided to SKH1 mice treated with CMX001 at day 3 post infection or earlier, but this is four or more days before detection of rash (ST-246 not tested). Although in this model rash could not be used as a treatment trigger, viral DNA was detected in blood by day 4 post infection and in the oropharyngeal secretions (saliva) by day 2-3 post infection - thus providing robust and specific markers of virus replication for therapy initiation. These findings are discussed in the context of current respiratory challenge animal models in use for the evaluation of poxvirus antivirals. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Flipped classroom model improves graduate student performance in cardiovascular, respiratory, and renal physiology.

    Science.gov (United States)

    Tune, Johnathan D; Sturek, Michael; Basile, David P

    2013-12-01

    The purpose of this study was to assess the effectiveness of a traditional lecture-based curriculum versus a modified "flipped classroom" curriculum of cardiovascular, respiratory, and renal physiology delivered to first-year graduate students. Students in both courses were provided the same notes and recorded lectures. Students in the modified flipped classroom were required to watch the prerecorded lectures before class and then attend class, where they received a quiz or homework covering material in each lecture (valued at 25% of the final grade) followed by a question and answer/problem-solving period. In the traditional curriculum, attending lectures was optional and there were no quizzes. Evaluation of effectiveness and student performance was achieved by having students in both courses take the same multiple-choice exams. Within a comparable group of graduate students, participants in the flipped course scored significantly higher (P ≤ 0.05) on the cardiovascular, respiratory, and weighted cumulative sections by an average of >12 percentage points. Exam averages for students in the flipped course also tended to be higher on the renal section by ∼11 percentage points (P = 0.06). Based on our experience and responses obtained in blinded student surveys, we propose that the use of homework and in-class quizzes were critical motivating factors that likely contributed to the increase in student exam performance. Taken together, our findings support that the flipped classroom model is a highly effective means in which to disseminate key physiological concepts to graduate students.

  9. Mouse Models of Acute Respiratory Distress Syndrome: A Review of Analytical Approaches, Pathologic Features, and Common Measurements.

    Science.gov (United States)

    Aeffner, Famke; Bolon, Brad; Davis, Ian C

    2015-12-01

    Acute respiratory distress syndrome (ARDS) is a severe pulmonary reaction requiring hospitalization, which is incited by many causes, including bacterial and viral pneumonia as well as near drowning, aspiration of gastric contents, pancreatitis, intravenous drug use, and abdominal trauma. In humans, ARDS is very well defined by a list of clinical parameters. However, until recently no consensus was available regarding the criteria of ARDS that should be evident in an experimental animal model. This lack was rectified by a 2011 workshop report by the American Thoracic Society, which defined the main features proposed to delineate the presence of ARDS in laboratory animals. These should include histological changes in parenchymal tissue, altered integrity of the alveolar capillary barrier, inflammation, and abnormal pulmonary function. Murine ARDS models typically are defined by such features as pulmonary edema and leukocyte infiltration in cytological preparations of bronchoalveolar lavage fluid and/or lung sections. Common pathophysiological indicators of ARDS in mice include impaired pulmonary gas exchange and histological evidence of inflammatory infiltrates into the lung. Thus, morphological endpoints remain a vital component of data sets assembled from animal ARDS models.

  10. Haemophilus haemolyticus: A Human Respiratory Tract Commensal to Be Distinguished from Haemophilus influenzae

    DEFF Research Database (Denmark)

    Murphy, T.F.; Brauer, A.L.; Sethi, S.

    2007-01-01

    Background. Haemophilus influenzae is a common pathogen in adults with chronic obstructive pulmonary disease (COPD). In a prospective study, selected isolates of apparent H. influenzae had an altered phenotype. We tested the hypothesis that these variant strains were genetically different from ty...... distinguish H. haemolyticus from H. influenzae. H. haemolyticus is a respiratory tract commensal. The recognition that some strains of apparent H. influenzae are H. haemolyticus substantially strengthens the association of true H. influenzae with clinical infection....

  11. Induction, duration, and resolution of airway goblet cell hyperplasia in a murine model of atopic asthma: effect of concurrent infection with respiratory syncytial virus and response to dexamethasone.

    Science.gov (United States)

    Blyth, D I; Pedrick, M S; Savage, T J; Bright, H; Beesley, J E; Sanjar, S

    1998-07-01

    We recently described a murine model of atopic asthma in which a marked, extensive hyperplasia of airway goblet cells is induced by repeated challenge of ovalbumin (OA)-sensitized mice with intratracheally administered allergen (Am. J. Respir. Cell Mol. Biol. 1996;14:425-438). We report here the time course of the duration of this feature and of its spontaneous resolution in the absence of further allergen exposure. Induction of severe neutrophilic inflammation in the airways by repeated intratracheal administration of lipopolysaccharide failed to induce goblet cell hyperplasia (GCH) to as great a degree as that induced by allergen, suggesting that nonallergic inflammation is a relatively poor inducer of this phenotype change in mice. When a "subclinical" infection of the lungs with the human A2 strain of respiratory syncytial virus was superimposed on the model of atopic asthma, recruitment of monocytes and lymphocytes to the airways was enhanced and a discharge of goblet cell mucin contents was observed. This may partly explain the respiratory difficulty that typifies virally induced exacerbations of asthma in humans. Daily systemic treatment of sensitized mice with dexamethasone during the period of allergen challenge produced a dose-related suppression of developing GCH, while similar treatment during the period following the establishment of extensive hyperplasia induced an accelerated resolution toward a normal epithelial phenotype. These results confirm and extend the relevance of this model as a representation of the human disease.

  12. Association of respiratory complications and elevated serum immunoglobulins with drinking water arsenic toxicity in human.

    Science.gov (United States)

    Islam, Laila N; Nabi, A H M Nurun; Rahman, M Mahfuzur; Zahid, M Shamim H

    2007-10-01

    We assessed the relationship between chronic arsenic exposure through drinking water with respiratory complications and humoral immune response by measuring serum immunoglobulin profiles in the affected subjects (arsenicosis patients) living in the arsenic endemic rural villages of Bangladesh. The duration of exposure was determined through detailed history of the patients (n=125) and the levels of arsenic in the drinking water and urine samples were determined. The mean duration of exposure in the patients was 7.4+/-5.3 y, and the levels of arsenic in the drinking water and urine samples were 216+/-211 and 223+/-302 micro g/L, respectively, compared to 11+/-20 and 29+/-19 microg/L, respectively, in the unexposed subjects. There was high prevalence of respiratory complications like breathing problems including chest sound, asthma, bronchitis and cough associated with drinking water arsenic toxicity. Arsenicosis patients had significantly elevated levels of IgG (Pdiseases, rather it could be due to direct effects of arsenic. We found significant linear relationships between the levels of serum IgE and inorganic phosphorus (Pcaused respiratory complications, induced changes in the humoral as well as mucosal immune responses.

  13. Respiratory acidosis prolongs, while alkalosis shortens, the duration and recovery time of vecuronium in humans.

    Science.gov (United States)

    Yamauchi, Masanori; Takahashi, Hiromi; Iwasaki, Hiroshi; Namiki, Akiyoshi

    2002-03-01

    To determine the effects of respiratory acidosis and alkalosis by mechanical ventilation on the onset, duration, and recovery times of vecuronium. Randomized, prospective study. Operating rooms in the Sapporo Medical University Hospital and Kitami Red Cross Hospital. 90 ASA physical status I and II patients undergoing lower abdominal surgery. Patients were randomly allocated to one of three groups by arterial carbon dioxide tension level (PaCO2; mmHg) after induction: hyperventilation group (PaCO2 = 25-35), normoventilation group (PaCO2 = 35-45), and hypoventilation group (PaCO2 = 45-55). Anesthesia was maintained by spinal block with inhalation of 50% to 66% nitrous oxide in oxygen and intermittent intravenous administration of fentanyl and midazolam with tracheal intubation. After vecuronium 0.08 mg/kg was given, onset, duration, and recovery time were measured by mechanomyography (Biometer Myograph 2,000, Odense, Denmark). There were significant differences in the duration and recovery time of vecuronium among the normoventilation group (12.7 +/- 3.3 min and 11.8 +/- 2.8 min, respectively), the hyperventilation group (10.6 +/- 3.5 min and 9.2 +/- 2.7 min, respectively; p respiratory acidosis and shortened in respiratory alkalosis.

  14. Respiratory acidosis

    Science.gov (United States)

    Ventilatory failure; Respiratory failure; Acidosis - respiratory ... Causes of respiratory acidosis include: Diseases of the airways (such as asthma and COPD ) Diseases of the lung tissue (such as pulmonary fibrosis , ...

  15. A biophysical model of the mitochondrial respiratory system and oxidative phosphorylation.

    Directory of Open Access Journals (Sweden)

    Daniel A Beard

    2005-09-01

    Full Text Available A computational model for the mitochondrial respiratory chain that appropriately balances mass, charge, and free energy transduction is introduced and analyzed based on a previously published set of data measured on isolated cardiac mitochondria. The basic components included in the model are the reactions at complexes I, III, and IV of the electron transport system, ATP synthesis at F1F0 ATPase, substrate transporters including adenine nucleotide translocase and the phosphate-hydrogen co-transporter, and cation fluxes across the inner membrane including fluxes through the K+/H+ antiporter and passive H+ and K+ permeation. Estimation of 16 adjustable parameter values is based on fitting model simulations to nine independent data curves. The identified model is further validated by comparison to additional datasets measured from mitochondria isolated from rat heart and liver and observed at low oxygen concentration. To obtain reasonable fits to the available data, it is necessary to incorporate inorganic-phosphate-dependent activation of the dehydrogenase activity and the electron transport system. Specifically, it is shown that a model incorporating phosphate-dependent activation of complex III is able to reasonably reproduce the observed data. The resulting validated and verified model provides a foundation for building larger and more complex systems models and investigating complex physiological and pathophysiological interactions in cardiac energetics.

  16. A Biophysical Model of the Mitochondrial Respiratory System and Oxidative Phosphorylation.

    Directory of Open Access Journals (Sweden)

    2005-09-01

    Full Text Available A computational model for the mitochondrial respiratory chain that appropriately balances mass, charge, and free energy transduction is introduced and analyzed based on a previously published set of data measured on isolated cardiac mitochondria. The basic components included in the model are the reactions at complexes I, III, and IV of the electron transport system, ATP synthesis at F(1F(0 ATPase, substrate transporters including adenine nucleotide translocase and the phosphate-hydrogen co-transporter, and cation fluxes across the inner membrane including fluxes through the K/H antiporter and passive H and K permeation. Estimation of 16 adjustable parameter values is based on fitting model simulations to nine independent data curves. The identified model is further validated by comparison to additional datasets measured from mitochondria isolated from rat heart and liver and observed at low oxygen concentration. To obtain reasonable fits to the available data, it is necessary to incorporate inorganic-phosphate-dependent activation of the dehydrogenase activity and the electron transport system. Specifically, it is shown that a model incorporating phosphate-dependent activation of complex III is able to reasonably reproduce the observed data. The resulting validated and verified model provides a foundation for building larger and more complex systems models and investigating complex physiological and pathophysiological interactions in cardiac energetics.

  17. Respiratory syncytial virus inhibits ciliagenesis in differentiated normal human bronchial epithelial cells: effectiveness of N-acetylcysteine.

    Science.gov (United States)

    Mata, Manuel; Sarrion, Irene; Armengot, Miguel; Carda, Carmen; Martinez, Isidoro; Melero, Jose A; Cortijo, Julio

    2012-01-01

    Persistent respiratory syncytial virus (RSV) infections have been associated with the exacerbation of chronic inflammatory diseases, including chronic obstructive pulmonary disease (COPD). This virus infects the respiratory epithelium, leading to chronic inflammation, and induces the release of mucins and the loss of cilia activity, two factors that determine mucus clearance and the increase in sputum volume. These alterations involve reactive oxygen species-dependent mechanisms. The antioxidant N-acetylcysteine (NAC) has proven useful in the management of COPD, reducing symptoms, exacerbations, and accelerated lung function decline. NAC inhibits RSV infection and mucin release in human A549 cells. The main objective of this study was to analyze the effects of NAC in modulating ciliary activity, ciliagenesis, and metaplasia in primary normal human bronchial epithelial cell (NHBEC) cultures infected with RSV. Our results indicated that RSV induced ultrastructural abnormalities in axonemal basal bodies and decreased the expression of β-tubulin as well as two genes involved in ciliagenesis, FOXJ1 and DNAI2. These alterations led to a decrease in ciliary activity. Furthermore, RSV induced metaplastic changes to the epithelium and increased the number of goblet cells and the expression of MUC5AC and GOB5. NAC restored the normal functions of the epithelium, inhibiting ICAM1 expression, subsequent RSV infection through mechanisms involving nuclear receptor factor 2, and the expression of heme oxygenase 1, which correlated with the restoration of the antioxidant capacity, the intracellular H(2)O(2) levels and glutathione content of NHBECs. The results presented in this study support the therapeutic use of NAC for the management of chronic respiratory diseases, including COPD.

  18. Isolation of human β-defensin-4 in lung tissue and its increase in lower respiratory tract infection

    Directory of Open Access Journals (Sweden)

    Mukae Hiroshi

    2005-11-01

    Full Text Available Abstract Background Human β-defensin-4 (hBD-4, a new member of the β-defensin family, was discovered by an analysis of the genomic sequence. The objective of this study was to clarify hBD-4 expression in human lung tissue, along with the inducible expression in response to infectious stimuli, localization, and antimicrobial activities of hBD-4 peptides. We also investigated the participation of hBD-4 in chronic lower respiratory tract infections (LRTI by measuring the concentrations of hBD-4 peptides in human bronchial epithelial lining fluid (ELF. Methods The antimicrobial activity of synthetic hBD-4 peptides against E. coli and P. aeruginosa was measured by radial diffusion and colony count assays. We identified hBD-4 in homogenated human lung tissue by reverse-phase high-performance liquid chromatography coupled with a radioimmunoassay (RIA. Localization of hBD-4 was studied through immunohistochemical analysis (IHC. We investigated the effects of lipopolysaccharide (LPS on hBD-4 expression and its release from small airway epithelial cells (SAEC. We collected ELF from patients with chronic LRTI using bronchoscopic microsampling to measure hBD-4 concentrations by RIA. Results hBD-4 exhibited salt-sensitive antimicrobial activity against P. aeruginosa. We detected the presence of hBD-4 peptides in human lung tissue. IHC demonstrated the localization of hBD-4-producing cells in bronchial and bronchiolar epithelium. The levels of hBD-4 peptides released from LPS-treated SAECs were higher than those of untreated control cells. ELF hBD-4 was detectable in 4 of 6 patients with chronic LRTI, while the amounts in controls were all below the detectable level. Conclusion This study suggested that hBD-4 plays a significant role in the innate immunity of the lower respiratory tract.

  19. Low CCR7-mediated migration of human monocyte derived dendritic cells in response to human respiratory syncytial virus and human metapneumovirus.

    Directory of Open Access Journals (Sweden)

    Cyril Le Nouën

    2011-06-01

    Full Text Available Human respiratory syncytial virus (HRSV and, to a lesser extent, human metapneumovirus (HMPV and human parainfluenza virus type 3 (HPIV3, can re-infect symptomatically throughout life without significant antigenic change, suggestive of incomplete or short-lived immunity. In contrast, re-infection by influenza A virus (IAV largely depends on antigenic change, suggestive of more complete immunity. Antigen presentation by dendritic cells (DC is critical in initiating the adaptive immune response. Antigen uptake by DC induces maturational changes that include decreased expression of the chemokine receptors CCR1, CCR2, and CCR5 that maintain DC residence in peripheral tissues, and increased expression of CCR7 that mediates the migration of antigen-bearing DC to lymphatic tissue. We stimulated human monocyte-derived DC (MDDC with virus and found that, in contrast to HPIV3 and IAV, HMPV and HRSV did not efficiently decrease CCR1, 2, and 5 expression, and did not efficiently increase CCR7 expression. Consistent with the differences in CCR7 mRNA and protein expression, MDDC stimulated with HRSV or HMPV migrated less efficiently to the CCR7 ligand CCL19 than did IAV-stimulated MDDC. Using GFP-expressing recombinant virus, we showed that the subpopulation of MDDC that was robustly infected with HRSV was particularly inefficient in chemokine receptor modulation. HMPV- or HRSV-stimulated MDDC responded to secondary stimulation with bacterial lipopolysaccharide or with a cocktail of proinflammatory cytokines by increasing CCR7 and decreasing CCR1, 2 and 5 expression, and by more efficient migration to CCL19, suggesting that HMPV and HRSV suboptimally stimulate rather than irreversibly inhibit MDDC migration. This also suggests that the low concentration of proinflammatory cytokines released from HRSV- and HMPV-stimulated MDDC is partly responsible for the low CCR7-mediated migration. We propose that inefficient migration of HRSV- and HMPV-stimulated DC to

  20. Correlation of Klebsiella pneumoniae comparative genetic analyses with virulence profiles in a murine respiratory disease model.

    Directory of Open Access Journals (Sweden)

    Ramy A Fodah

    Full Text Available Klebsiella pneumoniae is a bacterial pathogen of worldwide importance and a significant contributor to multiple disease presentations associated with both nosocomial and community acquired disease. ATCC 43816 is a well-studied K. pneumoniae strain which is capable of causing an acute respiratory disease in surrogate animal models. In this study, we performed sequencing of the ATCC 43816 genome to support future efforts characterizing genetic elements required for disease. Furthermore, we performed comparative genetic analyses to the previously sequenced genomes from NTUH-K2044 and MGH 78578 to gain an understanding of the conservation of known virulence determinants amongst the three strains. We found that ATCC 43816 and NTUH-K2044 both possess the known virulence determinant for yersiniabactin, as well as a Type 4 secretion system (T4SS, CRISPR system, and an acetonin catabolism locus, all absent from MGH 78578. While both NTUH-K2044 and MGH 78578 are clinical isolates, little is known about the disease potential of these strains in cell culture and animal models. Thus, we also performed functional analyses in the murine macrophage cell lines RAW264.7 and J774A.1 and found that MGH 78578 (K52 serotype was internalized at higher levels than ATCC 43816 (K2 and NTUH-K2044 (K1, consistent with previous characterization of the antiphagocytic properties of K1 and K2 serotype capsules. We also examined the three K. pneumoniae strains in a novel BALB/c respiratory disease model and found that ATCC 43816 and NTUH-K2044 are highly virulent (LD50<100 CFU while MGH 78578 is relatively avirulent.

  1. Model-based setting of inspiratory pressure and respiratory rate in pressure-controlled ventilation.

    Science.gov (United States)

    Schranz, C; Becher, T; Schädler, D; Weiler, N; Möller, K

    2014-03-01

    Mechanical ventilation carries the risk of ventilator-induced-lung-injury (VILI). To minimize the risk of VILI, ventilator settings should be adapted to the individual patient properties. Mathematical models of respiratory mechanics are able to capture the individual physiological condition and can be used to derive personalized ventilator settings. This paper presents model-based calculations of inspiration pressure (pI), inspiration and expiration time (tI, tE) in pressure-controlled ventilation (PCV) and a retrospective evaluation of its results in a group of mechanically ventilated patients. Incorporating the identified first order model of respiratory mechanics in the basic equation of alveolar ventilation yielded a nonlinear relation between ventilation parameters during PCV. Given this patient-specific relation, optimized settings in terms of minimal pI and adequate tE can be obtained. We then retrospectively analyzed data from 16 ICU patients with mixed pathologies, whose ventilation had been previously optimized by ICU physicians with the goal of minimization of inspiration pressure, and compared the algorithm's 'optimized' settings to the settings that had been chosen by the physicians. The presented algorithm visualizes the patient-specific relations between inspiration pressure and inspiration time. The algorithm's calculated results highly correlate to the physician's ventilation settings with r = 0.975 for the inspiration pressure, and r = 0.902 for the inspiration time. The nonlinear patient-specific relations of ventilation parameters become transparent and support the determination of individualized ventilator settings according to therapeutic goals. Thus, the algorithm is feasible for a variety of ventilated ICU patients and has the potential of improving lung-protective ventilation by minimizing inspiratory pressures and by helping to avoid the build-up of clinically significant intrinsic positive end-expiratory pressure.

  2. Online model checking for monitoring surrogate-based respiratory motion tracking in radiation therapy.

    Science.gov (United States)

    Antoni, Sven-Thomas; Rinast, Jonas; Ma, Xintao; Schupp, Sibylle; Schlaefer, Alexander

    2016-11-01

    Correlation between internal and external motion is critical for respiratory motion compensation in radiosurgery. Artifacts like coughing, sneezing or yawning or changes in the breathing pattern can lead to misalignment between beam and tumor and need to be detected to interrupt the treatment. We propose online model checking (OMC), a model-based verification approach from the field of formal methods, to verify that the breathing motion is regular and the correlation holds. We demonstrate that OMC may be more suitable for artifact detection than the prediction error. We established a sinusoidal model to apply OMC to the verification of respiratory motion. The method was parameterized to detect deviations from typical breathing motion. We analyzed the performance on synthetic data and on clinical episodes showing large correlation error. In comparison, we considered the prediction error of different state-of-the-art methods based on least mean squares (LMS; normalized LMS, nLMS; wavelet-based multiscale autoregression, wLMS), recursive least squares (RLSpred) and support vector regression (SVRpred). On synthetic data, OMC outperformed wLMS by at least 30 % and SVRpred by at least 141 %, detecting 70 % of transitions. No artifacts were detected by nLMS and RLSpred. On patient data, OMC detected 23-49 % of the episodes correctly, outperforming nLMS, wLMS, RLSpred and SVRpred by up to 544, 491, 408 and 258 %, respectively. On selected episodes, OMC detected up to 94 % of all events. OMC is able to detect changes in breathing as well as artifacts which previously would have gone undetected, outperforming prediction error-based detection. Synthetic data analysis supports the assumption that prediction is very insensitive to specific changes in breathing. We suggest using OMC as an additional safety measure ensuring reliable and fast stopping of irradiation.

  3. Respiratory mechanics during high-frequency oscillatory ventilation: a physical model and preterm infant study.

    Science.gov (United States)

    Singh, Rachana; Courtney, Sherry E; Weisner, Michael D; Habib, Robert H

    2012-04-01

    Accurate mechanics measurements during high-frequency oscillatory ventilation (HFOV) facilitate optimizing ventilator support settings. Yet, these are influenced substantially by endotracheal tube (ETT) contributions, which may dominate when leaks around uncuffed ETT are present. We hypothesized that 1) the effective removal of ETT leaks may be confirmed via direct comparison of measured vs. model-predicted mean intratracheal pressure [mPtr (meas) vs. mPtr (pred)], and 2) reproducible respiratory system resistance (Rrs) and compliance (Crs) may be derived from no-leak oscillatory Ptr and proximal flow. With the use of ETT test-lung models, proximal airway opening (Pao) and distal (Ptr) pressures and flows were measured during slow-cuff inflations until leaks are removed. These were repeated for combinations of HFOV settings [frequency, mean airway pressure (Paw), oscillation amplitudes (ΔP), and inspiratory time (%t(I))] and varying test-lung Crs. Results showed that leaks around the ETT will 1) systematically reduce the effective distending pressures and lung-delivered oscillatory volumes, and 2) derived mechanical properties are increasingly nonphysiologic as leaks worsen. Mean pressures were systematically reduced along the ventilator circuit and ETT (Paw > Pao > Ptr), even for no-leak conditions. ETT size-specific regression models were then derived for predicting mPtr based on mean Pao (mPao), ΔP, %t(I), and frequency. Next, in 10 of 11 studied preterm infants (0.77 ± 0.24 kg), no-to-minimal leak was confirmed based on excellent agreement between mPtr (meas) and mPtr (pred), and consequently, their oscillatory respiratory mechanics were evaluated. Infant resistance at the proximal ETT (R(ETT); resistance airway opening = R(ETT) + Rrs; P mechanical properties that can objectively guide ventilatory management of HFOV-treated preterm infants.

  4. 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 P....... aeruginosa in mice and to promote adhesion of P. aeruginosa to human respiratory cells. Findings We tested 50 lung specimens from mink with hemorrhagic pneumonia for bovine RSV by reverse transcriptase polymerase chain reaction (PCR) and for human RSV by a commercial real-time PCR. RSV was not found...

  5. Flexible Bayesian Human Fecundity Models.

    Science.gov (United States)

    Kim, Sungduk; Sundaram, Rajeshwari; Buck Louis, Germaine M; Pyper, Cecilia

    2012-12-01

    Human fecundity is an issue of considerable interest for both epidemiological and clinical audiences, and is dependent upon a couple's biologic capacity for reproduction coupled with behaviors that place a couple at risk for pregnancy. Bayesian hierarchical models have been proposed to better model the conception probabilities by accounting for the acts of intercourse around the day of ovulation, i.e., during the fertile window. These models can be viewed in the framework of a generalized nonlinear model with an exponential link. However, a fixed choice of link function may not always provide the best fit, leading to potentially biased estimates for probability of conception. Motivated by this, we propose a general class of models for fecundity by relaxing the choice of the link function under the generalized nonlinear model framework. We use a sample from the Oxford Conception Study (OCS) to illustrate the utility and fit of this general class of models for estimating human conception. Our findings reinforce the need for attention to be paid to the choice of link function in modeling conception, as it may bias the estimation of conception probabilities. Various properties of the proposed models are examined and a Markov chain Monte Carlo sampling algorithm was developed for implementing the Bayesian computations. The deviance information criterion measure and logarithm of pseudo marginal likelihood are used for guiding the choice of links. The supplemental material section contains technical details of the proof of the theorem stated in the paper, and contains further simulation results and analysis.

  6. 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.

  7. 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.

  8. The Shigella human challenge model.

    Science.gov (United States)

    Porter, C K; Thura, N; Ranallo, R T; Riddle, M S

    2013-02-01

    Shigella is an important bacterial cause of infectious diarrhoea globally. The Shigella human challenge model has been used since 1946 for a variety of objectives including understanding disease pathogenesis, human immune responses and allowing for an early assessment of vaccine efficacy. A systematic review of the literature regarding experimental shigellosis in human subjects was conducted. Summative estimates were calculated by strain and dose. While a total of 19 studies evaluating nine strains at doses ranging from 10 to 1 × 1010 colony-forming units were identified, most studies utilized the S. sonnei strain 53G and the S. flexneri strain 2457T. Inoculum solution and pre-inoculation buffering has varied over time although diarrhoea attack rates do not appear to increase above 75-80%, and dysentery rates remain fairly constant, highlighting the need for additional dose-ranging studies. Expansion of the model to include additional strains from different serotypes will elucidate serotype and strain-specific outcome variability.

  9. Novel avian-origin influenza A (H7N9) virus attaches to epithelium in both upper and lower respiratory tract of humans

    NARCIS (Netherlands)

    D.A.J. van Riel (Debby); L.M.E. Leijten (Lonneke); M.T. de Graaf (Marieke); J.Y. Siegers (Jurre); K.R. Short (Kirsty); M.I. Spronken (Monique); E.J.A. Schrauwen (Eefje); R.A.M. Fouchier (Ron); A.D.M.E. Osterhaus (Albert); T. Kuiken (Thijs)

    2013-01-01

    textabstractInfluenza A viruses from animal reservoirs have the capacity to adapt to humans and cause influenza pandemics. The occurrence of an influenza pandemic requires efficient virus transmission among humans, which is associated with virus attachment to the upper respiratory tract. Pandemic se

  10. Multicomponent aerosol particle deposition in a realistic cast of the human upper respiratory tract.

    Science.gov (United States)

    Nordlund, Markus; Belka, Miloslav; Kuczaj, Arkadiusz K; Lizal, Frantisek; Jedelsky, Jan; Elcner, Jakub; Jicha, Miroslav; Sauser, Youri; Le Bouhellec, Soazig; Cosandey, Stephane; Majeed, Shoaib; Vuillaume, Grégory; Peitsch, Manuel C; Hoeng, Julia

    2017-02-01

    Inhalation of aerosols generated by electronic cigarettes leads to deposition of multiple chemical compounds in the human airways. In this work, an experimental method to determine regional deposition of multicomponent aerosols in an in vitro segmented, realistic human lung geometry was developed and applied to two aerosols, i.e. a monodisperse glycerol aerosol and a multicomponent aerosol. The method comprised the following steps: (1) lung cast model preparation, (2) aerosol generation and exposure, (3) extraction of deposited mass, (4) chemical quantification and (5) data processing. The method showed good agreement with literature data for the deposition efficiency when using a monodisperse glycerol aerosol, with a mass median aerodynamic diameter (MMAD) of 2.3 μm and a constant flow rate of 15 L/min. The highest deposition surface density rate was observed in the bifurcation segments, indicating inertial impaction deposition. The experimental method was also applied to the deposition of a nebulized multicomponent aerosol with a MMAD of 0.50 μm and a constant flow rate of 15 L/min. The deposited amounts of glycerol, propylene glycol and nicotine were quantified. The three analyzed compounds showed similar deposition patterns and fractions as for the monodisperse glycerol aerosol, indicating that the compounds most likely deposited as parts of the same droplets. The developed method can be used to determine regional deposition for multicomponent aerosols, provided that the compounds are of low volatility. The generated data can be used to validate aerosol deposition simulations and to gain insight in deposition of electronic cigarette aerosols in human airways.

  11. Bayesian model averaging method for evaluating associations between air pollution and respiratory mortality: a time-series study

    Science.gov (United States)

    Fang, Xin; Li, Runkui; Kan, Haidong; Bottai, Matteo; Fang, Fang

    2016-01-01

    Objective To demonstrate an application of Bayesian model averaging (BMA) with generalised additive mixed models (GAMM) and provide a novel modelling technique to assess the association between inhalable coarse particles (PM10) and respiratory mortality in time-series studies. Design A time-series study using regional death registry between 2009 and 2010. Setting 8 districts in a large metropolitan area in Northern China. Participants 9559 permanent residents of the 8 districts who died of respiratory diseases between 2009 and 2010. Main outcome measures Per cent increase in daily respiratory mortality rate (MR) per interquartile range (IQR) increase of PM10 concentration and corresponding 95% confidence interval (CI) in single-pollutant and multipollutant (including NOx, CO) models. Results The Bayesian model averaged GAMM (GAMM+BMA) and the optimal GAMM of PM10, multipollutants and principal components (PCs) of multipollutants showed comparable results for the effect of PM10 on daily respiratory MR, that is, one IQR increase in PM10 concentration corresponded to 1.38% vs 1.39%, 1.81% vs 1.83% and 0.87% vs 0.88% increase, respectively, in daily respiratory MR. However, GAMM+BMA gave slightly but noticeable wider CIs for the single-pollutant model (−1.09 to 4.28 vs −1.08 to 3.93) and the PCs-based model (−2.23 to 4.07 vs −2.03 vs 3.88). The CIs of the multiple-pollutant model from two methods are similar, that is, −1.12 to 4.85 versus −1.11 versus 4.83. Conclusions The BMA method may represent a useful tool for modelling uncertainty in time-series studies when evaluating the effect of air pollution on fatal health outcomes. PMID:27531727

  12. Spatio-temporal and stochastic modelling of severe acute respiratory syndrome

    Directory of Open Access Journals (Sweden)

    Poh-Chin Lai

    2013-11-01

    Full Text Available This study describes the development of a spatio-temporal disease model based on the episodes of severe acute respiratory syndrome (SARS that took place in Hong Kong in 2003. In contrast to conventional, deterministic modelling approaches, the model described here is predominantly spatial. It incorporates stochastic processing of environmental and social variables that interact in space and time to affect the patterns of disease transmission in a community. The model was validated through a comparative assessment between actual and modelled distribution of diseased locations. Our study shows that the inclusion of location-specific characteristics satisfactorily replicates the spatial dynamics of an infectious disease. The Pearson’s correlation coefficients for five trials based on 3-day aggregation of disease counts for 1-3, 4-6 and 7-9 day forecasts were 0.57- 0.95, 0.54-0.86 and 0.57-0.82, respectively, while the correlation based on 5-day aggregation for the 1-5 day forecast was 0.55- 0.94 and 0.58-0.81 for the 6-10 day forecast. The significant and strong relationship between actual results and forecast is encouraging for the potential development of an early warning system for detecting this type of disease outbreaks.

  13. MicroRNA Expression Profiling of Human Respiratory Epithelium Affected by Invasive Candida Infection.

    Directory of Open Access Journals (Sweden)

    Syed Aun Muhammad

    Full Text Available Invasive candidiasis is potentially life-threatening systemic fungal infection caused by Candida albicans (C. albicans. Candida enters the blood stream and disseminate throughout the body and it is often observed in hospitalized patients, immunocompromised individuals or those with chronic diseases. This infection is opportunistic and risk starts with the colonization of C. albicans on mucocutaneous surfaces and respiratory epithelium. MicroRNAs (miRNAs are small non-coding RNAs which are involved in the regulation of virtually every cellular process. They regulate and control the levels of mRNA stability and post-transcriptional gene expression. Aberrant expression of miRNAs has been associated in many disease states, and miRNA-based therapies are in progress. In this study, we investigated possible variations of miRNA expression profiles of respiratory epithelial cells infected by invasive Candida species. For this purpose, respiratory epithelial tissues of infected individuals from hospital laboratory were accessed before their treatment. Invasive Candida infection was confirmed by isolation of Candia albicans from the blood cultures of the same infected individuals. The purity of epithelial tissues was assessed by flow cytometry (FACSCalibur cytometer; BD Biosciences, Heidelberg, Germany using statin antibody (S-44. TaqMan quantitative real-time PCR (in a TaqMan Low Density Array format was used for miRNA expression profiling. MiRNAs investigated, the levels of expression of 55 miRNA were significantly altered in infected tissues. Some miRNAs showed dramatic increase (miR-16-1 or decrease of expression (miR-17-3p as compared to control. Gene ontology enrichment analysis of these miRNA-targeted genes suggests that Candidal infection affect many important biological pathways. In summary, disturbance in miRNA expression levels indicated the change in cascade of pathological processes and the regulation of respiratory epithelial functions

  14. Saccharomyces cerevisiae in the respiratory system, digestive system and on the skin in humans

    Directory of Open Access Journals (Sweden)

    Maria Dynowska

    2013-12-01

    Full Text Available The results of observations on the occurrence of S. cerevisiae in the respiratory and digestive systems and on the skin in hospitalised individuals, mostly belonging to so-called risk groups of fungal infections, conducted over a period of five years (1999-2004, are described and discussed. The participation of S. cerevisiae in the mycocoenoses studied was 11.04% of all the recorded fungi. A significant increase in its prevalence, especially on the skin, was noticed. The fungus was mostly isolated with fungi of the genera Candida and Trichosporon, as well as separately in the last two years of the study.

  15. Characterization of the interaction between human respiratory syncytial virus and the cell cycle in continuous cell culture and primary human airway epithelial cells.

    Science.gov (United States)

    Wu, Weining; Munday, Diane C; Howell, Gareth; Platt, Gareth; Barr, John N; Hiscox, Julian A

    2011-10-01

    Viruses can modify conditions inside cells to make them more favorable for replication and progeny virus production. One way of doing this is through manipulation of the cell cycle, a process that describes the ordered growth and division of cells. Analysis of model cell lines, such as A549 cells and primary airway epithelial cells, infected with human respiratory syncytial virus (HRSV) has shown alteration of the cell cycle during infection, although the signaling events were not clearly understood. In this study, targeted transcriptomic analysis of HRSV-infected primary airway epithelial cells revealed alterations in the abundances of many mRNAs encoding cell cycle-regulatory molecules, including decreases in the D-type cyclins and corresponding cyclin-dependent kinases (CDK4 and CDK6 [CDK4/6]). These alterations were reflected in changes in protein abundance and/or relocalization in HRSV-infected cells; taken together, they were predicted to result in G(0)/G(1) phase arrest. In contrast, there was no change in the abundances of D-type cyclins in A549 cells infected with HRSV. However, the abundance of the G(1)/S phase progression inhibitor p21(WAF1/CIP1) was increased over that in mock-treated cells, and this, again, was predicted to result in G(0)/G(1) phase arrest. The G(0)/G(1) phase arrest in both HRSV-infected primary cells and A549 cells was confirmed using dual-label flow cytometry that accurately measured the different stages of the cell cycle. Comparison of progeny virus production in primary and A549 cells enriched in G(0)/G(1) using a specific CDK4/6 kinase inhibitor with asynchronously replicating cells indicated that this phase of the cell cycle was more efficient for virus production.

  16. Characterization of the Interaction between Human Respiratory Syncytial Virus and the Cell Cycle in Continuous Cell Culture and Primary Human Airway Epithelial Cells▿

    Science.gov (United States)

    Wu, Weining; Munday, Diane C.; Howell, Gareth; Platt, Gareth; Barr, John N.; Hiscox, Julian A.

    2011-01-01

    Viruses can modify conditions inside cells to make them more favorable for replication and progeny virus production. One way of doing this is through manipulation of the cell cycle, a process that describes the ordered growth and division of cells. Analysis of model cell lines, such as A549 cells and primary airway epithelial cells, infected with human respiratory syncytial virus (HRSV) has shown alteration of the cell cycle during infection, although the signaling events were not clearly understood. In this study, targeted transcriptomic analysis of HRSV-infected primary airway epithelial cells revealed alterations in the abundances of many mRNAs encoding cell cycle-regulatory molecules, including decreases in the D-type cyclins and corresponding cyclin-dependent kinases (CDK4 and CDK6 [CDK4/6]). These alterations were reflected in changes in protein abundance and/or relocalization in HRSV-infected cells; taken together, they were predicted to result in G0/G1 phase arrest. In contrast, there was no change in the abundances of D-type cyclins in A549 cells infected with HRSV. However, the abundance of the G1/S phase progression inhibitor p21WAF1/CIP1 was increased over that in mock-treated cells, and this, again, was predicted to result in G0/G1 phase arrest. The G0/G1 phase arrest in both HRSV-infected primary cells and A549 cells was confirmed using dual-label flow cytometry that accurately measured the different stages of the cell cycle. Comparison of progeny virus production in primary and A549 cells enriched in G0/G1 using a specific CDK4/6 kinase inhibitor with asynchronously replicating cells indicated that this phase of the cell cycle was more efficient for virus production. PMID:21795354

  17. Solubilization of the O2(-)-forming activity responsible for the respiratory burst in human neutrophils.

    Science.gov (United States)

    Gabig, T G; Kipnes, R S; Babior, B M

    1978-10-10

    On exposure to suitable activating agents, neutrophils sharply alter their oxygen metabolism, showing large increases in oxygen uptake, O2 and H2O2 production, and glucose consumption via the hexose monophosphate shunt. These metabolic alterations, which together are designated the "respiratory burst," are due to the activation of a system which catalyzes the reaction: 2O2 + NADPH leads to 2O2(-) + NADP. This O2(-)-forming system is found in a particulate fraction isolated from neutrophils which had been activated with opsonized zymosan. When these particles were treated with detergent under suitable conditions, the O2(-)-forming activity was released in a form which passed through a membrane filter capable of retaining species of Mr greater than 3000,000. Soluble O2(-)-forming activity was obtained from normal activated neutrophils, but not from normal resting neutrophils or from activated neutrophils obtained from patients with chronic granulomatous disease, an inherited condition in which the respiratory burst is defective. O2(-)production by the soluble system required a reduced pyridine nucleotide as electron donor, and showed a quadratic dependence on the concentration of the solubilized preparation.

  18. Role for membrane fusion in the activation of the respiratory burst in human neutrophils

    Energy Technology Data Exchange (ETDEWEB)

    Manara-Shediac, F.S.

    1986-01-01

    Components of the respiratory burst oxidase reside in intracellular membranes of the tertiary granules in resting cells, yet oxidase activity in the activated cells occurs at the neutrophil surface. The role of degranulation in activation of the neutrophil respiratory burst was therefore investigated. Surface labeling experiments were carried out on resting and activated neutrophils using three impermeant labeling methods. Activated neutrophils labeled with (/sup 35/S) diazobenzene sulfonic acid showed a fourfold higher specific radioactivity than resting neutrophils. Similar results were obtained with the pyridoxal phosphate/borotritide labeling method. On the other hand, little difference in labeling was seen using the periodate/borotritide method which detects the carbohydrate of glycoproteins. These results suggest that either a large amount of protein, or a highly reactive protein becomes exposed upon activation. Resting, activated, and enucleated cells were labeled using the (/sup 125/I) lactoperoxidase method, then subjected to polyacrylamide gel electrophoresis. Autoradiograms of these gels showed that two proteins of about 75 and 45 kD, are labeled at the external surface of enucleated and activated cells but not resting cells.

  19. Effects of wood smoke particles from wood-burning stoves on the respiratory health of atopic humans

    Directory of Open Access Journals (Sweden)

    Riddervold Ingunn

    2012-04-01

    Full Text Available Abstract Background There is growing evidence that particulate air pollution derived from wood stoves causes acute inflammation in the respiratory system, increases the incidence of asthma and other allergic diseases, and increases respiratory morbidity and mortality. The objective of this study was to evaluate acute respiratory effects from short-term wood smoke exposure in humans. Twenty non-smoking atopic volunteers with normal lung function and without bronchial responsiveness were monitored during three different experimental exposure sessions, aiming at particle concentrations of about 200 μg/m3, 400 μg/m3, and clean air as control exposure. A balanced cross-over design was used and participants were randomly allocated to exposure orders. Particles were generated in a wood-burning facility and added to a full-scale climate chamber where the participants were exposed for 3 hours under controlled environmental conditions. Health effects were evaluated in relation to: peak expiratory flow (PEF, forced expiratory volume in the first second (FEV1, and forced vital capacity (FVC. Furthermore, the effects were assessed in relation to changes in nasal patency and from markers of airway inflammation: fractional exhaled nitric oxide (FENO, exhaled breath condensate (EBC and nasal lavage (NAL samples were collected before, and at various intervals after exposure. Results No statistically significant effect of wood smoke exposure was found for lung function, for FENO, for NAL or for the nasal patency. Limited signs of airway inflammation were found in EBC. Conclusion In conclusion, short term exposure with wood smoke at a concentration normally found in a residential area with a high density of burning wood stoves causes only mild inflammatory response.

  20. Microecological succession in respiratory system and human health%呼吸系统微生态演替与人类健康

    Institute of Scientific and Technical Information of China (English)

    侯辰侠; 辛毅; 张翠丽; 曹雪姣; 吴大畅

    2014-01-01

    Microecology of respiratory system is an important part of human microecology.The normal microbiota in respiratory tract are the natural barrier of human organism,which not only play an important role in resisting invade of foreign bacteria,but also involve in local immunological reactions.Normally the species and quantity of microbes in each part of the respiratory tract are relatively stable.Our research on the succession and variation of the normal flora in respiratory tract will provide theoretical basis for understanding the mechanisms of inflammation in respiratory system,and developing novel respiratory probiotics.%呼吸系统微生态是人体微生态重要组成部分.呼吸道正常菌群相当于机体的天然屏障,这些固有的微生物群在抵御外籍菌入侵方面具有重要的作用,同时还发挥着局部免疫功能.正常情况下,呼吸道各部位的微生物种类和数量相对稳定.对呼吸道正常菌群演替次序和变化特征的深入研究是认识呼吸系统炎症本质、开发呼吸道益生菌的理论基础.

  1. Sialic acid receptor detection in the human respiratory tract: evidence for widespread distribution of potential binding sites for human and avian influenza viruses

    Directory of Open Access Journals (Sweden)

    Guan Yi

    2007-10-01

    Full Text Available Abstract Background Influenza virus binds to cell receptors via sialic acid (SA linked glycoproteins. They recognize SA on host cells through their haemagglutinins (H. The distribution of SA on cell surfaces is one determinant of host tropism and understanding its expression on human cells and tissues is important for understanding influenza pathogenesis. The objective of this study therefore was to optimize the detection of α2,3-linked and α2,6-linked SA by lectin histochemistry by investigating the binding of Sambucus nigra agglutinin (SNA for SAα2,6Gal and Maackia amurensis agglutinin (MAA for SAα2,3Gal in the respiratory tract of normal adults and children. Methods We used fluorescent and biotinylated SNA and MAA from different suppliers on archived and prospectively collected biopsy and autopsy specimens from the nasopharynx, trachea, bronchus and lungs of fetuses, infants and adults. We compared different methods of unmasking for tissue sections to determine if these would affect lectin binding. Using serial sections we then compared the lectin binding of MAA from different suppliers. Results We found that unmasking using microwave treatment in citrate buffer produced increased lectin binding to the ciliated and glandular epithelium of the respiratory tract. In addition we found that there were differences in tissue distribution of the α2,3 linked SA when 2 different isoforms of MAA (MAA1 and MAA2 lectin were used. MAA1 had widespread binding throughout the upper and lower respiratory tract and showed more binding to the respiratory epithelium of children than in adults. By comparison, MAA2 binding was mainly restricted to the alveolar epithelial cells of the lung with weak binding to goblet cells. SNA binding was detected in bronchial and alveolar epithelial cells and binding of this lectin was stronger to the paediatric epithelium compared to adult epithelium. Furthermore, the MAA lectins from 2 suppliers (Roche and EY Labs tended

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Dectin-1-Mediated Pathway Contributes to Fusarium proliferatum-Induced CXCL-8 Release from Human Respiratory Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Chang-Ching Yeh

    2017-03-01

    Full Text Available Fusarium species are causative agents of human respiratory disorders and are distributed widely in our environment. Little is known of their interaction with human respiratory epithelial cells, which may contribute to allergic airway responses. In this study, we report on the release of C–X–C motif chemokine ligand 8 (CXCL-8 from human bronchial epithelial BEAS-2B cells upon stimulation with Fusarium proliferatum extracts. F. proliferatum-induced cytokine release from BEAS-2B cells was determined by cytokine array and CXCL-8 enzyme-linked immunosorbent assay (ELISA kits. Blocking antibodies and signaling pathway inhibitors were employed to delineate cell surface receptors and signaling pathways participating in CXCL-8 release. F. proliferatum extracts induced the release of CXCL-8 in a time-dependent manner. The dectin-1 receptor ligands, curdlan and laminarin, reduced CXCL-8 release. Cells pre-treated with anti-Dectin-1 antibodies (2 µg/mL decreased CXCL-8 release by 24%. Furthermore, F. proliferatum-stimulated CXCL-8 release was reduced by 32%, 53%–81%, 40% and 26% after BEAS-2B cells were pretreated with activation inhibitors of spleen tyrosine kinase (Syk—piceatannol—, mitogen-activated protein kinases (MAPKs—PD98059, U0126, SB202190, SP600125—, phosphatidylinositol-3-kinase (PI3K—LY294002—and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB—BAY117082—, respectively. These results suggest that Dectin-1-mediated activation of the Syk, MAPKs, PI3K and NF-κB signaling pathways contributes to F. proliferatum-stimulated CXCL-8 release from BEAS-2B cells and provides an important basis for developing novel therapeutic strategies in clinical allergy.

  4. A MURINE MODEL FOR LOW MOLECULAR WEIGHT CHEMICALS: DIFFERENTIATION OF RESPIRATORY SENSITIZERS (TMA) FROM CONTACT SENSITIZERS (DNFB)

    Science.gov (United States)

    Exposure to low molecular weight (LMW) chemicals contributes to both dermal and respiratory sensitization and is an important occupational health problem. Our goal was to establish an in vivo murine model for hazard identification of LMW chemicals that have the potential to indu...

  5. Isoflurane anesthetic hypersensitivity and progressive respiratory depression in a mouse model with isolated mitochondrial complex I deficiency

    NARCIS (Netherlands)

    Roelofs, S.; Manjeri, G.R.; Willems, P.H.G.M.; Scheffer, G.J.; Smeitink, J.A.M.; Driessen, J.J.

    2014-01-01

    BACKGROUND: Children with mitochondrial disorders are frequently anesthetized for a wide range of operations. These disorders may interfere with the response to surgery and anesthesia. We examined anesthetic sensitivity to and respiratory effects of isoflurane in the Ndufs4 knockout (KO) mouse model

  6. Modeling Associations between Principals’ Reported Indoor Environmental Quality and Students’ Self-Reported Respiratory Health Outcomes Using GLMM and ZIP Models

    Directory of Open Access Journals (Sweden)

    Oluyemi Toyinbo

    2016-03-01

    Full Text Available Background: The aim of this paper was to examine associations between school building characteristics, indoor environmental quality (IEQ, and health responses using questionnaire data from both school principals and students. Methods: From 334 randomly sampled schools, 4248 sixth grade students from 297 schools participated in a questionnaire. From these schools, 134 principals returned questionnaires concerning 51 IEQ related questions of their school. Generalized linear mixed models (GLMM were used to study the associations between IEQ indicators and existence of self-reported upper respiratory symptoms, while hierarchical Zero Inflated Poisson (ZIP—models were used to model the number of symptoms. Results: Significant associations were established between existence of upper respiratory symptoms and unsatisfactory classroom temperature during the heating season (ORs 1.45 for too hot and cold, and 1.27 for too cold as compared to satisfactory temperature and dampness or moisture damage during the year 2006–2007 (OR: 1.80 as compared to no moisture damage, respectively. The number of upper respiratory symptoms was significantly associated with inadequate ventilation and dampness or moisture damage. A higher number of missed school days due to respiratory infections were reported in schools with inadequate ventilation (RR: 1.16. Conclusions: The school level IEQ indicator variables described in this paper could explain a relatively large part of the school level variation observed in the self-reported upper respiratory symptoms and missed school days due to respiratory infections among students.

  7. Detection of human bocavirus from children and adults with acute respiratory tract illness in Guangzhou, southern China

    Directory of Open Access Journals (Sweden)

    Liu Wen-Kuan

    2011-12-01

    Full Text Available Abstract Background Human bocavirus (HBoV is a newly discovered parvovirus associated with acute respiratory tract illness (ARTI and gastrointestinal illness. Our study is the first to analyze the characteristics of HBoV-positive samples from ARTI patients with a wide age distribution from Guangzhou, southern China. Methods Throat swabs (n=2811 were collected and analyzed from children and adults with ARTI over a 13-month period. The HBoV complete genome from a 60 year-old female patient isolate was also determined. Results HBoV DNA was detected in 65/2811 (2.3% samples, of which 61/1797 were from children (Mycoplasma pneumoniae had the highest frequency of 16.9% (11/65. Upper and lower respiratory tract illness were common symptoms, with 19/65 (29.2% patients diagnosed with pneumonia by chest radiography. All four adult patients had systemic influenza-like symptoms. Phylogenetic analysis of the complete genome revealed a close relationship with other HBoVs, and a more distant relationship with HBoV2 and HBoV3. Conclusions HBoV was detected from children and adults with ARTI from Guangzhou, southern China. Elderly people were also susceptive to HBoV. A single lineage of HBoV was detected among a wide age distribution of patients with ARTI.

  8. Source and role of diacylglycerol formed during phagocytosis of opsonized yeast particles and associated respiratory burst in human neutrophils

    Energy Technology Data Exchange (ETDEWEB)

    Della Bianca, V.; Grzeskowiak, M.; Lissandrini, D.; Rossi, F. (Univ. of Verona (Italy))

    1991-06-28

    The results presented in this paper demonstrate that in human neutrophils phagocytosis of C3b/bi and IgG-opsonized yeast particles is associated with activation of phospholipase D and that this reaction is the main source of diglycerides. The demonstration is based upon the following findings: (1) the challenge of neutrophils with these opsonized particles was followed by a rapid formation of (3H)alkyl-phosphatidic acid (( 3H)alkyl-PA) and (3H)alkyl-diglyceride (( 3H)alkyl-DG) in cells labeled with (3H)alkyl-lyso-phosphatidylcholine; (2) in the presence of ethanol (3H)alkyl-phosphatidylethanol was formed, and accumulation of (3H)alkyl-PA and (3H)alkyl-DG was depressed; (3) propranolol, by inhibiting the dephosphorylation of (3H)alkyl-PA, completely inhibited the accumulation of (3H)alkyl-DG and depressed by about 75% the formation of diglyceride mass. Evidence is also presented that phagocytosis of C3b/bi and IgG-opsonized yeast particles and associated respiratory burst can take place independently of diglyceride formation and of the activity of this second messenger on protein kinase C. In fact: (a) propranolol while completely inhibited the formation of diglyceride mass did not modify either the phagocytosis or respiratory burst; (b) these two processes were insensitive to staurosporine.

  9. Genotyping of human rhinovirus in adult patients with acute respiratory infections identified predominant infections of genotype A21

    Science.gov (United States)

    Ren, Lili; Yang, Donghong; Ren, Xianwen; Li, Mingkun; Mu, Xinlin; Wang, Qi; Cao, Jie; Hu, Ke; Yan, Chunliang; Fan, Hongwei; Li, Xiangxin; Chen, Yusheng; Wang, Ruiqin; An, Fucheng; An, Shuchang; Luo, Ming; Wang, Ying; Xiao, Yan; Xiang, Zichun; Xiao, Yan; Li, Li; Huang, Fang; Jin, Qi; Gao, Zhancheng; Wang, Jianwei

    2017-01-01

    Human rhinovirus (HRV) is an important causative agent of acute respiratory tract infections (ARTIs). The roles of specific HRV genotypes in patients suffering from ARTIs have not been well established. We recruited 147 adult inpatients with community-acquired pneumonia (CAP) and 291 adult outpatients with upper ARTIs (URTIs). Respiratory pathogens were screened via PCR assays. HRV was detected in 42 patients, with 35 species A, five B and two C. Seventeen genotypes were identified, and HRV-A21 ranked the highest (9/42, 21.4%). The HRV-A21-positive infections were detected in four patients with CAP and in five with URTIs, all without co-infections. The HRV-A21 genome sequenced in this study contained 12 novel coding polymorphisms in viral protein (VP) 1, VP2 EF loop, VP3 knob and 3D regions. The infections of HRV-A21 virus obtained in this study could not be neutralized by antiserum of HRV-A21 prototype strain (VR-1131), indicating remarkable antigenic variation. Metagenomic analysis showed the HRV-A21 reads were dominant in bronchoalveolar lavage fluid of the three HRV-A21-positive patients with severe CAP, in which two dead. Our results highlight an unexpected infection of genotype HRV-A21 in the clinic, indicating the necessity of precise genotyping and surveillance of HRVs to improve the clinical management of ARTIs. PMID:28128353

  10. Induced respiratory system modeling by high frequency chest compression using lumped system identification method.

    Science.gov (United States)

    Lee, Jongwon; Lee, Yong Wan; O'Clock, George; Zhu, Xiaoming; Parhi, Keshab K; Warwick, Warren J

    2009-01-01

    High frequency chest compression (HFCC) treatment systems are used to promote mucus transport and mitigate pulmonary system clearance problems to remove sputum from the airways in patients with Cystic Fibrosis (CF) and at risk of developing chronic obstructive pulmonary disease (COPD). Every HFCC system consists of a pump generator, one or two hoses connected to a vest, to deliver the pulsation. There are three different waveforms in use; symmetric sine, the asymmetric sine and the trapezoid waveforms. There have been few studies that compared the efficacy of a sine waveform with the HFCC pulsations. In this study we present a model of the respiratory system for a young normal subject who is one of co-authors. The input signal is the pressure applied by the vest to chest, at a frequency of 6Hz. Using the system model simulation, the effectiveness of different source waveforms is evaluated and compared by observing the waveform response associated with air flow at the mouth. Also the study demonstrated that the ideal rectangle wave produced the maximum peak air flow, and followed by the trapezoid, triangle and sine waveform. The study suggests that a pulmonary system evaluation or modeling effort for CF patient might be useful as a method to optimize frequency and waveform structure choices for HFCC therapeutic intervention.

  11. Comparison of a priori calibration models for respiratory inductance plethysmography during running.

    Science.gov (United States)

    Leutheuser, Heike; Heyde, Christian; Gollhofer, Albert; Eskofier, Bjoern M

    2014-01-01

    Respiratory inductive plethysmography (RIP) has been introduced as an alternative for measuring ventilation by means of body surface displacement (diameter changes in rib cage and abdomen). Using a posteriori calibration, it has been shown that RIP may provide accurate measurements for ventilatory tidal volume under exercise conditions. Methods for a priori calibration would facilitate the application of RIP. Currently, to the best knowledge of the authors, none of the existing ambulant procedures for RIP calibration can be used a priori for valid subsequent measurements of ventilatory volume under exercise conditions. The purpose of this study is to develop and validate a priori calibration algorithms for ambulant application of RIP data recorded in running exercise. We calculated Volume Motion Coefficients (VMCs) using seven different models on resting data and compared the root mean squared error (RMSE) of each model applied on running data. Least squares approximation (LSQ) without offset of a two-degree-of-freedom model achieved the lowest RMSE value. In this work, we showed that a priori calibration of RIP exercise data is possible using VMCs calculated from 5 min resting phase where RIP and flowmeter measurements were performed simultaneously. The results demonstrate that RIP has the potential for usage in ambulant applications.

  12. Modeling of Human Joint Structures.

    Science.gov (United States)

    1982-09-01

    Radial Lateral " epicondyle Olecranon Radius Ulna Figure 3. Lateral aspect of the right elbow joint. -17- Annular Ligament This strong band encircles... elbow joint, knee joint, human joints, shoulder joint, ankle joint, joint models, hip joint, ligaments. 20. ABSTRACT (Continue on reverse side If...ligaments. -A rather extended discussion of the articulations and anatomical descriptions of the elbow , shoulder, hip, knee and ankle joints are

  13. Effects of human metapneumovirus and respiratory syncytial virus antigen insertion in two 3' proximal genome positions of bovine/human parainfluenza virus type 3 on virus replication and immunogenicity

    NARCIS (Netherlands)

    R.S. Tang (Roderick); J.H. Schickli (Jeanne); M. MacPhail (Mia); F. Fernandes (Fiona); L. Bicha (Leenas); J. Spaete (Joshua); R.A.M. Fouchier (Ron); A.D.M.E. Osterhaus (Albert); R. Spaete (Richard); A.A. Haller (Aurelia)

    2003-01-01

    textabstractA live attenuated bovine parainfluenza virus type 3 (PIV3), harboring the fusion (F) and hemagglutinin-neuraminidase (HN) genes of human PIV3, was used as a virus vector to express surface glycoproteins derived from two human pathogens, human metapneumovirus (hMPV) and respiratory syncyt

  14. Local forearm and whole-body respiratory quotient in humans after an oral glucose load

    DEFF Research Database (Denmark)

    Simonsen, L; Bülow, J; Madsen, J

    1993-01-01

    The effects of an oral glucose load of 75 g on the local forearm and whole-body energy thermogenesis were measured in normal subjects during the 4 h after the glucose intake. Simultaneous assessment of substrate metabolism in the forearm was performed. Energy expenditure (EE) increased after...... the glucose load and had not returned to baseline level at the end of the experiment. Whole-body respiratory quotient (RQ) was, on average, 0.80 (SD 0.05) in the baseline condition and increased to a maximum of 0.91 (0.03) and then decreased to baseline level at the end of the experiment. The local forearm.......17) to 0.63 (0.17) 30 min after the glucose load (P body RQ...

  15. Cellular reactivity to respiratory syncytial virus in human colostrum and breast milk.

    Science.gov (United States)

    Scott, R; Scott, M; Toms, G L

    1985-09-01

    Colostrum and breast-milk samples were taken from 23 mothers between 2 days and 7 weeks postpartum and were examined for the presence of cellular reactivity to respiratory syncytial (RS) virus using a lymphocyte transformation assay. Positive responses were detected in nine of the 23 (39%) samples taken at 2-5 days postpartum, but this reactivity was undetectable at 3 weeks. Positive responses developed in a further three mothers during the 3-7-week period of lactation, suggesting a response to virus infection. Colostral whey was found to suppress the cellular response to RS virus and inhibition was related to the level of specific IgA antibody to RS virus present in the whey. The role of colostral cellular reactivity in protection of breast-fed infants from RS virus bronchiolitis is discussed.

  16. In vivo models of human airway epithelium repair and regeneration

    Directory of Open Access Journals (Sweden)

    C. Coraux

    2005-12-01

    Full Text Available Despite an efficient defence system, the airway surface epithelium, in permanent contact with the external milieu, is frequently injured by inhaled pollutants, microorganisms and viruses. The response of the airway surface epithelium to an acute injury includes a succession of cellular events varying from the loss of the surface epithelium integrity to partial shedding of the epithelium or even to complete denudation of the basement membrane. The epithelium has then to repair and regenerate to restore its functions. The in vivo study of epithelial regeneration in animal models has shown that airway epithelial cells are able to dedifferentiate, spread, migrate over the denuded basement membrane and progressively redifferentiate to reconstitute a functional respiratory epithelium after several weeks. Humanised tracheal xenograft models have been developed in immunodeficient nude and severe combined immunodeficient (SCID mice in order to mimic the natural regeneration process of the human airway epithelium and to analyse the cellular and molecular events involved during the different steps of airway epithelial reconstitution. These models represent very powerful tools for analysing the modulation of the biological functions of the epithelium during its regeneration. They are also very useful for identifying stem/progenitor cells of the human airway epithelium. A better knowledge of the mechanisms involved in airway epithelium regeneration, as well as the characterisation of the epithelial stem and progenitor cells, may pave the way to regenerative therapeutics, allowing the reconstitution of a functional airway epithelium in numerous respiratory diseases, such as asthma, chronic obstructive pulmonary diseases, cystic fibrosis and bronchiolitis.

  17. Novel avian-origin influenza A (H7N9) virus attachment to the respiratory tract of five animal models

    NARCIS (Netherlands)

    J.Y. Siegers (Jurre); K.R. Short (Kirsty); L.M.E. Leijten (Lonneke); M.T. de Graaf (Marieke); M.I. Spronken (Monique); E.J.A. Schrauwen (Eefje); N. Marshall (Nicolle); A.C. Lowen (Anice); G. Gabriel (Gülsah); A.D.M.E. Osterhaus (Albert); T. Kuiken (Thijs); D.A.J. van Riel (Debby)

    2014-01-01

    textabstractWe determined the pattern of attachment of the avian-origin H7N9 influenza viruses A/Anhui/1/2013 and A/Shanghai/1/2013 to the respiratory tract in ferrets, macaques, mice, pigs, and guinea pigs and compared it to that in humans. The H7N9 attachment pattern in macaques, mice, and to a le

  18. Ghrelin ameliorates catabolic conditions and respiratory dysfunction in a chronic obstructive pulmonary disease model of chronic cigarette smoke-exposed rats.

    Science.gov (United States)

    Kamiide, Yoshiyuki; Inomata, Norio; Furuya, Mayumi; Yada, Toshihiko

    2015-05-15

    Cigarette smoking, which is a well-known major risk factor for chronic obstructive pulmonary disease (COPD), causes both pulmonary and extrapulmonary abnormalities. Ghrelin is a gastric peptide that regulates energy homeostasis. In the present study, we investigated the effects of ghrelin on the catabolic changes, respiratory function and emphysema in an animal model of COPD induced by chronic exposure to cigarette smoke. Rats were exposed to cigarette smoke, and they were administered human ghrelin (0.1 or 1 mg/kg, subcutaneous, twice daily) for 12 weeks. Compared with air-exposed rats, body weight gain, food intake, food efficiency, tidal volume, peak expiratory flow rate, and forced expiratory volume at 100 ms were significantly lower, while functional residual capacity, lung capacity, and neutrophils in bronchoalveolar lavage fluid were significantly higher in cigarette smoke-exposed rats. These indicated that the systemic abnormalities associated with COPD developed after the exposure to cigarette smoke. Ghrelin significantly and dose-dependently increased the body weight gain and food efficiency in cigarette smoke-exposed rats. In ghrelin-treated rats, skeletal muscle strength, which tended to be lowered by cigarette smoke exposure, was improved. Ghrelin ameliorated respiratory function and emphysema in a dose-dependent manner, but did not inhibit the increase in neutrophils in the bronchoalveolar lavage fluid. The respiratory functional parameters and lung capacity were significantly correlated with body weight gain. These results suggest that ghrelin inhibited the development of the catabolic changes, respiratory dysfunction, and emphysema that were induced by cigarette smoke exposure in rats, at least in part, through the amelioration of nutritional status. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Peripheral erythrocytes decrease upon specific respiratory challenge with grass pollen allergen in sensitized mice and in human subjects.

    Directory of Open Access Journals (Sweden)

    Galateja Jordakieva

    Full Text Available BACKGROUND AND AIMS: Specific hyper-responsiveness towards an allergen and non-specific airway hyperreactivity both impair quality of life in patients with respiratory allergic diseases. We aimed to investigate cellular responses following specific and non-specific airway challenges locally and systemically in i sensitized BALB/c mice challenged with grass pollen allergen Phl p 5, and in ii grass pollen sensitized allergic rhinitis subjects undergoing specific airway challenge in the Vienna Challenge Chamber (VCC. METHODS AND RESULTS: BALB/c mice (n = 20 were intraperitoneally immunized with grass pollen allergen Phl p 5 and afterwards aerosol challenged with either the specific allergen Phl p 5 (n = 10 or the non-specific antigen ovalbumin (OVA (n = 10. A protocol for inducing allergic asthma as well as allergic rhinitis, according to the united airway concept, was used. Both groups of exposed mice showed significantly reduced physical activity after airway challenge. Specific airway challenge further resulted in goblet cell hyperplasia, enhanced mucous secretion, intrapulmonary leukocyte infiltration and lymphoid follicle formation, associated with significant expression of IL-4, IL-5 and IL-13 in splenocytes and also partially in lung tissue. Concerning circulating blood cell dynamics, we observed a significant drop of erythrocyte counts, hemoglobin and hematocrit levels in both mouse groups, challenged with allergen or OVA. A significant decrease in circulating erythrocytes and hematocrit levels after airway challenges with grass pollen allergen was also found in grass pollen sensitized human rhinitis subjects (n = 42 at the VCC. The effects on peripheral leukocyte counts in mice and humans however were opposed, possibly due to the different primary inflammation sites. CONCLUSION: Our data revealed that, besides significant leukocyte dynamics, particularly erythrocytes are involved in acute hypersensitivity reactions to respiratory allergens

  20. Absence of detectable influenza RNA transmitted via aerosol during various human respiratory activities--experiments from Singapore and Hong Kong.

    Directory of Open Access Journals (Sweden)

    Julian W Tang

    Full Text Available Two independent studies by two separate research teams (from Hong Kong and Singapore failed to detect any influenza RNA landing on, or inhaled by, a life-like, human manikin target, after exposure to naturally influenza-infected volunteers. For the Hong Kong experiments, 9 influenza-infected volunteers were recruited to breathe, talk/count and cough, from 0.1 m and 0.5 m distance, onto a mouth-breathing manikin. Aerosolised droplets exhaled from the volunteers and entering the manikin's mouth were collected with PTFE filters and an aerosol sampler, in separate experiments. Virus detection was performed using an in-house influenza RNA reverse-transcription polymerase chain reaction (RT-PCR assay. No influenza RNA was detected from any of the PTFE filters or air samples. For the Singapore experiments, 6 influenza-infected volunteers were asked to breathe (nasal/mouth breathing, talk (counting in English/second language, cough (from 1 m/0.1 m away and laugh, onto a thermal, breathing manikin. The manikin's face was swabbed at specific points (around both eyes, the nostrils and the mouth before and after exposure to each of these respiratory activities, and was cleaned between each activity with medical grade alcohol swabs. Shadowgraph imaging was used to record the generation of these respiratory aerosols from the infected volunteers and their impact onto the target manikin. No influenza RNA was detected from any of these swabs with either team's in-house diagnostic influenza assays. All the influenza-infected volunteers had diagnostic swabs taken at recruitment that confirmed influenza (A/H1, A/H3 or B infection with high viral loads, ranging from 10(5-10(8 copies/mL (Hong Kong volunteers/assay and 10(4-10(7 copies/mL influenza viral RNA (Singapore volunteers/assay. These findings suggest that influenza RNA may not be readily transmitted from naturally-infected human source to susceptible recipients via these natural respiratory activities, within

  1. Extrapolation modeling of aerosol deposition in human and laboratory rat lungs

    Energy Technology Data Exchange (ETDEWEB)

    Martonen, T.B.; Zhang, Z.; Yang, Y.

    1992-01-01

    Laboratory test animals are often used as surrogates in exposure studies to assess the potential threat to human health following inhalation of airborne contaminants. To aid in the interpretation and extrapolation of data to man, dosimetric considerations need to be addressed. Therefore, a mathematical model describing the behavior and fate of inhaled particulate matter within the respiratory tracts of man and rats has been developed. In the computer simulations, the CO2 concentrations of inhalation exposure chamber atmospheres are controlled to produce desired breathing patterns in the rat which mimic human breathing patterns as functions of physical activity levels. Herein, deposition patterns in human and rat lung airways are specifically examined as functions of respiratory intensities and particle parameters. The model provides a basis for the re-evaluation of data from past experiments, and, perhaps most importantly, permits new inhalation exposure tests to be designed and conducted in a sound scientific manner regarding this endpoint: the extrapolation of results to human conditions.

  2. Human Sentinel Surveillance of Influenza and Other Respiratory Viral Pathogens in Border Areas of Western Cambodia.

    Directory of Open Access Journals (Sweden)

    Ans Timmermans

    Full Text Available Little is known about circulation of influenza and other respiratory viruses in remote populations along the Thai-Cambodia border in western Cambodia. We screened 586 outpatients (median age 5, range 1-77 presenting with influenza-like-illness (ILI at 4 sentinel sites in western Cambodia between May 2010 and December 2012. Real-time reverse transcriptase (rRT PCR for influenza was performed on combined nasal and throat specimens followed by viral culture, antigenic analysis, antiviral susceptibility testing and full genome sequencing for phylogenetic analysis. ILI-specimens negative for influenza were cultured, followed by rRT-PCR for enterovirus and rhinovirus (EV/RV and EV71. Influenza was found in 168 cases (29% and occurred almost exclusively in the rainy season from June to November. Isolated influenza strains had close antigenic and phylogenetic relationships, matching vaccine and circulating strains found elsewhere in Cambodia. Influenza vaccination coverage was low (<20%. Western Cambodian H1N1(2009 isolate genomes were more closely related to 10 earlier Cambodia isolates (94.4% genome conservation than to 13 Thai isolates (75.9% genome conservation, despite sharing the majority of the amino acid changes with the Thai references. Most genes showed signatures of purifying selection. Viral culture detected only adenovirus (5.7% and parainfluenza virus (3.8%, while non-polio enteroviruses (10.3% were detected among 164 culture-negative samples including coxsackievirus A4, A6, A8, A9, A12, B3, B4 and echovirus E6 and E9 using nested RT-PCR methods. A single specimen of EV71 was found. Despite proximity to Thailand, influenza epidemiology of these western Cambodian isolates followed patterns observed elsewhere in Cambodia, continuing to support current vaccine and treatment recommendations from the Cambodian National Influenza Center. Amino acid mutations at non-epitope sites, particularly hemagglutinin genes, require further investigation in

  3. Human Thermal Model Evaluation Using the JSC Human Thermal Database

    Science.gov (United States)

    Bue, Grant; Makinen, Janice; Cognata, Thomas

    2012-01-01

    Human thermal modeling has considerable long term utility to human space flight. Such models provide a tool to predict crew survivability in support of vehicle design and to evaluate crew response in untested space environments. It is to the benefit of any such model not only to collect relevant experimental data to correlate it against, but also to maintain an experimental standard or benchmark for future development in a readily and rapidly searchable and software accessible format. The Human thermal database project is intended to do just so; to collect relevant data from literature and experimentation and to store the data in a database structure for immediate and future use as a benchmark to judge human thermal models against, in identifying model strengths and weakness, to support model development and improve correlation, and to statistically quantify a model s predictive quality. The human thermal database developed at the Johnson Space Center (JSC) is intended to evaluate a set of widely used human thermal models. This set includes the Wissler human thermal model, a model that has been widely used to predict the human thermoregulatory response to a variety of cold and hot environments. These models are statistically compared to the current database, which contains experiments of human subjects primarily in air from a literature survey ranging between 1953 and 2004 and from a suited experiment recently performed by the authors, for a quantitative study of relative strength and predictive quality of the models.

  4. SU-E-J-163: A Biomechanical Lung Model for Respiratory Motion Study

    Energy Technology Data Exchange (ETDEWEB)

    Liu, X; Belcher, AH; Grelewicz, Z; Wiersma, RD [The University of Chicago, Chicago, IL (United States)

    2015-06-15

    Purpose: This work presents a biomechanical model to investigate the complex respiratory motion for the lung tumor tracking in radiosurgery by computer simulation. Methods: The models include networked massspring-dampers to describe the tumor motion, different types of surrogate signals, and the force generated by the diaphragm. Each mass-springdamper has the same mechanical structure and each model can have different numbers of mass-spring-dampers. Both linear and nonlinear stiffness parameters were considered, and the damping ratio was tuned in a range so that the tumor motion was over-damped (no natural tumor oscillation occurs without force from the diaphragm). The simulation was run by using ODE45 (ordinary differential equations by Runge-Kutta method) in MATLAB, and all time courses of motions and inputs (force) were generated and compared. Results: The curvature of the motion time courses around their peaks was sensitive to the damping ratio. Therefore, the damping ratio can be determined based on the clinical data of a high sampling rate. The peak values of different signals and the time the peaks occurred were compared, and it was found that the diaphragm force had a time lead over the tumor motion, and the lead time (0.1–0.4 seconds) depended on the distance between the tumor and the diaphragm. Conclusion: We reported a model based analysis approach for the spatial and temporal relation between the motion of the lung tumor and the surrogate signals. Due to the phase lead of the diaphragm in comparing with the lung tumor motion, the measurement of diaphragm motion (or its electromyography signal) can be used as a beam gating signal in radiosurgery, and it can also be an additional surrogate signal for better tumor motion tracking. The research is funded by the American Cancer Society (ACS) grant. The grant name is: Frameless SRS Based on Robotic Head Motion Cancellation. The grant number is: RSG-13-313-01-CCE.

  5. TU-F-17A-03: An Analytical Respiratory Perturbation Model for Lung Motion Prediction

    Energy Technology Data Exchange (ETDEWEB)

    Li, G; Yuan, A [Memorial Sloan Kettering Cancer Center, New York, NY (United States); Wei, J [City College of New York, New York, NY (United States)

    2014-06-15

    Purpose: Breathing irregularity is common, causing unreliable prediction in tumor motion for correlation-based surrogates. Both tidal volume (TV) and breathing pattern (BP=ΔVthorax/TV, where TV=ΔVthorax+ΔVabdomen) affect lung motion in anterior-posterior and superior-inferior directions. We developed a novel respiratory motion perturbation (RMP) model in analytical form to account for changes in TV and BP in motion prediction from simulation to treatment. Methods: The RMP model is an analytical function of patient-specific anatomic and physiologic parameters. It contains a base-motion trajectory d(x,y,z) derived from a 4-dimensional computed tomography (4DCT) at simulation and a perturbation term Δd(ΔTV,ΔBP) accounting for deviation at treatment from simulation. The perturbation is dependent on tumor-specific location and patient-specific anatomy. Eleven patients with simulation and treatment 4DCT images were used to assess the RMP method in motion prediction from 4DCT1 to 4DCT2, and vice versa. For each patient, ten motion trajectories of corresponding points in the lower lobes were measured in both 4DCTs: one served as the base-motion trajectory and the other as the ground truth for comparison. In total, 220 motion trajectory predictions were assessed. The motion discrepancy between two 4DCTs for each patient served as a control. An established 5D motion model was used for comparison. Results: The average absolute error of RMP model prediction in superior-inferior direction is 1.6±1.8 mm, similar to 1.7±1.6 mm from the 5D model (p=0.98). Some uncertainty is associated with limited spatial resolution (2.5mm slice thickness) and temporal resolution (10-phases). Non-corrected motion discrepancy between two 4DCTs is 2.6±2.7mm, with the maximum of ±20mm, and correction is necessary (p=0.01). Conclusion: The analytical motion model predicts lung motion with accuracy similar to the 5D model. The analytical model is based on physical relationships, requires no

  6. Modeling Forces on the Human Body.

    Science.gov (United States)

    Pagonis, Vasilis; Drake, Russel; Morgan, Michael; Peters, Todd; Riddle, Chris; Rollins, Karen

    1999-01-01

    Presents five models of the human body as a mechanical system which can be used in introductory physics courses: human arms as levers, humans falling from small heights, a model of the human back, collisions during football, and the rotating gymnast. Gives ideas for discussions and activities, including Interactive Physics (TM) simulations. (WRM)

  7. 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

    in a three-week period. Sweat and blood samples were obtained at inclusion. The presence of RSV and hMPV RNA was detected using real-time RT-PCR. RESULTS: We detected RSV RNA in 28 saliva specimens, 5 stool samples, and 3 sweat samples. hMPV RNA was detected in one saliva specimen and two sweat samples. Four...... of the five children shedding RNA in faeces had diarrhoea and children shedding RNA in sweat were either less than five weeks of age or had a chronic lung disease. RSV and hMPV RNA was shed in nasal secretions for a median of 11.5 and 5.0 days respectively (p = 0.001). More than 75% of the family members...... 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....

  8. Phase synchronization of oscillations in cardiovascular and respiratory systems in humans

    Science.gov (United States)

    Tankanag, Arina V.; Grinevich, Andrey A.; Tikhonova, Irina V.; Chaplygina, Alina V.; Chemeris, Nikolay K.

    2017-04-01

    Phase synchronization between blood flow oscillations of left and right forearm skin sites, heart rate variability (HRV) and breath rate were studied from healthy volunteers at rest. The degree of synchronization between the phases of the analyzed signals was estimated from the value of the wavelet phase coherence. High medians of values of phase wavelet coherence function were obtained for the endothelial, neurogenic, myogenic and cardiac intervals. Significant phase synchronization were demonstrated between HRV and skin blood flow oscillations in both left and right forearms in a wide frequency range from 0.04 to 0.4 Hz. Six participants exhibited low phase synchronization (rate and HRV, while nine participants had high phase synchronization (> 0.5). This distribution was not affected by the sex or sympathovagal status of volunteers. Participants with low phase synchronization between breath rate and HRV featured low phase synchronization (rate and blood flow oscillations in both forearms. Contrariwise, in subjects with high phase synchronization between respiratory rhythm and HRV both low and high phase synchronization between breath rate and blood flow oscillations in both forearms was observed. The results obtained allow us to suggest that the organism possesses a mechanism mediating the synchronization of blood flow oscillations in the skin microvasculature with all other periodical processes across the cardiovascular system, in particular, with HRV and breath rate over a wide frequency range.

  9. Internalization and trafficking of nontypeable Haemophilus influenzae in human respiratory epithelial cells and roles of IgA1 proteases for optimal invasion and persistence.

    Science.gov (United States)

    Clementi, Cara F; Håkansson, Anders P; Murphy, Timothy F

    2014-01-01

    Nontypeable Haemophilus influenzae (NTHI) is a leading cause of opportunistic infections of the respiratory tract in children and adults. Although considered an extracellular pathogen, NTHI has been observed repeatedly within and between cells of the human respiratory tract, and these observations have been correlated to symptomatic infection. These findings are intriguing in light of the knowledge that NTHI persists in the respiratory tract despite antibiotic therapy and the development of bactericidal antibodies. We hypothesized that intracellular NTHI avoids, escapes, or neutralizes the endolysosomal pathway and persists within human respiratory epithelial cells and that human IgA1 proteases are required for optimal internalization and persistence of NTHI. Virtually all strains encode a human IgA1 protease gene, igaA, and we previously characterized a novel human IgA1 protease gene, igaB, that is associated with disease-causing strains and is homologous to the IgA1 protease that is unique to pathogenic Neisseria spp. Here, we show that NTHI invades human bronchial epithelial cells in vitro in a lipid raft-independent manner, is subsequently trafficked via the endolysosomal pathway, and is killed in lysosomes after variable durations of persistence. IgaA is required for optimal invasion. IgaB appears to play little or no role in adherence or invasion but is required for optimal intracellular persistence of NTHI. IgaB cleaves lysosome-associated membrane protein 1 (LAMP1) at pHs characteristic of the plasma membrane, early endosome, late endosome, and lysosome. However, neither IgA1 protease inhibits acidification of intracellular vesicles containing NTHI. NTHI IgA1 proteases play important but different roles in NTHI invasion and trafficking in respiratory epithelial cells.

  10. DigitalHuman (DH): An Integrative Mathematical Model ofHuman Physiology

    Science.gov (United States)

    Hester, Robert L.; Summers, Richard L.; lIescu, Radu; Esters, Joyee; Coleman, Thomas G.

    2010-01-01

    Mathematical models and simulation are important tools in discovering the key causal relationships governing physiological processes and improving medical intervention when physiological complexity is a central issue. We have developed a model of integrative human physiology called DigitalHuman (DH) consisting of -5000 variables modeling human physiology describing cardiovascular, renal, respiratory, endocrine, neural and metabolic physiology. Users can view time-dependent solutions and interactively introduce perturbations by altering numerical parameters to investigate new hypotheses. The variables, parameters and quantitative relationships as well as all other model details are described in XML text files. All aspects of the model, including the mathematical equations describing the physiological processes are written in XML open source, text-readable files. Model structure is based upon empirical data of physiological responses documented within the peer-reviewed literature. The model can be used to understand proposed physiological mechanisms and physiological interactions that may not be otherwise intUitively evident. Some of the current uses of this model include the analyses of renal control of blood pressure, the central role of the liver in creating and maintaining insulin resistance, and the mechanisms causing orthostatic hypotension in astronauts. Additionally the open source aspect of the modeling environment allows any investigator to add detailed descriptions of human physiology to test new concepts. The model accurately predicts both qualitative and more importantly quantitative changes in clinically and experimentally observed responses. DigitalHuman provides scientists a modeling environment to understand the complex interactions of integrative physiology. This research was supported by.NIH HL 51971, NSF EPSCoR, and NASA

  11. The combination of PRRS virus and bacterial endotoxin as a model for multifactorial respiratory disease in pigs.

    Science.gov (United States)

    Van Gucht, Steven; Labarque, Geoffrey; Van Reeth, Kristien

    2004-12-08

    This paper reviews in vivo studies on the interaction between porcine reproductive and respiratory syndrome virus (PRRSV) and LPS performed in the authors' laboratory. The main aim was to develop a reproducible model to study the pathogenesis of PRRSV-induced multifactorial respiratory disease. The central hypothesis was that respiratory disease results from an overproduction of proinflammatory cytokines in the lungs. In a first series of studies, PRRSV was shown to be a poor inducer of TNF-alpha and IFN-alpha in the lungs, whereas IL-1 and the anti-inflammatory cytokine IL-10 were produced consistently during infection. We then set up a dual inoculation model in which pigs were inoculated intratracheally with PRRSV and 3-14 days later with LPS. PRRSV-infected pigs developed acute respiratory signs for 12-24h upon intratracheal LPS inoculation, in contrast to pigs inoculated with PRRSV or LPS only. Moreover, peak TNF-alpha, IL-1 and IL-6 titers were 10-100 times higher in PRRSV-LPS inoculated pigs than in the singly inoculated pigs and the cytokine overproduction was associated with disease. To further prove the role of proinflammatory cytokines, we studied the effect of pentoxifylline, a known inhibitor of TNF-alpha and IL-1, on PRRSV-LPS induced cytokine production and disease. The clinical effects of two non-steroidal anti-inflammatory drugs (NSAIDs), meloxicam and flunixin meglumine, were also examined. Pentoxifylline, but not the NSAIDs, significantly reduced fever and respiratory signs from 2 to 6h after LPS. The levels of TNF-alpha and IL-1 in the lungs of pentoxifylline-treated pigs were moderately reduced, but were still 26 and 3.5-fold higher than in pigs inoculated with PRRSV or LPS only. This indicates that pathways other than inhibition of cytokine production contributed to the clinical improvement. Finally, we studied a mechanism by which PRRSV may sensitize the lungs for LPS. We hypothesized that PRRSV would increase the amount of LPS receptor

  12. Recombinant human DNase in children with airway malacia and lower respiratory tract infection.

    NARCIS (Netherlands)

    Boogaard, R.; Jongste, J.C. de; Vaessen-Verberne, A.A.; Hop, W.C.J.; Merkus, P.J.F.M.

    2009-01-01

    BACKGROUND: Children with airway malacia often have protracted courses of airway infections, because dynamic airway collapse during coughing results in impaired mucociliary clearance. The aim of this study was to determine the effect of the mucolytic drug recombinant human deoxyribonuclease

  13. The Genotoxicity of Titanium Dioxide and Cerium Dioxide Nanoparticles in Human Respiratory Epithelial Cells

    Science.gov (United States)

    Due to the exponential growth of the nanomaterial industry, risk assessment of human exposure to nanomaterials in consumer products is of paramount importance. The genotoxicity of nanomaterials is an important aspect of hazard identification and regulatory guidance. However, this...

  14. Genotoxic Effects of Titanium Dioxide and Cerium Dioxide Nanoparticles in Human Respiratory Epithelial Cells

    Science.gov (United States)

    The nanomaterial industry has recently seen rapid growth, therefore, the risk assessment of human exposure to nanomaterials in consumer products is of paramount importance. The genotoxicity of nanomaterials is a fundamental aspect of hazard identification and regulatory guidance....

  15. 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...

  16. 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...

  17. Complete Genome Sequence of Human Adenovirus Type 55 Associated with Acute Respiratory Disease, Isolated from a Military Base in the Republic of Korea

    Science.gov (United States)

    Gu, Se Hun; Song, Dong Hyun; Lee, Daesang; Huh, Kyungmin; Yoo, Hongseok; Oh, Hong Sang; Jung, Jaehun; Woo, Koung In; Kim, Mirang; Seog, Woong; Hwang, Il-Ung

    2017-01-01

    ABSTRACT Human adenovirus (HAdV) (genus Mastadenovirus; family Adenoviridae) serotype 55 is a reemerging pathogen associated with acute respiratory disease. Here, we report the complete genome sequence of HAdV-55 strain AFMC 16-0011, isolated from a military recruit, using next-generation sequencing technology. PMID:28280019

  18. Avian influenza A virus (H7N7) associated with human conjunctivitis and a fatal case of acute respiratory distress syndrome.

    NARCIS (Netherlands)

    R.A.M. Fouchier (Ron); P.M. Schneeberger (Peter); F.W. Rozendaal (Frans); J.M. Broekman (Jan); S.A. Kemink (Stiena); V.J. Munster (Vincent); G.F. Rimmelzwaan (Guus); M. Schutten (Martin); G.J.J. van Doornum (Gerard); G. Koch (Guus); A. Bosman (Arnold); M.P.G. Koopmans D.V.M. (Marion); A.D.M.E. Osterhaus (Albert); T. Kuiken (Thijs)

    2004-01-01

    textabstractHighly pathogenic avian influenza A viruses of subtypes H5 and H7 are the causative agents of fowl plague in poultry. Influenza A viruses of subtype H5N1 also caused severe respiratory disease in humans in Hong Kong in 1997 and 2003, including at least seven fatal cases, posing a serious

  19. Towards human exploration of space: the THESEUS review series on cardiovascular, respiratory, and renal research priorities

    OpenAIRE

    Aubert, André E.; André E. Larina, Irina; Momken, Iman; Blanc, Stéphane; White, Olivier; Prisk, Kim; Linnarsson, Dag

    2016-01-01

    International audience; The THESEUS project (Towards Human Exploration of Space: aEUropean Strategy) was initiated within the seventh FrameworkProgramme by the European Commission. This project aimed toprovide a cross-cutting, life science-based roadmap for Europe’sstrategy towards human exploration of space, especially for deepspace missions and its relevance to applications on Earth. Toaddress these challenges, relevance of space research on thecardiovascular system, the lungs and kidneys, ...

  20. Influence of respiratory substrate in carbon steel corrosion by a Sulphate Reducing Prokaryote model organism.

    Science.gov (United States)

    Dall'agnol, Leonardo T; Cordas, Cristina M; Moura, José J G

    2014-06-01

    Sulphate Reducing Prokaryotes (SRP) are an important group of microorganisms involved in biocorrosion processes. Sulphide production is recognized as a fundamental cause of corrosion and nitrate is often used as treatment. The present work analyses the influence of respiratory substrates in the metal, from off-shore installations, SRP influenced corrosion, using Desulfovibrio desulfuricans ATTC 27774 as model organism, since this can switch from sulphate to nitrate. Open Circuit Potential over 6days in different conditions was measured, showing an increase around 200 and 90mV for the different media. Tafel plots were constructed allowing Ecorr and jcorr calculations. For SRP in sulphate and nitrate media Ecorr values of -824 and -728mV, and jcorr values of 2.5 and 3.7μAcm(-2), respectively, were attained indicating that in nitrate, the resultant corrosion rate is larger than in sulphate. Also, it is shown that the equilibrium of sulphide in the solution/gas phases is a key factor to the evolution of corrosion Nitrate prevents pitting but promotes general corrosion and increases the corrosion potential and iron dissolution 40 times when compared to sulphate. Our results demonstrate that nitrate injection strategy in oil fields has to be considered carefully as option to reduce souring and localized corrosion.

  1. Comparison of heart and respiratory rate variability measures using an intermittent incremental submaximal exercise model.

    Science.gov (United States)

    Barrera-Ramirez, Juliana; Bravi, Andrea; Green, Geoffrey; Seely, Andrew J; Kenny, Glen P

    2013-11-01

    To better understand the alterations in cardiorespiratory variability during exercise, the present study characterized the patterns of change in heart rate variability (HRV), respiratory rate variability (RRV), and combined cardiorespiratory variability (HRV-RRV) during an intermittent incremental submaximal exercise model. Six males and six females completed a submaximal exercise protocol consisting of an initial baseline resting period followed by three 10-min bouts of exercise at 20%, 40%, and 60% of maximal aerobic capacity (V̇O2max). The R-R interval and interbreath interval variability were measured at baseline rest and throughout the submaximal exercise. A group of 93 HRV, 83 RRV, and 28 HRV-RRV measures of variability were tracked over time through a windowed analysis using a 5-min window size and 30-s window step. A total of 91 HRV measures were able to detect the presence of exercise, whereas only 46 RRV and 3 HRV-RRV measures were able to detect the same stimulus. Moreover, there was a loss of overall HRV and RRV, loss of complexity of HRV and RRV, and loss of parasympathetic modulation of HRV (up to 40% V̇O2max) with exercise. Conflicting changes in scale-invariant structure of HRV and RRV with increases in exercise intensity were also observed. In summary, in this simultaneous evaluation of HRV and RRV, we found more consistent changes across HRV metrics compared with RRV and HRV-RRV.

  2. 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.

  3. Roflumilast inhibits respiratory syncytial virus infection in human differentiated bronchial epithelial cells.

    Directory of Open Access Journals (Sweden)

    Manuel Mata

    Full Text Available Respiratory syncytial virus (RSV causes acute exacerbations in COPD and asthma. RSV infects bronchial epithelial cells (HBE that trigger RSV associated lung pathology. This study explores whether the phosphodiesterase 4 (PDE4 inhibitor Roflumilast N-oxide (RNO, alters RSV infection of well-differentiated HBE (WD-HBE in vitro. WD-HBE were RSV infected in the presence or absence of RNO (0.1-100 nM. Viral infection (staining of F and G proteins, nucleoprotein RNA level, mRNA of ICAM-1, ciliated cell markers (digital high speed videomicroscopy, β-tubulin immunofluorescence, Foxj1 and Dnai2 mRNA, Goblet cells (PAS, mRNA of MUC5AC and CLCA1, mRNA and protein level of IL-13, IL-6, IL-8, TNFα, formation of H2O2 and the anti-oxidative armamentarium (mRNA of Nrf2, HO-1, GPx; total antioxidant capacity (TAC were measured at day 10 or 15 post infection. RNO inhibited RSV infection of WD-HBE, prevented the loss of ciliated cells and markers, reduced the increase of MUC5AC and CLCA1 and inhibited the increase of IL-13, IL-6, IL-8, TNFα and ICAM-1. Additionally RNO reversed the reduction of Nrf2, HO-1 and GPx mRNA levels and consequently restored the TAC and reduced the H2O2 formation. RNO inhibits RSV infection of WD-HBE cultures and mitigates the cytopathological changes associated to this virus.

  4. Experimental determination of the regional deposition of aerosol particles in the human respiratory tract

    Energy Technology Data Exchange (ETDEWEB)

    Stahlhofen, W.; Gebhart, J.; Heyder, J.

    1980-06-01

    The experimental techniques and the results of inhalation studies with radioaerosols on normal non-smokers for mouth-breathing are described and discussed. Monodisperse iron oxide particles tagged with /sup 198/Au are produced with a spinning top generator in the aerodynamic size range between 1 to 10 ..mu..m. An aerosol inhalation apparatus enables the subjects to breathe under standardized conditions with respect to tidal volume and breathing frequency. The calculation of total deposition is based upon measurements of the number of in- and exhaled particles per breath by means of photometric methods and pneumotachography. The retention of the radioactive particles present in the body after aerosol administration is measured with a body counter designed and constructed for these experiments. Retention measurements as functions of time after inhalation are carried out in extrathoracic-, chest- and stomach-position. The body counter consists of four shielded NaF(Tl)-dectors. Characteristic feature of the body counter is its low sensitivity to neighboring organs and to neighboring regions within the respiratory tract. For the evaluation of extrathoracic deposition, the activity measured in the stomach immediately after inhalation is added to extrathoracic activity. The elimination of material from the chest is found to be much slower for the material deposited in the alveolar region than for the amount deposited in the tracheobronchial tree. This allows the intrathoracic deposition to be divided into tracheolbronchial and alveolar deposition by means of the different slopes of the normalized chest retention function. Different normalized chest retention functions are presented and analyzed with respect to their different elimination rats belonging to the tracheobronchial and alveolar region. Total, tracheobronchial, alveolar and extrathoracic deposition data are reported in the aerodynamic diameter range between 1 and 10 ..mu..m.

  5. 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

    Directory of Open Access Journals (Sweden)

    Salomonsen Charlotte M

    2012-11-01

    Full Text Available Abstract 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 P. aeruginosa in mice and to promote adhesion of P. aeruginosa to human respiratory cells. Findings We tested 50 lung specimens from mink with hemorrhagic pneumonia for bovine RSV by reverse transcriptase polymerase chain reaction (PCR and for human RSV by a commercial real-time PCR. RSV was not found. Conclusions This study indicates that human and bovine RSV is not a major co-factor for development of hemorrhagic pneumonia in Danish mink.

  6. Effects of human respiratory syncytial virus, metapneumovirus, parainfluenza virus 3 and influenza virus on CD4+ T cell activation by dendritic cells.

    Directory of Open Access Journals (Sweden)

    Cyril Le Nouën

    Full Text Available BACKGROUND: Human respiratory syncytial virus (HRSV, and to a lesser extent human metapneumovirus (HMPV and human parainfluenza virus type 3 (HPIV3, re-infect symptomatically throughout life without antigenic change, suggestive of incomplete immunity. One causative factor is thought to be viral interference with dendritic cell (DC-mediated stimulation of CD4+ T cells. METHODOLOGY, PRINCIPAL FINDINGS: We infected human monocyte-derived DC with purified HRSV, HMPV, HPIV3, or influenza A virus (IAV and compared their ability to induce activation and proliferation of autologous CD4+ T cells in vitro. IAV was included because symptomatic re-infection without antigenic change is less frequent, suggesting that immune protection is more complete and durable. We examined virus-specific memory responses and superantigen-induced responses by multiparameter flow cytometry. Live virus was more stimulatory than inactivated virus in inducing DC-mediated proliferation of virus-specific memory CD4+ T cells, suggesting a lack of strong suppression by live virus. There were trends of increasing proliferation in the order: HMPVrespiratory viruses are similar in their ability to induce DC to activate CD4+ T cells. Thus, the results do not support the common model in which viral suppression of CD4+ T cell activation and

  7. Comparing Human Metapneumovirus and Respiratory Syncytial Virus: Viral Co-Detections, Genotypes and Risk Factors for Severe Disease

    Science.gov (United States)

    Moe, Nina; Krokstad, Sidsel; Stenseng, Inger Heimdal; Christensen, Andreas; Skanke, Lars Høsøien; Risnes, Kari Ravndal; Nordbø, Svein Arne; Døllner, Henrik

    2017-01-01

    Background It is unclarified as to whether viral co-detection and human metapneumovirus (HMPV) genotypes relate to clinical manifestations in children with HMPV and lower respiratory tract infection (LRTI), and if the clinical course and risk factors for severe LRTI differ between HMPV and respiratory syncytial virus (RSV). Methods We prospectively enrolled hospitalized children aged <16 years with LRTI from 2006 to 2015. Children were clinically examined, and nasopharyngeal aspirates were analyzed using semi-quantitative, real-time polymerase chain reaction tests for HMPV, RSV and 17 other pathogens. HMPV-positive samples were genotyped. Results A total of 171 children had HMPV infection. HMPV-infected children with single virus (n = 106) and co-detections (n = 65) had similar clinical manifestations. No clinical differences were found between HMPV genotypes A (n = 67) and B (n = 80). The HMPV-infected children were older (median 17.2 months) than RSV-infected children (median 7.3 months, n = 859). Among single virus-infected children, no differences in age-adjusted LRTI diagnoses were found between HMPV and RSV. Age was an important factor for disease severity among single virus-infected children, where children <6 months old with HMPV had a milder disease than those with RSV, while in children 12–23 months old, the pattern was the opposite. In multivariable logistic regression analysis for each virus type, age ≥12 months (HMPV), and age <6 months (RSV), prematurity, ≥1 chronic disease and high viral loads of RSV, but not high HMPV viral loads, were risk factors for severe disease. Conclusions Among hospitalized children with LRTI, HMPV manifests independently of viral co-detections and HMPV genotypes. Disease severity in HMPV- and RSV-infected children varies in relation to age. A history of prematurity and chronic disease increases the risk of severe LRTI among HMPV- and RSV-infected children. PMID:28095451

  8. Potential role of hands in the spread of respiratory viral infections: studies with human parainfluenza virus 3 and rhinovirus 14.

    Science.gov (United States)

    Ansari, S A; Springthorpe, V S; Sattar, S A; Rivard, S; Rahman, M

    1991-10-01

    Hands often become contaminated with respiratory viruses, either directly or through contact with contaminated surfaces. Spread of such viruses could then occur by touching the nasal mucosa or the conjunctivae. In this quantitative study, we compared the survival of mucin-suspended human parainfluenza virus 3 (HPIV-3) and rhinovirus 14 (RV-14) and the transfer of the viruses to and from the fingers of adult volunteers. When each finger pad was contaminated with 10 microliters of either HPIV-3 (1.3 x 10(5) to 5.5 x 10(5) PFU) or RV-14 (2.1 x 10(4) to 1.1 x 10(5) PFU), less than 1.0% of HPIV-3 and 37.8% of RV-14 remained viable after 1 h; after 3 h, nearly 16% of RV-14 could still be detected, whereas HPIV-3 became undetectable. Tests on the potential spread of viruses from contaminated hands or surfaces were conducted 20 min after contamination of the donor surface by pressing together donor and recipient surfaces for 5 s. Transfer of HPIV-3 from finger to finger or finger to metal disk could not be detected, but 1.5% of infectious HPIV-3 was transferred from disk to finger. Irrespective of the type of donor or recipient surface, 0.7 to 0.9% of RV-14 was transferred. The relatively rapid loss of HPIV-3 infectivity on hands suggests that their role in the direct spread of parainfluenza viruses is limited. However, the findings of this study further reinforce the view that hands can be vehicles for rhinovirus colds. These results also suggest a role for nonporous environmental surfaces in the contamination of hands with respiratory viruses.

  9. Three-dimensional analysis of sexual dimorphism in human thoracic vertebrae: implications for the respiratory system and spine morphology.

    Science.gov (United States)

    Bastir, Markus; Higuero, Antonio; Ríos, Luís; García Martínez, Daniel

    2014-12-01

    Sexual dimorphism is important for intraspecific variation and well studied in the human skeleton. In the thoracic part of the spine sexual dimorphism is expected for differences in the respiratory system related to body mass, lung capacity, and energetics, and in the reproductive system for adaptations to pregnancy (lower spine lordosis, posture). However, little is known about sexual dimorphism in this anatomical region. We use three-dimensional (3D)-geometric morphometrics to test hypotheses on sexual dimorphism in the first 10 thoracic vertebrae (T1-T10). Forty-six 3D-landmarks were measured on vertebrae of 24 adult females and males of known age and sex. Results confirm that male vertebrae are consistently larger than female ones. Males show more dorsally oriented transverse processes and relatively larger vertebral bodies in upper and lower thoracic vertebrae. Sexual dimorphism in lower thoracic vertebrae affects the orientation of the spinous processes, which is more horizontal in females but more caudal in males. Such regional pattering of sexual dimorphism emerges also from principal component analyses reflecting a complex interaction between the effects of sex and serial position on shape variation. Greater dorsal orientation of male transverse processes reorients the ribs and could lead to greater radial thorax diameters. This fits with greater male respiratory capacities, but may indicate also greater invagination of the male spine within the thorax. Horizontal orientation of the spinous processes in females could allow for a greater thoraco-lumbar lordosis during pregnancy, but more comparative research is necessary to test these hypotheses.

  10. Genetic diversity in the G protein gene of group A human respiratory syncytial viruses circulating in Riyadh, Saudi Arabia.

    Science.gov (United States)

    Almajhdi, Fahad N; Farrag, Mohamed A; Amer, Haitham M

    2014-01-01

    Human respiratory syncytial virus (HRSV) is a frequent cause of hospitalization and mortality in children worldwide. The molecular epidemiology and circulation pattern of HRSV in Saudi Arabia is mostly uncharted. In the current study, the genetic variability and phylogenetic relationships of HRSV type A strains circulating in Riyadh Province were explored. Nasopharyngeal aspirates were collected from hospitalized children with acute respiratory symptoms during the winter-spring seasons of 2007/08 and 2008/09. Among 175 samples analyzed, 39 (22.3 %) were positive for HRSV by one-step RT-PCR (59 % type A and 41 % type B). Propagation of positive samples in HEp-2 cells permitted the recovery of the first Saudi HRSV isolates. Genetic variability among Saudi HRSV-A strains was evaluated by sequence analysis of the complete attachment (G) protein gene. The nucleotide sequence was compared to representatives of the previously identified HRSV-A genotypes. Sequence and phylogenetic analysis showed that the strains examined in this study were very closely related at both the nucleotide and amino acid level, and all of them are clustered in the GA2 genotype (and mostly belonged to the NA-1 subtype). A total of 23 mutation sites, 14 of which resulted in an amino acid change, were recorded only in Saudi strains. This is the first report on genetic diversity of HRSV-A strains in Saudi Arabia. Further analysis of strains on a geographical and temporal basis is needed to fully understand HRSV-A circulation patterns in Saudi Arabia.

  11. Detection of Human Rhinovirus C Viral Genome in Blood among Children with Severe Respiratory Infections in the Philippines

    Science.gov (United States)

    Fuji, Naoko; Suzuki, Akira; Lupisan, Socorro; Sombrero, Lydia; Galang, Hazel; Kamigaki, Taro; Tamaki, Raita; Saito, Mariko; Aniceto, Rapunzel; Olveda, Remigio; Oshitani, Hitoshi

    2011-01-01

    Human rhinovirus (HRV) C was recently identified as the third species of HRV using a molecular technique. Infections caused by previously identified HRVs (A and B) are thought to be limited to the respiratory tract; however, pathogenesis of HRVC is still largely unknown. A total of 816 nasopharyngeal swabs from hospitalized children with severe respiratory infections in the Philippines (May 2008–May 2009) were tested for HRV by reverse transcription polymerase chain reaction (RT-PCR), and 243 samples (29.8%) were positive for HRV. Among these patients, serum samples were also tested to determine whether specific HRV species were associated with viremia. Only 30 serum samples (12.3%) were positive for HRV. However, the HRV positive rates were different among HRV species, 3% (4/135) for HRVA, 0% (0/25) for HRVB, and 31% (26/83) for HRVC, and were the highest on 2 days after the onset of symptoms. These results suggest that HRVC may have a different pathogenicity and can more commonly cause viremia than HRVA and HRVB. Serum positive rates for HRV are affected by age, i.e., higher positive rates for those aged 1 year or more. HRVC that were detected from serum exhibited the same level of sequence diversity as those positive only for nasopharyngeal samples in phylogenetic analysis. However, all HRVA which were detected from serum were clustered in a monophyletic clade based on their 5′ non-coding region (NCR) sequences, which is closely related with a certain HRVC genotype (A2) in 5′-NCR. This finding suggests that the 5′NCR region may be associated with viremia. PMID:22087272

  12. 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.

  13. Human parainfluenza virus-associated respiratory tract infection among children and genetic analysis of HPIV-3 strains in Beijing, China.

    Directory of Open Access Journals (Sweden)

    Naiying Mao

    Full Text Available The relevance of human parainfluenza viruses (HPIVs to the epidemiology of acute respiratory infections (ARI in China is unclear. From May 2008 to September 2010, 443 nasopharyngeal aspirates (NPAs from hospitalized pediatric patients (age from 1 to 93 months in Beijing were collected and screened for HPIVs and other common respiratory viruses by real-time RT-PCR. Sixty-two of 443 samples were positive for HPIVs with 4 positive for HPIV-2 and 58 positive for HPIV-3, indicating that HPIV-3 was the predominant virus present during the study period. A phylogenetic tree based on all the available HN (hemagglutinin-neuraminidase sequences of HPIV-3 indicated that three distinct clusters (A,B, and C were circulating with some temporal and regional clustering. Cluster C was further divided into sub-clusters, C1, C2, C3 and C4. HPIV-3 from Beijing isolates belonged to sub-cluster C3, and were grouped with the isolates from two Provinces of China and the neighboring country of Japan. Genetic analysis based on entire HN gene revealed that the HPIV-3 isolates from Beijing were highly similar with 97.2%-100% identity at the nucleotide level and these could be divided into two closely related lineages, C3a and C3b. These findings suggested that there was co-circulation of multiple lineages of HPIV-3 in the Beijing region during the study period. This is the first study to describe the epidemiology and molecular characterization of HPIVs in China.

  14. Human respiratory syncytial virus in children with lower respiratory tract infections or influenza-like illness and its co-infection characteristics with viruses and atypical bacteria in Hangzhou, China.

    Science.gov (United States)

    Yu, Xinfen; Kou, Yu; Xia, Daozong; Li, Jun; Yang, Xuhui; Zhou, Yinyan; He, Xiaoyan

    2015-08-01

    Human respiratory syncytial virus (RSV) is the most important viral pathogen in children. However, its epidemic patterns and co-infection characteristics are not fully understood. We attempted to determine the level of genetic variation of RSV, and describe the prevalence and co-infection characteristics of RSV in Hangzhou during two epidemic seasons. Single respiratory samples from 1820 pediatric patients were screened for RSV and genotyped by RT-PCR and sequencing. In all RSV positive specimens, we screened for viruses and atypical bacteria. Demographic and clinical information was recorded and analyzed. A total of 34.5% and 3.8% of samples from acute lower respiratory tract infections (ALRI) and influenza-like illness (ILI) were positive for RSV, respectively. Phylogenetic analysis revealed that 61.1% of the selected 167 RSV strains were NA1, 31.1% were BA, 3.6% were ON1, 2.4% were CB1, and 1.8% were NA3. A new genotype, BA11 was identified, which comprised 98.1% of BA strains in this study, while the rest were BA10. A total of 36.4% and 9.1% of RSV-positive children with ALRI and ILI respectively were found to be co-infected. Rhinovirus was the most common additional respiratory virus, followed by human metapneumovirus. Except for fever, no significant differences in other clinical presentation between the RSV mono-infection and co-infection groups were observed. The circulating RSV strains had high genetic variability with RSV-B showing a more local pattern. In ALRI cases, co-infection of RSV with other viruses or atypical bacteria has no significant effect on the clinical presentation except fever. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. A community study of clinical traits and risk factors for human metapneumovirus and respiratory syncytial virus infection during the first year of life

    DEFF Research Database (Denmark)

    Linstow, Michael Ernst Von; Hogh, M.; Nordbo, S.A.;

    2008-01-01

    Human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) are important respiratory pathogens with similar symptomatology. The aim of this prospective birth cohort study was to identify risk factors for an hMPV or RSV infection during the first year of life in unselected healthy children......% CI:0.09-0.85). Risk factors for RSV hospitalisation (n = 11) were: (1) older siblings (OR = 4.49; 95% CI: 1.08-18.73) and (2) smoking in the household (OR = 5.06; 95% CI: 1.36-18.76). Exclusive breastfeeding for the first 14 days of life protected against hospitalisation (OR = 0.21; 95% CI:0...

  16. Respiratory epithelial cells require Toll-like receptor 4 for induction of Human β-defensin 2 by Lipopolysaccharide

    Directory of Open Access Journals (Sweden)

    McElvaney Noel

    2005-10-01

    Full Text Available Abstract Background The respiratory epithelium is a major portal of entry for pathogens and employs innate defense mechanisms to prevent colonization and infection. Induced expression of human β-defensin 2 (HBD2 represents a direct response by the epithelium to potential infection. Here we provide evidence for the critical role of Toll-like receptor 4 (TLR4 in lipopolysaccharide (LPS-induced HBD2 expression by human A549 epithelial cells. Methods Using RTPCR, fluorescence microscopy, ELISA and luciferase reporter gene assays we quantified interleukin-8, TLR4 and HBD2 expression in unstimulated or agonist-treated A549 and/or HEK293 cells. We also assessed the effect of over expressing wild type and/or mutant TLR4, MyD88 and/or Mal transgenes on LPS-induced HBD2 expression in these cells. Results We demonstrate that A549 cells express TLR4 on their surface and respond directly to Pseudomonas LPS with increased HBD2 gene and protein expression. These effects are blocked by a TLR4 neutralizing antibody or functionally inactive TLR4, MyD88 and/or Mal transgenes. We further implicate TLR4 in LPS-induced HBD2 production by demonstrating HBD2 expression in LPS non-responsive HEK293 cells transfected with a TLR4 expression plasmid. Conclusion This data defines an additional role for TLR4 in the host defense in the lung.

  17. Identification of a novel human papillomavirus by metagenomic analysis of samples from patients with febrile respiratory illness.

    Directory of Open Access Journals (Sweden)

    John L Mokili

    Full Text Available As part of a virus discovery investigation using a metagenomic approach, a highly divergent novel Human papillomavirus type was identified in pooled convenience nasal/oropharyngeal swab samples collected from patients with febrile respiratory illness. Phylogenetic analysis of the whole genome and the L1 gene reveals that the new HPV identified in this study clusters with previously described gamma papillomaviruses, sharing only 61.1% (whole genome and 63.1% (L1 sequence identity with its closest relative in the Papillomavirus episteme (PAVE database. This new virus was named HPV_SD2 pending official classification. The complete genome of HPV-SD2 is 7,299 bp long (36.3% G/C and contains 7 open reading frames (L2, L1, E6, E7, E1, E2 and E4 and a non-coding long control region (LCR between L1 and E6. The metagenomic procedures, coupled with the bioinformatic methods described herein are well suited to detect small circular genomes such as those of human papillomaviruses.

  18. Francisella tularensis LVS evades killing by human neutrophils via inhibition of the respiratory burst and phagosome escape.

    Science.gov (United States)

    McCaffrey, Ramona L; Allen, Lee-Ann H

    2006-12-01

    Francisella tularensis is a Gram-negative bacterium and the causative agent of tularemia. Recent data indicate that F. tularensis replicates inside macrophages, but its fate in other cell types, including human neutrophils, is unclear. We now show that F. tularensis live vaccine strain (LVS), opsonized with normal human serum, was rapidly ingested by neutrophils but was not eliminated. Moreover, evasion of intracellular killing can be explained, in part, by disruption of the respiratory burst. As judged by luminol-enhanced chemiluminescence and nitroblue tetrazolium staining, neutrophils infected with live F. tularensis did not generate reactive oxygen species. Confocal microscopy demonstrated that NADPH oxidase assembly was disrupted, and LVS phagosomes did not acquire gp91/p22(phox) or p47/p67(phox). At the same time, F. tularensis also impaired neutrophil activation by heterologous stimuli such as phorbol esters and opsonized zymosan particles. Later in infection, LVS escaped the phagosome, and live organisms persisted in the neutrophil cytosol for at least 12 h. To our knowledge, our data are the first demonstration of a facultative intracellular pathogen, which disrupts the oxidative burst and escapes the phagosome to evade elimination inside neutrophils, and as such, our data define a novel mechanism of virulence.

  19. Modelling the scaling properties of human mobility

    Science.gov (United States)

    Song, Chaoming; Koren, Tal; Wang, Pu; Barabási, Albert-László

    2010-10-01

    Individual human trajectories are characterized by fat-tailed distributions of jump sizes and waiting times, suggesting the relevance of continuous-time random-walk (CTRW) models for human mobility. However, human traces are barely random. Given the importance of human mobility, from epidemic modelling to traffic prediction and urban planning, we need quantitative models that can account for the statistical characteristics of individual human trajectories. Here we use empirical data on human mobility, captured by mobile-phone traces, to show that the predictions of the CTRW models are in systematic conflict with the empirical results. We introduce two principles that govern human trajectories, allowing us to build a statistically self-consistent microscopic model for individual human mobility. The model accounts for the empirically observed scaling laws, but also allows us to analytically predict most of the pertinent scaling exponents.

  20. 人呼吸道合胞病毒的研究与防治进展%Advances in Human Respiratory Syncytial Virus Research and Control

    Institute of Scientific and Technical Information of China (English)

    郭恺; 张玉彬

    2013-01-01

    人呼吸道合胞病毒是全世界婴幼儿下呼吸道感染最常见的病原体,导致每年超过300万人住院和20万以上的人死亡,给全球带来了非常严重的经济和社会负担.目前,尚不存在防治RSV的疫苗,也没有特异性强、安全性高的抗RSV药物.对HRSV的结构、流行病学特征以及疾病模型构建方面的研究进展进行综述,并对已有的检测和治疗方法进行总结,旨在为今后开发抗HRSV的药物提供全面的参考信息.%Human respiratory syncytial virus is the most common cause of infection in lower respiratory tract in infants and children around the world,which leads to more than 3 million inpatients and 200 thousand death and brings very serious economic and social burden.So far there are no vaccines or drugs with strong specificity and high safety that can prevent people from RSV infection.The research progress in the structure,epidemiological characteristics and disease modeling of HRSV was reviewed and the existing methods of detection and treatment HRSV were summarized in order to provide a comprehensive reference information for the future development of anti-HRSV drugs.

  1. A novel pancoronavirus RT-PCR assay: frequent detection of human coronavirus NL63 in children hospitalized with respiratory tract infections in Belgium

    Directory of Open Access Journals (Sweden)

    Berkhout Ben

    2005-02-01

    Full Text Available Abstract Background Four human coronaviruses are currently known to infect the respiratory tract: human coronaviruses OC43 (HCoV-OC43 and 229E (HCoV-229E, SARS associated coronavirus (SARS-CoV and the recently identified human coronavirus NL63 (HCoV-NL63. In this study we explored the incidence of HCoV-NL63 infection in children diagnosed with respiratory tract infections in Belgium. Methods Samples from children hospitalized with respiratory diseases during the winter seasons of 2003 and 2004 were evaluated for the presence of HCoV-NL63 using a optimized pancoronavirus RT-PCR assay. Results Seven HCoV-NL63 positive samples were identified, six were collected during January/February 2003 and one at the end of February 2004. Conclusions Our results support the notation that HCoV-NL63 can cause serious respiratory symptoms in children. Sequence analysis of the S gene showed that our isolates could be classified into two subtypes corresponding to the two prototype HCoV-NL63 sequences isolated in The Netherlands in 1988 and 2003, indicating that these two subtypes may currently be cocirculating.

  2. Expression of Prothrombinase/fibroleukin Gene fg12 in Lung Impairment in a Murine Severe Acute Respiratory Syndrome Model

    Institute of Scientific and Technical Information of China (English)

    Wei-ming YAN; Jia-quan HUANG; Xiao-ping LUO; Qin NING

    2007-01-01

    To evaluate the role of murine fibrinogen like protein 2 (mfgl2) /fibroleukin in lung impairment in Severe acute respiratory syndrome (SARS), a murine SARS model induced by Murine hepatitis virus strain 3 (MHV-3) through trachea was established. Impressively, all the animals developed interstitial pneumonia with extensive hyaline membranes formation within alveoli, and presence of micro-vascular thrombosis in the pulmonary vessels. MHV-3 nucleocapsid gene transcripts were identified in multiple organs including lungs, spleen etc. As a representative proinflammatory gene, mfgl2 prothrombinase expression was evident in terminal and respiratory bronchioles, alveolar epithelia and infiltrated cells in the lungs associated with fibrin deposition and micro-vascular thrombosis. In summary, the established murine SARS model could mimic the pathologic characteristics of lungs in patients with SARS. Besides the physical damages due to virus replication in organs, the up-regulation of novel gene mfgl2 in lungs may play a vital role in the development of SARS associated lung damage.

  3. Identification of Probiotic Strains from Human Milk in Breastfed Infants with Respiratory Infections

    Directory of Open Access Journals (Sweden)

    Neamtu Bogdan

    2014-12-01

    Full Text Available Isolation and industrial exploitation of probiotics from human milk is a goal for worldwide milk biotechnology centres because of their modulation effect on the immune system in infants and adults. In the proposed study we have analysed fermentation patterns of Lactobacilli isolated from human milk, the reliability of API 50 CH carbohydrate fermentation system and a possible link between lactose concentrations and fermentation profiles on carbohydrates. We had succesfully identified three species of Lactobacillus (paracasei ssp paracasei, fermentum, acidophilus and one unsatisfactory identification of Lactoccocus lactis ssp lactis. These strains had different carbohydrate fermentation patterns but with common characteristics and showed no statistically significant correlations between their carbohydrate metabolic trends and lactose concentrations in the milk samples.

  4. Hypoxia Selectively Inhibits Respiratory Burst Activity and Killing of Staphylococcus aureus in Human Neutrophils

    OpenAIRE

    McGovern, Naomi N.; Cowburn, Andrew S.; Porter, Linsey; Walmsley, Sarah R.; Summers, Charlotte; Thompson, Alfred A. R.; Anwar, Sadia; Willcocks, Lisa C.; Moira K B Whyte; Condliffe, Alison M; Chilvers, Edwin R.

    2010-01-01

    Neutrophils play a central role in the innate immune response and a critical role in bacterial killing. Most studies of neutrophil function have been conducted under conditions of ambient oxygen, but inflamed sites where neutrophils operate may be extremely hypoxic. Previous studies indicate that neutrophils sense and respond to hypoxia via the ubiquitous prolyl hydroxylase/hypoxia-inducible factor pathway and that this can signal for enhanced survival. In the current study, human neutrophils...

  5. Human Performance Modeling for Dynamic Human Reliability Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Boring, Ronald Laurids [Idaho National Laboratory; Joe, Jeffrey Clark [Idaho National Laboratory; Mandelli, Diego [Idaho National Laboratory

    2015-08-01

    Part of the U.S. Department of Energy’s (DOE’s) Light Water Reac- tor Sustainability (LWRS) Program, the Risk-Informed Safety Margin Charac- terization (RISMC) Pathway develops approaches to estimating and managing safety margins. RISMC simulations pair deterministic plant physics models with probabilistic risk models. As human interactions are an essential element of plant risk, it is necessary to integrate human actions into the RISMC risk framework. In this paper, we review simulation based and non simulation based human reliability analysis (HRA) methods. This paper summarizes the founda- tional information needed to develop a feasible approach to modeling human in- teractions in RISMC simulations.

  6. Innate immune response of human alveolar type II cells infected with severe acute respiratory syndrome-coronavirus.

    Science.gov (United States)

    Qian, Zhaohui; Travanty, Emily A; Oko, Lauren; Edeen, Karen; Berglund, Andrew; Wang, Jieru; Ito, Yoko; Holmes, Kathryn V; Mason, Robert J

    2013-06-01

    Severe acute respiratory syndrome (SARS)-coronavirus (CoV) produces a devastating primary viral pneumonia with diffuse alveolar damage and a marked increase in circulating cytokines. One of the major cell types to be infected is the alveolar type II cell. However, the innate immune response of primary human alveolar epithelial cells infected with SARS-CoV has not been defined. Our objectives included developing a culture system permissive for SARS-CoV infection in primary human type II cells and defining their innate immune response. Culturing primary human alveolar type II cells at an air-liquid interface (A/L) improved their differentiation and greatly increased their susceptibility to infection, allowing us to define their primary interferon and chemokine responses. Viral antigens were detected in the cytoplasm of infected type II cells, electron micrographs demonstrated secretory vesicles filled with virions, virus RNA concentrations increased with time, and infectious virions were released by exocytosis from the apical surface of polarized type II cells. A marked increase was evident in the mRNA concentrations of interferon-β and interferon-λ (IL-29) and in a large number of proinflammatory cytokines and chemokines. A surprising finding involved the variability of expression of angiotensin-converting enzyme-2, the SARS-CoV receptor, in type II cells from different donors. In conclusion, the cultivation of alveolar type II cells at an air-liquid interface provides primary cultures in which to study the pulmonary innate immune responses to infection with SARS-CoV, and to explore possible therapeutic approaches to modulating these innate immune responses.

  7. Developing a multi-component immune model for evaluating the risk of respiratory illness in athletes.

    Science.gov (United States)

    Gleeson, Maree; Pyne, David B; Elkington, Lisa J; Hall, Sharron T; Attia, John R; Oldmeadow, Christopher; Wood, Lisa G; Callister, Robin

    2017-01-01

    Clinical and laboratory identification of the underlying risk of respiratory illness in athletes has proved problematic. The aim of this study was to determine whether clinical data, combined with immune responses to standardised exercise protocols and genetic cytokine polymorphism status, could identify the risk of respiratory illness (symptoms) in a cohort of highly-trained athletes. Male endurance athletes (n=16; VO2max 66.5 ± 5.1 mL.kg-1.min-1) underwent a clinical evaluation of known risk factors by a physician and comprehensive laboratory analysis of immune responses both at rest and after two cycling ergometer tests: 60 min at 65% VO2max (LONG); and 6 x 3 min intervals at 90% VO2max (INTENSE). Blood tests were performed to determine Epstein Barr virus (EBV) status and DNA was genotyped for a panel of cytokine gene polymorphisms. Saliva was collected for measurement of IgA and detection of EBV DNA. Athletes were then followed for 9 months for self-reported episodes of respiratory illness, with confirmation of the underlying cause by a sports physician. There were no associations with risk of respiratory illness identified for any parameter assessed in the clinical evaluations. The laboratory parameters associated with an increased risk of respiratory illnesses in highly-trained athletes were cytokine gene polymorphisms for the high expression of IL-6 and IFN-ɣ; expression of EBV-DNA in saliva; and low levels of salivary IgA concentration. A genetic risk score was developed for the cumulative number of minor alleles for the cytokines evaluated. Athletes prone to recurrent respiratory illness were more likely to have immune disturbances that allow viral reactivation, and a genetic predisposition to pro-inflammatory cytokine responses to intense exercise.

  8. Heat and Water Vapor Transfer in the Human Respiratory System at Hyperbaric Conditions.

    Science.gov (United States)

    1981-09-01

    element ( Meriam Model 50 MC2-4) was placed in series wih the pipe model to record gas volumetric flow rates. The pressure differential generated by...SOITDISRMNASSIOTE DATA CQUISTION YSTE 44 a. Flow Measurement The Meriam laminar flow element (LFE) depends for its accuracy and metering indication on...average of the horizontal and vertical re- cordings. The volumetric flow rate recorded with the Meriam laminar flow element was used to calculate average

  9. Association of individual-level concentrations and human respiratory tract deposited doses of fine particulate matter with alternation in blood pressure.

    Science.gov (United States)

    Yin, Wenjun; Hou, Jian; Xu, Tian; Cheng, Juan; Wang, Xiaoying; Jiao, Shilin; Wang, Lin; Huang, Cheng; Zhang, Youjian; Yuan, Jing

    2017-11-01

    Fine particulate matter (PM2.5) contributes to the risk of cardiovascular events, partially owing to its deposition in the human respiratory tract. To investigate short-term effects of ambient PM2.5 exposure on alternation of blood pressure (BP), this study was conducted during the winter-summer period between 2014 and 2015. The study included 106 community residents in Wuhan city, China. We repeatedly monitored the household and outdoor PM2.5 concentrations as well as individual-level PM2.5 in each season, and then assessed personal PM2.5 exposure (including deposited doses of PM2.5 in the human respiratory tract) by using different methodology (such as using a dosimetry model). All participants took part in the physical examination, including the inflammatory indicators, BP and lung function parameters measurements. Subsequently, we assessed the health damage of exposure to PM2.5 using generalized additive models. We observed increased BP at 2-day lag for an interquartile range increase in ambient fixed-site, households, individual-level PM2.5 exposure and the corresponding lung deposited doses of each exposure concentration (p < 0.05), decreased BP at 3-day lag for an interquartile range increase in ambient fixed-site, households PM2.5 and the corresponding lung deposited doses of each exposure concentration (p < 0.05). The estimated deposited doses of PM2.5 by the deposition fractions in this study and the referenced deposition fractions by previous reported method were equivalent associated with alternation in BP. In conclusion, lung deposited dose of PM2.5 as a quantitative indicator may be used to assess adverse cardiovascular effects following the systemic inflammation. However, we require careful assessment of acute adverse cardiovascular effects using ambient fixed-site PM2.5 after short-term PM2.5 exposure. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. [Pulmonary cystic disease may be a rare complication to recurrent respiratory human papilloma virus infection].

    Science.gov (United States)

    Laurberg, Peter Thaysen; Weinreich, Ulla M Øller

    2014-12-01

    A 19-year-old woman with a history of juvenile laryngeal papillomatosis (JLP), treated since childhood with multiple resections, was admitted with symptoms of pneumonia. A chest X-ray and CAT-scan revealed multiple lung cysts and a bronchoalveolar lavage detected human papilloma virus 11. The patient responded well to antibiotics. A body plethysmography showed small lung volumes and low diffusion capacity for carbon monoxide, but normal volume diffusion capacity divided by alveolar volume. Pulmonary cystic disease should be considered when patients with JLP have symptoms of pneumonia.

  11. Characterization of human and Staphylococcus aureus proteins in respiratory mucosa by in vivo- and immunoproteomics.

    Science.gov (United States)

    Schmidt, Frank; Meyer, Tanja; Sundaramoorthy, Nandakumar; Michalik, Stephan; Surmann, Kristin; Depke, Maren; Dhople, Vishnu; Gesell Salazar, Manuela; Holtappels, Gabriele; Zhang, Nan; Bröker, Barbara M; Bachert, Claus; Völker, Uwe

    2017-02-23

    Staphylococcus aureus is a Gram-positive opportunistic bacterium which can be found as a commensal in the nares of about 50% of the human population. Besides asymptomatic carriage, S. aureus has also been found to colonize nasal polyps, a subform of chronic rhinosinusitis, in 60 to 100% of cases, and even reside intracellularly in nasal polyp tissue. The aim of this study was to shed light on the behavior of S. aureus in the human airways by analyzing S. aureus-specific proteins in nasal polyp tissue from patients with chronic rhinosinusitis and to characterize the immunogenic potential of the identified (mainly secreted) proteins. As a result, in total >600 S. aureus proteins were identified by high resolution mass spectrometry or multiple reaction monitoring. Of those roughly 180 are typically localized in the membrane, surface exposed or secreted. For 115 S. aureus proteins, partially also detected in vivo by mass spectrometry, IgA- and IgG-specific antibody signals were profiled. Strong antibody signals were predominantly found for surface expose or secreted proteins.

  12. Models to predict both sensible and latent heat transfer in the respiratory tract of Morada Nova sheep under semiarid tropical environment

    Science.gov (United States)

    Fonseca, Vinícius Carvalho; Saraiva, Edilson Paes; Maia, Alex Sandro Campos; Nascimento, Carolina Cardoso Nagib; da Silva, Josinaldo Araújo; Pereira, Walter Esfraim; Filho, Edgard Cavalcanti Pimenta; Almeida, Maria Elivânia Vieira

    2016-10-01

    The aim of this study was to build a prediction model both sensible and latent heat transfer by respiratory tract for Morada Nova sheep under field conditions in a semiarid tropical environment, using easily measured physiological and environmental parameters. Twelve dry Morada Nova ewes with an average of 3 ± 1.2 years old and average body weight of 32.76 ± 3.72 kg were used in a Latin square design 12 × 12 (12 days of records and 12 schedules). Tidal volume, respiratory rate, expired air temperature, and partial vapor pressure of the expired air were obtained from the respiratory facial mask and using a physiological measurement system. Ewes were evaluated from 0700 to 1900 h in each day under shade. A simple nonlinear model to estimate tidal volume as a function of respiratory rate was developed. Equation to estimate the expired air temperature was built, and the ambient air temperature was the best predictor together with relative humidity and ambient vapor pressure. In naturalized Morada Nova sheep, respiratory convection seems to be a mechanism of heat transfer of minor importance even under mild air temperature. Evaporation from the respiratory system increased together with ambient air temperature. At ambient air temperature, up to 35 °C respiratory evaporation accounted 90 % of the total heat lost by respiratory system, on average. Models presented here allow to estimate the heat flow from the respiratory tract for Morada Nova sheep bred in tropical region, using easily measured physiological and environmental traits as respiratory rate, ambient air temperature, and relative humidity.

  13. Models to predict both sensible and latent heat transfer in the respiratory tract of Morada Nova sheep under semiarid tropical environment

    Science.gov (United States)

    Fonseca, Vinícius Carvalho; Saraiva, Edilson Paes; Maia, Alex Sandro Campos; Nascimento, Carolina Cardoso Nagib; da Silva, Josinaldo Araújo; Pereira, Walter Esfraim; Filho, Edgard Cavalcanti Pimenta; Almeida, Maria Elivânia Vieira

    2017-05-01

    The aim of this study was to build a prediction model both sensible and latent heat transfer by respiratory tract for Morada Nova sheep under field conditions in a semiarid tropical environment, using easily measured physiological and environmental parameters. Twelve dry Morada Nova ewes with an average of 3 ± 1.2 years old and average body weight of 32.76 ± 3.72 kg were used in a Latin square design 12 × 12 (12 days of records and 12 schedules). Tidal volume, respiratory rate, expired air temperature, and partial vapor pressure of the expired air were obtained from the respiratory facial mask and using a physiological measurement system. Ewes were evaluated from 0700 to 1900 h in each day under shade. A simple nonlinear model to estimate tidal volume as a function of respiratory rate was developed. Equation to estimate the expired air temperature was built, and the ambient air temperature was the best predictor together with relative humidity and ambient vapor pressure. In naturalized Morada Nova sheep, respiratory convection seems to be a mechanism of heat transfer of minor importance even under mild air temperature. Evaporation from the respiratory system increased together with ambient air temperature. At ambient air temperature, up to 35 °C respiratory evaporation accounted 90 % of the total heat lost by respiratory system, on average. Models presented here allow to estimate the heat flow from the respiratory tract for Morada Nova sheep bred in tropical region, using easily measured physiological and environmental traits as respiratory rate, ambient air temperature, and relative humidity.

  14. Diverse and Tissue Specific Mitochondrial Respiratory Response in A Mouse Model of Sepsis-Induced Multiple Organ Failure

    DEFF Research Database (Denmark)

    Karlsson, Michael; Hara, Naomi; Morata, Saori

    2016-01-01

    Mitochondrial function is thought to play a role in sepsis-induced multiple organ failure. However, the temporal and organ specific alterations in mitochondrial function has yet to be fully elucidated. Many studies show reduced phosphorylating capacity while others have indicated that mitochondrial...... respiration is enhanced. The objective of the study was to evaluate the temporal dynamics of brain and liver mitochondrial function in a mouse model of sepsis.Sepsis was induced by cecal ligation and puncture. Controls were sham operated. Using high-resolution respirometry, brain and liver homogenates from 31......-production was detected.Liver homogenate from the septic mice displayed a significant increase of the respiratory control ratio at 6 hours. In the 24-hour group, the rate of maximal oxidative phosphorylation, as well as LEAK respiration, was significantly increased compared to controls and the resultant respiratory...

  15. A Combined Tissue Kinetics and Dosimetric Model of Respiratory Tissue Exposed to Radiation

    Energy Technology Data Exchange (ETDEWEB)

    John R. Ford

    2005-11-01

    Existing dosimetric models of the radiation response of tissues are essentially static. Consideration of changes in the cell populations over time has not been addressed realistically. For a single acute dose this is not a concern, but for modeling chronic exposures or fractionated acute exposures, the natural turnover and progression of cells could have a significant impact on a variety of endpoints. This proposal addresses the shortcomings of current methods by combining current dose-based calculation techniques with information on the cell turnover for a model tissue. The proposed model will examine effects at the single-cell level for an exposure of a section of human bronchiole. The cell model will be combined with Monte Carlo calculations of doses to cells and cell nuclei due to varying dose-rates of different radiation qualities. Predictions from the model of effects on survival, apoptosis rates, and changes in the number of cycling and differentiating cells will be tested experimentally. The availability of dynamic dosimetric models of tissues at the single-cell level will be useful for analysis of low-level radiation exposures and in the development of new radiotherapy protocols.

  16. Humanized in vivo Model for Autoimmune Diabetes

    Science.gov (United States)

    2009-02-01

    AWARD NUMBER: W81XWH-07-1-0121 TITLE: Humanized in vivo Model for Autoimmune Diabetes PRINCIPAL INVESTIGATOR: Gerald T Nepom, M.D., Ph.D...4. TITLE AND SUBTITLE Sa. CONTRACT NUMBER Humanized in vivo Model for Autoimmune Diabetes Sb. GRANT NUMBER W81XWH-07-1-0121 Sc. PROGRAM ELEMENT...therapies. This research study entails using humanized mice manifesting type 1 diabetes (T1 D)-associated human HLA molecules to address the fate and

  17. Molecular characterization and mutational analysis of the human B17 subunit of the mitochondrial respiratory chain complex I.

    Science.gov (United States)

    Smeitink, J; Loeffen, J; Smeets, R; Triepels, R; Ruitenbeek, W; Trijbels, F; van den Heuvel, L

    1998-08-01

    Bovine NADH:ubiquinone oxidoreductase (complex 1) of the mitochondrial respiratory chain consists of about 36 nuclear-encoded subunits. We review the current knowledge of the 15 human complex I subunits cloned so far, and report the 598-bp cDNA sequence, the chromosomal localization and the tissue expression of an additional subunit, the B17 subunit. The cDNA open reading frame of B17 comprises 387 bp and encodes a protein of 128 amino acids (calculated Mr 15.5 kDa). There is 82.7% and 78.1% homology, respectively, at the cDNA and amino acid level with the bovine counterpart. The gene of the B17 subunit has been mapped to chromosome 2. Multiple-tissue dot-blots showed ubiquitous expression of the mRNA with relatively higher expression in tissues known for their high energy demand. Of these, kidney showed the highest expression. Mutational analysis of the subunit revealed no mutations or polymorphisms in 20 patients with isolated enzymatic complex I deficiency in cultured skin fibroblasts.

  18. Diesel exhaust particulate extracts inhibit transcription of nuclear respiratory factor-1 and cell viability in human umbilical vein endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Mattingly, Kathleen A.; Klinge, Carolyn M. [University of Louisville School of Medicine, Department of Biochemistry and Molecular Biology, Center for Genetics and Molecular Medicine, Louisville, KY (United States)

    2012-04-15

    Endothelial dysfunction precedes cardiovascular disease and is accompanied by mitochondrial dysfunction. Here we tested the hypothesis that diesel exhaust particulate extracts (DEPEs), prepared from a truck run at different speeds and engine loads, would inhibit genomic estrogen receptor activation of nuclear respiratory factor-1 (NRF-1) transcription in human umbilical vein endothelial cells (HUVECs). Additionally, we examined how DEPEs affect NRF-1-regulated TFAM expression and, in turn, Tfam-regulated mtDNA-encoded cytochrome c oxidase subunit I (COI, MTCO1) and NADH dehydrogenase subunit I (NDI) expression as well as cell proliferation and viability. We report that 17{beta}-estradiol (E{sub 2}), 4-hydroxytamoxifen (4-OHT), and raloxifene increased NRF-1 transcription in HUVECs in an ER-dependent manner. DEPEs inhibited NRF-1 transcription, and this suppression was not ablated by concomitant treatment with E{sub 2}, 4-OHT, or raloxifene, indicating that the effect was not due to inhibition of ER activity. While E{sub 2} increased HUVEC proliferation and viability, DEPEs inhibited viability but not proliferation. Resveratrol increased NRF-1 transcription in an ER-dependent manner in HUVECs, and ablated DEPE inhibition of basal NRF-1 expression. Given that NRF-1 is a key nuclear transcription factor regulating genes involved in mitochondrial activity and biogenesis, these data suggest that DEPEs may adversely affect mitochondrial function leading to endothelial dysfunction and resveratrol may block these effects. (orig.)

  19. Contribution of cysteine residues in the extracellular domain of the F protein of human respiratory syncytial virus to its function

    Directory of Open Access Journals (Sweden)

    Melero José A

    2006-05-01

    Full Text Available Abstract The mature F protein of all known isolates of human respiratory syncytial virus (HRSV contains fifteen absolutely conserved cysteine (C residues that are highly conserved among the F proteins of other pneumoviruses as well as the paramyxoviruses. To explore the contribution of the cysteines in the extracellular domain to the fusion activity of HRSV F protein, each cysteine was changed to serine. Mutation of cysteines 37, 313, 322, 333, 343, 358, 367, 393, 416, and 439 abolished or greatly reduced cell surface expression suggesting these residues are critical for proper protein folding and transport to the cell surface. As expected, the fusion activity of these mutations was greatly reduced or abolished. Mutation of cysteine residues 212, 382, and 422 had little to no effect upon cell surface expression or fusion activity at 32°C, 37°C, or 39.5°C. Mutation of C37 and C69 in the F2 subunit either abolished or reduced cell surface expression by 75% respectively. None of the mutations displayed a temperature sensitive phenotype.

  20. Kinetics of antibody-induced modulation of respiratory syncytial virus antigens in a human epithelial cell line

    Directory of Open Access Journals (Sweden)

    Gómez-Garcia Beatriz

    2007-07-01

    Full Text Available Abstract Background The binding of viral-specific antibodies to cell-surface antigens usually results in down modulation of the antigen through redistribution of antigens into patches that subsequently may be internalized by endocytosis or may form caps that can be expelled to the extracellular space. Here, by use of confocal-laser-scanning microscopy we investigated the kinetics of the modulation of respiratory syncytial virus (RSV antigen by RSV-specific IgG. RSV-infected human epithelial cells (HEp-2 were incubated with anti-RSV polyclonal IgG and, at various incubation times, the RSV-cell-surface-antigen-antibody complexes (RSV Ag-Abs and intracellular viral proteins were detected by indirect immunoflourescence. Results Interaction of anti-RSV polyclonal IgG with RSV HEp-2 infected cells induced relocalization and aggregation of viral glycoproteins in the plasma membrane formed patches that subsequently produced caps or were internalized through clathrin-mediated endocytosis participation. Moreover, the concentration of cell surface RSV Ag-Abs and intracellular viral proteins showed a time dependent cyclic variation and that anti-RSV IgG protected HEp-2 cells from viral-induced death. Conclusion The results from this study indicate that interaction between RSV cell surface proteins and specific viral antibodies alter the expression of viral antigens expressed on the cells surface and intracellular viral proteins; furthermore, interfere with viral induced destruction of the cell.

  1. Flipped Classroom Model Improves Graduate Student Performance in Cardiovascular, Respiratory, and Renal Physiology

    Science.gov (United States)

    Tune, Johnathan D.; Sturek, Michael; Basile, David P.

    2013-01-01

    The purpose of this study was to assess the effectiveness of a traditional lecture-based curriculum versus a modified "flipped classroom" curriculum of cardiovascular, respiratory, and renal physiology delivered to first-year graduate students. Students in both courses were provided the same notes and recorded lectures. Students in the…

  2. 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 ...

  3. Respiratory alkalosis.

    Science.gov (United States)

    Foster, G T; Vaziri, N D; Sassoon, C S

    2001-04-01

    Respiratory alkalosis is an extremely common and complicated problem affecting virtually every organ system in the body. This article reviews the various facets of this interesting problem. Respiratory alkalosis produces multiple metabolic abnormalities, from changes in potassium, phosphate, and calcium, to the development of a mild lactic acidosis. Renal handling of the above ions is also affected. The etiologies may be related to pulmonary or extrapulmonary disorders. Hyperventilation syndrome is a common etiology of respiratory alkalosis in the emergency department setting and is a diagnosis by exclusion. There are many cardiac effects of respiratory alkalosis, such as tachycardia, ventricular and atrial arrhythmias, and ischemic and nonischemic chest pain. In the lungs, vasodilation occurs, and in the gastrointestinal system there are changes in perfusion, motility, and electrolyte handling. Therapeutically, respiratory alkalosis is used for treatment of elevated intracranial pressure. Correction of a respiratory alkalosis is best performed by correcting the underlying etiology.

  4. A Bayesian SIRS model for the analysis of respiratory syncytial virus in the region of Valencia, Spain.

    Science.gov (United States)

    Corberán-Vallet, Ana; Santonja, Francisco J

    2014-09-01

    We present a Bayesian stochastic susceptible-infected-recovered-susceptible (SIRS) model in discrete time to understand respiratory syncytial virus dynamics in the region of Valencia, Spain. A SIRS model based on ordinary differential equations has also been proposed to describe RSV dynamics in the region of Valencia. However, this continuous-time deterministic model is not suitable when the initial number of infected individuals is small. Stochastic epidemic models based on a probability of disease transmission provide a more natural description of the spread of infectious diseases. In addition, by allowing the transmission rate to vary stochastically over time, the proposed model provides an improved description of RSV dynamics. The Bayesian analysis of the model allows us to calculate both the posterior distribution of the model parameters and the posterior predictive distribution, which facilitates the computation of point forecasts and prediction intervals for future observations. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. RESPIRATORY SYSTEM

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    10.1 Respiratory failure2003068 Evaluation of non-invasive ventilation in a-cute respiratory failure with chronic obstructive pulmonary disease. GU Jianyong(顾俭勇), et al. Dept E-mergen, Zhongshan Hosp, Fudan Univ, Shanghai 200032. Shanghai J Med 2002; 25 (12): 741 - 743.Objective:To observe the effect of non-invasive venti-lation(NIV) in acute respiratory failure with chronic

  6. Quorum-sensing systems LuxS/autoinducer 2 and Com regulate Streptococcus pneumoniae biofilms in a bioreactor with living cultures of human respiratory cells.

    Science.gov (United States)

    Vidal, Jorge E; Howery, Kristen E; Ludewick, Herbert P; Nava, Porfirio; Klugman, Keith P

    2013-04-01

    Streptococcus pneumoniae forms organized biofilms in the human upper respiratory tract that may play an essential role in both persistence and acute respiratory infection. However, the production and regulation of biofilms on human cells is not yet fully understood. In this work, we developed a bioreactor with living cultures of human respiratory epithelial cells (HREC) and a continuous flow of nutrients, mimicking the microenvironment of the human respiratory epithelium, to study the production and regulation of S. pneumoniae biofilms (SPB). SPB were also produced under static conditions on immobilized HREC. Our experiments demonstrated that the biomass of SPB increased significantly when grown on HREC compared to the amount on abiotic surfaces. Additionally, pneumococcal strains produced more early biofilms on lung cells than on pharyngeal cells. Utilizing the bioreactor or immobilized human cells, the production of early SPB was found to be regulated by two quorum-sensing systems, Com and LuxS/AI-2, since a mutation in either comC or luxS rendered the pneumococcus unable to produce early biofilms on HREC. Interestingly, while LuxS/autoinducer 2 (AI-2) regulated biofilms on both HREC and abiotic surfaces, Com control was specific for those structures produced on HREC. The biofilm phenotypes of strain D39-derivative ΔcomC and ΔluxS QS mutants were reversed by genetic complementation. Of note, SPB formed on immobilized HREC and incubated under static conditions were completely lysed 24 h postinoculation. Biofilm lysis was also regulated by the Com and LuxS/AI-2 quorum-sensing systems.

  7. Novel recombinant DNA vaccine candidates for human respiratory syncytial virus: Preclinical evaluation of immunogenicity and protection efficiency.

    Science.gov (United States)

    Farrag, Mohamed A; Amer, Haitham M; Öhlschläger, Peter; Hamad, Maaweya E; Almajhdi, Fahad N

    2017-03-08

    The development of safe and potent vaccines for human respiratory syncytial virus (HRSV) is still a challenge for researchers worldwide. DNA-based immunization is currently a promising approach that has been used to generate human vaccines for different age groups. In this study, novel HRSV DNA vaccine candidates were generated and preclinically tested in BALB/c mice. Three different versions of the codon-optimized HRSV fusion (F) gene were individually cloned into the pPOE vector. The new recombinant vectors either express full-length (pPOE-F), secretory (pPOE-TF), or M282-90 linked (pPOE-FM2) forms of the F protein. Distinctive expression of the F protein was identified in HEp-2 cells transfected with the different recombinant vectors using ELISA and immunofluorescence. Mice immunization verified the potential for recombinant vectors to elicit significant levels of neutralizing antibodies and CD8(+) T-cell lymphocytes. pPOE-TF showed higher levels of gene expression in cell culture and better induction of the humoral and cellular immune responses. Following virus challenge, mice that had been immunized with the recombinant vectors were able to control virus replication and displayed lower inflammation compared with mice immunized with empty pPOE vector or formalin-inactivated HRSV vaccine. Moreover, pulmonary cytokine profiles of mice immunized with the 3 recombinant vectors were similar to those of the mock infected group. In conclusion, recombinant pPOE vectors are promising HRSV vaccine candidates in terms of their safety, immunogenicity and protective efficiency. These data encourage further evaluation in phase I clinical trials.

  8. SU-E-I-80: Quantification of Respiratory and Cardiac Motion Effect in SPECT Acquisitions Using Anthropomorphic Models: A Monte Carlo Simulation Study

    Energy Technology Data Exchange (ETDEWEB)

    Papadimitroulas, P; Kostou, T; Kagadis, G [University of Patras, Rion, Ahaia (Greece); Loudos, G [Technological Educational Institute of Athens, Egaleo, Attika (Greece)

    2015-06-15

    Purpose: The purpose of the present study was to quantify, evaluate the impact of cardiac and respiratory motion on clinical nuclear imaging protocols. Common SPECT and scintigraphic scans are studied using Monte Carlo (MC) simulations, comparing the resulted images with and without motion. Methods: Realistic simulations were executed using the GATE toolkit and the XCAT anthropomorphic phantom as a reference model for human anatomy. Three different radiopharmaceuticals based on 99mTc were studied, namely 99mTc-MDP, 99mTc—N—DBODC and 99mTc—DTPA-aerosol for bone, myocardium and lung scanning respectively. The resolution of the phantom was set to 3.5 mm{sup 3}. The impact of the motion on spatial resolution was quantified using a sphere with 3.5 mm diameter and 10 separate time frames, in the ECAM modeled SPECT scanner. Finally, respiratory motion impact on resolution and imaging of lung lesions was investigated. The MLEM algorithm was used for data reconstruction, while the literature derived biodistributions of the pharmaceuticals were used as activity maps in the simulations. Results: FWHM was extracted for a static and a moving sphere which was ∼23 cm away from the entrance of the SPECT head. The difference in the FWHM was 20% between the two simulations. Profiles in thorax were compared in the case of bone scintigraphy, showing displacement and blurring of the bones when respiratory motion was inserted in the simulation. Large discrepancies were noticed in the case of myocardium imaging when cardiac motion was incorporated during the SPECT acquisition. Finally the borders of the lungs are blurred when respiratory motion is included resulting to a dislocation of ∼2.5 cm. Conclusion: As we move to individualized imaging and therapy procedures, quantitative and qualitative imaging is of high importance in nuclear diagnosis. MC simulations combined with anthropomorphic digital phantoms can provide an accurate tool for applications like motion correction

  9. Photoacoustic spectroscopy of the expired air at a human respiratory pathology

    Science.gov (United States)

    Ageev, B. G.; Kapitanov, V. A.; Ponomarev, Yu. N.; Nikiforova, O. Yu.; Karapuzikov, A. I.; Sherstov, I. V.; Volkova, L. I.; Djakova, E. Yu.; Kapilevich, L. V.; Kapitanova, D. V.; Kistenev, Yu. V.; Smotrova, N. A.; Fokin, V. A.; Plohotin, A. V.; Berendeeva, T. A.

    2006-12-01

    There are about 600 volatile compounds in air expired by man, including molecules-biomarkers of endogenous (produced in organism) origin, the specificity of generation and excretion mechanisms of which is sufficient for studies of both normal and pathologic processes. The goal of this work is analysis of the human-expired air by means of the intracavity laser photoacoustic sensor intended for detection of air gas admixtures having the absorption bands in the wavelength spectral range 9.2 - 10.8 μm. The sensor principle of operation is based on the photoacoustic effect caused by gas absorption of the CO II laser radiation. Measurements were conducted with a test group consisting of 100 persons and a group of patients (60 persons) affected by different bronchopulnionary pathologies. The state of health of each group members was determined from questioning data. The spectral absorption dependences were normalized to referent points and then investigated in respect to a qualitative coincidence. The typical results are presented below.

  10. A numerical model of the respiratory modulation of pulmonary shunt and PaO2 oscillations for acute lung injury.

    Science.gov (United States)

    Beda, Alessandro; Jandre, Frederico C; Giannella-Neto, Antonio

    2010-03-01

    It is an accepted hypothesis that the amplitude of the respiratory-related oscillations of arterial partial pressure of oxygen (DeltaPaO2) is primarily modulated by fluctuations of pulmonary shunt (Deltas), the latter generated mainly by cyclic alveolar collapse/reopening, when present. A better understanding of the relationship between DeltaPaO2, Deltas, and cyclic alveolar collapse/reopening can have clinical relevance for minimizing the severe lung damage that the latter can cause, for example during mechanical ventilation (MV) of patients with acute lung injury (ALI). To this aim, we numerically simulated the effect of such a relationship on an animal model of ALI under MV, using a combination of a model of lung gas exchange during tidal ventilation with a model of time dependence of shunt on alveolar collapse/opening. The results showed that: (a) the model could adequately replicate published experimental results regarding the complex dependence of DeltaPaO2 on respiratory frequency, driving pressure (DeltaP), and positive end-expiratory pressure (PEEP), while simpler models could not; (b) such a replication strongly depends on the value of the model parameters, especially of the speed of alveolar collapse/reopening; (c) the relationship between DeltaPaO2 and Deltas was overall markedly nonlinear, but approximately linear for PEEP>or=6 cmH2O, with very large DeltaPaO2 associated with relatively small Deltas.

  11. Human mammary microenvironment better regulates the biology of human breast cancer in humanized mouse model.

    Science.gov (United States)

    Zheng, Ming-Jie; Wang, Jue; Xu, Lu; Zha, Xiao-Ming; Zhao, Yi; Ling, Li-Jun; Wang, Shui

    2015-02-01

    During the past decades, many efforts have been made in mimicking the clinical progress of human cancer in mouse models. Previously, we developed a human breast tissue-derived (HB) mouse model. Theoretically, it may mimic the interactions between "species-specific" mammary microenvironment of human origin and human breast cancer cells. However, detailed evidences are absent. The present study (in vivo, cellular, and molecular experiments) was designed to explore the regulatory role of human mammary microenvironment in the progress of human breast cancer cells. Subcutaneous (SUB), mammary fat pad (MFP), and HB mouse models were developed for in vivo comparisons. Then, the orthotopic tumor masses from three different mouse models were collected for primary culture. Finally, the biology of primary cultured human breast cancer cells was compared by cellular and molecular experiments. Results of in vivo mouse models indicated that human breast cancer cells grew better in human mammary microenvironment. Cellular and molecular experiments confirmed that primary cultured human breast cancer cells from HB mouse model showed a better proliferative and anti-apoptotic biology than those from SUB to MFP mouse models. Meanwhile, primary cultured human breast cancer cells from HB mouse model also obtained the migratory and invasive biology for "species-specific" tissue metastasis to human tissues. Comprehensive analyses suggest that "species-specific" mammary microenvironment of human origin better regulates the biology of human breast cancer cells in our humanized mouse model of breast cancer, which is more consistent with the clinical progress of human breast cancer.

  12. Modelling of polysomnographic respiratory measurements for artefact detection and signal restoration.

    Science.gov (United States)

    Rathnayake, S I; Abeyratne, U R; Hukins, C; Duce, B

    2008-09-01

    Polysomnography (PSG), which incorporates measures of sleep with measures of EEG arousal, air flow, respiratory movement and oxygenation, is universally regarded as the reference standard in diagnosing sleep-related respiratory diseases such as obstructive sleep apnoea syndrome. Over 15 channels of physiological signals are measured from a subject undergoing a typical overnight PSG session. The signals often suffer from data losses, interferences and artefacts. In a typical sleep scoring session, artefact-corrupted signal segments are visually detected and removed from further consideration. This is a highly time-consuming process, and subjective judgement is required for the job. During typical sleep scoring sessions, the target is the detection of segments of diagnostic interest, and signal restoration is not utilized for distorted segments. In this paper, we propose a novel framework for artefact detection and signal restoration based on the redundancy among respiratory flow signals. We focus on the air flow (thermistor sensors) and nasal pressure signals which are clinically significant in detecting respiratory disturbances. The method treats the respiratory system and other organs that provide respiratory-related inputs/outputs to it (e.g., cardiovascular, brain) as a possibly nonlinear coupled-dynamical system, and uses the celebrated Takens embedding theorem as the theoretical basis for signal prediction. Nonlinear prediction across time (self-prediction) and signals (cross-prediction) provides us with a mechanism to detect artefacts as unexplained deviations. In addition to detection, the proposed method carries the potential to correct certain classes of artefacts and restore the signal. In this study, we categorize commonly occurring artefacts and distortions in air flow and nasal pressure measurements into several groups and explore the efficacy of the proposed technique in detecting/recovering them. The results we obtained from a database of clinical

  13. Detection of Human Bocavirus in Children with Acute Respiratory Tract Infections in Lanzhou and Nanjing, China

    Institute of Scientific and Technical Information of China (English)

    WU Jian Jun; ZHANG Jing; ZHAO Yang; GAO Xiao Qian; DUAN Zhao Jun; JIN Yu; LIN Na; XIE Zhi Ping; YU Jie Mei; LI Jin Song; CAO Chang Qing; YUAN Xin Hui; SONG Jin Rong

    2014-01-01

    Objective The aim of this study was to explore the prevalent characteristics of HBoV1 and its co-infection. Methods PCR was used to detect HBoV1-DNA (HBoV1) and other viruses. A multivariate logistic regression model was used to explore possibility of co-detected for related viruses. Results The positivity rates in Nanjing and Lanzhou were 9.38% (74/789) and 11.62% (161/1386), respectively (P>0.05). The HBoV1 positive group was younger than negative group (P Conclusions Presence of HBoV1 in nasopharyngeal aspirates did not correlate with region or gender, although the prevalence of HBoV1 was higher in younger children. There were no correlations between HBoV1 and other variables, except for the season and ADV, RSV, or IFVA infections.

  14. Genetics, recombination and clinical features of human rhinovirus species C (HRV-C infections; interactions of HRV-C with other respiratory viruses.

    Directory of Open Access Journals (Sweden)

    Anne Wisdom

    Full Text Available To estimate the frequency, molecular epidemiological and clinical associations of infection with the newly described species C variants of human rhinoviruses (HRV, 3243 diagnostic respiratory samples referred for diagnostic testing in Edinburgh were screened using a VP4-encoding region-based selective polymerase chain reaction (PCR for HRV-C along with parallel PCR testing for 13 other respiratory viruses. HRV-C was the third most frequently detected behind respiratory syncytial virus (RSV and adenovirus, with 141 infection episodes detected among 1885 subjects over 13 months (7.5%. Infections predominantly targeted the very young (median age 6-12 months; 80% of infections in those <2 years, occurred throughout the year but with peak incidence in early winter months. HRV-C was detected significantly more frequently among subjects with lower (LRT and upper respiratory tract (URT disease than controls without respiratory symptoms; HRV-C mono-infections were the second most frequently detected virus (behind RSV in both disease presentations (6.9% and 7.8% of all cases respectively. HRV variants were classified by VP4/VP2 sequencing into 39 genotypically defined types, increasing the current total worldwide to 60. Through sequence comparisons of the 5'untranslated region (5'UTR, the majority grouped with species A (n = 96; 68%, described as HRV-Ca, the remainder forming a phylogenetically distinct 5'UTR group (HRV-Cc. Multiple and bidirectional recombination events between HRV-Ca and HRV-Cc variants and with HRV species A represents the most parsimonious explanation for their interspersed phylogeny relationships in the VP4/VP2-encoding region. No difference in age distribution, seasonality or disease associations was identified between HRV-Ca and HRV-Cc variants. HRV-C-infected subjects showed markedly reduced detection frequencies of RSV and other respiratory viruses, providing evidence for a major interfering effect of HRV-C on susceptibility to

  15. Genetically Modified Pig Models for Human Diseases

    Institute of Scientific and Technical Information of China (English)

    Nana Fan; Liangxue Lai

    2013-01-01

    Genetically modified animal models are important for understanding the pathogenesis of human disease and developing therapeutic strategies.Although genetically modified mice have been widely used to model human diseases,some of these mouse models do not replicate important disease symptoms or pathology.Pigs are more similar to humans than mice in anatomy,physiology,and genome.Thus,pigs are considered to be better animal models to mimic some human diseases.This review describes genetically modified pigs that have been used to model various diseases including neurological,cardiovascular,and diabetic disorders.We also discuss the development in gene modification technology that can facilitate the generation of transgenic pig models for human diseases.

  16. Respiratory Health – Exposure Measurements and Modeling in the Fragrance and Flavour Industry

    OpenAIRE

    Eric Angelini; Gerard Camerini; Malick Diop; Patrice Roche; Thomas Rodi; Christine Schippa; Thierry Thomas

    2016-01-01

    Although the flavor and fragrance industry is about 150 years old, the use of synthetic materials started more than 100 years ago, and the awareness of the respiratory hazard presented by some flavoring substances emerged only recently. In 2001, the US National Institute of Occupational Safety and Health (NIOSH) identified for the first time inhalation exposure to flavoring substances in the workplace as a possible occupational hazard. As a consequence, manufacturers must comply with a variet...

  17. Induction of IL-6 and CCL5 (RANTES in human respiratory epithelial (A549 cells by clinical isolates of respiratory syncytial virus is strain specific

    Directory of Open Access Journals (Sweden)

    Levitz Ruth

    2012-09-01

    Full Text Available Abstract Background Respiratory syncytial virus (RSV is the major respiratory pathogen of infants and young children. During each seasonal epidemic, multiple strains of both subgroup A and B viruses circulate in the community. Like other RNA viruses, RSV genome replication is prone to errors that results in a heterogeneous population of viral strains some of which may possess differences in virulence. We sought to determine whether clinical isolates of RSV differ in their capacity to induce inflammatory cytokines IL-6 and CCL5 (previously known as RANTES [regulated upon activation, normal T-cell expressed and secreted protein], which are known to be induced in vitro and in vivo in response to RSV, during infection of A549 cells. Results Screening of subgroup A and B isolates revealed heterogeneity among strains to induce IL-6 and CCL5. We chose two subgroup B strains, New Haven (NH1067 and NH1125, for further analysis because of their marked differences in cytokine inducing properties and because subgroup B strains, in general, are less genetically heterogeneous as compared to subgroup A strains. At 12 and 24 hours post infection RSV strains, NH1067 and NH1125 differed in their capacity to induce IL-6 by an order of magnitude or more. The concentrations of IL-6 and CCL5 were dependent on the dose of infectious virus and the concentration of these cytokines induced by NH1125 was greater than that of those induced by NH1067 when the multiplicity of infection of NH1067 used was as much as 10-fold higher than that of NH1125. The induction of IL-6 was dependent on viable virus as infection with UV-inactivated virus did not induce IL-6. The difference in IL-6 induction most likely could not be explained by differences in viral replication kinetics. The intracellular level of RSV RNA, as determined by quantitative RT-PCR, was indistinguishable between the 2 strains though the titer of progeny virus produced by NH1125 was greater than that produced by

  18. Clinical protection from falciparum malaria correlates with neutrophil respiratory bursts induced by merozoites opsonized with human serum antibodies.

    Directory of Open Access Journals (Sweden)

    Charlotte Joos

    Full Text Available BACKGROUND: Effective vaccines to combat malaria are urgently needed, but have proved elusive in the absence of validated correlates of natural immunity. Repeated blood stage infections induce antibodies considered to be the main arbiters of protection from pathology, but their essential functions have remained speculative. METHODOLOGY/PRINCIPAL FINDINGS: This study evaluated antibody dependent respiratory burst (ADRB activity in polymorphonuclear neutrophils (PMN induced by Plasmodium falciparum merozoites and antibodies in the sera of two different African endemic populations, and investigated its association with naturally acquired clinical protection. Respiratory bursts by freshly isolated PMN were quantified by chemiluminescence readout in the presence of isoluminol, which preferentially detects extra-cellular reactive oxygen species (ROS. Using a standardized, high throughput protocol, 230 sera were analyzed from individuals of all age groups living in meso- (Ndiop or holo-endemic (Dielmo Senegalese villages, and enrolled in a cross-sectional prospective study with intensive follow-up. Statistical significance was determined using non-parametric tests and Poisson regression models. The most important finding was that PMN ADRB activity was correlated with acquired clinical protection from malaria in both high and low transmission areas (P = 0.006 and 0.036 respectively. Strikingly, individuals in Dielmo with dichotomized high ADRB indexes were seventeen fold less susceptible to malaria attacks (P = 0.006. Complementary results showed that ADRB activity was (i dependent on intact merozoites and IgG opsonins, but not parasitized erythrocytes, or complement, (ii correlated with merozoite specific cytophilic IgG1 and IgG3 antibody titers (P<0.001 for both, and (iii stronger in antisera from a holo-endemic compared to a meso-endemic site (P = 0.002, and reduced in asymptomatic carriers (P<0.001. CONCLUSIONS/SIGNIFICANCE: This work presents the

  19. Attached and unattached fractions of short-lived radon decay products in outdoor environments: effect on the human respiratory system.

    Science.gov (United States)

    Amrane, M; Oufni, L; Misdaq, M A

    2014-12-01

    The authors developed a model for determining the alpha- and beta-activities per unit volume of air due to radon ((222)Rn), thoron ((220)Rn) and their decay products attached and unattached to the aerosol in the outdoor air at the workplace in natural conditions at different locations in Morocco by using both CR-39 and LR-115 type II solid-state nuclear track detectors. In addition, the percentage of (218)Po, (214)Pb and (214)Po radionuclides attached to the aerosols and the unattached fraction f(j) for different values of the attachment rate were evaluated. Radon and thoron concentrations in outdoor air of the studied different locations were found to vary from 9.20±0.8 to 16.30±1.50 Bq m(-3) and 0.22±0.02 to 1.80±0.20 Bq m(-3), respectively. The committed equivalent doses due to the radon short-lived progeny (218)Po and (214)Po attached and unattached to the aerosol air were evaluated in different tissues of the respiratory tract of the members of the public from the inhalation of outdoor air.

  20. 3-D Human Modeling and Animation

    CERN Document Server

    Ratner, Peter

    2012-01-01

    3-D Human Modeling and Animation Third Edition All the tools and techniques you need to bring human figures to 3-D life Thanks to today's remarkable technology, artists can create and animate realistic, three-dimensional human figures that were not possible just a few years ago. This easy-to-follow book guides you through all the necessary steps to adapt your own artistic skill in figure drawing, painting, and sculpture to this exciting digital canvas. 3-D Human Modeling and Animation, Third Edition starts you off with simple modeling, then prepares you for more advanced techniques for crea

  1. Human hand modelling: kinematics, dynamics, applications

    NARCIS (Netherlands)

    Gustus, A.; Stillfried, G.; Visser, J.; Jörntell, H.; Van der Smagt, P.

    2012-01-01

    An overview of mathematical modelling of the human hand is given. We consider hand models from a specific background: rather than studying hands for surgical or similar goals, we target at providing a set of tools with which human grasping and manipulation capabilities can be studied, and hand funct

  2. Human respiratory syncytial virus nucleoprotein and inclusion bodies antagonize the innate immune response mediated by MDA5 and MAVS.

    Science.gov (United States)

    Lifland, Aaron W; Jung, Jeenah; Alonas, Eric; Zurla, Chiara; Crowe, James E; Santangelo, Philip J

    2012-08-01

    Currently, the spatial distribution of human respiratory syncytial virus (hRSV) proteins and RNAs in infected cells is still under investigation, with many unanswered questions regarding the interaction of virus-induced structures and the innate immune system. Very few studies of hRSV have used subcellular imaging as a means to explore the changes in localization of retinoic-acid-inducible gene-I (RIG-I)-like receptors or the mitochondrial antiviral signaling (MAVS) protein, in response to the infection and formation of viral structures. In this investigation, we found that both RIG-I and melanoma differentiation-associated gene 5 (MDA5) colocalized with viral genomic RNA and the nucleoprotein (N) as early as 6 h postinfection (hpi). By 12 hpi, MDA5 and MAVS were observed within large viral inclusion bodies (IB). We used a proximity ligation assay (PLA) and determined that the N protein was in close proximity to MDA5 and MAVS in IBs throughout the course of the infection. Similar results were found with the transient coexpression of N and the phosphoprotein (P). Additionally, we demonstrated that the localization of MDA5 and MAVS in IBs inhibited the expression of interferon β mRNA 27-fold following Newcastle disease virus infection. From these data, we concluded that the N likely interacts with MDA5, is in close proximity to MAVS, and localizes these molecules within IBs in order to attenuate the interferon response. To our knowledge, this is the first report of a specific function for hRSV IBs and of the hRSV N protein as a modulator of the innate immune response.

  3. Hidden Markov Models for Human Genes

    DEFF Research Database (Denmark)

    Baldi, Pierre; Brunak, Søren; Chauvin, Yves

    1997-01-01

    We analyse the sequential structure of human genomic DNA by hidden Markov models. We apply models of widely different design: conventional left-right constructs and models with a built-in periodic architecture. The models are trained on segments of DNA sequences extracted such that they cover...

  4. Respiratory chain complex I, a main regulatory target of the cAMP/PKA pathway is defective in different human diseases

    DEFF Research Database (Denmark)

    Papa, S.; De Rasmo, D.; Technikova-Dobrova, Z.;

    2012-01-01

    In mammals, complex I (NADH-ubiquinone oxidoreductase) of the mitochondrial respiratory chain has 31 supernumerary subunits in addition to the 14 conserved from prokaryotes to humans. Multiplicity of structural protein components, as well as of biogenesis factors, makes complex I a sensible pace...... to genetic and sporadic pathological factors. Complex I dysfunction has, indeed, been found, to be associated with several human diseases. Knowledge of the pathogenetic mechanisms of these diseases can help to develop new therapeutic strategies. (C) 2011 Federation of European Biochemical Societies...

  5. Viscoelastic Model for Lung Parenchyma for Multi-Scale Modeling of Respiratory System, Phase II: Dodecahedral Micro-Model

    Energy Technology Data Exchange (ETDEWEB)

    Freed, Alan D.; Einstein, Daniel R.; Carson, James P.; Jacob, Rick E.

    2012-03-01

    In the first year of this contractual effort a hypo-elastic constitutive model was developed and shown to have great potential in modeling the elastic response of parenchyma. This model resides at the macroscopic level of the continuum. In this, the second year of our support, an isotropic dodecahedron is employed as an alveolar model. This is a microscopic model for parenchyma. A hopeful outcome is that the linkage between these two scales of modeling will be a source of insight and inspiration that will aid us in the final year's activity: creating a viscoelastic model for parenchyma.

  6. Efficacy of a new fluoroquinolone, JNJ-Q2, in murine models of Staphylococcus aureus and Streptococcus pneumoniae skin, respiratory, and systemic infections.

    Science.gov (United States)

    Fernandez, Jeffrey; Hilliard, Jamese J; Morrow, Brian J; Melton, John L; Flamm, Robert K; Barron, Alfred M; Lynch, A Simon

    2011-12-01

    The in vivo efficacy of JNJ-Q2, a new broad-spectrum fluoroquinolone (FQ), was evaluated in a murine septicemia model with methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) and in a Streptococcus pneumoniae lower respiratory tract infection model. JNJ-Q2 and comparators were also evaluated in an acute murine skin infection model using a community-acquired MRSA strain and in an established skin infection (ESI) model using a hospital-acquired strain, for which the selection of resistant mutants was also determined. JNJ-Q2 demonstrated activity in the MSSA septicemia model that was comparable to that moxifloxacin (JNJ-Q2 50% effective dose [ED(50)], 0.2 mg/kg of body weight administered subcutaneously [s.c.] and 2 mg/kg administered orally [p.o.]) and activity in the MRSA septicemia model that was superior to that of vancomycin (JNJ-Q2 ED(50), 1.6 mg/kg administered s.c.). In an S. pneumoniae lower respiratory tract infection model, JNJ-Q2 displayed activity (ED(50), 1.9 mg/kg administered s.c. and 7.4 mg/kg administered p.o.) that was comparable to that of gemifloxacin and superior to that of moxifloxacin. In both MRSA skin infection models, treatment with JNJ-Q2 resulted in dose-dependent reductions in bacterial titers in the skin, with the response to JNJ-Q2 at each dose exceeding the responses of the comparators ciprofloxacin, moxifloxacin, linezolid, and vancomycin. Additionally, in the ESI model, JNJ-Q2 showed a low or nondetectable propensity for ciprofloxacin resistance selection, in contrast to the selection of ciprofloxacin-resistant mutants observed for both ciprofloxacin and moxifloxacin. JNJ-Q2 demonstrated activity that was comparable or superior to the activity of fluoroquinolone or antistaphylococcal comparators in several local and systemic skin infection models performed with both S. aureus and S. pneumoniae and is currently being evaluated in phase II human clinical trials.

  7. Structure and functional dynamics characterization of the ion channel of the human respiratory syncytial virus (hRSV) small hydrophobic protein (SH) transmembrane domain by combining molecular dynamics with excited normal modes.

    Science.gov (United States)

    Araujo, Gabriela C; Silva, Ricardo H T; Scott, Luis P B; Araujo, Alexandre S; Souza, Fatima P; de Oliveira, Ronaldo Junio

    2016-12-01

    The human respiratory syncytial virus (hRSV) is the major cause of lower respiratory tract infection in children and elderly people worldwide. Its genome encodes 11 proteins including SH protein, whose functions are not well known. Studies show that SH protein increases RSV virulence degree and permeability to small compounds, suggesting it is involved in the formation of ion channels. The knowledge of SH structure and function is fundamental for a better understanding of its infection mechanism. The aim of this study was to model, characterize, and analyze the structural behavior of SH protein in the phospholipids bilayer environment. Molecular modeling of SH pentameric structure was performed, followed by traditional molecular dynamics (MD) simulations of the protein immersed in the lipid bilayer. Molecular dynamics with excited normal modes (MDeNM) was applied in the resulting system in order to investigate long time scale pore dynamics. MD simulations support that SH protein is stable in its pentameric form. Simulations also showed the presence of water molecules within the bilayer by density distribution, thus confirming that SH protein is a viroporin. This water transport was also observed in MDeNM studies with histidine residues of five chains (His22 and His51), playing a key role in pore permeability. The combination of traditional MD and MDeNM was a very efficient protocol to investigate functional conformational changes of transmembrane proteins that act as molecular channels. This protocol can support future investigations of drug candidates by acting on SH protein to inhibit viral infection. Graphical Abstract The ion channel of the human respiratory syncytial virus (hRSV) small hydrophobic protein (SH) transmembrane domainᅟ.

  8. The AIMAR recommendations for early diagnosis of chronic obstructive respiratory disease based on the WHO/GARD model*.

    Science.gov (United States)

    Nardini, Stefano; Annesi-Maesano, Isabella; Del Donno, Mario; Delucchi, Maurizio; Bettoncelli, Germano; Lamberti, Vincenzo; Patera, Carlo; Polverino, Mario; Russo, Antonio; Santoriello, Carlo; Soverina, Patrizio

    2014-01-01

    to the Italian context; the document of the Agency for Regional Healthcare Services (AGE.NA.S) is a more suited compendium for consultation, and the recent joint statement on integrated COPD management of the three major Italian scientific Associations in the respiratory area together with the contribution of a Society of General Medicine deals prevalently with some critical issues (appropriateness of diagnosis, pharmacological treatment, rehabilitation, continuing care); also the document "Care Continuity: Chronic Obstructive Pulmonary Disease (COPD)" of the Global Alliance against chronic Respiratory Diseases (GARD)-Italy does not treat in depth the issue of early diagnosis. The present document - produced by the AIMAR (Interdisciplinary Association for Research in Lung Disease) Task Force for early diagnosis of chronic respiratory disease based on the WHO/GARD model and on available evidence and expertise -after a general examination of the main epidemiologic aspects, proposes to integrate the above-mentioned existing documents. In particular: a) it formally indicates on the basis of the available evidence the modalities and the instruments necessary for carrying out secondary prevention at the primary care level (a pro-active,'case-finding'approach; assessment of the individual's level of risk of COPD; use of short questionnaires for an initial screening based on symptoms; use of simple spirometry for the second level of screening); b) it identifies possible ways of including these activities within primary care practice; c) it places early diagnosis within the "systemic", consequential management of chronic respiratory diseases, which will be briefly described with the aid of schemes taken from the Italian and international reference documents.

  9. Human Centered Hardware Modeling and Collaboration

    Science.gov (United States)

    Stambolian Damon; Lawrence, Brad; Stelges, Katrine; Henderson, Gena

    2013-01-01

    In order to collaborate engineering designs among NASA Centers and customers, to in clude hardware and human activities from multiple remote locations, live human-centered modeling and collaboration across several sites has been successfully facilitated by Kennedy Space Center. The focus of this paper includes innovative a pproaches to engineering design analyses and training, along with research being conducted to apply new technologies for tracking, immersing, and evaluating humans as well as rocket, vehic le, component, or faci lity hardware utilizing high resolution cameras, motion tracking, ergonomic analysis, biomedical monitoring, wor k instruction integration, head-mounted displays, and other innovative human-system integration modeling, simulation, and collaboration applications.

  10. Polyethylene glycol-coupled IGF1 delays motor function defects in a mouse model of spinal muscular atrophy with respiratory distress type 1.

    Science.gov (United States)

    Krieger, Frank; Elflein, Nicole; Saenger, Stefanie; Wirthgen, Elisa; Rak, Kristen; Frantz, Stefan; Hoeflich, Andreas; Toyka, Klaus V; Metzger, Friedrich; Jablonka, Sibylle

    2014-05-01

    Spinal muscular atrophy with respiratory distress type 1 is a neuromuscular disorder characterized by progressive weakness and atrophy of the diaphragm and skeletal muscles, leading to death in childhood. No effective treatment is available. The neuromuscular degeneration (Nmd(2J)) mouse shares a crucial mutation in the immunoglobulin mu-binding protein 2 gene (Ighmbp2) with spinal muscular atrophy with respiratory distress type 1 patients and also displays some basic features of the human disease. This model serves as a promising tool in understanding the complex mechanisms of the disease and in exploring novel treatment modalities such as insulin-like growth factor 1 (IGF1) which supports myogenic and neurogenic survival and stimulates differentiation during development. Here we investigated the treatment effects with polyethylene glycol-coupled IGF1 and its mechanisms of action in neurons and muscles. Polyethylene glycol-coupled IGF1 was applied subcutaneously every second day from post-natal Day 14 to post-natal Day 42 and the outcome was assessed by morphology, electromyography, and molecular studies. We found reduced IGF1 serum levels in Nmd(2J) mice 2 weeks after birth, which was normalized by polyethylene glycol-coupled IGF1 treatment. Nmd(2J) mice showed marked neurogenic muscle fibre atrophy in the gastrocnemius muscle and polyethylene glycol-coupled IGF1 treatment resulted in muscle fibre hypertrophy and slowed fibre degeneration along with significantly higher numbers of functionally active axonal sprouts. In the diaphragm with predominant myogenic changes a profound protection from muscle fibre degeneration was observed under treatment. No effects of polyethylene glycol-coupled IGF1 were monitored at the level of motor neuron survival. The beneficial effects of polyethylene glycol-coupled IGF1 corresponded to a marked activation of the IGF1 receptor, resulting in enhanced phosphorylation of Akt (protein kinase B) and the ribosomal protein S6 kinase in

  11. Human Exposure Modeling - Databases to Support Exposure Modeling

    Science.gov (United States)

    Human exposure modeling relates pollutant concentrations in the larger environmental media to pollutant concentrations in the immediate exposure media. The models described here are available on other EPA websites.

  12. RESPIRATORY SYSTEM

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    2004494 Respiratory control in obstructive sleep apnea hypopnea syndrome. WANG Wei (王玮), et al. Instit Respir Dis, 1st Affili Hosp, China Med Limy, Shenyang 110001. Chin J Intern Med 2004; 43 (9): 647-650.

  13. Knowledge Brokering: An Innovative Model for Supporting Evidence-Informed Practice in Respiratory Care

    Directory of Open Access Journals (Sweden)

    Alison M Hoens

    2013-01-01

    Full Text Available The process of adopting research findings in the clinical setting is challenging, regardless of the area of practice. One strategy to facilitate this process is the use of knowledge brokering. Knowledge brokers (KBs are individuals who work to bridge the gap between researchers and knowledge users. In the health care setting, KBs work closely with clinicians to facilitate enhanced uptake of research findings into clinical practice. They also work with researchers to ensure research findings are translatable and meaningful to clinical practice. The present article discusses a KB’s role in a respiratory care setting. Working closely with both researchers and clinicians, the KB has led teams in the process of conceptualizing, developing, testing, disseminating and evaluating several projects related to respiratory care, including projects related to mobility in critical care settings and acute exacerbations of chronic obstructive pulmonary disease; inspiratory muscle training; and the use of incentive spirometry in postsurgical populations. The KB role has provided an important communication link between researcher and knowledge user that has facilitated evidence-informed practice to improve patient care.

  14. Human Operator Control Strategy Model.

    Science.gov (United States)

    1980-04-01

    fashion. HOPE reflects the two-store theory of memory current in the psycho- logical literature ( Atkinson & Shiffrin , 1968; Broadbent, 1971). Two...uncertainty. In P.M.A. Rabbit & S. Dornic (Eds.), Attention and performance V. New York: Academic Press, 1975. Atkinson , R. C., & Shiffrin , R. M. Human...48 2. The Perception Process ... ............... 50 3. The Command Memory and Command Selection Process

  15. Chemical exposure-response relationship between air pollutants and reactive oxygen species in the human respiratory tract

    Science.gov (United States)

    Lakey, P. S. J.; Berkemeier, T.; Tong, H.; Arangio, A. M.; Lucas, K.; Poeschl, U.; Shiraiwa, M.

    2016-12-01

    The inhalation of air pollutants such as O3 and particulate matter can lead to the formation of reactive oxygen species (ROS) which can cause damage to biosurfaces such as the lung epithelium unless they are effectively scavenged. Although the chemical processes that lead to ROS formation within the ELF upon inhalation of pollutants are well understood qualitatively, ROS concentrations within the ELF have hardly been quantified so far. The kinetic multi-layer model of surface and bulk chemistry in the epithelial lining fluid (KM-SUB-ELF) has been developed to describe chemical reactions and mass transport and to quantify ROS production rates and concentrations within the epithelial lining fluid. KM-SUB-ELF simulations suggest that O3 will rapidly saturate the ELF whereas antioxidants and surfactant species are effective scavengers of OH. High ambient concentrations of O3 can lead to the depletion of surfactants and antioxidants within the ELF, potentially leading to oxidative stress. KM-SUB-ELF reproduced measurements for the formation of H2O2 and OH due to the presence of iron, copper and quinones in surrogate lung lining fluid. This enabled ROS production rates and concentrations in the ELF to be quantified. We found that in polluted megacities the ROS concentration in the ELF due to inhalation of pollutants was at least as high as the concentrations in the ELF of patients suffering from respiratory diseases. Cu and Fe are found to be the most important redox-active aerosol components for ROS production upon inhalation of PM2.5 in polluted regions. Therefore, a reduction in the emission of Cu and Fe should be major targets of air pollution control. Chemical exposure-response relations provide a quantitative basis for assessing the relative importance of specific air pollutants in different regions of the world, showing that aerosol-induced epithelial ROS levels in polluted megacity air can be several orders of magnitude higher than in pristine rainforest air.

  16. In vivo measurements of relaxation process in the human liver by MRI. The role of respiratory gating/triggering

    DEFF Research Database (Denmark)

    Thomsen, C; Henriksen, O; Ring, P

    1988-01-01

    In vivo estimation of relaxation processes in the liver by magnetic resonance imaging (MRI) may be helpful for characterization of various pathological conditions in the liver. However, such measurements may be significantly hampered by movement of the liver with the respiration. The effect...... of synchronization of data acquisition to the respiratory cycle on measured T1- and T2-relaxation curves was studied in normal subjects, patients with diffuse liver disease, and patients with focal liver pathology. Multi spin echo sequences with five different repetition times were used. The measurements were...... different, when respiratory synchronization was employed. The results indicate that respiratory synchronization is only necessary for estimation of relaxation processes in the liver with focal pathology....

  17. Evaluation of pulmonary dysfunctions and acid-base imbalances induced by Chlamydia psittaci in a bovine model of respiratory infection.

    Science.gov (United States)

    Ostermann, Carola; Linde, Susanna; Siegling-Vlitakis, Christiane; Reinhold, Petra

    2014-01-01

    Chlamydia psittaci (Cp) is a respiratory pathogen capable of inducing acute pulmonary zoonotic disease (psittacosis) or persistent infection. To elucidate the pathogenesis of this infection, a translational large animal model was recently introduced by our group. This study aims at quantifying and differentiating pulmonary dysfunction and acid-base imbalances induced by Cp. Forty-two calves were grouped in (i) animals inoculated with Cp (n = 21) and (ii) controls sham-inoculated with uninfected cell culture (n = 21). For pulmonary function testing, impulse oscillometry, capnography, and FRC (functional residual capacity) measurement were applied to spontaneously breathing animals. Variables of acid-base status were assessed in venous blood using both (i) traditional Henderson-Hasselbalch and (ii) strong ion approach. Both obstructive and restrictive pulmonary disorders were induced in calves experimentally inoculated with Cp. Although disorders in respiratory mechanics lasted for 8-11 days, the pattern of spontaneous breathing was mainly altered in the period of acute illness (until 4 days post inoculation, dpi). Expiration was more impaired than inspiration, resulting in elevated FRC. Ventilation was characterised by a reduction in tidal volume (-25%) combined with an increased percentage of dead space volume and a significant reduction of alveolar volume by 10%. Minute ventilation increased significantly (+50%) due to a compensatory doubling of respiratory rate. Hyperventilatory hypocapnia at 2-3 dpi resulted in slightly increased blood pH at 2 dpi. However, the acid-base equilibrium was additionally influenced by metabolic components, i.e. the systemic inflammatory response, all of which were detected with help of the strong ion theory. Decreased concentrations of albumin (2-10 dpi), a negative acute-phase marker, resulted in a decrease in the sum of non-volatile weak acids (Atot), revealing an alkalotic effect. This was counterbalanced by acidic effects

  18. Muscle weakness in respiratory and peripheral skeletal muscles in a mouse model for nebulin-based nemaline myopathy.

    Science.gov (United States)

    Joureau, Barbara; de Winter, Josine M; Stam, Kelly; Granzier, Henk; Ottenheijm, Coen A C

    2017-01-01

    Nemaline myopathy is among the most common non-dystrophic congenital myopathies, and is characterized by the presence of nemaline rods in skeletal muscles fibers, general muscle weakness, and hypotonia. Although respiratory failure is the main cause of death in nemaline myopathy, only little is known regarding the contractile strength of the diaphragm, the main muscle of inspiration. To investigate diaphragm contractility, in the present study we took advantage of a mouse model for nebulin-based nemaline myopathy that we recently developed. In this mouse model, exon 55 of Neb is deleted (Neb(ΔExon55)), a mutation frequently found in patients. Diaphragm contractility was determined in permeabilized muscle fibers and was compared to the contractility of permeabilized fibers from three peripheral skeletal muscles: soleus, extensor digitorum longus, and gastrocnemius. The force generating capacity of diaphragm muscle fibers of Neb(ΔExon55) mice was reduced to 25% of wildtype levels, indicating severe contractile weakness. The contractile weakness of diaphragm fibers was more pronounced than that observed in soleus muscle, but not more pronounced than that observed in extensor digitorum longus and gastrocnemius muscles. The reduced muscle contractility was at least partly caused by changes in cross-bridge cycling kinetics which reduced the number of bound cross-bridges. The severe diaphragm weakness likely contributes to the development of respiratory failure in Neb(ΔExon55) mice and might explain their early, postnatal death. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. SU-E-J-73: Generation of Volumetric Images with a Respiratory Motion Model Based On An External Surrogate Signal

    Energy Technology Data Exchange (ETDEWEB)

    Hurwitz, M; Williams, C; Mishra, P; Dhou, S; Lewis, J [Brigham and Women' s Hospital, Dana-Farber Cancer Center, Harvard Medical School, Boston, MA, Boston, MA (United States)

    2014-06-01

    Purpose: Respiratory motion during radiotherapy treatment can differ significantly from motion observed during imaging for treatment planning. Our goal is to use an initial 4DCT scan and the trace of an external surrogate marker to generate 3D images of patient anatomy during treatment. Methods: Deformable image registration is performed on images from an initial 4DCT scan. The deformation vectors are used to develop a patient-specific linear relationship between the motion of each voxel and the trajectory of an external surrogate signal. Correlations in motion are taken into account with principal component analysis, reducing the number of free parameters. This model is tested with digital phantoms reproducing the breathing patterns of ten measured patient tumor trajectories, using five seconds of data to develop the model and the subsequent thirty seconds to test its predictions. The model is also tested with a breathing physical anthropomorphic phantom programmed to reproduce a patient breathing pattern. Results: The error (mean absolute, 95th percentile) over 30 seconds in the predicted tumor centroid position ranged from (0.8, 1.3) mm to (2.2, 4.3) mm for the ten patient breathing patterns. The model reproduced changes in both phase and amplitude of the breathing pattern. Agreement between prediction and truth over the entire image was confirmed by assessing the global voxel intensity RMS error. In the physical phantom, the error in the tumor centroid position was less than 1 mm for all images. Conclusion: We are able to reconstruct 3D images of patient anatomy with a model correlating internal respiratory motion with motion of an external surrogate marker, reproducing the expected tumor centroid position with an average accuracy of 1.4 mm. The images generated by this model could be used to improve dose calculations for treatment planning and delivered dose estimates. This work was partially funded by a research grant from Varian Medical Systems.

  20. Human Adaptive Mechatronics and Human-System Modelling

    Directory of Open Access Journals (Sweden)

    Satoshi Suzuki

    2013-03-01

    Full Text Available Several topics in projects for mechatronics studies, which are 'Human Adaptive Mechatronics (HAM' and 'Human-System Modelling (HSM', are presented in this paper. The main research theme of the HAM project is a design strategy for a new intelligent mechatronics system, which enhances operators' skills during machine operation. Skill analyses and control system design have been addressed. In the HSM project, human modelling based on hierarchical classification of skills was studied, including the following five types of skills: social, planning, cognitive, motion and sensory-motor skills. This paper includes digests of these research topics and the outcomes concerning each type of skill. Relationships with other research activities, knowledge and information that will be helpful for readers who are trying to study assistive human-mechatronics systems are also mentioned.

  1. [Respiratory distress].

    Science.gov (United States)

    Galili, D; Garfunkel, A; Elad, S; Zusman, S P; Malamed, S F; Findler, M; Kaufman, E

    2002-01-01

    Dental treatment is usually conducted in the oral cavity and in very close proximity to the upper respiratory airway. The possibility of unintentionally compromising this airway is high in the dental environment. The accumulation of fluid (water or blood) near to the upper respiratory airway or the loosening of teeth fragmentations and fallen dental instruments can occur. Also, some of the drugs prescribed in the dental practice are central nervous system depressants and some are direct respiratory drive depressors. For this reason, awareness of the respiratory status of the dental patient is of paramount importance. This article focuses on several of the more common causes of respiratory distress, including airway obstruction, hyperventilation, asthma, bronchospasm, pulmonary edema, pulmonary embolism and cardiac insufficiency. The common denominator to all these conditions described here is that in most instances the patient is conscious. Therefore, on the one hand, valuable information can be retrieved from the patient making diagnosis easier than when the patient is unconscious. On the other hand, the conscious patient is under extreme apprehension and stress under such situations. Respiratory depression which occurs during conscious sedation or following narcotic analgesic medication will not be dealt with in this article. Advanced pain and anxiety control techniques such as conscious sedation and general anesthesia should be confined only to operators who undergo special extended training.

  2. Human body modeling in injury biomechanics

    NARCIS (Netherlands)

    Happee, R.; Morsink, P.L.J.; Horst, M.J. van der; Wismans, J.S.H.M.

    1999-01-01

    Mathematical modelling is widely used for crash-safety research and design. However, most occupant models used in crash simulations are based on crash dummies and thereby inherit their apparent limitations. This paper describes a mathematical model of the real human body for impact loading. A combin

  3. Modeling human operator involvement in robotic systems

    NARCIS (Netherlands)

    Wewerinke, P.H.

    1991-01-01

    A modeling approach is presented to describe complex manned robotic systems. The robotic system is modeled as a (highly) nonlinear, possibly time-varying dynamic system including any time delays in terms of optimal estimation, control and decision theory. The role of the human operator(s) is modeled

  4. Infection of a human respiratory epithelial cell line with rhinovirus. Induction of cytokine release and modulation of susceptibility to infection by cytokine exposure.

    OpenAIRE

    Subauste, M C; Jacoby, D B; Richards, S M; Proud, D

    1995-01-01

    Rhinovirus infections cause over one third of all colds and are a contributing factor to exacerbations of asthma. To gain insights into the early biochemical events that occur in infected epithelial cells, we develop, for the first time, a model in which a pure respiratory epithelial cell population can be routinely infected by rhinovirus. Viral infection was confirmed by demonstrating that viral titers of supernatants and lysates from infected cell increased with time and by PCR. Infection b...

  5. Cognitive modelling of human temporal reasoning

    NARCIS (Netherlands)

    ter Meulen, AGB

    2003-01-01

    Modelling human reasoning characterizes the fundamental human cognitive capacity to describe our past experience and use it to form expectations as well as plan and direct our future actions. Natural language semantics analyzes dynamic forms of reasoning in which the real-time order determines the

  6. Characterization of human coronavirus etiology in Chinese adults with acute upper respiratory tract infection by real-time RT-PCR assays.

    Directory of Open Access Journals (Sweden)

    Roujian Lu

    Full Text Available BACKGROUND: In addition to SARS associated coronaviruses, 4 non-SARS related human coronaviruses (HCoVs are recognized as common respiratory pathogens. The etiology and clinical impact of HCoVs in Chinese adults with acute upper respiratory tract infection (URTI needs to be characterized systematically by molecular detection with excellent sensitivity. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we detected 4 non-SARS related HCoV species by real-time RT-PCR in 981 nasopharyngeal swabs collected from March 2009 to February 2011. All specimens were also tested for the presence of other common respiratory viruses and newly identified viruses, human metapneumovirus (hMPV and human bocavirus (HBoV. 157 of the 981 (16.0% nasopharyngeal swabs were positive for HCoVs. The species detected were 229E (96 cases, 9.8%, OC43 (42 cases, 4.3%, HKU1 (16 cases, 1.6% and NL63 (11 cases, 1.1%. HCoV-229E was circulated in 21 of the 24 months of surveillance. The detection rates for both OC43 and NL63 were showed significantly year-to-year variation between 2009/10 and 2010/11, respectively (P<0.001 and P = 0.003, and there was a higher detection frequency of HKU1 in patients aged over 60 years (P = 0.03. 48 of 157(30.57% HCoV positive patients were co-infected. Undifferentiated human rhinoviruses and influenza (Flu A were the most common viruses detected (more than 35% in HCoV co-infections. Respiratory syncytial virus (RSV, human parainfluenza virus (PIV and HBoV were detected in very low rate (less than 1% among adult patients with URTI. CONCLUSIONS/SIGNIFICANCE: All 4 non-SARS-associated HCoVs were more frequently detected by real-time RT-PCR assay in adults with URTI in Beijing and HCoV-229E led to the most prevalent infection. Our study also suggested that all non-SARS-associated HCoVs contribute significantly to URTI in adult patients in China.

  7. Murine models of human wound healing.

    Science.gov (United States)

    Chen, Jerry S; Longaker, Michael T; Gurtner, Geoffrey C

    2013-01-01

    In vivo wound healing experiments remain the most predictive models for studying human wound healing, allowing an accurate representation of the complete wound healing environment including various cell types, environmental cues, and paracrine interactions. Small animals are economical, easy to maintain, and allow researchers to take advantage of the numerous transgenic strains that have been developed to investigate the specific mechanisms involved in wound healing and regeneration. Here we describe three reproducible murine wound healing models that recapitulate the human wound healing process.

  8. Respiratory-like rhythmic activity can be produced by an excitatory network of non-pacemaker neuron models.

    Science.gov (United States)

    Kosmidis, Efstratios K; Pierrefiche, Olivier; Vibert, Jean-François

    2004-08-01

    It is still unclear whether the respiratory-like rhythm observed in slice preparations containing the pre-Bötzinger complex is of pacemaker or network origin. The rhythm persists in the absence of inhibition, but blocking pacemaker activity did not always result in rhythm abolition. We developed a computational model of the slice to show that respiratory-like rhythm can emerge as a network property without pacemakers or synaptic inhibition. The key currents of our model cell are the low- and high-threshold calcium currents and the calcium-dependent potassium current. Depolarization of a single unit by current steps or by raising the external potassium concentration can induce periodic bursting activity. Gaussian stimulation increased the excitability of the model without evoking oscillatory activity, as indicated by autocorrelation analysis. In response to hyperpolarizing pulses, the model produces prolonged relative refractory periods. At the network level, an increase of external potassium concentration triggers rhythmic activity that can be attributed to cellular periodic bursting, network properties, or both, depending on different parameters. Gaussian stimulation also induces rhythmic activity that depends solely on network properties. In all cases, the calcium-dependent potassium current has a central role in burst termination and interburst duration. However, when periodic inhibition is considered, the activation of this current is responsible for the characteristic amplification ramp of the emerged rhythm. Our results may explain controversial results from studies blocking pacemakers in vitro and show a shift in the role of the calcium-dependent potassium current in the presence of network inhibition.

  9. Airway remodeling in a mouse asthma model assessed by in-vivo respiratory-gated micro-computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Lederlin, Mathieu; Montaudon, Michel [Universite Bordeaux 2, Laboratoire de Physiologie Cellulaire Respiratoire, Bordeaux (France); Institut National de la Sante et de la Recherche Medicale (INSERM), U885, Bordeaux (France); CHU Bordeaux, Unite d' Imagerie Thoracique, Pessac (France); Ozier, Annaig; Begueret, Hugues; Ousova, Olga; Marthan, Roger; Berger, Patrick [Universite Bordeaux 2, Laboratoire de Physiologie Cellulaire Respiratoire, Bordeaux (France); Institut National de la Sante et de la Recherche Medicale (INSERM), U885, Bordeaux (France); Laurent, Francois [Universite Bordeaux 2, Laboratoire de Physiologie Cellulaire Respiratoire, Bordeaux (France); Institut National de la Sante et de la Recherche Medicale (INSERM), U885, Bordeaux (France); CHU Bordeaux, Unite d' Imagerie Thoracique, Pessac (France); CHU de Bordeaux, Hopital du Haut-Leveque, Hopital Cardiologique, Unite d' Imagerie Thoracique et Cardiovasculaire, Pessac (France)

    2010-01-15

    The aim of our study was to evaluate the feasibility of non-invasive respiratory-gated micro-computed tomography (micro-CT) for assessment of airway remodelling in a mouse asthma model. Six female BALB/c mice were challenged intranasally with ovalbumin. A control group of six mice received saline inhalation. All mice underwent plethysmographic study and micro-CT. For each mouse, peribronchial attenuation values of 12 bronchi were measured, from which a peribronchial density index (PBDI) was computed. Mice were then sacrificed and lungs examined histologically. Final analysis involved 10 out of 12 mice. Agreement of measurements across observers and over time was very good (intraclass correlation coefficients: 0.94-0.98). There was a significant difference in PBDI between asthmatic and control mice (-210 vs. -338.9 HU, P=0.008). PBDI values were correlated to bronchial muscle area (r=0.72, P=0.018). This study shows that respiratory-gated micro-CT may allow non-invasive monitoring of bronchial remodelling in asthmatic mice and evaluation of innovative treatment effects. (orig.)

  10. [Effect of anti-inflammatory drugs, alone and combined with ofloxacin, on the respiratory burst of human polymorphonuclear leukocytes].

    Science.gov (United States)

    Cabrera, E; Velert, M M; Orero, A; Martínez, P; Cantón, E

    2001-06-01

    The antibacterial activity of polymorphonuclear leukocytes (PMNs) is based on the production of superoxide anion and H(2)O(2) in the respiratory burst and can be impaired in different ways. The combination of an antibacterial agent and an antiinflammatory drug is quite common in immunodepressed patients whose respiratory burst of PMN could be impaired. In this study we examine in vitro the effect of pretreating (35 degrees C for 30 min) PMNs with the antiinflammatory drugs dexamethasone (0.4, 4 and 40 microgram/ml), methylprednisolone (0.37, 3.7 and 37 microgram/ ml), hydrocortisone (0.048, 0.48 and 4.8 microgram/ml), betamethasone (0.1, 1, 5 and 10 mg/ml), phenylbutazone (1000 microgram/ml) and acetylsalicylic acid (25, 250, 2500 microgram/ml) alone, and combined with 10 mg/ml of ofloxacin on the respiratory burst. Superoxide anion was measured by the cytochrome c reduction microtechnique and H(2)O(2) by phenol red. The antiinflammatory drugs alone decreased the production of H(2)O(2) (except dexamethasone and methylprednisolone) and superoxide anion (except betamethasone) from 15-45%, depending on the antiinflammatory drug and concentration, while ofloxacin increased the production of superoxide anion (20.2 +/- 6.7%). The combination of antiinflammatory drugs with ofloxacin neutralizes the inhibitory effect of the former on the respiratory burst of PMNs. It is therefore important to know the effect of drugs on the respiratory burst in order to choose those that have the same therapeutic effect without interfering with PMN functions.