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Sample records for mouse respiratory system

  1. Mn Enhancement and Respiratory Gating for In Utero MRI of the Embryonic Mouse Central Nervous System

    PubMed Central

    Deans, Abby E.; Wadghiri, Youssef Zaim; Berrios-Otero, César A.; Turnbull, Daniel H.

    2009-01-01

    The mouse is the preferred model organism for genetic studies of mammalian brain development. MRI has potential for in utero studies of mouse brain development, but has been limited previously by challenges of maximizing image resolution and contrast while minimizing artifacts due to physiological motion. Manganese (Mn)-enhanced MRI (MEMRI) studies have demonstrated central nervous system (CNS) contrast enhancement in mice from the earliest postnatal stages. The purpose of this study was to expand MEMRI to in utero studies of the embryonic CNS in combination with respiratory gating to decrease motion artifacts. We investigated MEMRI-facilitated CNS segmentation and three-dimensional (3D) analysis in wild-type mouse embryos from midgestation, and explored effects of Mn on embryonic survival and image contrast. Motivated by observations that MEMRI provided an effective method for visualization and volumetric analysis of embryonic CNS structures, especially in ventral regions, we used MEMRI to examine Nkx2.1 mutant mice that were previously reported to have ventral forebrain defects. Quantitative MEMRI analysis of Nkx2.1 knockout mice demonstrated volumetric changes in septum (SE) and basal ganglia (BG), as well as alterations in hypothalamic structures. This method may provide an effective means for in utero analysis of CNS phenotypes in a variety of mouse mutants. PMID:18506798

  2. Respiratory system

    NASA Technical Reports Server (NTRS)

    Bartlett, R. G., Jr.

    1973-01-01

    The general anatomy and function of the human respiratory system is summarized. Breathing movements, control of breathing, lung volumes and capacities, mechanical relations, and factors relevant to respiratory support and equipment design are discussed.

  3. Avian respiratory system disorders

    USGS Publications Warehouse

    Olsen, G.H.

    1989-01-01

    Diagnosing and treating respiratory diseases in avian species requires a basic knowledge about the anatomy and physiology of this system in birds. Differences between mammalian and avian respiratory system function, diagnosis, and treatment are highlighted.

  4. The respiratory system.

    PubMed

    Zifko, U; Chen, R

    1996-10-01

    Neurological disorders frequently contribute to respiratory failure in critically ill patients. They may be the primary reason for the initiation of mechanical ventilation, or may develop later as a secondary complication. Disorders of the central nervous system leading to respiratory failure include metabolic encephalopathies, acute stroke, lesions of the motor cortex and brain-stem respiratory centres, and their descending pathways. Guillan-Barré syndrome, critical illness polyneuropathy and acute quadriplegic myopathy are the more common neuromuscular causes of respiratory failure. Clinical observations and pulmonary function tests are important in monitoring respiratory function. Respiratory electrophysiological studies are useful in the investigation and monitoring of respiratory failure. Transcortical and cervical magnetic stimulation can assess the central respiratory drive, and may be useful in determining the prognosis in ventilated patients, with cervical cord dysfunction. It is also helpful in the assessment of failure to wean, which is often caused by a combination of central and peripheral nervous system disorders. Phrenic nerve conduction studies and needle electromyography of the diaphragm and chest wall muscles are useful to characterize neuropathies and myopathies affecting the diaphragm. Repetitive phrenic nerve stimulation can assess neuromuscular transmission defects. It is important to identify patients at risk of respiratory failure. They should be carefully monitored and mechanical ventilation should be initiated before the development of severe hypoxaemia. PMID:9117072

  5. Respiratory System Disease.

    PubMed

    Goetz, Danielle M; Singh, Shipra

    2016-08-01

    Respiratory system involvement in cystic fibrosis is the leading cause of morbidity and mortality. Defects in the cystic fibrosis transmembrane regulator (CFTR) gene throughout the sinopulmonary tract result in recurrent infections with a variety of organisms including Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, and nontuberculous mycobacteria. Lung disease occurs earlier in life than once thought and ideal methods of monitoring lung function, decline, or improvement with therapy are debated. Treatment of sinopulmonary disease may include physiotherapy, mucus-modifying and antiinflammatory agents, antimicrobials, and surgery. In the new era of personalized medicine, CFTR correctors and potentiators may change the course of disease. PMID:27469180

  6. NATIONAL RESPIRATORY AND ENTERIC VIRUS SURVEILLANCE SYSTEM

    EPA Science Inventory

    The National Respiratory and Enteric Virus Surveillance System is a lab based system which monitors temporal and geographic patterns associated with the detection of respiratory syncytial virus (RSV), human parainfluenza viruses (HPIV), respiratory and enteric adenoviruses, and r...

  7. Mouse Model of Respiratory Tract Infection Induced by Waddlia chondrophila

    PubMed Central

    Pilloux, Ludovic; LeRoy, Didier; Brunel, Christophe

    2016-01-01

    Waddlia chondrophila, an obligate intracellular bacterium belonging to the Chlamydiales order, is considered as an emerging pathogen. Some clinical studies highlighted a possible role of W. chondrophila in bronchiolitis, pneumonia and miscarriage. This pathogenic potential is further supported by the ability of W. chondrophila to infect and replicate within human pneumocytes, macrophages and endometrial cells. Considering that W. chondrophila might be a causative agent of respiratory tract infection, we developed a mouse model of respiratory tract infection to get insight into the pathogenesis of W. chondrophila. Following intranasal inoculation of 2 x 108 W. chondrophila, mice lost up to 40% of their body weight, and succumbed rapidly from infection with a death rate reaching 50% at day 4 post-inoculation. Bacterial loads, estimated by qPCR, increased from day 0 to day 3 post-infection and decreased thereafter in surviving mice. Bacterial growth was confirmed by detecting dividing bacteria using electron microscopy, and living bacteria were isolated from lungs 14 days post-infection. Immunohistochemistry and histopathology of infected lungs revealed the presence of bacteria associated with pneumonia characterized by an important multifocal inflammation. The high inflammatory score in the lungs was associated with the presence of pro-inflammatory cytokines in both serum and lungs at day 3 post-infection. This animal model supports the role of W. chondrophila as an agent of respiratory tract infection, and will help understanding the pathogenesis of this strict intracellular bacterium. PMID:26950066

  8. MOUSE UNCERTAINTY ANALYSIS SYSTEM

    EPA Science Inventory

    The original MOUSE (Modular Oriented Uncertainty System) system was designed to deal with the problem of uncertainties in Environmental engineering calculations, such as a set of engineering cost or risk analysis equations. t was especially intended for use by individuals with li...

  9. A molecular atlas of Xenopus respiratory system development

    PubMed Central

    Rankin, Scott A.; Tran, Hong Thi; Wlizla, Marcin; Mancini, Pamela; Shifley, Emily T.; Bloor, Sean D.; Han, Lu; Vleminckx, Kris; Wert, Susan E.; Zorn, Aaron M.

    2014-01-01

    Background Respiratory system development is regulated by a complex series of endoderm – mesoderm interactions that are not fully understood. Recently Xenopus has emerged as an alternative model to investigate early respiratory system development, but the extent to which the morphogenesis and molecular pathways involved are conserved between Xenopus and mammals has not been systematically documented. Results In this study we provide a histological and molecular atlas of Xenopus respiratory system development, focusing on Nkx2.1+ respiratory cell fate specification in the developing foregut. We document the expression patterns of Wnt/β-catenin, FGF, and BMP signaling components in the foregut and show that the molecular mechanisms of respiratory lineage induction are remarkably conserved between Xenopus and mice. Finally, using a number of functional experiments we refine the epistatic relationships between FGF, Wnt and BMP signaling in early Xenopus respiratory system development. Conclusions We demonstrate that Xenopus trachea and lung development, before metamorphosis, is comparable at the cellular and molecular levels to embryonic stages of mouse respiratory system development between E8.5 to E10.5. This molecular atlas provides a fundamental starting point for further studies using Xenopus as a model to define the conserved genetic programs controlling early respiratory system development. PMID:25156440

  10. Activated mouse eosinophils protect against lethal respiratory virus infection

    PubMed Central

    Percopo, Caroline M.; Dyer, Kimberly D.; Ochkur, Sergei I.; Luo, Janice L.; Fischer, Elizabeth R.; Lee, James J.; Lee, Nancy A.; Domachowske, Joseph B.

    2014-01-01

    Eosinophils are recruited to the airways as a prominent feature of the asthmatic inflammatory response where they are broadly perceived as promoting pathophysiology. Respiratory virus infections exacerbate established asthma; however, the role of eosinophils and the nature of their interactions with respiratory viruses remain uncertain. To explore these questions, we established acute infection with the rodent pneumovirus, pneumonia virus of mice (PVM), in 3 distinct mouse models of Th2 cytokine–driven asthmatic inflammation. We found that eosinophils recruited to the airways of otherwise naïve mice in response to Aspergillus fumigatus, but not ovalbumin sensitization and challenge, are activated by and degranulate specifically in response to PVM infection. Furthermore, we demonstrate that activated eosinophils from both Aspergillus antigen and cytokine-driven asthma models are profoundly antiviral and promote survival in response to an otherwise lethal PVM infection. Thus, although activated eosinophils within a Th2-polarized inflammatory response may have pathophysiologic features, they are also efficient and effective mediators of antiviral host defense. PMID:24297871

  11. A miniaturised respiratory sensor system

    NASA Astrophysics Data System (ADS)

    Hoffmann, U.; Fasoulas, S.; Linnarsson, D.; Paiva, M.; Stoll, R.; Hammer, F.; Stangl, R.; Martinot, Guy

    2005-10-01

    Solid-electrolyte gas sensors, originally designed for residual oxygen detection in low Earth orbit, have provided the basis for developing a multi-function sensor system for respiratory investigations. These sensors allow the detection of oxygen and carbon dioxide partial pressures simultaneously with total flow rates. Moreover, with only minor modifications, other gases of interest in cardio-respiratory testing, such as carbon monoxide and hydrogen, can be detected. The sensors are highly miniaturised and can be positioned in the mainstream of the breath. Thus there is no delay through sample transport. The characteristics of the flow detection are comparable with common sensors used in spirometry. The oxygen and carbon dioxide sensitivities have reached a level that is comparable to or even better than those of mass spectrometers optimised for respiratory analysis. Data from this sensor system allow single-breath or breath-by-breath analysis. Integrated into a portable system, the system provides greater flexibility than other devices, significantly increasing the range of scientific and health-monitoring applications.

  12. Effects of Aging on the Respiratory System.

    ERIC Educational Resources Information Center

    Levitzky, Michael G.

    1984-01-01

    Relates alterations in respiratory system functions occurring with aging to changes in respiratory system structure during the course of life. Main alterations noted include loss of alveolar elastic recoil, alteration in chest wall structure and decreased respiratory muscle strength, and loss of surface area and changes in pulmonary circulation.…

  13. Respiratory analysis system and method

    NASA Technical Reports Server (NTRS)

    Liu, F. F. (Inventor)

    1973-01-01

    A system is described for monitoring the respiratory process in which the gas flow rate and the frequency of respiration and expiration cycles can be determined on a real time basis. A face mask is provided with one-way inlet and outlet valves where the gas flow is through independent flowmeters and through a mass spectrometer. The opening and closing of a valve operates an electrical switch, and the combination of the two switches produces a low frequency electrical signal of the respiratory inhalation and exhalation cycles. During the time a switch is operated, the corresponsing flowmeter produces electric pulses representative of the flow rate; the electrical pulses being at a higher frequency than that of the breathing cycle and combined with the low frequency signal. The high frequency pulses are supplied to conventional analyzer computer which also receives temperature and pressure inputs and computes mass flow rate and totalized mass flow of gas. From the mass spectrometer, components of the gas are separately computed as to flow rate. The electrical switches cause operation of up-down inputs of a reversible counter. The respective up and down cycles can be individually monitored and combined for various respiratory measurements.

  14. Computational Modeling of Nanoscale and Microscale Particle Deposition, Retention and Dosimetry in the Mouse Respiratory Tract

    PubMed Central

    Asgharian, B.; Price, O.T.; Oldham, M.; Chen, L.C.; Saunders, E.L.; Gordon, T.; Mikheev, V.B.; Minard, K.R.; Teeguarden, J. G.

    2015-01-01

    Comparing effects of inhaled particles across rodent test systems and between rodent test systems and humans is a key obstacle to the interpretation of common toxicological test systems for human risk assessment. These comparisons, correlation with effects and prediction of effects, are best conducted using measures of tissue dose in the respiratory tract. Differences in lung geometry, physiology and the characteristics of ventilation can give rise to differences in the regional deposition of particles in the lung in these species. Differences in regional lung tissue doses cannot currently be measured experimentally. Regional lung tissue dosimetry can however be predicted using models developed for rats, monkeys, and humans. A computational model of particle respiratory tract deposition and clearance was developed for BALB/c and B6C3F1 mice, creating a cross species suite of available models for particle dosimetry in the lung. Airflow and particle transport equations were solved throughout the respiratory tract of these mice strains to obtain temporal and spatial concentration of inhaled particles from which deposition fractions were determined. Particle inhalability (Inhalable fraction, IF) and upper respiratory tract (URT) deposition were directly related to particle diffusive and inertial properties. Measurements of the retained mass at several post-exposure times following exposure to iron oxide nanoparticles, micro and nanoscale C60 fullerene, and nanoscale silver particles were used to calibrate and verify model predictions of total lung dose. Interstrain (mice) and interspecies (mouse, rat, human) differences in particle inhalability, fractional deposition and tissue dosimetry are described for ultrafine, fine and coarse particles. PMID:25373829

  15. Computational modeling of nanoscale and microscale particle deposition, retention and dosimetry in the mouse respiratory tract.

    PubMed

    Asgharian, B; Price, O T; Oldham, M; Chen, Lung-Chi; Saunders, E L; Gordon, T; Mikheev, V B; Minard, K R; Teeguarden, J G

    2014-12-01

    Comparing effects of inhaled particles across rodent test systems and between rodent test systems and humans is a key obstacle to the interpretation of common toxicological test systems for human risk assessment. These comparisons, correlation with effects and prediction of effects, are best conducted using measures of tissue dose in the respiratory tract. Differences in lung geometry, physiology and the characteristics of ventilation can give rise to differences in the regional deposition of particles in the lung in these species. Differences in regional lung tissue doses cannot currently be measured experimentally. Regional lung tissue dosimetry can however be predicted using models developed for rats, monkeys, and humans. A computational model of particle respiratory tract deposition and clearance was developed for BALB/c and B6C3F1 mice, creating a cross-species suite of available models for particle dosimetry in the lung. Airflow and particle transport equations were solved throughout the respiratory tract of these mice strains to obtain temporal and spatial concentration of inhaled particles from which deposition fractions were determined. Particle inhalability (Inhalable fraction, IF) and upper respiratory tract (URT) deposition were directly related to particle diffusive and inertial properties. Measurements of the retained mass at several post-exposure times following exposure to iron oxide nanoparticles, micro- and nanoscale C60 fullerene, and nanoscale silver particles were used to calibrate and verify model predictions of total lung dose. Interstrain (mice) and interspecies (mouse, rat and human) differences in particle inhalability, fractional deposition and tissue dosimetry are described for ultrafine, fine and coarse particles. PMID:25373829

  16. Brca1/p53 deficient mouse breast tumor hemodynamics during hyperoxic respiratory challenge monitored by a novel wide-field functional imaging (WiFI) system

    NASA Astrophysics Data System (ADS)

    Moy, Austin; Kim, Jae G.; Lee, Eva Y. H. P.; Tromberg, Bruce; Cerussi, Albert; Choi, Bernard

    2009-02-01

    Current imaging modalities allow precise visualization of tumors but do not enable quantitative characterization of the tumor metabolic state. Such quantitative information would enhance our understanding of tumor progression and response to treatment, and to our overall understanding of tumor biology. To address this problem, we have developed a wide-field functional imaging (WiFI) instrument which combines two optical imaging modalities, spatially modulated imaging (MI) and laser speckle imaging (LSI). Our current WiFI imaging protocol consists of multispectral imaging in the near infrared (650-980 nm) spectrum, over a wide (7 cm × 5 cm) field of view. Using MI, the spatially-resolved reflectance of sinusoidal patterns projected onto the tissue is assessed, and optical properties of the tissue are estimated using a Monte Carlo model. From the spatial maps of local absorption and reduced scattering coefficients, tissue composition information is extracted in the form of oxy-, deoxy-, and total hemoglobin concentrations, and percentage of lipid and water. Using LSI, the reflectance of a 785 nm laser speckle pattern on the tissue is acquired and analyzed to compute maps of blood perfusion in the tissue. Tissue metabolism state is estimated from the values of blood perfusion, volume and oxygenation state. We currently are employing the WiFI instrument to study tumor development in a BRCA1/p53 deficient mice breast tumor model. The animals are monitored with WiFI during hyperoxic respiratory challenge. At present, four tumors have been measured with WiFI, and preliminary data suggest that tumor metabolic changes during hyperoxic respiratory challenge can be determined.

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

    PubMed Central

    Kneyber, Martin CJ; van Heerde, Marc; Twisk, Jos WR; Plötz, Frans B; Markhors, Dick G

    2009-01-01

    Introduction Respiratory syncytial virus (RSV) lower respiratory tract disease is characterised by narrowing of the airways resulting in increased airway resistance, air-trapping and respiratory acidosis. These problems might be overcome using helium-oxygen gas mixture. However, the effect of mechanical ventilation with heliox in these patients is unclear. The objective of this prospective cross-over study was to determine the effects of mechanical ventilation with heliox 60/40 versus conventional gas on respiratory system resistance, air-trapping and CO2 removal. Methods Mechanically ventilated, sedated and paralyzed infants with proven RSV were enrolled within 24 hours after paediatric intensive care unit (PICU)admission. At T = 0, respiratory system mechanics including respiratory system compliance and resistance, and peak expiratory flow rate were measured with the AVEA ventilator. The measurements were repeated at each interval (after 30 minutes of ventilation with heliox, after 30 minutes of ventilation with nitrox and again after 30 minutes of ventilation with heliox). Indices of gas exchange (ventilation and oxygenation index) were calculated at each interval. Air-trapping (defined by relative change in end-expiratory lung volume) was determined by electrical impedance tomography (EIT) at each interval. Results Thirteen infants were enrolled. In nine, EIT measurements were performed. Mechanical ventilation with heliox significantly decreased respiratory system resistance. This was not accompanied by an improved CO2 elimination, decreased peak expiratory flow rate or decreased end-expiratory lung volume. Importantly, oxygenation remained unaltered throughout the experimental protocol. Conclusions Respiratory system resistance is significantly decreased by mechanical ventilation with heliox (ISCRTN98152468). PMID:19450268

  18. Auscultation of the respiratory system

    PubMed Central

    Sarkar, Malay; Madabhavi, Irappa; Niranjan, Narasimhalu; Dogra, Megha

    2015-01-01

    Auscultation of the lung is an important part of the respiratory examination and is helpful in diagnosing various respiratory disorders. Auscultation assesses airflow through the trachea-bronchial tree. It is important to distinguish normal respiratory sounds from abnormal ones for example crackles, wheezes, and pleural rub in order to make correct diagnosis. It is necessary to understand the underlying pathophysiology of various lung sounds generation for better understanding of disease processes. Bedside teaching should be strengthened in order to avoid erosion in this age old procedure in the era of technological explosion. PMID:26229557

  19. Respiratory system involvement in Costello syndrome.

    PubMed

    Gomez-Ospina, Natalia; Kuo, Christin; Ananth, Amitha Lakshmi; Myers, Angela; Brennan, Marie-Luise; Stevenson, David A; Bernstein, Jonathan A; Hudgins, Louanne

    2016-07-01

    Costello syndrome (CS) is a multisystem disorder caused by heterozygous germline mutations in the HRAS proto-oncogene. Respiratory system complications have been reported in individuals with CS, but a comprehensive description of the full spectrum and incidence of respiratory symptoms in these patients is not available. Here, we report the clinical course of four CS patients with respiratory complications as a major cause of morbidity. Review of the literature identified 56 CS patients with descriptions of their neonatal course and 17 patients in childhood/adulthood. We found that in the neonatal period, respiratory complications are seen in approximately 78% of patients with transient respiratory distress reported in 45% of neonates. Other more specific respiratory diagnoses were reported in 62% of patients, the majority of which comprised disorders of the upper and lower respiratory tract. Symptoms of upper airway obstruction were reported in CS neonates but were more commonly diagnosed in childhood/adulthood (71%). Analysis of HRAS mutations and their respiratory phenotype revealed that the common p.Gly12Ser mutation is more often associated with transient respiratory distress and other respiratory diagnoses. Respiratory failure and dependence on mechanical ventilation occurs almost exclusively with rare mutations. In cases of prenatally diagnosed CS, the high incidence of respiratory complications in the neonatal period should prompt anticipatory guidance and development of a postnatal management plan. This may be important in cases involving rarer mutations. Furthermore, the high frequency of airway obstruction in CS patients suggests that otorhinolaryngological evaluation and sleep studies should be considered. © 2016 Wiley Periodicals, Inc. PMID:27102959

  20. Investigations of respiratory control systems simulation

    NASA Technical Reports Server (NTRS)

    Gallagher, R. R.

    1973-01-01

    The Grodins' respiratory control model was investigated and it was determined that the following modifications were necessary before the model would be adaptable for current research efforts: (1) the controller equation must be modified to allow for integration of the respiratory system model with other physiological systems; (2) the system must be more closely correlated to the salient physiological functionings; (3) the respiratory frequency and the heart rate should be expanded to illustrate other physiological relationships and dependencies; and (4) the model should be adapted to particular individuals through a better defined set of initial parameter values in addition to relating these parameter values to the desired environmental conditions. Several of Milhorn's respiratory control models were also investigated in hopes of using some of their features as modifications for Grodins' model.

  1. Evaluation of exercise-respiratory system modifications and preliminary respiratory-circulatory system integration scheme

    NASA Technical Reports Server (NTRS)

    Gallagher, R. R.

    1974-01-01

    The respiratory control system, functioning as an independent system, is presented with modifications of the exercise subroutine. These modifications illustrate an improved control of ventilation rates and arterial and compartmental gas tensions. A very elementary approach to describing the interactions of the respiratory and circulatory system is presented.

  2. Improvement in the accuracy of respiratory-gated radiation therapy using a respiratory guiding system

    NASA Astrophysics Data System (ADS)

    Kang, Seong-Hee; Kim, Dong-Su; Kim, Tae-Ho; Suh, Tae-Suk; Yoon, Jai-Woong

    2013-01-01

    The accuracy of respiratory-gated radiation therapy (RGRT) depends on the respiratory regularity because external respiratory signals are used for gating the radiation beam at particular phases. Many studies have applied a respiratory guiding system to improve the respiratory regularity. This study aims to evaluate the effect of an in-house-developed respiratory guiding system to improve the respiratory regularity for RGRT. To verify the effectiveness of this system, we acquired respiratory signals from five volunteers. The improvement in respiratory regularity was analyzed by comparing the standard deviations of the amplitudes and the periods between free and guided breathing. The reduction in residual motion at each phase was analyzed by comparing the standard deviations of sorted data within each corresponding phase bin as obtained from free and guided breathing. The results indicate that the respiratory guiding system improves the respiratory regularity, and that most of the volunteers showed significantly less average residual motion at each phase. The average residual motion measured at phases of 40, 50, and 60%, which showed lower variation than other phases, were, respectively, reduced by 41, 45, and 44% during guided breathing. The results show that the accuracy of RGRT can be improved by using the in-house-developed respiratory guiding system. Furthermore, this system should reduce artifacts caused by respiratory motion in 4D CT imaging.

  3. Region-Specific Defects of Respiratory Capacities in the Ndufs4(KO) Mouse Brain

    PubMed Central

    Kayser, Ernst-Bernhard; Sedensky, Margaret M.; Morgan, Philip G.

    2016-01-01

    Background Lack of NDUFS4, a subunit of mitochondrial complex I (NADH:ubiquinone oxidoreductase), causes Leigh syndrome (LS), a progressive encephalomyopathy. Knocking out Ndufs4, either systemically or in brain only, elicits LS in mice. In patients as well as in KO mice distinct regions of the brain degenerate while surrounding tissue survives despite systemic complex I dysfunction. For the understanding of disease etiology and ultimately for the development of rationale treatments for LS, it appears important to uncover the mechanisms that govern focal neurodegeneration. Results Here we used the Ndufs4(KO) mouse to investigate whether regional and temporal differences in respiratory capacity of the brain could be correlated with neurodegeneration. In the KO the respiratory capacity of synaptosomes from the degeneration prone regions olfactory bulb, brainstem and cerebellum was significantly decreased. The difference was measurable even before the onset of neurological symptoms. Furthermore, neither compensating nor exacerbating changes in glycolytic capacity of the synaptosomes were found. By contrast, the KO retained near normal levels of synaptosomal respiration in the degeneration-resistant/resilient “rest” of the brain. We also investigated non-synaptic mitochondria. The KO expectedly had diminished capacity for oxidative phosphorylation (state 3 respiration) with complex I dependent substrate combinations pyruvate/malate and glutamate/malate but surprisingly had normal activity with α-ketoglutarate/malate. No correlation between oxidative phosphorylation (pyruvate/malate driven state 3 respiration) and neurodegeneration was found: Notably, state 3 remained constant in the KO while in controls it tended to increase with time leading to significant differences between the genotypes in older mice in both vulnerable and resilient brain regions. Neither regional ROS damage, measured as HNE-modified protein, nor regional complex I stability, assessed by blue

  4. The respiratory neuromuscular system in Pompe disease☆

    PubMed Central

    Fuller, David D.; ElMallah, Mai K.; Smith, Barbara K.; Corti, Manuela; Lawson, Lee Ann; Falk, Darin J.; Byrne, Barry J.

    2014-01-01

    Pompe disease is due to mutations in the gene encoding the lysosomal enzyme acid α-glucosidase (GAA). Absence of functional GAA typically results in cardiorespiratory failure in the first year; reduced GAA activity is associated with progressive respiratory failure later in life. While skeletal muscle pathology contributes to respiratory insufficiency in Pompe disease, emerging evidence indicates that respiratory neuron dysfunction is also a significant part of dysfunction in motor units. Animal models show profound glycogen accumulation in spinal and medullary respiratory neurons and altered neural activity. Tissues from Pompe patients show central nervous system glycogen accumulation and motoneuron pathology. A neural mechanism raises considerations about the current clinical approach of enzyme replacement since the recombinant protein does not cross the blood-brain-barrier. Indeed, clinical data suggest that enzyme replacement therapy delays symptom progression, but many patients eventually require ventilatory assistance, especially during sleep. We propose that treatments which restore GAA activity to respiratory muscles, neurons and networks will be required to fully correct ventilatory insufficiency in Pompe disease. PMID:23797185

  5. [Effect of furfural on the respiratory system].

    PubMed

    Pawłowicz, A; Droszcz, W; Garlicki, A; Kutyła, J; Kowalczyk, M

    1984-01-01

    Fifty-one workers of Butadien Plant, exposed to furfurol , had their respiratory system examined. Questionnaire studies demonstrated chronic bronchitis in 23.5% of subjects. Spirometric tests do not show subjective complaints. This seems to be related to hypercortisolemia, as experiments on animals indicate that furfurol inhalations increase corticosteroids concentrations in blood serum. PMID:6738348

  6. Detection of Mouse Cough Based on Sound Monitoring and Respiratory Airflow Waveforms

    PubMed Central

    Chen, Liyan; Lai, Kefang; Lomask, Joseph Mark; Jiang, Bert; Zhong, Nanshan

    2013-01-01

    Detection for cough in mice has never yielded clearly audible sounds, so there is still a great deal of debates as to whether mice can cough in response to tussive stimuli. Here we introduce an approach for detection of mouse cough based on sound monitoring and airflow signals. 40 Female BALB/c mice were pretreated with normal saline, codeine, capasazepine or desensitized with capsaicin. Single mouse was put in a plethysmograph, exposed to aerosolized 100 µmol/L capsaicin for 3 min, followed by continuous observation for 3 min. Airflow signals of total 6 min were recorded and analyzed to detect coughs. Simultaneously, mouse cough sounds were sensed by a mini-microphone, monitored manually by an operator. When manual and automatic detection coincided, the cough was positively identified. Sound and sound waveforms were also recorded and filtered for further analysis. Body movements were observed by operator. Manual versus automated counts were compared. Seven types of airflow signals were identified by integrating manual and automated monitoring. Observation of mouse movements and analysis of sound waveforms alone did not produce meaningful data. Mouse cough numbers decreased significantly after all above drugs treatment. The Bland-Altman and consistency analysis between automatic and manual counts was 0.968 and 0.956. The study suggests that the mouse is able to present with cough, which could be detected by sound monitoring and respiratory airflow waveform changes. PMID:23555643

  7. Microgravity and the respiratory system.

    PubMed

    Prisk, G Kim

    2014-05-01

    The structure of the lung, with its delicate network of airspaces and capillaries, means that gravity has a profound influence on its function. Studies of lung function in the absence of gravity provide valuable insight into how, for we Earth-bound individuals, its unavoidable effects shape our lung function. Gravity causes uneven ventilation in the lung through the deformation of lung tissue (the so-called Slinky effect), and uneven perfusion through a combination of the Slinky effect and the zone model of pulmonary perfusion. Both ventilation and perfusion exhibit persisting heterogeneity in microgravity, indicating important other mechanisms. However, gravity serves to maintain a degree of matching of these two processes, so that the ventilation/perfusion ratio, and thus gas exchange, remains efficient. Therefore, while both ventilation and perfusion are more uniform in spaceflight, gas exchange is seemingly no more efficient than on Earth. Despite the changes in lung function when gravity is removed, the lung continues to function well in weightlessness. Unlike many other organ systems, the lung does not appear to undergo structural adaptive changes when gravity is removed, and so there is no apparent degradation in lung function upon return to earth, even after 6 months in space. PMID:24603820

  8. Inhibition of protein kinase G activity protects neonatal mouse respiratory network from hyperthermic and hypoxic stress.

    PubMed

    Armstrong, Gary A B; López-Guerrero, Juan J; Dawson-Scully, Ken; Peña, Fernando; Robertson, R Meldrum

    2010-01-22

    In spite of considerable research attention focused on clarifying the mechanisms by which the mammalian respiratory rhythm is generated, little attention has been given to examining how this neuronal circuit can be protected from heat stress. Hyperthermia has a profound effect on neuronal circuits including the circuit that generates breathing in mammals. As temperature of the brainstem increases, respiratory frequency concomitantly rises. If temperature continues to increase respiratory arrest (apnea) and death can occur. Previous research has implicated protein kinase G (PKG) activity in regulating neuronal thermosensitivity of neuronal circuits in invertebrates. Here we examine if pharmacological manipulation of PKG activity in a brainstem slice preparation could alter the thermosensitivity of the fictive neonatal mouse respiratory rhythm. We report a striking effect following alteration of PKG activity in the brainstem such that slices treated with the PKG inhibitor KT5823 recovered fictive respiratory rhythm generation significantly faster than control slices and slices treated with a PKG activator (8-Br-cGMP). Furthermore, slices treated with 8-Br-cGMP arrested fictive respiration at a significantly lower temperature than all other treatment groups. In a separate set of experiments we examined if altered PKG activity could regulate the response of slices to hypoxia by altering the protective switch to fictive gasping. Slices treated with 8-Br-cGMP did not switch to the fictive gasp-like pattern following exposure to hypoxia whereas slices treated with KT5823 did display fictive gasping. We propose that PKG activity inversely regulates the amount of stress the neonatal mammalian respiratory rhythm can endure. PMID:19945442

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

    PubMed Central

    Schijf, Marcel A.; Kruijsen, Debby; Bastiaans, Jacqueline; Coenjaerts, Frank E. J.; Garssen, Johan; van Bleek, Grada M.

    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 present in human milk, were evaluated in a C57BL/6 mouse RSV infection model. During primary RSV infection, increased numbers of RSV-specific CD4+ T cells producing gamma interferon (IFN-γ) were found in the lungs at days 8 to 10 postinfection in mice receiving diet containing short-chain galactooligosacharides, long-chain fructooligosaccharides, and pectin-derived acidic oligosaccharides (termed scGOS/lcFOS/pAOS). In a Th2-skewed formalin-inactivated (FI)-RSV vaccination model, the prebiotic diet reduced RSV-specific Th2 cytokine (interleukin-4 [IL-4], IL-5, and IL-13)-producing CD4+ T cells in the lung and the magnitude of airway eosinophilia at day 4 and 6 after infection. This was accompanied by a decreased influx of inflammatory dendritic cells (CD11b+/CD11c+) and increased numbers of IFN-γ-producing CD4+ and CD8+ T cells at day 8 after viral challenge. These findings suggest that specific dietary oligosaccharides can influence trafficking and/or effector functions of innate immune, CD4+, and CD8+ T cell subsets in the lungs of RSV-infected mice. In our models, scGOS/lcFOS/pAOS had no effect on weight but increased viral clearance in FI-RSV-vaccinated mice 8 days after infection. The increased systemic Th1 responses potentiated by scGOS/lcFOS/pAOS might contribute to an accelerated Th1/Th2 shift of the neonatal immune system, which might favor protective immunity against viral infections with a high attack rate in early infancy, such as RSV. PMID:22896622

  10. Specific dietary oligosaccharides increase Th1 responses in a mouse respiratory syncytial virus infection model.

    PubMed

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

    2012-11-01

    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 present in human milk, were evaluated in a C57BL/6 mouse RSV infection model. During primary RSV infection, increased numbers of RSV-specific CD4(+) T cells producing gamma interferon (IFN-γ) were found in the lungs at days 8 to 10 postinfection in mice receiving diet containing short-chain galactooligosacharides, long-chain fructooligosaccharides, and pectin-derived acidic oligosaccharides (termed scGOS/lcFOS/pAOS). In a Th2-skewed formalin-inactivated (FI)-RSV vaccination model, the prebiotic diet reduced RSV-specific Th2 cytokine (interleukin-4 [IL-4], IL-5, and IL-13)-producing CD4(+) T cells in the lung and the magnitude of airway eosinophilia at day 4 and 6 after infection. This was accompanied by a decreased influx of inflammatory dendritic cells (CD11b(+)/CD11c(+)) and increased numbers of IFN-γ-producing CD4(+) and CD8(+) T cells at day 8 after viral challenge. These findings suggest that specific dietary oligosaccharides can influence trafficking and/or effector functions of innate immune, CD4(+), and CD8(+) T cell subsets in the lungs of RSV-infected mice. In our models, scGOS/lcFOS/pAOS had no effect on weight but increased viral clearance in FI-RSV-vaccinated mice 8 days after infection. The increased systemic Th1 responses potentiated by scGOS/lcFOS/pAOS might contribute to an accelerated Th1/Th2 shift of the neonatal immune system, which might favor protective immunity against viral infections with a high attack rate in early infancy, such as RSV. PMID:22896622

  11. Chronic serotonin-norepinephrine reuptake transporter inhibition modifies basal respiratory output in adult mouse in vitro and in vivo

    PubMed Central

    Warren, Kelly A.; Solomon, Irene C.

    2012-01-01

    Respiratory disturbances are a common feature of panic disorder and present as breathing irregularity, hyperventilation, and increased sensitivity to carbon dioxide. Common therapeutic interventions, such as tricyclic (TCA) and selective serotonin reuptake inhibitor (SSRI) antidepressants, have been shown to ameliorate not only the psychological components of panic disorder but also the respiratory disturbances. These drugs are also prescribed for generalized anxiety and depressive disorders, neither of which are characterized by respiratory disturbances, and previous studies have demonstrated that TCAs and SSRIs exert effects on basal respiratory activity in animal models without panic disorder symptoms. Whether serotonin-norepinephrine reuptake inhibitors (SNRIs) have similar effects on respiratory activity remains to be determined. Therefore, the current study was designed to investigate the effects of chronic administration of the SNRI antidepressant venlafaxine (VHCL) on basal respiratory output. For these experiments, we recorded phrenic nerve discharge in an in vitro arterially-perfused adult mouse preparation and diaphragm electromyogram (EMG) activity in an in vivo urethane-anesthetized adult mouse preparation. We found that following 28-d VHCL administration, basal respiratory burst frequency was markedly reduced due to an increase in expiratory duration (TE), and the inspiratory duty cycle (TI/Ttot) was significantly shortened. In addition, post-inspiratory and spurious expiratory discharges were seen in vitro. Based on our observations, we suggest that drugs capable of simultaneously blocking both 5-HT and NE reuptake transporters have the potential to influence the respiratory control network in patients using SNRI therapy. PMID:22871263

  12. Low-cost respiratory motion tracking system

    NASA Astrophysics Data System (ADS)

    Goryawala, Mohammed; Del Valle, Misael; Wang, Jiali; Byrne, James; Franquiz, Juan; McGoron, Anthony

    2008-03-01

    Lung cancer is the cause of more than 150,000 deaths annually in the United States. Early and accurate detection of lung tumors with Positron Emission Tomography has enhanced lung tumor diagnosis. However, respiratory motion during the imaging period of PET results in the reduction of accuracy of detection due to blurring of the images. Chest motion can serve as a surrogate for tracking the motion of the tumor. For tracking chest motion, an optical laser system was designed which tracks the motion of a patterned card placed on the chest by illuminating the pattern with two structured light sources, generating 8 positional markers. The position of markers is used to determine the vertical, translational, and rotational motion of the card. Information from the markers is used to decide whether the patient's breath is abnormal compared to their normal breathing pattern. The system is developed with an inexpensive web-camera and two low-cost laser pointers. The experiments were carried out using a dynamic phantom developed in-house, to simulate chest movement with different amplitudes and breathing periods. Motion of the phantom was tracked by the system developed and also by a pressure transducer for comparison. The studies showed a correlation of 96.6% between the respiratory tracking waveforms by the two systems, demonstrating the capability of the system. Unlike the pressure transducer method, the new system tracks motion in 3 dimensions. The developed system also demonstrates the ability to track a sliding motion of the patient in the direction parallel to the bed and provides the potential to stop the PET scan in case of such motion.

  13. [The environment and human respiratory system].

    PubMed

    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

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

    PubMed

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

    2016-01-01

    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. PMID:26446604

  15. The effect of culture conditions on cytodifferentiation of fetal mouse lung respiratory passageways.

    PubMed

    Hilfer, S R; Schneck, S L; Brown, J W

    1986-01-01

    Differentiation of the respiratory region of fetal mouse lungs was investigated in serum-free medium supplemented with growth factors and hormones. Terminal buds from the margins of a lobe were removed from 16-day fetuses and organ cultures prepared either in submersion culture or at the air-medium interface. It was found that glycyl-L-histidyl-L-lysine, transferrin, and somatostatin were sufficient to promote branching in the absence of serum. However, type II pneumocytes containing lamellar bodies formed only in the presence of thyroxine or dexamethasone. At concentrations of these hormones slightly above the physiological range most of the cells became cuboidal and contained lamellar bodies; at lower concentrations regions of flattened cells appeared. In submersion culture a large, central cavity surrounded by saccules was formed rather than a branched tree. Thus, the pattern of differentiation is significantly influenced by culture conditions. PMID:2869941

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

    PubMed Central

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

    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 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

  17. Optimal branching designs in respiratory systems

    NASA Astrophysics Data System (ADS)

    Park, Keunhwan; Kim, Wonjung; Kim, Ho-Young

    2015-11-01

    In nature, the size of the flow channels systematically decreases with multiple generations of branching, and a mother branch is ultimately divided into numerous terminal daughters. One important feature of branching designs is an increase in the total cross-sectional area along with generation, which provide more time and area for mass transfer at the terminal branches. However, the expansion of the total cross-sectional area can be costly due to the maintenance of redundant branches or the additional viscous resistance. Accordingly, we expect to find optimal designs in natural branching systems. Here we present two examples of branching designs in respiratory systems: fish gills and human lung airways. Fish gills consist of filaments with well-ordered lamellar structures. By developing a mathematical model of oxygen transfer rate as a function of the dimensions of fish gills, we demonstrate that the interlamellar distance has been optimized to maximize the oxygen transfer rate. Using the same framework, we examine the diameter reduction ratio in human lung airways, which branch by dichotomy with a systematic reduction of their diameters. Our mathematical model for oxygen transport in the airways enables us to unveil the design principle of human lung airways.

  18. Molecular determinants of severe acute respiratory syndrome coronavirus pathogenesis and virulence in young and aged mouse models of human disease.

    PubMed

    Frieman, Matthew; Yount, Boyd; Agnihothram, Sudhakar; Page, Carly; Donaldson, Eric; Roberts, Anjeanette; Vogel, Leatrice; Woodruff, Becky; Scorpio, Diana; Subbarao, Kanta; Baric, Ralph S

    2012-01-01

    SARS coronavirus (SARS-CoV) causes severe acute respiratory tract disease characterized by diffuse alveolar damage and hyaline membrane formation. This pathology often progresses to acute respiratory distress (such as acute respiratory distress syndrome [ARDS]) and atypical pneumonia in humans, with characteristic age-related mortality rates approaching 50% or more in immunosenescent populations. The molecular basis for the extreme virulence of SARS-CoV remains elusive. Since young and aged (1-year-old) mice do not develop severe clinical disease following infection with wild-type SARS-CoV, a mouse-adapted strain of SARS-CoV (called MA15) was developed and was shown to cause lethal infection in these animals. To understand the genetic contributions to the increased pathogenesis of MA15 in rodents, we used reverse genetics and evaluated the virulence of panels of derivative viruses encoding various combinations of mouse-adapted mutations. We found that mutations in the viral spike (S) glycoprotein and, to a much less rigorous extent, in the nsp9 nonstructural protein, were primarily associated with the acquisition of virulence in young animals. The mutations in S likely increase recognition of the mouse angiotensin-converting enzyme 2 (ACE2) receptor not only in MA15 but also in two additional, independently isolated mouse-adapted SARS-CoVs. In contrast to the findings for young animals, mutations to revert to the wild-type sequence in nsp9 and the S glycoprotein were not sufficient to significantly attenuate the virus compared to other combinations of mouse-adapted mutations in 12-month-old mice. This panel of SARS-CoVs provides novel reagents that we have used to further our understanding of differential, age-related pathogenic mechanisms in mouse models of human disease. PMID:22072787

  19. Molecular Determinants of Severe Acute Respiratory Syndrome Coronavirus Pathogenesis and Virulence in Young and Aged Mouse Models of Human Disease

    PubMed Central

    Yount, Boyd; Agnihothram, Sudhakar; Page, Carly; Donaldson, Eric; Roberts, Anjeanette; Vogel, Leatrice; Woodruff, Becky; Scorpio, Diana; Subbarao, Kanta; Baric, Ralph S.

    2012-01-01

    SARS coronavirus (SARS-CoV) causes severe acute respiratory tract disease characterized by diffuse alveolar damage and hyaline membrane formation. This pathology often progresses to acute respiratory distress (such as acute respiratory distress syndrome [ARDS]) and atypical pneumonia in humans, with characteristic age-related mortality rates approaching 50% or more in immunosenescent populations. The molecular basis for the extreme virulence of SARS-CoV remains elusive. Since young and aged (1-year-old) mice do not develop severe clinical disease following infection with wild-type SARS-CoV, a mouse-adapted strain of SARS-CoV (called MA15) was developed and was shown to cause lethal infection in these animals. To understand the genetic contributions to the increased pathogenesis of MA15 in rodents, we used reverse genetics and evaluated the virulence of panels of derivative viruses encoding various combinations of mouse-adapted mutations. We found that mutations in the viral spike (S) glycoprotein and, to a much less rigorous extent, in the nsp9 nonstructural protein, were primarily associated with the acquisition of virulence in young animals. The mutations in S likely increase recognition of the mouse angiotensin-converting enzyme 2 (ACE2) receptor not only in MA15 but also in two additional, independently isolated mouse-adapted SARS-CoVs. In contrast to the findings for young animals, mutations to revert to the wild-type sequence in nsp9 and the S glycoprotein were not sufficient to significantly attenuate the virus compared to other combinations of mouse-adapted mutations in 12-month-old mice. This panel of SARS-CoVs provides novel reagents that we have used to further our understanding of differential, age-related pathogenic mechanisms in mouse models of human disease. PMID:22072787

  20. Using Isolated Mitochondria from Minimal Quantities of Mouse Skeletal Muscle for High throughput Microplate Respiratory Measurements

    PubMed Central

    Boutagy, Nabil E.; Rogers, George W.; Pyne, Emily S.; Ali, Mostafa M.; Hulver, Matthew W.; Frisard, Madlyn I.

    2015-01-01

    Skeletal muscle mitochondria play a specific role in many disease pathologies. As such, the measurement of oxygen consumption as an indicator of mitochondrial function in this tissue has become more prevalent. Although many technologies and assays exist that measure mitochondrial respiratory pathways in a variety of cells, tissue and species, there is currently a void in the literature in regards to the compilation of these assays using isolated mitochondria from mouse skeletal muscle for use in microplate based technologies. Importantly, the use of microplate based respirometric assays is growing among mitochondrial biologists as it allows for high throughput measurements using minimal quantities of isolated mitochondria. Therefore, a collection of microplate based respirometric assays were developed that are able to assess mechanistic changes/adaptations in oxygen consumption in a commonly used animal model. The methods presented herein provide step-by-step instructions to perform these assays with an optimal amount of mitochondrial protein and reagents, and high precision as evidenced by the minimal variance across the dynamic range of each assay. PMID:26555567

  1. Limited Effects of Muc1 Deficiency on Mouse Adenovirus Type 1 Respiratory Infection

    PubMed Central

    Nguyen, Y; Procario, Megan C.; Ashley, Shanna L.; O'Neal, Wanda K.; Pickles, Raymond J.; Weinberg, Jason B.

    2011-01-01

    Muc1 (MUC1 in humans) is a membrane-tethered mucin that exerts anti-inflammatory effects in the lung during bacterial infection. Muc1 and other mucins are also likely to form a protective barrier in the lung. We used mouse adenovirus type 1 (MAV-1, also known as MAdV-1) to determine the role of Muc1 in the pathogenesis of an adenovirus in its natural host. Following intranasal inoculation of wild type mice, we detected increased TNF-α, a cytokine linked to Muc1 production, but no consistent changes in the production of lung Muc1, Muc5ac or overall lung mucus production. Viral loads were modestly higher in the lungs of Muc1−/− mice compared to Muc1+/+ mice at several early time points but decreased to similar levels by 14 days post infection in both groups. However, cellular inflammation and the expression of CXCL1, CCL5, and CCL2 did not significantly differ between Muc1−/− and Muc1+/+ mice. Our data therefore suggest that Muc1 may contribute to a physical barrier that protects against MAV-1 respiratory infection. However, our data do not reveal an anti-inflammatory effect of Muc1 that contributes to MAV-1 pathogenesis.. PMID:21816184

  2. The ventral medullary respiratory network of the mature mouse studied in a working heart-brainstem preparation.

    PubMed Central

    Paton, J F

    1996-01-01

    1. This report provides the first description of respiratory network activity within the ventrolateral medulla of the mature mouse obtained from a unique working heart-brainstem preparation (WHBP). 2. In the WHBP three distinct respiratory phases were evident in recordings of both phrenic and vagal efferent nerves. These included a ramp inspiratory (I) discharge, post-inspiratory (PI) activity and a silent or expiratory interval (E2). 3. Extracellular recordings were made from different types of respiratory neurones located within, or in close proximity to, the nucleus ambiguus. Based on firing patterns and phase relative to phrenic nerve discharge, respiratory neurone types, including pre-inspiratory (PreI), early-inspiratory, throughout inspiratory (I), late-inspiratory, post-inspiratory (PI) and stage II expiratory or E2 neurones were characterized. 4. Intracellular recordings were made from four types of respiratory neurones (PreI, I, PI and E2 neurones). PreI neurones were depolarized maximally during the E2-inspiratory transition. I neurones exhibited a ramp depolarization which started either before or at the onset of phrenic discharge. Based on the kinetics of the inspiratory-related hyperpolarizations and duration of discharge, two types of PI neurones were found (rapidly adapting and slowly adapting). E2 neurones were hyperpolarized during both the inspiratory and post-inspiratory phases. 5. Phase-dependent chloride-mediated inhibition was studied in PreI, PI and E2 neurones and included: late inspiratory inhibition of PreI neurones; inspiratory-related inhibition of PI and E2 neurones; and post-inspiratory inhibition of PreI and E2 neurones. In addition, pre-inspiratory inhibition of PI neurones was also demonstrated. 6. The WHBP appears to be viable for analysing reflex, synaptic and cellular mechanisms regulating respiratory activity in an in vitro milieu. The synaptic organization of the respiratory network of the mouse appears comparable to that of

  3. Rapid generation of a mouse model for Middle East respiratory syndrome

    PubMed Central

    Zhao, Jincun; Li, Kun; Wohlford-Lenane, Christine; Agnihothram, Sudhakar S.; Fett, Craig; Zhao, Jingxian; Gale, Michael J.; Baric, Ralph S.; Enjuanes, Luis; Gallagher, Tom; McCray, Paul B.; Perlman, Stanley

    2014-01-01

    In this era of continued emergence of zoonotic virus infections, the rapid development of rodent models represents a critical barrier to public health preparedness, including the testing of antivirus therapy and vaccines. The Middle East respiratory syndrome coronavirus (MERS-CoV) was recently identified as the causative agent of a severe pneumonia. Given the ability of coronavirus to rapidly adapt to new hosts, a major public health concern is that MERS-CoV will further adapt to replication in humans, triggering a pandemic. No small-animal model for this infection is currently available, but studies suggest that virus entry factors can confer virus susceptibility. Here, we show that mice were sensitized to MERS-CoV infection by prior transduction with adenoviral vectors expressing the human host-cell receptor dipeptidyl peptidase 4. Mice developed a pneumonia characterized by extensive inflammatory-cell infiltration with virus clearance occurring 6–8 d after infection. Clinical disease and histopathological changes were more severe in the absence of type-I IFN signaling whereas the T-cell response was required for virus clearance. Using these mice, we demonstrated the efficacy of a therapeutic intervention (poly I:C) and a potential vaccine [Venezuelan equine encephalitis replicon particles expressing MERS-CoV spike protein]. We also found little protective cross-reactivity between MERS-CoV and the severe acute respiratory syndrome-CoV. Our results demonstrate that this system will be useful for MERS-CoV studies and for the rapid development of relevant animal models for emerging respiratory viral infections. PMID:24599590

  4. Anatomy and physiology of respiratory system relevant to anaesthesia

    PubMed Central

    Patwa, Apeksh; Shah, Amit

    2015-01-01

    Clinical application of anatomical and physiological knowledge of respiratory system improves patient's safety during anaesthesia. It also optimises patient's ventilatory condition and airway patency. Such knowledge has influence on airway management, lung isolation during anaesthesia, management of cases with respiratory disorders, respiratory endoluminal procedures and optimising ventilator strategies in the perioperative period. Understanding of ventilation, perfusion and their relation with each other is important for understanding respiratory physiology. Ventilation to perfusion ratio alters with anaesthesia, body position and with one-lung anaesthesia. Hypoxic pulmonary vasoconstriction, an important safety mechanism, is inhibited by majority of the anaesthetic drugs. Ventilation perfusion mismatch leads to reduced arterial oxygen concentration mainly because of early closure of airway, thus leading to decreased ventilation and atelectasis during anaesthesia. Various anaesthetic drugs alter neuronal control of the breathing and bronchomotor tone. PMID:26556911

  5. Chronic complications of diabetes mellitus related to the respiratory system.

    PubMed

    Vojtková, Jarmila; Ciljaková, Miriam; Michnová, Zuzana; Turčan, Tomá

    2012-01-01

    The quality of life in patients with diabetes mellitus is mainly determined by chronic diabetic complications which may affect all organ tissues including respiratory system. Microangiopathy of pulmonary capillaries, autonomic neuropathy, myopathy of respiratory muscles or changes in collagen belong to supposed pathophysiological pathways. This paper brings brief review about reported functional consequences in subjects with diabetes - decreased vital lung capacity and pulmonary volumes, decreased diffuse lung capacity for carbon monoxide, lower basal bronchial tone, lower cough reflex sensitivity, increased incidence of sleep obstructive apnea, increase in respiratory infections, disorders in respiratory muscles or phrenical nerve. Examination of pulmonary functions may serve for early detection of chronic complications in patients with diabetes. PMID:23146790

  6. Anatomy and physiology of respiratory system relevant to anaesthesia.

    PubMed

    Patwa, Apeksh; Shah, Amit

    2015-09-01

    Clinical application of anatomical and physiological knowledge of respiratory system improves patient's safety during anaesthesia. It also optimises patient's ventilatory condition and airway patency. Such knowledge has influence on airway management, lung isolation during anaesthesia, management of cases with respiratory disorders, respiratory endoluminal procedures and optimising ventilator strategies in the perioperative period. Understanding of ventilation, perfusion and their relation with each other is important for understanding respiratory physiology. Ventilation to perfusion ratio alters with anaesthesia, body position and with one-lung anaesthesia. Hypoxic pulmonary vasoconstriction, an important safety mechanism, is inhibited by majority of the anaesthetic drugs. Ventilation perfusion mismatch leads to reduced arterial oxygen concentration mainly because of early closure of airway, thus leading to decreased ventilation and atelectasis during anaesthesia. Various anaesthetic drugs alter neuronal control of the breathing and bronchomotor tone. PMID:26556911

  7. Activity of respiratory system during laser irradiation of brain structures

    NASA Astrophysics Data System (ADS)

    Merkulova, N. A.; Sergeyeva, L. I.

    1984-06-01

    The performance of one of the principal links of the respiratory system, the respiratory center, was studied as a function of the exposure of the medulla oblongata and the sensomotor zone of the cerebral hemisphere cortex to low level laser irradiation in the red wavelength of the spectrum. Experiments were done on white rats under barbital anesthesia. Under such conditions a substantial effect was observed on the activity of the respiratory center. Laser light may display activating or inhibitory influences, in some cases the bilateral symmetry of the activity of the respiratory center is affected indicating deep changes in the integrative mechanism of the functioning of the right and left sides of the hemispheres. The laser beam effect depends on many factors: specific light properties, duration of the exposure, repetition of exposures, initial functional state of the CNS, etc.

  8. Air pollution and the respiratory system.

    PubMed

    Arbex, Marcos Abdo; Santos, Ubiratan de Paula; Martins, Lourdes Conceição; Saldiva, Paulo Hilário Nascimento; Pereira, Luiz Alberto Amador; Braga, Alfésio Luis Ferreira

    2012-01-01

    Over the past 250 years-since the Industrial Revolution accelerated the process of pollutant emission, which, until then, had been limited to the domestic use of fuels (mineral and vegetal) and intermittent volcanic emissions-air pollution has been present in various scenarios. Today, approximately 50% of the people in the world live in cities and urban areas and are exposed to progressively higher levels of air pollutants. This is a non-systematic review on the different types and sources of air pollutants, as well as on the respiratory effects attributed to exposure to such contaminants. Aggravation of the symptoms of disease, together with increases in the demand for emergency treatment, the number of hospitalizations, and the number of deaths, can be attributed to particulate and gaseous pollutants, emitted by various sources. Chronic exposure to air pollutants not only causes decompensation of pre-existing diseases but also increases the number of new cases of asthma, COPD, and lung cancer, even in rural areas. Air pollutants now rival tobacco smoke as the leading risk factor for these diseases. We hope that we can impress upon pulmonologists and clinicians the relevance of investigating exposure to air pollutants and of recognizing this as a risk factor that should be taken into account in the adoption of best practices for the control of the acute decompensation of respiratory diseases and for maintenance treatment between exacerbations. PMID:23147058

  9. A Review on the Respiratory System Toxicity of Carbon Nanoparticles

    PubMed Central

    Pacurari, Maricica; Lowe, Kristine; Tchounwou, Paul B.; Kafoury, Ramzi

    2016-01-01

    The respiratory system represents the main gateway for nanoparticles’ entry into the human body. Although there is a myriad of engineered nanoparticles, carbon nanoparticles/nanotubes (CNPs/CNTs) have received much attention mainly due to their light weight, very high surface area, durability, and their diverse applications. Since their discovery and manufacture over two decades ago, much has been learned about nanoparticles’ interactions with diverse biological system models. In particular, the respiratory system has been of great interest because various natural and man-made fibrous particles are known to be responsible for chronic and debilitating lung diseases. In this review, we present up-to-date the literature regarding the effects of CNTs or carbon nanofibers (CNFs) on the human respiratory system with respect to respiratory toxicity pathways and associated pathologies. This article is intended to emphasize the potentially dangerous effects to the human respiratory system if inadequate measures are used in the manufacture, handling, and preparation and applications of CNP or CNP-based products. PMID:26999172

  10. [A novel respiratory detecting system based on bio-impedance].

    PubMed

    Wang, Jian-bo; Deng, Qin-kai; Guo, Jin-song; Feng, Xue-ji

    2009-03-01

    This paper introduces the design and implementation of a novel respiratory detecting system based on bio-impedance method. By increasing electrodes in space, the system make multi-channel respiratory signals be superpositioned and filtered (SNR); Traditional filter methods by both hardware and software are also used to further increase anti-interference ability. A low consumption and portable instrument is designed based on MSP430 Micro Controller Unit (MCU), The experiment shows a better performance in the reduction of interference noises of heartbeat and blood flow especially the motion artifact. Also the system works stably. PMID:19565791

  11. Evaluation of performance of portable respiratory monitoring system based on micro-electro-mechanical-system for respiratory gated radiotherapy

    NASA Astrophysics Data System (ADS)

    Moon, Sun Young; Sung, Jiwon; Yoon, Myonggeun; Chung, Mijoo; Chung, Weon Kuu; Kim, Dong Wook

    2015-08-01

    In respiratory-gated radiotherapy of patients with lung or liver cancer, the patient's respiratory pattern and repeatability are important factors affecting therapy accuracy; it has been reported that these factors can be controlled if patients undergo respiration training. As such, this study evaluates the feasibility of micro-electro-mechanical-system (MEMS) in radiotherapy by investigating the effect of radiation on a miniature portable respiratory monitoring system based on the MEMS system, which is currently under development. Using a patient respiration simulation phantom, the time-acceleration graph measured by a normal sensor according to the phantom's respiratory movement before irradiation and the change in this graph with accumulated dose were compared using the baseline slope and the change in amplitude and period of the sine wave. The results showed that with a 400Gy accumulated dose in the sensor, a baseline shift occurred and both the amplitude and period changed. As a result, if the MEMS is applied in respiratory-gated radiotherapy, the sensor should be replaced after use with roughly 6-10 patients so as to ensure continued therapy accuracy, based on the characteristics of the sensor itself. In the future, a more diverse range of sensors should be similarly evaluated.

  12. Evaluation of exercise-respiratory system modifications and integration schemes for physiological systems

    NASA Technical Reports Server (NTRS)

    Gallagher, R. R.

    1974-01-01

    Exercise subroutine modifications are implemented in an exercise-respiratory system model yielding improvement of system response to exercise forcings. A more physiologically desirable respiratory ventilation rate in addition to an improved regulation of arterial gas tensions and cerebral blood flow is observed. A respiratory frequency expression is proposed which would be appropriate as an interfacing element of the respiratory-pulsatile cardiovascular system. Presentation of a circulatory-respiratory system integration scheme along with its computer program listing is given. The integrated system responds to exercise stimulation for both nonstressed and stressed physiological states. Other integration possibilities are discussed with respect to the respiratory, pulsatile cardiovascular, thermoregulatory, and the long-term circulatory systems.

  13. 76 FR 62164 - VASRD Improvement Forum-Updating Disability Criteria for the Respiratory System, Cardiovascular...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-06

    ... AFFAIRS VASRD Improvement Forum--Updating Disability Criteria for the Respiratory System, Cardiovascular...) Improvement Forum-- Updating Disability Criteria for the Respiratory System, Cardiovascular System, Hearing... four body systems: (1) Respiratory System (38 CFR 4.96-4.97), (2) the Cardiovascular System (38 CFR...

  14. Nanocarriers as pulmonary drug delivery systems to treat and to diagnose respiratory and non respiratory diseases

    PubMed Central

    Smola, Malgorzata; Vandamme, Thierry; Sokolowski, Adam

    2008-01-01

    The purpose of this review is to discuss the impact of nanocarriers administered by pulmonary route to treat and to diagnose respiratory and non respiratory diseases. Indeed, during the past 10 years, the removal of chlorofluorocarbon propellants from industrial and household products intended for the pulmonary route has lead to the developments of new alternative products. Amongst these ones, on one hand, a lot of attention has been focused to improve the bioavailability of marketed drugs intended for respiratory diseases and to develop new concepts for pulmonary administration of drugs and, on the other hand, to use the pulmonary route to administer drugs for systemic diseases. This has led to some marketed products through the last decade. Although the introduction of nanotechnology permitted to step over numerous problems and to improve the bioavailability of drugs, there are, however, unresolved delivery problems to be still addressed. These scientific and industrial innovations and challenges are discussed along this review together with an analysis of the current situation concerning the industrial developments. PMID:18488412

  15. Computational 3-D Model of the Human Respiratory System

    EPA Science Inventory

    We are developing a comprehensive, morphologically-realistic computational model of the human respiratory system that can be used to study the inhalation, deposition, and clearance of contaminants, while being adaptable for age, race, gender, and health/disease status. The model ...

  16. Role of the Bordetella pertussis minor fimbrial subunit, FimD, in colonization of the mouse respiratory tract.

    PubMed Central

    Geuijen, C A; Willems, R J; Bongaerts, M; Top, J; Gielen, H; Mooi, F R

    1997-01-01

    Bordetella pertussis fimbriae are composed of a major subunit, Fim2 or Fim3, and the minor subunit FimD. Using immunoelectron microscopy, we provide evidence that FimD is located at the fimbrial tip. The role of FimD in colonization of the mouse respiratory tract was studied by using two fimbrial mutants: a mutant completely devoid of fimbriae (designated FimD-) and a mutant devoid of the major fimbrial subunits but still producing the minor subunit (designated FimD+). The ability of the two fimbrial mutants to colonize the nasopharynx, trachea, and lungs was compared with those of the wild type parental strain and a filamentous hemagglutinin (FHA) mutant. Of the three mutants studied, the FimD- mutant showed the greatest defect, colonizing less well in the nasopharynx, trachea, and lungs. The most pronounced defect in colonizing ability of the three mutants was observed in the trachea. However, the colonizing defect of the FHA and FimD+ mutants in the trachea was observed only during the first 3 days of infection. After 10 days, the colonization level was nearly restored to wild-type levels. The FHA and FimD+ mutants showed a slight colonization defect in the nasopharynx but no defect in the lungs. A maltose binding protein-FimD fusion protein and a peptide derived from FimD were able to bind to heparin, a member of a class of sulfated sugars which are ubiquitous in the respiratory tract. Recently it was shown (W. L. W. Hazenbos, C. A. W. Geuijen, B. M. van den Berg, F. R. Mooi, and R. van Furth, J. Infect. Dis. 171:924-929, 1995) that FimD also binds to the integrin VLA-5, and our results suggest that the binding of B. pertussis to these two molecules plays an important role in colonization of the respiratory tract of the mouse. PMID:9317030

  17. Effect of Mouse Strain in a Model of Chemical-induced Respiratory Allergy

    PubMed Central

    Nishino, Risako; Fukuyama, Tomoki; Watanabe, Yuko; Kurosawa, Yoshimi; Ueda, Hideo; Kosaka, Tadashi

    2014-01-01

    The inhalation of many types of chemicals is a leading cause of allergic respiratory diseases, and effective protocols are needed for the detection of environmental chemical–related respiratory allergies. In our previous studies, we developed a method for detecting environmental chemical–related respiratory allergens by using a long-term sensitization–challenge protocol involving BALB/c mice. In the current study, we sought to improve our model by characterizing strain-associated differences in respiratory allergic reactions to the well-known chemical respiratory allergen glutaraldehyde (GA). According to our protocol, BALB/c, NC/Nga, C3H/HeN, C57BL/6N, and CBA/J mice were sensitized dermally with GA for 3 weeks and then challenged with intratracheal or inhaled GA at 2 weeks after the last sensitization. The day after the final challenge, all mice were euthanized, and total serum IgE levels were assayed. In addition, immunocyte counts, cytokine production, and chemokine levels in the hilar lymph nodes (LNs) and bronchoalveolar lavage fluids (BALF) were also assessed. In conclusion, BALB/c and NC/Nga mice demonstrated markedly increased IgE reactions. Inflammatory cell counts in BALF were increased in the treated groups of all strains, especially BALB/c, NC/Nga, and CBA/J strains. Cytokine levels in LNs were increased in all treated groups except for C3H/HeN and were particularly high in BALB/c and NC/Nga mice. According to our results, we suggest that BALB/c and NC/Nga are highly susceptible to respiratory allergic responses and therefore are good candidates for use in our model for detecting environmental chemical respiratory allergens. PMID:25048268

  18. Mechanisms Underlying Adaptation of Respiratory Network Activity to Modulatory Stimuli in the Mouse Embryo

    PubMed Central

    Chevalier, Marc; De Sa, Rafaël; Cardoit, Laura; Thoby-Brisson, Muriel

    2016-01-01

    Breathing is a rhythmic behavior that requires organized contractions of respiratory effector muscles. This behavior must adapt to constantly changing conditions in order to ensure homeostasis, proper body oxygenation, and CO2/pH regulation. Respiratory rhythmogenesis is controlled by neural networks located in the brainstem. One area considered to be essential for generating the inspiratory phase of the respiratory rhythm is the preBötzinger complex (preBötC). Rhythmogenesis emerges from this network through the interplay between the activation of intrinsic cellular properties (pacemaker properties) and intercellular synaptic connections. Respiratory activity continuously changes under the impact of numerous modulatory substances depending on organismal needs and environmental conditions. The preBötC network has been shown to become active during the last third of gestation. But only little is known regarding the modulation of inspiratory rhythmicity at embryonic stages and even less on a possible role of pacemaker neurons in this functional flexibility during the prenatal period. By combining electrophysiology and calcium imaging performed on embryonic brainstem slice preparations, we provide evidence showing that embryonic inspiratory pacemaker neurons are already intrinsically sensitive to neuromodulation and external conditions (i.e., temperature) affecting respiratory network activity, suggesting a potential role of pacemaker neurons in mediating rhythm adaptation to modulatory stimuli in the embryo. PMID:27239348

  19. Respiratory syncytial virus receptor expression in the mouse and viral tropism.

    PubMed

    Shakeri, Aria; Mastrangelo, Peter; Griffin, Jennifer K; Moraes, Theo J; Hegele, Richard G

    2015-04-01

    Human respiratory syncytial virus (RSV) infects airway epithelium and can cause serious illnesses such as bronchiolitis and pneumonia. With the discovery of cell-surface nucleolin as a fusion receptor for RSV, the question arose as to whether nucleolin could explain RSV tropism in vivo. Here, we report the distribution of cell-surface nucleolin expression in tissues of normal mice and how this distribution of expression relates to what is known about RSV tropism and its clinical manifestations. Our results show evidence of cell-surface nucleolin expression in the respiratory tract. In addition, cell-surface nucleolin is expressed in tissues outside of the respiratory tract, many of which correspond to previous reports of tissue-specific RSV infection, and others that may allude to additional potential sites for RSV infection in vivo. Furthermore, our work provides a foundation for the investigation of nucleolin's physiological function in various healthy mammalian tissues. PMID:25374027

  20. A respiratory-gated treatment system for proton therapy

    SciTech Connect

    Lu, H.-M.; Brett, Robert; Sharp, Gregory; Safai, Soiros; Jiang, Steve; Flanz, Jay; Kooy, Hanne

    2007-08-15

    Proton therapy offers the potential for excellent dose conformity and reduction in integral dose. The superior dose distribution is, however, much more sensitive to changes in radiological depths along the beam path than for photon fields. Respiratory motion can cause such changes for treatments sites like lung, liver, and mediastinum and thus affect the proton dose distribution significantly. We have implemented and commissioned a respiratory-gated system for range-modulated treatment fields. The gating system was designed to ensure that each gate always contains complete modulation cycles so that for any beam segment the delivered dose has the planned depth-dose distribution. Measurements have been made to estimate the time delays for the various components of the system. The total delay between the actual motion and the beam on/off control is in the range of 65-195 ms. Time-resolved dose measurements and film tests were also conducted to examine the overall gating effect.

  1. Respiratory protective device design using control system techniques

    NASA Technical Reports Server (NTRS)

    Burgess, W. A.; Yankovich, D.

    1972-01-01

    The feasibility of a control system analysis approach to provide a design base for respiratory protective devices is considered. A system design approach requires that all functions and components of the system be mathematically identified in a model of the RPD. The mathematical notations describe the operation of the components as closely as possible. The individual component mathematical descriptions are then combined to describe the complete RPD. Finally, analysis of the mathematical notation by control system theory is used to derive compensating component values that force the system to operate in a stable and predictable manner.

  2. Inhaled formulations and pulmonary drug delivery systems for respiratory infections.

    PubMed

    Zhou, Qi Tony; Leung, Sharon Shui Yee; Tang, Patricia; Parumasivam, Thaigarajan; Loh, Zhi Hui; Chan, Hak-Kim

    2015-05-01

    Respiratory infections represent a major global health problem. They are often treated by parenteral administrations of antimicrobials. Unfortunately, systemic therapies of high-dose antimicrobials can lead to severe adverse effects and this calls for a need to develop inhaled formulations that enable targeted drug delivery to the airways with minimal systemic drug exposure. Recent technological advances facilitate the development of inhaled anti-microbial therapies. The newer mesh nebulisers have achieved minimal drug residue, higher aerosolisation efficiencies and rapid administration compared to traditional jet nebulisers. Novel particle engineering and intelligent device design also make dry powder inhalers appealing for the delivery of high-dose antibiotics. In view of the fact that no new antibiotic entities against multi-drug resistant bacteria have come close to commercialisation, advanced formulation strategies are in high demand for combating respiratory 'super bugs'. PMID:25451137

  3. Revised Medical Criteria for Evaluating Respiratory System Disorders. Final rule.

    PubMed

    2016-06-01

    We are revising the criteria in the Listing of Impairments (listings) that we use to evaluate claims involving respiratory disorders in adults and children under titles II and XVI of the Social Security Act (Act). The revisions reflect our program experience and advances in medical knowledge since we last comprehensively revised this body system in 1993, as well as comments we received from medical experts and the public. PMID:27295734

  4. Examining the safety of respiratory and intravenous inoculation of Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus in a mouse model

    PubMed Central

    Shatzkes, Kenneth; Chae, Richard; Tang, Chi; Ramirez, Gregory C.; Mukherjee, Somdatta; Tsenova, Liana; Connell, Nancy D.; Kadouri, Daniel E.

    2015-01-01

    Bdellovibrio spp. and Micavibrio spp. are Gram-negative predators that feed on other Gram-negative bacteria, making predatory bacteria potential alternatives to antibiotics for treating multi-drug resistant infections. While the ability of predatory bacteria to control bacterial infections in vitro is well documented, the in vivo effect of predators on a living host has yet to be extensively examined. In this study, respiratory and intravenous inoculations were used to determine the effects of predatory bacteria in mice. We found no reduction in mouse viability after intranasal or intravenous inoculation of B. bacteriovorus 109J, HD100 or M. aeruginosavorus. Introducing predators into the respiratory tract of mice provoked a modest inflammatory response at 1 hour post-exposure, but was not sustained at 24 hours, as measured by RT-qPCR and ELISA. Intravenous injection caused an increase of IL-6 in the kidney and spleen, TNF in the liver and CXCL-1/KC in the blood at 3 hours post-exposure, returning to baseline levels by 18 hours. Histological analysis of tissues showed no pathological changes due to predatory bacteria. Furthermore, qPCR detected predators were cleared from the host quickly and efficiently. This work addresses some of the safety concerns regarding the potential use of predatory bacteria as a live antibiotic. PMID:26250699

  5. Examining the safety of respiratory and intravenous inoculation of Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus in a mouse model.

    PubMed

    Shatzkes, Kenneth; Chae, Richard; Tang, Chi; Ramirez, Gregory C; Mukherjee, Somdatta; Tsenova, Liana; Connell, Nancy D; Kadouri, Daniel E

    2015-01-01

    Bdellovibrio spp. and Micavibrio spp. are Gram-negative predators that feed on other Gram-negative bacteria, making predatory bacteria potential alternatives to antibiotics for treating multi-drug resistant infections. While the ability of predatory bacteria to control bacterial infections in vitro is well documented, the in vivo effect of predators on a living host has yet to be extensively examined. In this study, respiratory and intravenous inoculations were used to determine the effects of predatory bacteria in mice. We found no reduction in mouse viability after intranasal or intravenous inoculation of B. bacteriovorus 109J, HD100 or M. aeruginosavorus. Introducing predators into the respiratory tract of mice provoked a modest inflammatory response at 1 hour post-exposure, but was not sustained at 24 hours, as measured by RT-qPCR and ELISA. Intravenous injection caused an increase of IL-6 in the kidney and spleen, TNF in the liver and CXCL-1/KC in the blood at 3 hours post-exposure, returning to baseline levels by 18 hours. Histological analysis of tissues showed no pathological changes due to predatory bacteria. Furthermore, qPCR detected predators were cleared from the host quickly and efficiently. This work addresses some of the safety concerns regarding the potential use of predatory bacteria as a live antibiotic. PMID:26250699

  6. Influence of respiratory tract viral infection on endothelin-1-induced potentiation of cholinergic nerve-mediated contraction in mouse trachea.

    PubMed Central

    Carr, M. J.; Goldie, R. G.; Henry, P. J.

    1996-01-01

    1. This study examined the influence of respiratory tract infection with influenza A/PR-8/34 virus on endothelin receptor-mediated modulation of contraction induced by stimulation of cholinergic nerves in mouse isolated trachea. 2. The ETB receptor-selective agonist, sarafotoxin S6c (30 nM) induced large transient contractions (118 +/- 5% Cmax, n = 13; where Cmax is the contraction induced by 10 microM carbachol) of isolated tracheal segments from control mice. The peak contractile response to 30 nM sarafotoxin S6c was significantly lower in preparations from virus-inoculated mice at day 2 (57 +/- 8% Cmax, n = 3, P < 0.05) and 4 post-inoculation (90 +/- 8% Cmax, n = 9, P < 0.05), consistent with virus-induced attentuation of the ETB receptor-effector system linked to airway smooth muscle contraction. The mean peak contraction to 30 nM sarafotoxin S6c of preparations from virus-inoculated mice at day 8 post-inoculation (94 +/- 17% Cmax, n = 4) was not significantly different from that of control. 3. Electrical field stimulation (EFS; 90 V, 0.5 ms duration, 10 s train, 0.1-30 Hz) of preparations from control and virus-inoculated mice, caused contractions that were abolished by 0.1 microM atropine or 3 microM tetrodotoxin, indicating that these responses were mediated by neuronally released acetylcholine. Sarafotoxin S6c markedly potentiated contractions induced by a standard stimulus (0.3 Hz, every 3 min) in tracheal segments from control and virus-inoculated mice. In tracheal tissue from control mice, 30 nM sarafotoxin S6c significantly increased a standard EFS-induced contraction of 24 +/- 4% Cmax by a further 24 +/- 3% Cmax (i.e. 2 fold increase, n = 11). Sarafotoxin S6c (30 nM) also markedly potentiated standard EFS-induced contractions in preparations from virus-inoculated mice at day 2 (17 +/- 2% Cmax, n = 3), day 4 (17 +/- 5% Cmax, n = 9) and day 8 (26 +/- 5% Cmax, n = 4) post-inoculation. The level of potentiation of EFS-induced contractions in preparations

  7. Efficient Replication of Severe Acute Respiratory Syndrome Coronavirus in Mouse Cells Is Limited by Murine Angiotensin-Converting Enzyme 2

    PubMed Central

    Li, Wenhui; Greenough, Thomas C.; Moore, Michael J.; Vasilieva, Natalya; Somasundaran, Mohan; Sullivan, John L.; Farzan, Michael; Choe, Hyeryun

    2004-01-01

    Replication of viruses in species other than their natural hosts is frequently limited by entry and postentry barriers. The coronavirus that causes severe acute respiratory syndrome (SARS-CoV) utilizes the receptor angiotensin-converting enzyme 2 (ACE2) to infect cells. Here we compare human, mouse, and rat ACE2 molecules for their ability to serve as receptors for SARS-CoV. We found that, compared to human ACE2, murine ACE2 less efficiently bound the S1 domain of SARS-CoV and supported less-efficient S protein-mediated infection. Rat ACE2 was even less efficient, at near background levels for both activities. Murine 3T3 cells expressing human ACE2 supported SARS-CoV replication, whereas replication was less than 10% as efficient in the same cells expressing murine ACE2. These data imply that a mouse transgenically expressing human ACE2 may be a useful animal model of SARS. PMID:15452268

  8. Protective B-cell epitopes of Francisella tularensis O-polysaccharide in a mouse model of respiratory tularaemia

    PubMed Central

    Lu, Zhaohua; Madico, Guillermo; Roche, Marly I; Wang, Qi; Hui, Julia H; Perkins, Hillary M; Zaia, Joseph; Costello, Catherine E; Sharon, Jacqueline

    2012-01-01

    Antibodies to the lipopolysaccharide (LPS) of Francisella tularensis have been shown to be protective against respiratory tularaemia in mouse models, and we have previously described mouse monoclonal antibodies (mAbs) to non-overlapping terminal and internal epitopes of the F. tularensis LPS O-polysaccharide (OAg). In the current study, we used F. tularensis LPS oligosaccharides of defined OAg repeat length as molecular rulers in competition ELISA to demonstrate that the epitope targeted by the terminal OAg-binding mAb FB11 is contained within one tetrasaccharide repeat whereas the epitope targeted by the internal OAg-binding mAb Ab52 spans two tetrasaccharide repeats. Both mAbs conferred survival to BALB/c mice infected intranasally with the F. tularensis type B live vaccine strain and prolonged survival of BALB/c mice infected intranasally with the highly virulent F. tularensis type A strain SchuS4. The protective effects correlated with reduced bacterial burden in mAb-treated infected mice. These results indicate that an oligosaccharide with two OAg tetrasaccharide repeats covers both terminal and internal protective OAg epitopes, which may inform the design of vaccines for tularaemia. Furthermore, the FB11 and Ab52 mAbs could serve as reporters to monitor the response of vaccine recipients to protective B-cell epitopes of F. tularensis OAg. PMID:22486311

  9. Pharmacologic Activation of the Innate Immune System to Prevent Respiratory Viral Infections

    PubMed Central

    Cheng, Guanjun; Fridlender, Zvi G.; Cheng, Guang-Shing; Chen, Bei; Mangalmurti, Nilam S.; Saloura, Vassiliki; Yu, Zaifang; Kapoor, Veena; Mozdzanowska, Krystyna; Moon, Edmund; Sun, Jing; Kreindler, James L.; Cohen, Noam A.; Caton, Andrew J.; Erikson, Jan; Albelda, Steven M.

    2011-01-01

    Drugs that can rapidly inhibit respiratory infection from influenza or other respiratory pathogens are needed. One approach is to engage primary innate immune defenses against viral infection, such as activating the IFN pathway. In this study, we report that a small, cell-permeable compound called 5,6-di-methylxanthenone-4-acetic acid (DMXAA) can induce protection against vesicular stomatitis virus in vitro and H1N1 influenza A virus in vitro and in vivo through innate immune activation. Using the mouse C10 bronchial epithelial cell line and primary cultures of nasal epithelial cells, we demonstrate DMXAA activates the IFN regulatory factor-3 pathway leading to production of IFN-β and subsequent high-level induction of IFN-β–dependent proteins, such as myxovirus resistance 1 (Mx1) and 2′,5′-oligoadenylate synthetase 1 (OAS1). Mice treated with DMXAA intranasally elevate mRNA/protein expression of Mx1 and OAS1 in the nasal mucosa, trachea, and lung. When challenged intranasally with a lethal dose of H1N1 influenza A virus, DMXAA reduced viral titers in the lungs and protected 80% of mice from death, even when given at 24 hours before infection. These data show that agents, like DMXAA, that can directly activate innate immune pathways, such as the IFN regulatory factor-3/IFN-β system, in respiratory epithelial cells can be used to protect from influenza pneumonia and potentially in other respiratory viral infections. Development of this approach in humans could be valuable for protecting health care professionals and “first responders” in the early stages of viral pandemics or bioterror attacks. PMID:21148741

  10. 38 CFR 4.97 - Schedule of ratings-respiratory system.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... catheterization), or; episode(s) of acute respiratory failure, or; requires outpatient oxygen therapy 100 FEV-1 of...-respiratory system. 4.97 Section 4.97 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings The Respiratory System § 4.97 Schedule of...

  11. 38 CFR 4.97 - Schedule of ratings-respiratory system.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... catheterization), or; episode(s) of acute respiratory failure, or; requires outpatient oxygen therapy 100 FEV-1 of...-respiratory system. 4.97 Section 4.97 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings The Respiratory System § 4.97 Schedule of...

  12. 38 CFR 4.97 - Schedule of ratings-respiratory system.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... catheterization), or; episode(s) of acute respiratory failure, or; requires outpatient oxygen therapy 100 FEV-1 of...-respiratory system. 4.97 Section 4.97 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings The Respiratory System § 4.97 Schedule of...

  13. 38 CFR 4.97 - Schedule of ratings-respiratory system.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... catheterization), or; episode(s) of acute respiratory failure, or; requires outpatient oxygen therapy 100 FEV-1 of...-respiratory system. 4.97 Section 4.97 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings The Respiratory System § 4.97 Schedule of...

  14. 38 CFR 4.97 - Schedule of ratings-respiratory system.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... catheterization), or; episode(s) of acute respiratory failure, or; requires outpatient oxygen therapy 100 FEV-1 of...-respiratory system. 4.97 Section 4.97 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings The Respiratory System § 4.97 Schedule of...

  15. Mouse Genome Editing using CRISPR/Cas System

    PubMed Central

    Harms, Donald W; Quadros, Rolen M; Seruggia, Davide; Ohtsuka, Masato; Takahashi, Gou

    2015-01-01

    The availability of techniques to create desired genetic mutations has enabled the laboratory mouse as an extensively used model organism in biomedical research including human genetics. A new addition to this existing technical repertoire is the CRISPR/Cas system. Specifically, this system allows editing of the mouse genome much faster than the previously used techniques and more importantly multiple mutations can be created in a single experiment. Here we provide protocols for preparation of CRISPR/Cas reagents and microinjection into one cell mouse embryos to create knockout or knock-in mouse models. PMID:25271839

  16. OSCILLATION MECHANICS OF THE RESPIRATORY SYSTEM: APPLICATIONS TO LUNG DISEASE

    PubMed Central

    Kaczka, David W.; Dellacá, Raffaele L.

    2011-01-01

    Since its introduction in the 1950s, the forced oscillation technique (FOT) and the measurement of respiratory impedance have evolved into powerful tools for the assessment of various mechanical phenomena in the mammalian lung during health and disease. In this review, we highlight the most recent developments in instrumentation, signal processing, and modeling relevant to FOT measurements. We demonstrate how FOT provides unparalleled information on the mechanical status of the respiratory system compared to more widely-used pulmonary function tests. The concept of mechanical impedance is reviewed, as well as the various measurement techniques used to acquire such data. Emphasis is placed on the analysis of lower, physiologic frequency ranges (typically less than 10 Hz) that are most sensitive to normal physical processes as well as pathologic structural alterations. Various inverse modeling approaches used to interpret alterations in impedance are also discussed, specifically in the context of three common respiratory diseases: asthma, chronic obstructive pulmonary disease, and acute lung injury. Finally, we speculate on the potential role for FOT in the clinical arena. PMID:22011237

  17. Flow Transport in Microtubes Inspired by Insect Respiratory Systems

    NASA Astrophysics Data System (ADS)

    Aboelkaasem, Yasser; Staples, Anne

    2010-11-01

    The mechanics of insect respiration and tracheal ventilation generally follow either highly discontinuous, or cyclic gas exchange patterns. In the former, gases are exchanged by diffusion, while in the latter, recent imaging of internal respiratory flow dynamics in insects performed at the x-ray synchrotron imaging facility at Argonne indicates that convective gas exchange is accomplished by changes in internal pressure due to rhythmic compressions of the tracheal tubes that comprise the respiratory network. These localized tracheal compressions are induced by global body movements and are used to enhance the oxygen transport to the tissue. Inspired by the dynamics of insect respiratory networks in the cyclic gas exchange regime, we study fluid transport in a mixed rigid/elastic microtube that undergoes localized single and multiple periodic collapses. The latter induces a streaming of flows and therefore enhances convection and flow transport in the tube downstream of the collapse site. The shape of the microtube, the material properties, and the compression and reinflation spatial and temporal profiles are selected to mimic those observed in insect tracheal tubes. A low Reynolds number assumption and lubrication theory are used to develop a mathematical model for the system. The effects of tube shape, collapse amplitude, collapse-to-collapse distance, and collapse phase lags on the net flow rate, pressure gradient, wall shear stress, velocity are investigated.

  18. The avian respiratory system: a unique model for studies of respiratory toxicosis and for monitoring air quality.

    PubMed Central

    Brown, R E; Brain, J D; Wang, N

    1997-01-01

    There are many distinct differences (morphologic, physiologic, and mechanical) between the bird's lung-air-sac respiratory system and the mammalian bronchoalveolar lung. In this paper, we review the physiology of the avian respiratory system with attention to those mechanisms that may lead to significantly different results, relative to those in mammals, following exposure to toxic gases and airborne particulates. We suggest that these differences can be productively exploited to further our understanding of the basic mechanisms of inhalant toxicology (gases and particulates). The large mass-specific gas uptake by the avian respiratory system, at rest and especially during exercise, could be exploited as a sensitive monitor of air quality. Birds have much to offer in our understanding of respiratory toxicology, but that expectation can only be realized by investigating, in a wide variety of avian taxa, the pathophysiologic interactions of a broad range of inhaled toxicants on the bird's unique respiratory system. Images p188-a Figure 1. Figure 2. Figure 3. Figure 4. Figure 5. A Figure 5. B Figure 5. C Figure 6. Figure 7. Figure 8. PMID:9105794

  19. Post-Translational Decrease in Respiratory Chain Proteins in the Polg Mutator Mouse Brain

    PubMed Central

    Hauser, David N.; Dillman, Allissa A.; Ding, Jinhui; Li, Yan; Cookson, Mark R.

    2014-01-01

    Mitochondrial DNA damage is thought to be a causal contributor to aging as mice with inactivating mutations in polymerase gamma (Polg) develop a progeroid phenotype. To further understand the molecular mechanisms underlying this phenotype, we used iTRAQ and RNA-Seq to determine differences in protein and mRNA abundance respectively in the brains of one year old Polg mutator mice compared to control animals. We found that mitochondrial respiratory chain proteins are specifically decreased in abundance in the brains of the mutator mice, including several nuclear encoded mitochondrial components. However, we found no evidence that the changes we observed in protein levels were the result of decreases in mRNA expression. These results show that there are post-translational effects associated with mutations in Polg. PMID:24722488

  20. The in vivo respiratory phenotype of the adenosine A1 receptor knockout mouse.

    PubMed

    Heitzmann, Dirk; Buehler, Philipp; Schweda, Frank; Georgieff, Michael; Warth, Richard; Thomas, Joerg

    2016-02-01

    The nucleoside adenosine has been implicated in the regulation of respiration, especially during hypoxia in the newborn. In this study the role of adenosine A1 receptors for the control of respiration was investigated in vivo. To this end, respiration of unrestrained adult and neonatal adenosine A1 receptor knockout mice (A1R(-/-)) was measured in a plethysmographic device. Under control conditions (21% O2) and mild hypoxia (12-15% O2) no difference of respiratory parameters was observed between adult wildtype (A1R(+/+)) and A1R(-/-) mice. Under more severe hypoxia (6-10% O2) A1R(+/+) mice showed, after a transient increase of respiration, a decrease of respiration frequency (fR) and tidal volume (VT) leading to a decrease of minute volume (MV). This depression of respiration during severe hypoxia was absent in A1R(-/-) mice which displayed a stimulated respiration as indicated by the enhancement of MV by some 50-60%. During hypercapnia-hyperoxia (3-10% CO2/97-90 % O2), no obvious differences in respiration of A1R(-/-) and A1R(+/+) was observed. In neonatal mice, the respiratory response to hypoxia was surprisingly similar in both genotypes. However, neonatal A1R(-/-) mice appeared to have more frequently periods of apnea during hypoxia and in the post-hypoxic control period. In conclusion, these data indicate that the adenosine A1 receptor is an important molecular component mediating hypoxic depression in adult mice and it appears to stabilize respiration of neonatal mice. PMID:26593641

  1. Respiratory system mechanics in sedated, paralyzed, morbidly obese patients.

    PubMed

    Pelosi, P; Croci, M; Ravagnan, I; Cerisara, M; Vicardi, P; Lissoni, A; Gattinoni, L

    1997-03-01

    The effects of inspiratory flow and inflation volume on the mechanical properties of the respiratory system in eight sedated and paralyzed postoperative morbidly obese patients (aged 37.6 +/- 11.8 yr who had never smoked and had normal preoperative seated spirometry) were investigated by using the technique of rapid airway occlusion during constant-flow inflation. With the patients in the supine position, we measured the interrupter resistance (Rint,rs), which in humans probably reflects airway resistance, the "additional" resistance (delta Rrs) due to viscoelastic pressure dissipation and time-constant inequalities, and static respiratory elastance (Est,rs). Intra-abdominal pressure (IAP) was measured by using a bladder catheter, and functional residual capacity was measured by the heliumdilution technique. The results were compared with a previous study on 16 normal anesthetized paralyzed humans. Compared with normal persons, we found that in obese subjects: 1) functional residual capacity was markedly lower (0.645 +/- 0.208 liter) and IAP was higher (24 +/- 2.2 cmH2O); 2) alveolar-arterial oxygenation gradient was increased (178 +/- 59 mmHg); 3) the volume-pressure curve of the respiratory system was curvilinear with an "inflection" point; 4) Est,rs, Rint,rs, and delta Rrs were higher than normal (29.3 +/- 5.04 cmH2O/l, 5.9 +/- 2.4 cmH2O.l-1.s, and 6.4 +/- 1.6 cmH2O.l-1.s, respectively); 5) Rint,rs increased with increasing inspiratory flow, Est,rs did not change, and delta Rrs decreased progressively; and 6) with increasing inflation volume, Rint,rs and Est,rs decreased, whereas delta Rrs rose progressively. Overall, our data suggest that obese subjects during sedation and paralysis are characterized by hypoxemia and marked alterations of the mechanical properties of the respiratory system, largely explained by a reduction in lung volume due to the excessive unopposed IAP. PMID:9074968

  2. Mitochondrial free radical overproduction due to respiratory chain impairment in the brain of a mouse model of Rett syndrome: protective effect of CNF1.

    PubMed

    De Filippis, Bianca; Valenti, Daniela; de Bari, Lidia; De Rasmo, Domenico; Musto, Mattia; Fabbri, Alessia; Ricceri, Laura; Fiorentini, Carla; Laviola, Giovanni; Vacca, Rosa Anna

    2015-06-01

    Rett syndrome (RTT) is a pervasive neurodevelopmental disorder mainly caused by mutations in the X-linked MECP2 gene associated with severe intellectual disability, movement disorders, and autistic-like behaviors. Its pathogenesis remains mostly not understood and no effective therapy is available. High circulating levels of oxidative stress markers in patients and the occurrence of oxidative brain damage in MeCP2-deficient mouse models suggest the involvement of oxidative stress in RTT pathogenesis. However, the molecular mechanism and the origin of the oxidative stress have not been elucidated. Here we demonstrate that a redox imbalance arises from aberrant mitochondrial functionality in the brain of MeCP2-308 heterozygous female mice, a condition that more closely recapitulates that of RTT patients. The marked increase in the rate of hydrogen peroxide generation in the brain of RTT mice seems mainly produced by the dysfunctional complex II of the mitochondrial respiratory chain. In addition, both membrane potential generation and mitochondrial ATP synthesis are decreased in RTT mouse brains when succinate, the complex II respiratory substrate, is used as an energy source. Respiratory chain impairment is brain area specific, owing to a decrease in either cAMP-dependent phosphorylation or protein levels of specific complex subunits. Further, we investigated whether the treatment of RTT mice with the bacterial protein CNF1, previously reported to ameliorate the neurobehavioral phenotype and brain bioenergetic markers in an RTT mouse model, exerts specific effects on brain mitochondrial function and consequently on hydrogen peroxide production. In RTT brains treated with CNF1, we observed the reactivation of respiratory chain complexes, the rescue of mitochondrial functionality, and the prevention of brain hydrogen peroxide overproduction. These results provide definitive evidence of mitochondrial reactive oxygen species overproduction in RTT mouse brain and

  3. Development of pacemaker properties and rhythmogenic mechanisms in the mouse embryonic respiratory network

    PubMed Central

    Chevalier, Marc; Toporikova, Natalia; Simmers, John; Thoby-Brisson, Muriel

    2016-01-01

    Breathing is a vital rhythmic behavior generated by hindbrain neuronal circuitry, including the preBötzinger complex network (preBötC) that controls inspiration. The emergence of preBötC network activity during prenatal development has been described, but little is known regarding inspiratory neurons expressing pacemaker properties at embryonic stages. Here, we combined calcium imaging and electrophysiological recordings in mouse embryo brainstem slices together with computational modeling to reveal the existence of heterogeneous pacemaker oscillatory properties relying on distinct combinations of burst-generating INaP and ICAN conductances. The respective proportion of the different inspiratory pacemaker subtypes changes during prenatal development. Concomitantly, network rhythmogenesis switches from a purely INaP/ICAN-dependent mechanism at E16.5 to a combined pacemaker/network-driven process at E18.5. Our results provide the first description of pacemaker bursting properties in embryonic preBötC neurons and indicate that network rhythmogenesis undergoes important changes during prenatal development through alterations in both circuit properties and the biophysical characteristics of pacemaker neurons. DOI: http://dx.doi.org/10.7554/eLife.16125.001 PMID:27434668

  4. MITOCHONDRIAL DISEASES PART I: MOUSE MODELS OF OXPHOS DEFICIENCIES CAUSED BY DEFECTS ON RESPIRATORY COMPLEX SUBUNITS OR ASSEMBLY FACTORS

    PubMed Central

    Torraco, Alessandra; Peralta, Susana; Iommarini, Luisa; Diaz, Francisca

    2015-01-01

    Mitochondrial disorders are the most common inborn errors of metabolism affecting the oxidative phosphorylation system (OXPHOS). Because the poor knowledge of the pathogenic mechanisms, a cure for these disorders is still unavailable and all the treatments currently in use are supportive more than curative. Therefore, in the past decade a great variety of mouse models have been developed to assess the in vivo function of several mitochondrial proteins involved in human diseases. Due to the genetic and physiological similarity to humans, mice represent reliable models to study the pathogenic mechanisms of mitochondrial disorders and are precious to test new therapeutic approaches. Here we summarize the features of several mouse models of mitochondrial diseases directly related to defects in subunits of the OXPHOS complexes or in assembly factors. We discuss how these models recapitulate many human conditions and how they have contributed to the understanding of mitochondrial function in health and disease. PMID:25660179

  5. Verification and compensation of respiratory motion using an ultrasound imaging system

    SciTech Connect

    Chuang, Ho-Chiao Hsu, Hsiao-Yu; Chiu, Wei-Hung; Tien, Der-Chi; Wu, Ren-Hong; Hsu, Chung-Hsien

    2015-03-15

    Purpose: The purpose of this study was to determine if it is feasible to use ultrasound imaging as an aid for moving the treatment couch during diagnosis and treatment procedures associated with radiation therapy, in order to offset organ displacement caused by respiratory motion. A noninvasive ultrasound system was used to replace the C-arm device during diagnosis and treatment with the aims of reducing the x-ray radiation dose on the human body while simultaneously being able to monitor organ displacements. Methods: This study used a proposed respiratory compensating system combined with an ultrasound imaging system to monitor the compensation effect of respiratory motion. The accuracy of the compensation effect was verified by fluoroscopy, which means that fluoroscopy could be replaced so as to reduce unnecessary radiation dose on patients. A respiratory simulation system was used to simulate the respiratory motion of the human abdomen and a strain gauge (respiratory signal acquisition device) was used to capture the simulated respiratory signals. The target displacements could be detected by an ultrasound probe and used as a reference for adjusting the gain value of the respiratory signal used by the respiratory compensating system. This ensured that the amplitude of the respiratory compensation signal was a faithful representation of the target displacement. Results: The results show that performing respiratory compensation with the assistance of the ultrasound images reduced the compensation error of the respiratory compensating system to 0.81–2.92 mm, both for sine-wave input signals with amplitudes of 5, 10, and 15 mm, and human respiratory signals; this represented compensation of the respiratory motion by up to 92.48%. In addition, the respiratory signals of 10 patients were captured in clinical trials, while their diaphragm displacements were observed simultaneously using ultrasound. Using the respiratory compensating system to offset, the diaphragm

  6. The Respiratory System. Instructional Materials in Anatomy and Physiology for Pennsylvania Health Occupations Programs.

    ERIC Educational Resources Information Center

    National Evaluation Systems, Inc., Amherst, MA.

    This instructional modular unit with instructor's guide provides materials on aspects of one of the major systems of the human body--the respiratory system. Its purpose is to introduce the student to the structures and functions of the human respiratory system--and the interrelationships of the two--and to famlliarize the student with some of the…

  7. Host Proteome Correlates of Vaccine-Mediated Enhanced Disease in a Mouse Model of Respiratory Syncytial Virus Infection

    PubMed Central

    van Diepen, Angela; Brand, H. Kim; de Waal, Leon; Bijl, Maarten; Jong, Victor L.; Kuiken, Thijs; van Amerongen, Geert; van den Ham, Henk-Jan; Eijkemans, Marinus J.; Osterhaus, Albert D. M. E.; Hermans, Peter W. M.

    2015-01-01

    ABSTRACT Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants. Despite over 50 years of research, to date no safe and efficacious RSV vaccine has been licensed. Many experimental vaccination strategies failed to induce balanced T-helper (Th) responses and were associated with adverse effects such as hypersensitivity and immunopathology upon challenge. In this study, we explored the well-established recombinant vaccinia virus (rVV) RSV-F/RSV-G vaccination-challenge mouse model to study phenotypically distinct vaccine-mediated host immune responses at the proteome level. In this model, rVV-G priming and not rVV-F priming results in the induction of Th2 skewed host responses upon RSV challenge. Mass spectrometry-based spectral count comparisons enabled us to identify seven host proteins for which expression in lung tissue is associated with an aberrant Th2 skewed response characterized by the influx of eosinophils and neutrophils. These proteins are involved in processes related to the direct influx of eosinophils (eosinophil peroxidase [Epx]) and to chemotaxis and extravasation processes (Chil3 [chitinase-like-protein 3]) as well as to eosinophil and neutrophil homing signals to the lung (Itgam). In addition, the increased levels of Arg1 and Chil3 proteins point to a functional and regulatory role for alternatively activated macrophages and type 2 innate lymphoid cells in Th2 cytokine-driven RSV vaccine-mediated enhanced disease. IMPORTANCE RSV alone is responsible for 80% of acute bronchiolitis cases in infants worldwide and causes substantial mortality in developing countries. Clinical trials performed with formalin-inactivated RSV vaccine preparations in the 1960s failed to induce protection upon natural RSV infection and even predisposed patients for enhanced disease. Despite the clinical need, to date no safe and efficacious RSV vaccine has been licensed. Since RSV vaccines have a tendency to prime for

  8. Fatigue and the design of the respiratory system.

    PubMed

    Lindstedt, S L; Hoppeler, H

    1995-01-01

    One source of muscle fatigue may be the failure to provide the required oxygen by any step in the oxygen transport cascade or a lack of the necessary machinery to utilize that oxygen. We favor abandoning the concept of a single rate-limiting step for the concept of tuned resistors, each contributing to the overall resistance to oxygen flow. However, because some of these steps have considerably less phenotypic plasticity than others, these are the component parts of the respiratory system that must be built with adequate "reserve" to accommodate adaptive increases in the other steps (Lindstedt et al., 1988; Weibel et al., 1992; Lindstedt et al., 1994). These structures will usually appear to be over built except in those rare individual animals at the species-specific limit of VO2 in which these less malleable structures may be limiting. PMID:8585466

  9. Systems biology unravels interferon responses to respiratory virus infections

    PubMed Central

    Kroeker, Andrea L; Coombs, Kevin M

    2014-01-01

    Interferon production is an important defence against viral replication and its activation is an attractive therapeutic target. However, it has long been known that viruses perpetually evolve a multitude of strategies to evade these host immune responses. In recent years there has been an explosion of information on virus-induced alterations of the host immune response that have resulted from data-rich omics technologies. Unravelling how these systems interact and determining the overall outcome of the host response to viral infection will play an important role in future treatment and vaccine development. In this review we focus primarily on the interferon pathway and its regulation as well as mechanisms by which respiratory RNA viruses interfere with its signalling capacity. PMID:24600511

  10. Mathematical modelling of a human external respiratory system

    NASA Technical Reports Server (NTRS)

    1977-01-01

    A closed system of algebraic and common differential equations solved by computer is investigated. It includes equations which describe the activity pattern of the respiratory center, the phrenic nerve, the thrust produced by the diaphragm as a function of the lung volume and discharge frequency of the phrenic nerve, as well as certain relations of the lung stretch receptors and chemoreceptors on various lung and blood characteristics, equations for lung biomechanics, pulmonary blood flow, alveolar gas exchange and capillary blood composition equations to determine various air and blood flow and gas exchange parameters, and various gas mixing and arterial and venous blood composition equations, to determine other blood, air and gas mixing characteristics. Data are presented by means of graphs and tables, and some advantages of this model over others are demonstrated by test results.

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

    SciTech Connect

    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.

  12. Simulation of Flow Patterns Within the Human Respiratory System

    NASA Astrophysics Data System (ADS)

    Quatember, Bernhard; Mayr, Martin; Recheis, Wolfgang

    2008-09-01

    A nonlinear simulation model of the respiratory system is presented here. It describes the flow patterns as well as the specific gas mixing and distribution processes that occur in the tracheobronchial tree. The model is based on the commonly used morphometric scheme of E. Weibel. It consists of a "pressure-flow submodel" and a "gas mixing submodel. The former is a lumped parameter model consisting of 24 lumped components. The second type, the "gas mixing submodel," enables the simulation of the mixing processes in the trachea and in the larger bronchi (up to the 10th generation). Several simulation studies that are based on it have been carried out; they deal with both the physiological conditions and the specific pathological changes that occur in the small airways during the early stages of chronic obstructive bronchitis.

  13. National Training Course. Emergency Medical Technician. Paramedic. Instructor's Lesson Plans. Module V. Respiratory System.

    ERIC Educational Resources Information Center

    National Highway Traffic Safety Administration (DOT), Washington, DC.

    This instructor's lesson plan guide on the respiratory system is one of fifteen modules designed for use in the training of emergency medical technicians (paramedics). Five units of study are presented: (1) anatomy and physiology of the respiratory system; (2) pathophysiology assessment of the patient; (3) pathophysiology and management of…

  14. Characterization and Demonstration of the Value of a Lethal Mouse Model of Middle East Respiratory Syndrome Coronavirus Infection and Disease

    PubMed Central

    Tao, Xinrong; Garron, Tania; Agrawal, Anurodh Shankar; Algaissi, Abdullah; Peng, Bi-Hung; Wakamiya, Maki; Chan, Teh-Sheng; Lu, Lu; Du, Lanying; Jiang, Shibo; Couch, Robert B.

    2015-01-01

    ABSTRACT Characterized animal models are needed for studying the pathogenesis of and evaluating medical countermeasures for persisting Middle East respiratory syndrome-coronavirus (MERS-CoV) infections. Here, we further characterized a lethal transgenic mouse model of MERS-CoV infection and disease that globally expresses human CD26 (hCD26)/DPP4. The 50% infectious dose (ID50) and lethal dose (LD50) of virus were estimated to be <1 and 10 TCID50 of MERS-CoV, respectively. Neutralizing antibody developed in the surviving mice from the ID50/LD50 determinations, and all were fully immune to challenge with 100 LD50 of MERS-CoV. The tissue distribution and histopathology in mice challenged with a potential working dose of 10 LD50 of MERS-CoV were subsequently evaluated. In contrast to the overwhelming infection seen in the mice challenged with 105 LD50 of MERS-CoV, we were able to recover infectious virus from these mice only infrequently, although quantitative reverse transcription-PCR (qRT-PCR) tests indicated early and persistent lung infection and delayed occurrence of brain infection. Persistent inflammatory infiltrates were seen in the lungs and brain stems at day 2 and day 6 after infection, respectively. While focal infiltrates were also noted in the liver, definite pathology was not seen in other tissues. Finally, using a receptor binding domain protein vaccine and a MERS-CoV fusion inhibitor, we demonstrated the value of this model for evaluating vaccines and antivirals against MERS. As outcomes of MERS-CoV infection in patients differ greatly, ranging from asymptomatic to overwhelming disease and death, having available both an infection model and a lethal model makes this transgenic mouse model relevant for advancing MERS research. IMPORTANCE Fully characterized animal models are essential for studying pathogenesis and for preclinical screening of vaccines and drugs against MERS-CoV infection and disease. When given a high dose of MERS-CoV, our transgenic

  15. [The role of opioidergic and GABAergic systems in the mechanosensitivity regulation of the respiratory system in rats].

    PubMed

    Tikhomirova, L N; Safina, N F; Tarakanov, I A

    2015-01-01

    In anaesthetized white outbred male rats we investigated the change of respiratory mechanoreceptors sensitivity to morphine and phenibut. Bilateral transection of the vagus nerves causes a severely slowdown of respiratory rate in 30 minutes after the systemic administration of morphine, however after administration of phenibut the respiratory rate and other respiration parameters have not changed significantly. It means that the activation of opioid receptors by morphine does not significantly affect the function of the respiratory mechanoreceptor control loop, and transection of the vagus nerves on this background increases the probability of respiratory rhythm disorders. Activation of GABAergic system by phenibut significantly weakened the impact of the regulating contour of the respiratory mechanoreceptor on breathing parameters, up to effect of "central vagotomy": that is, to no changes in respiratory parameters after cutting the vagus nerves. PMID:27116874

  16. The respiratory-vocal system of songbirds: Anatomy, physiology, and neural control

    PubMed Central

    Schmidt, Marc F.; Wild, J. Martin

    2015-01-01

    This wide-ranging review presents an overview of the respiratory-vocal system in songbirds, which are the only other vertebrate group known to display a degree of respiratory control during song rivalling that of humans during speech; this despite the fact that the peripheral components of both the respiratory and vocal systems differ substantially in the two groups. We first provide a brief description of these peripheral components in songbirds (lungs, air sacs and respiratory muscles, vocal organ (syrinx), upper vocal tract) and then proceed to a review of the organization of central respiratory-related neurons in the spinal cord and brainstem, the latter having an organization fundamentally similar to that of the ventral respiratory group of mammals. The second half of the review describes the nature of the motor commands generated in a specialized “cortical” song control circuit and how these might engage brainstem respiratory networks to shape the temporal structure of song. We also discuss a bilaterally projecting “respiratory-thalamic” pathway that links the respiratory system to “cortical” song control nuclei. This necessary pathway for song originates in the brainstem’s primary inspiratory center and is hypothesized to play a vital role in synchronizing song motor commands both within and across hemispheres. PMID:25194204

  17. The respiratory-vocal system of songbirds: anatomy, physiology, and neural control.

    PubMed

    Schmidt, Marc F; Martin Wild, J

    2014-01-01

    This wide-ranging review presents an overview of the respiratory-vocal system in songbirds, which are the only other vertebrate group known to display a degree of respiratory control during song rivalling that of humans during speech; this despite the fact that the peripheral components of both the respiratory and vocal systems differ substantially in the two groups. We first provide a brief description of these peripheral components in songbirds (lungs, air sacs and respiratory muscles, vocal organ (syrinx), upper vocal tract) and then proceed to a review of the organization of central respiratory-related neurons in the spinal cord and brainstem, the latter having an organization fundamentally similar to that of the ventral respiratory group of mammals. The second half of the review describes the nature of the motor commands generated in a specialized "cortical" song control circuit and how these might engage brainstem respiratory networks to shape the temporal structure of song. We also discuss a bilaterally projecting "respiratory-thalamic" pathway that links the respiratory system to "cortical" song control nuclei. This necessary pathway for song originates in the brainstem's primary inspiratory center and is hypothesized to play a vital role in synchronizing song motor commands both within and across hemispheres. PMID:25194204

  18. Recording system and data fusion algorithm for enhancing the estimation of the respiratory rate from photoplethysmogram.

    PubMed

    Cernat, Roxana A; Ciorecan, Silvia I; Ungureanu, Constantin; Arends, Johan; Strungaru, Rodica; Ungureanu, G Mihaela

    2015-08-01

    The respiratory rate is a vital parameter that can provide valuable information about the health condition of a patient. The extraction of respiratory information from photoplethysmographic signal (PPG) was actually encouraged by the reported results, our main goal being to obtain accurate respiratory rate estimation from the PPG signal. We developed a fusion algorithm that identifies the best derived respiratory signals, from which is possible to extract the respiratory rate; based on these, a global respiratory rate is computed using the proposed fusion algorithm. The algorithm is qualitatively tested on real PPG signals recorded by an acquisition system we implemented, using a reflection pulse oximeter sensor. Its performance is also statistically evaluated using benchmark dataset publically available from CapnoBase.Org. PMID:26737653

  19. Effects of respiratory mechanics on the capnogram phases: importance of dynamic compliance of the respiratory system

    PubMed Central

    2012-01-01

    Introduction The slope of phase III of the capnogram (SIII) relates to progressive emptying of the alveoli, a ventilation/perfusion mismatch, and ventilation inhomogeneity. SIII depends not only on the airway geometry, but also on the dynamic respiratory compliance (Crs); this latter effect has not been evaluated. Accordingly, we established the value of SIII for monitoring airway resistance during mechanical ventilation. Methods Sidestream capnography was performed during mechanical ventilation in patients undergoing elective cardiac surgery (n = 144). The airway resistance (Raw), total respiratory resistance and Crs displayed by the ventilator, the partial pressure of arterial oxygen (PaO2) and SIII were measured in time domain (ST-III) and in a smaller cohort (n = 68) by volumetry (SV-III) with and without normalization to the average CO2 phase III concentration. Measurements were performed at positive end-expiratory pressure (PEEP) levels of 3, 6 and 9 cmH2O in patients with healthy lungs (Group HL), and in patients with respiratory symptoms involving low (Group LC), medium (Group MC) or high Crs (Group HC). Results ST-III and SV-III exhibited similar PEEP dependencies and distribution between the protocol groups formed on the basis of Crs. A wide interindividual scatter was observed in the overall Raw-ST-III relationship, which was primarily affected by Crs. Decreases in Raw with increasing PEEP were reflected in sharp falls in SIII in Group HC, and in moderate decreases in SIII in Group MC, whereas ST-III was insensitive to changes in airway caliber in Groups LC and HL. Conclusions SIII assessed in the time domain and by volumetry provide meaningful information about alterations in airway caliber, but only within an individual patient. Although ST-III may be of value for bedside monitoring of the airway properties, its sensitivity depends on Crs. Thus, assessment of the capnogram shape should always be coupled with Crs when the airway resistance or

  20. Prevalence of chronic obstructive pulmonary disease among patients with systemic arterial hypertension without respiratory symptoms

    PubMed Central

    Rabahi, Marcelo Fouad; Pereira, Sheila Alves; Silva Júnior, José Laerte Rodrigues; de Rezende, Aline Pacheco; Castro da Costa, Adeliane; de Sousa Corrêa, Krislainy; Conde, Marcus Barreto

    2015-01-01

    Background The diagnosis of chronic obstructive pulmonary disease (COPD) is often delayed until later stages of the disease. The purpose of the present study was to determine the prevalence of COPD among adults on treatment for systemic arterial hypertension independently of the presence of respiratory symptoms. Methods This cross-sectional study included adults aged ≥40 years with tobacco/occupational exposure and systemic arterial hypertension diagnosed at three Primary Health Care facilities in Goiania, Brazil. Patients were evaluated using a standardized respiratory questionnaire and spirometry. COPD prevalence was measured considering the value of forced vital capacity and/or forced expiratory volume in 1 second <0.70. Results Of a total of 570 subjects, 316 (55%) met inclusion criteria and were invited to participate. Two hundred and thirty-three (73.7%) patients with arterial hypertension reported at least one respiratory symptom, while 83 (26.3%) reported no respiratory symptoms; 41 (17.6%) patients with arterial hypertension and at least one respiratory symptom, and 10 (12%) patients with arterial hypertension but no respiratory symptoms were diagnosed with COPD (P=0.24). The prevalence of COPD in people with no previous COPD diagnosis was greater among those with no respiratory symptoms (100%) than among those with respiratory symptoms (56.1%) (P=0.01). Conclusion Our findings suggest that regardless of the presence of respiratory symptoms, individuals aged ≥40 years with tobacco/occupational exposure and arterial hypertension may benefit from spirometric evaluation. PMID:26257517

  1. MODELING OF THE UPPER AND LOWER RESPIRATORY SYSTEMS

    EPA Science Inventory

    Casting of silicone rubber replica casts of upper respiratory airways including nose, larynx, trachea, and tracheobronchial airways is described for the human and for standard laboratory animals. Morphometric measurements were made on nasopharyngeal and tracheobronchial airway ca...

  2. Mouse vocal communication system: are ultrasounds learned or innate?

    PubMed

    Arriaga, Gustavo; Jarvis, Erich D

    2013-01-01

    Mouse ultrasonic vocalizations (USVs) are often used as behavioral readouts of internal states, to measure effects of social and pharmacological manipulations, and for behavioral phenotyping of mouse models for neuropsychiatric and neurodegenerative disorders. However, little is known about the neurobiological mechanisms of rodent USV production. Here we discuss the available data to assess whether male mouse song behavior and the supporting brain circuits resemble those of known vocal non-learning or vocal learning species. Recent neurobiology studies have demonstrated that the mouse USV brain system includes motor cortex and striatal regions, and that the vocal motor cortex sends a direct sparse projection to the brainstem vocal motor nucleus ambiguous, a projection previously thought be unique to humans among mammals. Recent behavioral studies have reported opposing conclusions on mouse vocal plasticity, including vocal ontogeny changes in USVs over early development that might not be explained by innate maturation processes, evidence for and against a role for auditory feedback in developing and maintaining normal mouse USVs, and evidence for and against limited vocal imitation of song pitch. To reconcile these findings, we suggest that the trait of vocal learning may not be dichotomous but encompass a broad spectrum of behavioral and neural traits we call the continuum hypothesis, and that mice possess some of the traits associated with a capacity for limited vocal learning. PMID:23295209

  3. Mouse vocal communication system: are ultrasounds learned or innate?

    PubMed Central

    Arriaga, Gustavo; Jarvis, Erich D.

    2013-01-01

    Mouse ultrasonic vocalizations (USVs) are often used as behavioral readouts of internal states, to measure effects of social and pharmacological manipulations, and for behavioral phenotyping of mouse models for neuropsychiatric and neurodegenerative disorders. However, little is known about the neurobiological mechanisms of rodent USV production. Here we discuss the available data to assess whether male mouse song behavior and the supporting brain circuits resemble those of known vocal non-learning or vocal learning species. Recent neurobiology studies have demonstrated that the mouse USV brain system includes motor cortex and striatal regions, and that the vocal motor cortex sends a direct sparse projection to the brainstem vocal motor nucleus ambiguous, a projection thought be unique to humans among mammals. Recent behavioral studies have reported opposing conclusions on mouse vocal plasticity, including vocal ontogeny changes in USVs over early development that might not be explained by innate maturation processes, evidence for and against a role for auditory feedback in developing and maintaining normal mouse USVs, and evidence for and against limited vocal imitation of song pitch. To reconcile these findings, we suggest that the trait of vocal learning may not be dichotomous but encompass a broad set of behavioral and neural traits we call the continuum hypothesis, and that mice possess some of the traits associated with a capacity for limited vocal learning. PMID:23295209

  4. Rapid response to systemic bevacizumab therapy in recurrent respiratory papillomatosis

    PubMed Central

    MOHR, MICHAEL; SCHLIEMANN, CHRISTOPH; BIERMANN, CHRISTOPH; SCHMIDT, LARS-HENNING; KESSLER, TORSTEN; SCHMIDT, JOACHIM; WIEBE, KARSTEN; MÜLLER, KLAUS-MICHAEL; HOFFMANN, THOMAS K.; GROLL, ANDREAS H.; WERNER, CLAUDIUS; KESSLER, CHRISTINA; WIEWRODT, RAINER; RUDACK, CLAUDIA; BERDEL, WOLFGANG E.

    2014-01-01

    Recurrent respiratory papillomatosis (RRP) is a primary benign disease, which is characterized by papillomatous growth in the respiratory tract. Malignant transformation occurs in only 3–5% of cases, however, local growth of the benign papillomas is interpreted as clinically malignant in a markedly higher proportion of patients. Local surgical or endoscopic interventional debulking or excision is currently the commonly selected treatment method and antiviral therapy is a potential adjuvant approach. However, the long-term management of RRP patients, who commonly require multiple procedures over numerous years, is challenging and the overall therapeutic armamentarium remains unsatisfactory. The administration of systemic bevacizumab treatment in a series of five patients with long histories of RRP, who required repeated local interventions to control papilloma growth is evaluated. Treatment with the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab was administered at a dose of 5 mg/kg (n=1), 10 mg/kg (n=3) or 15 mg/kg (n=1) intravenously to the five RRP patients, who were clinically classified as exhibiting progressive disease. Endoscopic evaluations were performed prior to the first infusion of bevacizumab and intermittently at variable time points during the course of therapy. Histopathological analyses were performed using pre- and post-treatment papilloma biopsies, including immunohistochemical analyses of VEGF and phosphorylated VEGF receptor (VEGFR)-2 expression. The patients received between three and 16 courses of bevacizumab (median, six courses). The first course was initiated when progression following the previous intervention was observed. An immediate response to bevacizumab treatment was demonstrated in all five RRP patients. While the cumulative number of interventions in the five patients was 18 throughout the 12 months prior to the initiation of bevacizumab treatment, only one patient required interventional treatment due to a

  5. AN IMPROVEMENT TO THE MOUSE COMPUTERIZED UNCERTAINTY ANALYSIS SYSTEM

    EPA Science Inventory

    The original MOUSE (Modular Oriented Uncertainty System) system was designed to deal with the problem of uncertainties in Environmental engineering calculations, such as a set of engineering cast or risk analysis equations. It was especially intended for use by individuals with l...

  6. Active impedance of respiratory system in anesthetized cats.

    PubMed

    Zin, W A; Pengelly, L D; Milic-Emili, J

    1982-07-01

    We have assessed the validity of the method of Siafakas et al. (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 51: 109-121, 1981) for determining active elastance (E'rs) and flow resistance (R'rs) of the respiratory system. In six cats anesthetized with pentobarbital sodium we have measured flow, volume, and tracheal occlusion pressure during spontaneous breathing. This allowed us to compute E'rs and R'rs. From these data and the occlusion pressure wave we predicted the time course of volume during inspirations with added linear flow resistances (delta R). These were compared to the actual loaded inspirograms. The agreement was generally good, except for small predictable discrepancies with the highest delta R values, which could be attributed to decompression of thoracic gas. These results indicate that the approach of Siakafas et al. to determine E'rs and R'rs is valid. In addition, we have quantified the "terminal inhibition" of inspiratory activity, which occurs toward the end of unoccluded breaths (both loaded and unloaded). PMID:7118628

  7. B lymphocyte lineage cells and the respiratory system

    PubMed Central

    Kato, Atsushi; Hulse, Kathryn E.; Tan, Bruce K.; Schleimer, Robert P.

    2013-01-01

    Adaptive humoral immune responses in the airways are mediated by B cells and plasma cells that express highly evolved and specific receptors and produce immunoglobulins of most isotypes. In some cases, such as autoimmune diseases or inflammatory diseases caused by excessive exposure to foreign antigens, these same immune cells can cause disease by virtue of overly vigorous responses. This review discusses the generation, differentiation, signaling, activation and recruitment pathways of B cells and plasma cells, with special emphasis on unique characteristics of subsets of these cells functioning within the respiratory system. The primary sensitization events that generate B cells responsible for effector responses throughout the airways usually occur in the upper airways, in tonsils and adenoid structures that make up Waldeyer’s Ring. Upon secondary exposure to antigen in the airways, antigen-processing dendritic cells migrate into secondary lymphoid organs such as lymph nodes that drain the upper and lower airways and further B cell expansion takes place at those sites. Antigen exposure in the upper or lower airways can also drive expansion of B lineage cells in the airway mucosal tissue and lead to the formation of inducible lymphoid follicles or aggregates that can mediate local immunity or disease. PMID:23540615

  8. B-lymphocyte lineage cells and the respiratory system.

    PubMed

    Kato, Atsushi; Hulse, Kathryn E; Tan, Bruce K; Schleimer, Robert P

    2013-04-01

    Adaptive humoral immune responses in the airways are mediated by B cells and plasma cells that express highly evolved and specific receptors and produce immunoglobulins of most isotypes. In some cases, such as autoimmune diseases or inflammatory diseases caused by excessive exposure to foreign antigens, these same immune cells can cause disease by virtue of overly vigorous responses. This review discusses the generation, differentiation, signaling, activation, and recruitment pathways of B cells and plasma cells, with special emphasis on unique characteristics of subsets of these cells functioning within the respiratory system. The primary sensitization events that generate B cells responsible for effector responses throughout the airways usually occur in the upper airways, tonsils, and adenoid structures that make up the Waldeyer ring. On secondary exposure to antigen in the airways, antigen-processing dendritic cells migrate into secondary lymphoid organs, such as lymph nodes, that drain the upper and lower airways, and further B-cell expansion takes place at those sites. Antigen exposure in the upper or lower airways can also drive expansion of B-lineage cells in the airway mucosal tissue and lead to the formation of inducible lymphoid follicles or aggregates that can mediate local immunity or disease. PMID:23540615

  9. Technical evaluation of different respiratory monitoring systems used for 4D CT acquisition under free breathing.

    PubMed

    Heinz, Christian; Reiner, Michael; Belka, Claus; Walter, Franziska; Söhn, Matthias

    2015-01-01

    Respiratory monitoring systems are required to supply CT scanners with information on the patient's breathing during the acquisition of a respiration-correlated computer tomography (RCCT), also referred to as 4D CT. The information a respiratory monitoring system has to provide to the CT scanner depends on the specific scanner. The purpose of this study is to compare two different respiratory monitoring systems (Anzai Respiratory Gating System; C-RAD Sentinel) with respect to their applicability in combination with an Aquilion Large Bore CT scanner from Toshiba. The scanner used in our clinic does not make use of the full time dependent breathing signal, but only single trigger pulses indicating the beginning of a new breathing cycle. Hence the attached respiratory monitoring system is expected to deliver accurate online trigger pulse for each breathing cycle. The accuracy of the trigger pulses sent to the CT scanner has to be ensured by the selected respiratory monitoring system. Since a trigger pulse (output signal) of a respiratory monitoring system is a function of the measured breathing signal (input signal), the typical clinical range of the input signal is estimated for both examined respiratory monitoring systems. Both systems are analyzed based on the following parameters: time resolution, signal amplitude, noise, signal-to-noise ratio (SNR), signal linearity, trigger compatibility, and clinical examples. The Anzai system shows a better SNR (≥ 28 dB) than the Sentinel system (≥ 14.6 dB). In terms of compatibility with the cycle-based image sorting algorithm of the Toshiba CT scanner, the Anzai system benefits from the possibility to generate cycle-based triggers, whereas the Sentinel system is only able to generate amplitude-based triggers. In clinical practice, the combination of a Toshiba CT scanner and the Anzai system will provide better results due to the compatibility of the image sorting and trigger release methods. PMID:26103168

  10. Effect of Spinal Cord Injury on the Respiratory System: Basic Research and Current Clinical Treatment Options

    PubMed Central

    Zimmer, M. Beth; Nantwi, Kwaku; Goshgarian, Harry G

    2007-01-01

    Summary: Spinal cord injury (SCI) often leads to an impairment of the respiratory system. The more rostral the level of injury, the more likely the injury will affect ventilation. In fact, respiratory insufficiency is the number one cause of mortality and morbidity after SCI. This review highlights the progress that has been made in basic and clinical research, while noting the gaps in our knowledge. Basic research has focused on a hemisection injury model to examine methods aimed at improving respiratory function after SCI, but contusion injury models have also been used. Increasing synaptic plasticity, strengthening spared axonal pathways, and the disinhibition of phrenic motor neurons all result in the activation of a latent respiratory motor pathway that restores function to a previously paralyzed hemidiaphragm in animal models. Human clinical studies have revealed that respiratory function is negatively impacted by SCI. Respiratory muscle training regimens may improve inspiratory function after SCI, but more thorough and carefully designed studies are needed to adequately address this issue. Phrenic nerve and diaphragm pacing are options available to wean patients from standard mechanical ventilation. The techniques aimed at improving respiratory function in humans with SCI have both pros and cons, but having more options available to the clinician allows for more individualized treatment, resulting in better patient care. Despite significant progress in both basic and clinical research, there is still a significant gap in our understanding of the effect of SCI on the respiratory system. PMID:17853653

  11. Effects of acute oligohydramnios on respiratory system of fetal sheep.

    PubMed

    Savich, R D; Guerra, F A; Lee, C C; Padbury, J F; Kitterman, J A

    1992-08-01

    Prolonged oligohydramnios, or a lack of amniotic fluid, is associated with pulmonary hypoplasia and subsequent perinatal morbidity, but it is unclear whether short-term or acute oligohydramnios has any effect on the fetal respiratory system. To investigate the acute effects of removal of amniotic fluid, we studied nine chronically catheterized fetal sheep at 122-127 days gestation. During a control period, we measured the volume of fluid in the fetal potential airways and air spaces (VL), production rate of that fluid, incidence and amplitude of fetal breathing movements, tracheal pressures, and fetal plasma concentrations of cortisol, epinephrine, and norepinephrine. We then drained the amniotic fluid for a short period of time [24-48 h, 30.0 +/- 4.0 (SE) h] and repeated the above measurements. The volume of fluid drained for the initial studies was 1,004 +/- 236 ml. Acute oligohydramnios decreased VL from 35.4 +/- 2.9 ml/kg during control to 22.0 +/- 1.6 after oligohydramnios (P less than 0.004). Acute oligohydramnios did not affect the fetal lung fluid production rate, fetal breathing movements, or any of the other measured variables. Seven repeat studies were performed in six of the fetuses after reaccumulation of the amniotic fluid at 130-138 days, and in four of these studies the lung volume also decreased, although the overall mean for the repeat studies was not significantly different (27.0 +/- 5.2 ml/kg for control vs. 25.5 +/- 5.5 ml/kg for oligohydramnios). Again, none of the other measured variables were altered by oligohydramnios in the repeat studies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1399988

  12. Timely diagnosis of dairy calf respiratory disease using a standardized scoring system.

    PubMed

    McGuirk, Sheila M; Peek, Simon F

    2014-12-01

    Respiratory disease of young dairy calves is a significant cause of morbidity, mortality, economic loss, and animal welfare concern but there is no gold standard diagnostic test for antemortem diagnosis. Clinical signs typically used to make a diagnosis of respiratory disease of calves are fever, cough, ocular or nasal discharge, abnormal breathing, and auscultation of abnormal lung sounds. Unfortunately, routine screening of calves for respiratory disease on the farm is rarely performed and until more comprehensive, practical and affordable respiratory disease-screening tools such as accelerometers, pedometers, appetite monitors, feed consumption detection systems, remote temperature recording devices, radiant heat detectors, electronic stethoscopes, and thoracic ultrasound are validated, timely diagnosis of respiratory disease can be facilitated using a standardized scoring system. We have developed a scoring system that attributes severity scores to each of four clinical parameters; rectal temperature, cough, nasal discharge, ocular discharge or ear position. A total respiratory score of five points or higher (provided that at least two abnormal parameters are observed) can be used to distinguish affected from unaffected calves. This can be applied as a screening tool twice-weekly to identify pre-weaned calves with respiratory disease thereby facilitating early detection. Coupled with effective treatment protocols, this scoring system will reduce post-weaning pneumonia, chronic pneumonia, and otitis media. PMID:25410122

  13. Evaluation of in vivo low-dose mouse irradiation system

    NASA Astrophysics Data System (ADS)

    Noh, S. J.; Kim, H. J.; Kim, H.; Kye, Y.-U.; Kim, J. K.; Son, T. G.; Lee, M. W.; Jeong, D. H.; Yang, K. M.; Nam, S.-H.; Kang, Y.-R.

    2016-03-01

    This study aims to develop a facility that can irradiate subjects with a desired low dose, which can be used to assess the biological effects of low-dose radiation. We develop a single-occupancy mouse-cage and shelf system with adjustable geometric parameters, such as the distances and angles of the cages relative to the collimator. We assess the irradiation-level accuracy using two measurement methods. First, we calculate the angle and distance of each mouse cage relative to the irradiator. We employ a Monte Carlo n-particle simulation for all of the cages at a given distance from the radiation source to calculate the air kerma and the relative absorbed dose in the in-house designed shelving system; these are found to be approximately 0.108 and 0.109 Gy, respectively. Second, we measure the relative absorbed dose using glass dosimeters inserted directly into the heads and bodies of the mice. For a conventional irradiation system, the irradiation measurements show a maximum discrepancy of 42% between the absorbed and desired doses, whereas a discrepancy of only 6% from the desired dose is found for the designed mouse apartment system. In addition, multi-mouse cages are shown to yield to significantly greater differences in the mouse head and body relative absorbed doses, compared to the discrepancies found for single-occupancy cages in the conventional irradiation system. Our findings suggest that the in-house shelving system has greater reliability for the biological analysis of the effects of low-dose radiation.

  14. A new laboratory-based surveillance system (Respiratory DataMart System) for influenza and other respiratory viruses in England: results and experience from 2009 to 2012.

    PubMed

    Zhao, H; Green, H; Lackenby, A; Donati, M; Ellis, J; Thompson, C; Bermingham, A; Field, J; Sebastianpillai, P; Zambon, M; Watson, Jm; Pebody, R

    2014-01-01

    During the 2009 influenza A(H1N1) pandemic, a new laboratory-based virological sentinel surveillance system, the Respiratory DataMart System (RDMS), was established in a network of 14 Health Protection Agency (now Public Health England (PHE)) and National Health Service (NHS) laboratories in England. Laboratory results (both positive and negative) were systematically collected from all routinely tested clinical respiratory samples for a range of respiratory viruses including influenza, respiratory syncytial virus (RSV), rhinovirus, parainfluenza virus, adenovirus and human metapneumovirus (hMPV). The RDMS also monitored the occurrence of antiviral resistance of influenza viruses. Data from the RDMS for the 2009–2012 period showed that the 2009 pandemic influenza virus caused three waves of activity with different intensities during the pandemic and post pandemic periods. Peaks in influenza A(H1N1)pdm09 positivity (defined as number of positive samples per total number of samples tested) were seen in summer and autumn in 2009, with slightly higher peak positivity observed in the first post-pandemic season in 2010/2011. The influenza A(H1N1)pdm09 virus strain almost completely disappeared in the second postpandemic season in 2011/2012. The RDMS findings are consistent with other existing community-based virological and clinical surveillance systems. With a large sample size, this new system provides a robust supplementary mechanism, through the collection of routinely available laboratory data at minimum extra cost, to monitor influenza as well as other respiratory virus activity. A near real-time, daily reporting mechanism in the RDMS was established during the London 2012 Olympic and Paralympic Games. Furthermore, this system can be quickly adapted and used to monitor future influenza pandemics and other major outbreaks of respiratory infectious disease, including novel pathogens. PMID:24480060

  15. Respiratory and Circulatory Systems, Science (Experimental): 5363.04.

    ERIC Educational Resources Information Center

    Weiss, Alan; And Others

    This biology course is especially recommended for students interested in a vocation in nursing, medical technology, dental hygiene or other para-medical areas. In part, it is considered a second course in biology. The course includes an intensive in-depth study of the respiratory structures, nerve and chemical control of breathing, gas exchange,…

  16. Contraindications to Athletic Participation. Cardiac, Respiratory, and Central Nervous System Conditions.

    ERIC Educational Resources Information Center

    Moeller, James L.

    1996-01-01

    Discusses contraindications to athletic participation, examining the cardiac, respiratory, and central nervous system conditions that warrant activity disqualification. Provides guidelines about when it is safe for individuals to participate, and discusses the physician's responsibility. (SM)

  17. Influence of the Ageing Process on the Resistive and Reactive Properties of the Respiratory System

    PubMed Central

    e Tramont, Caio Vinicius Villalón; Faria, Alvaro Camilo Dias; Lopes, Agnaldo José; Jansen, José Manoel; de Melo, Pedro Lopes

    2009-01-01

    INTRODUCTION In an increasingly old society, the study of the respiratory system changes and new techniques dedicated to older patients are of interest in physiologic studies as well as in the diagnosis of respiratory diseases. OBJECTIVES (1) To investigate the impact of ageing on the resistive and reactive properties of the respiratory system, and (2) to compare the easiness of accomplishment of spirometry and forced oscillation for assessing lung function. METHODS We conducted a cross-sectional study in which forced oscillation was used to investigate respiratory system resistive and reactive properties, while spirometry was used as a reference test to evaluate 80 normal subjects aged between 20 and 86 years. A questionnaire was used to evaluate the easiness of accomplishment of spirometry and forced oscillation. RESULTS There was a significant increase in the respiratory system resonance frequency (p<0.003) and a reduction in the mean reactance (p<0.004) with increasing age. Respiratory system resistance and dynamic compliance were not related to the ageing process. The easiness of accomplishment of forced oscillation measurements was greater than that of spirometry. This result was particularly relevant in subjects over 70 years old (p<0.05). CONCLUSIONS Respiratory system resistance and dynamic compliance are not modified with ageing. On the other hand, respiratory system homogeneity decreases during the ageing process. Forced oscillation is easy to perform and provides information complementary to spirometry. This technique may be a promising alternative and/or complement to other conventional exams used to evaluate older people who are unable to adequately perform spirometric tests. PMID:19936180

  18. Influence of Industrial Environments on the Development of Respiratory Systems and Morphofunctional Features in Preadolescent Boys

    PubMed Central

    Dziubek, Wioletta; Ignasiak, Zofia; Rozek, Krystyna

    2011-01-01

    The present study examines the differences between levels of selected structural and functional features of boys 11–13 years in age from regions with varying levels of air pollution, including an industrial and rural region. The sample consisted of 213 boys from the industrial region and 98 from the rural region. Somatic, respiratory parameters and motor abilities were evaluated in both groups. The analysis of respiratory parameters revealed significantly better development of respiratory systems in boys from the rural region. Additionally, motor abilities were also better developed in boys from the rural region. PMID:23486548

  19. The Respiratory System [and] Instructor's Guide: The Respiratory System. Health Occupations Education Module: Instructional Materials in Anatomy and Physiology for Pennsylvania Health Occupations Programs.

    ERIC Educational Resources Information Center

    National Evaluation Systems, Inc., Amherst, MA.

    This module on the respiratory system is one of 17 modules designed for individualized instruction in health occupations education programs at both the secondary and postsecondary levels. It is part of an eight-unit miniseries on anatomy and physiology within the series of 17 modules. Following a preface which explains to the student how to use…

  20. Development of an integrated sensor module for a non-invasive respiratory monitoring system

    NASA Astrophysics Data System (ADS)

    Kang, Seok-Won; Chang, Keun-Shik

    2013-09-01

    A respiratory monitoring system has been developed for analyzing the carbon dioxide (CO2) and oxygen (O2) concentrations in the expired air using gas sensors. The data can be used to estimate some medical conditions, including diffusion capability of the lung membrane, oxygen uptake, and carbon dioxide output. For this purpose, a 3-way valve derived from a servomotor was developed, which operates synchronously with human respiratory signals. In particular, the breath analysis system includes an integrated sensor module for valve control, data acquisition through the O2 and CO2 sensors, and respiratory rate monitoring, as well as software dedicated to analysis of respiratory gasses. In addition, an approximation technique for experimental data based on Haar-wavelet-based decomposition is explored to remove noise as well as to reduce the file size of data for long-term monitoring.

  1. Periodic properties of the histaminergic system of the mouse brain.

    PubMed

    Rozov, Stanislav V; Zant, Janneke C; Karlstedt, Kaj; Porkka-Heiskanen, Tarja; Panula, Pertti

    2014-01-01

    Brain histamine is involved in the regulation of the sleep-wake cycle and alertness. Despite the widespread use of the mouse as an experimental model, the periodic properties of major markers of the mouse histaminergic system have not been comprehensively characterized. We analysed the daily levels of histamine and its first metabolite, 1-methylhistamine, in different brain structures of C57BL/6J and CBA/J mouse strains, and the mRNA level and activity of histidine decarboxylase and histamine-N-methyltransferase in C57BL/6J mice. In the C57BL/6J strain, histamine release, assessed by in vivo microdialysis, underwent prominent periodic changes. The main period was 24 h peaking during the activity period. Additional 8 h periods were also observed. The release was highly positively correlated with active wakefulness, as shown by electroencephalography. In both mouse strains, tissue histamine levels remained steady for 24 h in all structures except for the hypothalamus of CBA/J mice, where 24-h periodicity was observed. Brain tissue 1-methylhistamine levels in both strains reached their maxima in the periods of activity. The mRNA level of histidine decarboxylase in the tuberomamillary nucleus and the activities of histidine decarboxylase and histamine-N-methyltransferase in the striatum and cortex did not show a 24-h rhythm, whereas in the hypothalamus the activities of both enzymes had a 12-h periodicity. These results show that the activities of histamine-metabolizing enzymes are not under simple direct circadian regulation. The complex and non-uniform temporal patterns of the histaminergic system of the mouse brain suggest that histamine is strongly involved in the maintenance of active wakefulness. PMID:24438489

  2. Physiological system integrations with emphasis on the respiratory-cardiovascular system

    NASA Technical Reports Server (NTRS)

    Gallagher, R. R.

    1975-01-01

    The integration of two types of physiological system simulations is presented. The long term model is a circulatory system model which simulates long term blood flow variations and compartmental fluid shifts. The short term models simulate transient phenomena of the respiratory, thermoregulatory, and pulsatile cardiovascular systems as they respond to stimuli such as LBNP, exercise, and environmental gaseous variations. An overview of the interfacing approach is described. Descriptions of the variable interface for long term to short term and between the three short term models are given.

  3. Development of Non-contact Respiratory Monitoring System for Newborn Using a FG Vision Sensor

    NASA Astrophysics Data System (ADS)

    Kurami, Yoshiyuki; Itoh, Yushi; Natori, Michiya; Ohzeki, Kazuo; Aoki, Yoshimitsu

    In recent years, development of neonatal care is strongly hoped, with increase of the low-birth-weight baby birth rate. Especially respiration of low-birth-weight baby is incertitude because central nerve and respiratory function is immature. Therefore, a low-birth-weight baby often causes a disease of respiration. In a NICU (Neonatal Intensive Care Unit), neonatal respiration is monitored using cardio-respiratory monitor and pulse oximeter at all times. These contact-type sensors can measure respiratory rate and SpO2 (Saturation of Peripheral Oxygen). However, because a contact-type sensor might damage the newborn's skin, it is a real burden to monitor neonatal respiration. Therefore, we developed the respiratory monitoring system for newborn using a FG (Fiber Grating) vision sensor. FG vision sensor is an active stereo vision sensor, it is possible for non-contact 3D measurement. A respiratory waveform is calculated by detecting the vertical motion of the thoracic and abdominal region with respiration. We attempted clinical experiment in the NICU, and confirmed the accuracy of the obtained respiratory waveform was high. Non-contact respiratory monitoring of newborn using a FG vision sensor enabled the minimally invasive procedure.

  4. Predicting Performance and Plasticity in the Development of Respiratory Structures and Metabolic Systems

    PubMed Central

    Montooth, Kristi L.; Helm, Bryan R.

    2014-01-01

    The scaling laws governing metabolism suggest that we can predict metabolic rates across taxonomic scales that span large differences in mass. Yet, scaling relationships can vary with development, body region, and environment. Within species, there is variation in metabolic rate that is independent of mass and which may be explained by genetic variation, the environment or their interaction (i.e., metabolic plasticity). Additionally, some structures, such as the insect tracheal respiratory system, change throughout development and in response to the environment to match the changing functional requirements of the organism. We discuss how study of the development of respiratory function meets multiple challenges set forth by the NSF Grand Challenges Workshop. Development of the structure and function of respiratory and metabolic systems (1) is inherently stable and yet can respond dynamically to change, (2) is plastic and exhibits sensitivity to environments, and (3) can be examined across multiple scales in time and space. Predicting respiratory performance and plasticity requires quantitative models that integrate information across scales of function from the expression of metabolic genes and mitochondrial biogenesis to the building of respiratory structures. We present insect models where data are available on the development of the tracheal respiratory system and of metabolic physiology and suggest what is needed to develop predictive models. Incorporating quantitative genetic data will enable mapping of genetic and genetic-by-environment variation onto phenotypes, which is necessary to understand the evolution of respiratory and metabolic systems and their ability to enable respiratory homeostasis as organisms walk the tightrope between stability and change. PMID:24812329

  5. Brainstem Respiratory Oscillators Develop Independently of Neuronal Migration Defects in the Wnt/PCP Mouse Mutant looptail

    PubMed Central

    Thoby-Brisson, Muriel; Bouvier, Julien; Glasco, Derrick M.; Stewart, Michelle E.; Dean, Charlotte; Murdoch, Jennifer N.; Champagnat, Jean; Fortin, Gilles; Chandrasekhar, Anand

    2012-01-01

    The proper development and maturation of neuronal circuits require precise migration of component neurons from their birthplace (germinal zone) to their final positions. Little is known about the effects of aberrant neuronal position on the functioning of organized neuronal groups, especially in mammals. Here, we investigated the formation and properties of brainstem respiratory neurons in looptail (Lp) mutant mice in which facial motor neurons closely apposed to some respiratory neurons fail to migrate due to loss of function of the Wnt/Planar Cell Polarity (PCP) protein Vangl2. Using calcium imaging and immunostaining on embryonic hindbrain preparations, we found that respiratory neurons constituting the embryonic parafacial oscillator (e-pF) settled at the ventral surface of the medulla in Vangl2Lp/+ and Vangl2Lp/Lp embryos despite the failure of tangential migration of its normally adjacent facial motor nucleus. Anatomically, the e-pF neurons were displaced medially in Lp/+ embryos and rostro-medially Lp/Lp embryos. Pharmacological treatments showed that the e-pF oscillator exhibited characteristic network properties in both Lp/+ and Lp/Lp embryos. Furthermore, using hindbrain slices, we found that the other respiratory oscillator, the preBötzinger complex, was also anatomically and functionally established in Lp mutants. Importantly, the displaced e-pF oscillator established functional connections with the preBötC oscillator in Lp/+ mutants. Our data highlight the robustness of the developmental processes that assemble the neuronal networks mediating an essential physiological function. PMID:22363567

  6. Aging-related changes in respiratory system mechanics and morphometry in mice.

    PubMed

    Elliott, Jonathan E; Mantilla, Carlos B; Pabelick, Christina M; Roden, Anja C; Sieck, Gary C

    2016-07-01

    Previous work investigating respiratory system mechanics in mice has reported an aging-related increase in compliance and mean linear intercept (Lm). However, these changes were assessed using only a young (2-mo-old) and old (20- and 26-mo-old) group yet were interpreted to reflect a linear evolution across the life span. Therefore, to investigate respiratory system mechanics and lung morphometry across a more complete spectrum of ages, we utilized 2 (100% survival, n = 6)-, 6 (100% survival, n = 12)-, 18 (90% survival, n = 12)-, 24 (75% survival, n = 12)-, and 30 (25% survival, n = 12)-mo-old C57BL/6 mice. We found a nonlinear aging-related decrease in respiratory system resistance and increase in dynamic compliance and hysteresis between 2- and 24-mo-old mice. However, in 30-mo-old mice, respiratory system resistance increased, and dynamic compliance and hysteresis decreased relative to 24-mo-old mice. Respiratory system impedance spectra were measured between 1-20.5 Hz at positive end-expiratory pressures (PEEP) of 1, 3, 5, and 7 cmH2O. Respiratory system resistance and reactance at each level of PEEP were increased and decreased, respectively, only in 2-mo-old animals. No differences in the respiratory system impedance spectra were observed in 6-, 18-, 24-, and 30-mo-old mice. Additionally, lungs were fixed following tracheal instillation of 4% paraformaldehyde at 25 cmH2O and processed for Lm and airway collagen deposition. There was an aging-related increase in Lm consistent with emphysematous-like changes and no evidence of increased airway collagen deposition. Accordingly, we demonstrate nonlinear aging-related changes in lung mechanics and morphometry in C57BL/6 mice. PMID:27288490

  7. Cytochrome redox states and respiratory control in mouse and beef heart mitochondria at steady-state levels of hypoxia.

    PubMed

    Harrison, David K; Fasching, Mario; Fontana-Ayoub, Mona; Gnaiger, Erich

    2015-11-15

    Mitochondrial control of cellular redox states is a fundamental component of cell signaling in the coordination of core energy metabolism and homeostasis during normoxia and hypoxia. We investigated the relationship between cytochrome redox states and mitochondrial oxygen consumption at steady-state levels of hypoxia in mitochondria isolated from beef and mouse heart (BHImt, MHImt), comparing two species with different cardiac dynamics and local oxygen demands. A low-noise, rapid spectrophotometric system using visible light for the measurement of cytochrome redox states was combined with high-resolution respirometry. Monophasic hyperbolic relationships were observed between oxygen consumption, JO2, and oxygen partial pressure, Po2, within the range <1.1 kPa (8.3 mmHg; 13 μM). P50j (Po2 at 0.5·Jmax) was 0.015 ± 0.0004 and 0.021 ± 0.003 kPa (0.11 and 0.16 mmHg) for BHImt and MHImt, respectively. Maximum oxygen consumption, Jmax, was measured at saturating ADP levels (OXPHOS capacity) with Complex I-linked substrate supply. Redox states of cytochromes aa3 and c were biphasic hyperbolic functions of Po2. The relationship between cytochrome oxidation state and oxygen consumption revealed a separation of distinct phases from mild to severe and deep hypoxia. When cytochrome c oxidation increased from fully reduced to 45% oxidized at 0.1 Jmax, Po2 was as low as 0.002 kPa (0.02 μM), and trace amounts of oxygen are sufficient to partially oxidize the cytochromes. At higher Po2 under severe hypoxia, respiration increases steeply, whereas redox changes are small. Under mild hypoxia, the steep slope of oxidation of cytochrome c when flux remains more stable represents a cushioning mechanism that helps to maintain respiration high at the onset of hypoxia. PMID:26251509

  8. SU-E-J-192: Comparative Effect of Different Respiratory Motion Management Systems

    SciTech Connect

    Nakajima, Y; Kadoya, N; Ito, K; Kanai, T; Jingu, K; Kida, S; Kishi, K; Sato, K; Dobashi, S; Takeda, K

    2015-06-15

    Purpose: Irregular breathing can influence the outcome of four-dimensional computed tomography imaging for causing artifacts. Audio-visual biofeedback systems associated with patient-specific guiding waveform are known to reduce respiratory irregularities. In Japan, abdomen and chest motion self-control devices (Abches), representing simpler visual coaching techniques without guiding waveform are used instead; however, no studies have compared these two systems to date. Here, we evaluate the effectiveness of respiratory coaching to reduce respiratory irregularities by comparing two respiratory management systems. Methods: We collected data from eleven healthy volunteers. Bar and wave models were used as audio-visual biofeedback systems. Abches consisted of a respiratory indicator indicating the end of each expiration and inspiration motion. Respiratory variations were quantified as root mean squared error (RMSE) of displacement and period of breathing cycles. Results: All coaching techniques improved respiratory variation, compared to free breathing. Displacement RMSEs were 1.43 ± 0.84, 1.22 ± 1.13, 1.21 ± 0.86, and 0.98 ± 0.47 mm for free breathing, Abches, bar model, and wave model, respectively. Free breathing and wave model differed significantly (p < 0.05). Period RMSEs were 0.48 ± 0.42, 0.33 ± 0.31, 0.23 ± 0.18, and 0.17 ± 0.05 s for free breathing, Abches, bar model, and wave model, respectively. Free breathing and all coaching techniques differed significantly (p < 0.05). For variation in both displacement and period, wave model was superior to free breathing, bar model, and Abches. The average reduction in displacement and period RMSE compared with wave model were 27% and 47%, respectively. Conclusion: The efficacy of audio-visual biofeedback to reduce respiratory irregularity compared with Abches. Our results showed that audio-visual biofeedback combined with a wave model can potentially provide clinical benefits in respiratory management

  9. Role of ventrolateral medulla in regulation of respiratory and cardiovascular systems.

    PubMed

    Millhorn, D E; Eldridge, F L

    1986-10-01

    It is now widely accepted that the ventrolateral aspect of the medulla oblongata (VLM) plays an important role in regulation of the respiratory and cardiovascular systems. The VLM has been implicated as being involved in a number of different physiological functions, including central chemoreception, integration of afferent inputs from certain sense organs to the respiratory and cardiovascular controllers, the source of excitatory input to preganglionic sympathetic neurons in the spinal cord, and location of synaptic relay between the higher brain defense areas and spinal cord sympathetic elements. In recent years there have been a number of important findings concerning both the anatomical substrate and neurophysiological characteristics of VLM neurons involved in regulation of the respiratory and cardiovascular systems. New anatomical findings show that neuronal networks located in the VLM send projections to and receive projections from brain stem nuclei that have traditionally been associated with respiratory and cardiovascular regulation. Nevertheless, there are still many important questions concerning the role of the VLM in control of these vital systems that have yet to be answered. For instance, are the same VLM neurons involved in control of both systems? Is the VLM the only site for central respiratory chemoreception? This review will endeavor to examine new findings and to reexamine some older findings concerning the VLM. PMID:3536832

  10. Antitussive activity and respiratory system effects of levodropropizine in man.

    PubMed

    Bossi, R; Braga, P C; Centanni, S; Legnani, D; Moavero, N E; Allegra, L

    1988-08-01

    Antitussive activity of the new antitussive drug, levodropropizine (S(-)-3-(4-phenyl-piperazin-1-yl)-propane-1,2-diol, DF 526), was evaluated in healthy volunteers by the classical method of citric acid-induced coughing. Levodropropizine dose-dependently reduced cough frequency. Maximal inhibition was observed at 6 h after administration. Cough intensity was also reduced, as shown by the analysis of cough noise. Levodropropizine, at the dosage of 60 mg t.i.d., had no adverse effects on respiratory function nor on airway clearance mechanisms: in fact, it did not affect spirometric parameters. Levodropropizine had no effects on the rheological properties of mucus nor on ciliary activity of airway epithelium. PMID:3196411

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

    PubMed Central

    Xing, Yu-Fei; Xu, Yue-Hua; Shi, Min-Hua

    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. PMID:26904255

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

    PubMed

    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. PMID:26904255

  13. System parameters for erythropoiesis control model: Comparison of normal values in human and mouse model

    NASA Technical Reports Server (NTRS)

    1979-01-01

    The computer model for erythropoietic control was adapted to the mouse system by altering system parameters originally given for the human to those which more realistically represent the mouse. Parameter values were obtained from a variety of literature sources. Using the mouse model, the mouse was studied as a potential experimental model for spaceflight. Simulation studies of dehydration and hypoxia were performed. A comparison of system parameters for the mouse and human models is presented. Aside from the obvious differences expected in fluid volumes, blood flows and metabolic rates, larger differences were observed in the following: erythrocyte life span, erythropoietin half-life, and normal arterial pO2.

  14. Prevalence and association of welding related systemic and respiratory symptoms in welders

    PubMed Central

    El-Zein, M; Malo, J; Infante-Rivard, C; Gautrin, D

    2003-01-01

    Background: The prevalence of welding related respiratory symptoms coexisting with welding related systemic symptoms in welders is unknown. Aims: To determine in a sample of welders the prevalence of coexisting welding related systemic symptoms indicative of metal fume fever (MFF) and welding related respiratory symptoms suggestive of occupational asthma (OA), and the strength and significance of any association between these two groups of symptoms. Methods: A respiratory symptoms questionnaire, a systemic symptoms questionnaire, and a questionnaire on occupational history were administered by telephone to 351 of a sample of 441 welders (79.6%) from two cities in Québec, Canada. Results: The co-occurrence of possible MFF (defined as having at least two symptoms of fever, feelings of flu, general malaise, chills, dry cough, metallic taste, and shortness of breath, occurring at the beginning of the working week, 3–10 hours after exposure to welding fumes) together with welding related respiratory symptoms suggestive of OA (defined as having at least two welding related symptoms of cough, wheezing, and chest tightness) was 5.8%. These two groups of symptoms were significantly associated (χ2 = 18.9, p < 0.001). Conclusion: There is a strong association between welding related MFF and welding related respiratory symptoms suggestive of OA. As such, MFF could be viewed as a pre-marker of welding related OA, a hypothesis that requires further investigation. PMID:12937186

  15. A review of recent findings about stress-relaxation in the respiratory system tissues.

    PubMed

    Rubini, Alessandro; Carniel, Emanuele Luigi

    2014-12-01

    This article reviews the state of the art about an unclear physiological phenomenon interesting respiratory system tissues, i.e., stress-relaxation. Due to their visco-elastic properties, the tissues do not maintain constant stress under constant deformation. Rather, the stress slowly relaxes and falls to a lower value. The exact molecular basis of this complex visco-elastic behavior is not well defined, but it has been suggested that it may be generated because of the anisotropic mechanical properties of elastin and collagen fibers in the alveolar septa and their interaction phenomena, such as reciprocal sliding, also in relation to interstitial liquid movements. The effects on stress-relaxation of various biochemical and physical factors are reviewed, including the consequences of body temperature variations, respiratory system inflammations and hyperbaric oxygen exposure, endocrinal factors, circulating blood volume variations, changes in inflation volume and/or flow, changes in intra-abdominal pressure because of pneumoperitoneum or Trendelenburg position. The effects of these factors on stress-relaxation have practical consequences because, depending on visco-elastic pressure amount which is requested to inflate the respiratory system in different conditions, respiratory muscles have to produce different values of inspiratory pressure during spontaneous breathing. High inspiratory pressure values might increase the risk of respiratory failure development on mechanical basis. PMID:25097096

  16. Statistical Determination of the Gating Windows for Respiratory-Gated Radiotherapy Using a Visible Guiding System.

    PubMed

    Oh, Se An; Yea, Ji Woon; Kim, Sung Kyu

    2016-01-01

    Respiratory-gated radiation therapy (RGRT) is used to minimize the radiation dose to normal tissue in lung-cancer patients. Although determining the gating window in the respiratory phase of patients is important in RGRT, it is not easy. Our aim was to determine the optimal gating window when using a visible guiding system for RGRT. Between April and October 2014, the breathing signals of 23 lung-cancer patients were recorded with a real-time position management (RPM) respiratory gating system (Varian, USA). We performed statistical analysis with breathing signals to find the optimal gating window for guided breathing in RGRT. When we compared breathing signals before and after the breathing training, 19 of the 23 patients showed statistically significant differences (p < 0.05). The standard deviation of the respiration signals after breathing training was lowest for phases of 30%-70%. The results showed that the optimal gating window in RGRT is 40% (30%-70%) with respect to repeatability for breathing after respiration training with the visible guiding system. RGRT was performed with the RPM system to confirm the usefulness of the visible guiding system. The RPM system and our visible guiding system improve the respiratory regularity, which in turn should improve the accuracy and efficiency of RGRT. PMID:27228097

  17. Statistical Determination of the Gating Windows for Respiratory-Gated Radiotherapy Using a Visible Guiding System

    PubMed Central

    Oh, Se An; Yea, Ji Woon

    2016-01-01

    Respiratory-gated radiation therapy (RGRT) is used to minimize the radiation dose to normal tissue in lung-cancer patients. Although determining the gating window in the respiratory phase of patients is important in RGRT, it is not easy. Our aim was to determine the optimal gating window when using a visible guiding system for RGRT. Between April and October 2014, the breathing signals of 23 lung-cancer patients were recorded with a real-time position management (RPM) respiratory gating system (Varian, USA). We performed statistical analysis with breathing signals to find the optimal gating window for guided breathing in RGRT. When we compared breathing signals before and after the breathing training, 19 of the 23 patients showed statistically significant differences (p < 0.05). The standard deviation of the respiration signals after breathing training was lowest for phases of 30%–70%. The results showed that the optimal gating window in RGRT is 40% (30%–70%) with respect to repeatability for breathing after respiration training with the visible guiding system. RGRT was performed with the RPM system to confirm the usefulness of the visible guiding system. The RPM system and our visible guiding system improve the respiratory regularity, which in turn should improve the accuracy and efficiency of RGRT. PMID:27228097

  18. Finger mouse system based on computer vision in complex backgrounds

    NASA Astrophysics Data System (ADS)

    Xu, Jun; Zhang, Xiong

    2013-12-01

    This paper presents a human-computer interaction system and realizes a real-time virtual mouse. Our system emulates the dragging and selecting functions of a mouse by recognizing bare hands, hence the control style is simple and intuitive. A single camera is used to capture hand images and a DSP chip is embedded as the image processing platform. To deal with complex backgrounds, particularly where skin-like or moving objects appear, we develop novel hand recognition algorithms. Hand segmentation is achieved by skin color cue and background difference. Each input image is corrected according to the luminance and then skin color is extracted by Gaussian model. We employ a Camshift tracking algorithm which receives feedbacks from the recognition module. In fingertip recognition, a method combining template matching and circle drawing is proposed. Our system has advantages of good real-time performance, easy integration and energy conservation. Experiments show that the system is robust to the scaling and rotation of hands.

  19. The respiratory system of the piezophile Photobacterium profundum SS9 grown under various pressures.

    PubMed

    Tamegai, Hideyuki; Nishikawa, Shun; Haga, Minami; Bartlett, Douglas H

    2012-01-01

    It is known that the facultative piezophile Shewanella violacea DSS12 alters its respiratory components under the influence of hydrostatic pressure during growth. This can be considered one of the mechanisms of bacterial adaptation to high pressure. In this study, we investigated the respiratory system of another well-studied piezophile, Photobacterium profundum SS9. We analyzed cytochrome contents, the expression of genes encoding respiratory components in P. profundum SS9 grown under various conditions, and the pressure dependency of the terminal oxidase activities. Activity was more tolerant of relatively high pressures, such as 125 MPa when the cells were grown under high pressure as compared with cells grown under atmospheric pressure. Such properties observed are similar to the case of S. violacea. However, the contents of the cytochromes and expression of the respiratory genes were not influenced by growth pressure in P. profundum SS9, inconsistent with the case of S. violacea. We suggest that the mechanism of the piezoadaptation of the respiratory system of P. profundum SS9 differs from that of S. violacea, as described above, and that each strain chooses its own strategy. PMID:22878211

  20. A mainstream monitoring system for respiratory CO2 concentration and gasflow.

    PubMed

    Yang, Jiachen; Chen, Bobo; Burk, Kyle; Wang, Haitao; Zhou, Jianxiong

    2016-08-01

    Continuous respiratory gas monitoring is an important tool for clinical monitoring. In particular, measurement of respiratory [Formula: see text] concentration and gasflow can reflect the status of a patient by providing parameters such as volume of carbon dioxide, end-tidal [Formula: see text] respiratory rate and alveolar deadspace. However, in the majority of previous work, [Formula: see text] concentration and gasflow have been studied separately. This study focuses on a mainstream system which simultaneously measures respiratory [Formula: see text] concentration and gasflow at the same location, allowing for volumetric capnography to be implemented. A non-dispersive infrared monitor is used to measure [Formula: see text] concentration and a differential pressure sensor is used to measure gasflow. In developing this new device, we designed a custom airway adapter which can be placed in line with the breathing circuit and accurately monitor relevant respiratory parameters. Because the airway adapter is used both for capnography and gasflow, our system reduces mechanical deadspace. The finite element method was used to design the airway adapter which can provide a strong differential pressure while reducing airway resistance. Statistical analysis using the coefficient of variation was performed to find the optimal driving voltage of the pressure transducer. Calibration between variations and flows was used to avoid pressure signal drift. We carried out targeted experiments using the proposed device and confirmed that the device can produce stable signals. PMID:26178886

  1. The effect of respiratory muscle training with CO2 breathing on cellular adaptation of mdx mouse diaphragm

    PubMed Central

    Matécki, Stefan; Rivier, François; Hugon, Gerald; Koechlin, Christelle; Michel, Alain; Préfaut, Christian; Mornet, Dominique; Ramonatxo, Michèle

    2005-01-01

    The aim of our study was to investigate the cellular mechanisms induced by hypercapnic stimulation of ventilation, during 6 weeks/30 min per day, in 10 mdx and 8 C57BL10 mice (10G0.2 months old). Ten mdx and eight C57BL10 mice served as control group. This respiratory training increases in vitro maximal tetanic tension of the diaphragm only in mdx mice. Western blot analysis of diaphragm showed: (1) an over-expression of a-dystrobrevin in mdx and C57BL10 training group compared to control group (8100G710 versus 6100G520 and 2800G400 versus 2200G250 arbitrary units); (2) a decrease in utrophin expression only in mdx training group compared to control group (2100G320 versus 3100G125 arbitrary units). Daily respiratory muscle training in mdx mice, induces a beneficial effect on diaphragm strength, with an over-expression of a-dystrobrevin. Further studies are needed to determine if, in absence of dystrophin, the over-expression of a-dystrobrevin could be interpreted as a possible pathway to improve function of dystrophic muscle. PMID:15907290

  2. Integrative approaches for modeling regulation and function of the respiratory system

    PubMed Central

    Ben-Tal, Alona

    2013-01-01

    Mathematical models have been central to understanding the interaction between neural control and breathing. Models of the entire respiratory system – which comprises the lungs and the neural circuitry that controls their ventilation - have been derived using simplifying assumptions to compartmentalise each component of the system and to define the interactions between components. These full system models often rely – through necessity - on empirically derived relationships or parameters, in addition to physiological values. In parallel with the development of whole respiratory system models are mathematical models that focus on furthering a detailed understanding of the neural control network, or of the several functions that contribute to gas exchange within the lung. These models are biophysically based, and rely on physiological parameters. They include single-unit models for a breathing lung or neural circuit, through to spatially-distributed models of ventilation and perfusion, or multi-circuit models for neural control. The challenge is to bring together these more recent advances in models of neural control with models of lung function, into a full simulation for the respiratory system that builds upon the more detailed models but remains computationally tractable. This requires first understanding the mathematical models that have been developed for the respiratory system at different levels, and which could be used to study how physiological levels of O2 and CO2 in the blood are maintained. PMID:24591490

  3. Instrumentation for the analysis of respiratory system disorders during sleep: Design and application

    NASA Astrophysics Data System (ADS)

    de Melo, Pedro Lopes; de Andrade Lemes, Lucas Neves

    2002-11-01

    Sleep breathing disorders are estimated to be present in 2%-4% of middle-aged adults. Serious adverse consequences, such as systemic arterial hypertension, myocardial infraction, and cerebrovascular disease, can be related to these conditions. Intellectual deficits associated with attention, memory, and problem-solving have also been associated with a poor quality of sleep. The main causes of these disorders are obstructions resulting from repetitive narrowing and closure of the pharyngeal airway, which have been monitored by indirect measurements of temperature, displacement, and other highly invasive procedures. The measurement of mechanical impedance of the respiratory system by the forced oscillation technique (FOT) has recently been suggested to quantify the respiratory obstruction during sleep. It is claimed that the noninvasive and dynamic characteristics of this technique would allow a noninvasive and accurate analysis of these events. In spite of this high scientific and clinical potential, there is no detailed description of a complete instrumentation system to implement this promising technique in sleep studies. In this context, the purpose of this study was twofold: (1) describe the development of a new computer-based system for identification of the mechanical impedance of the respiratory system during sleep by the FOT and (2) evaluate the performance of this device in the description of respiratory events in conditions including no, mild, serious disease, and therapeutic procedures. These evaluations confirmed the desirable features achieved in laboratory tests and the high scientific and clinical potential of this system.

  4. End-expiration respiratory gating for a high-resolution stationary cardiac SPECT system

    NASA Astrophysics Data System (ADS)

    Chan, Chung; Harris, Mark; Le, Max; Biondi, James; Grobshtein, Yariv; Liu, Yi-Hwa; Sinusas, Albert J.; Liu, Chi

    2014-10-01

    Respiratory and cardiac motions can degrade myocardial perfusion SPECT (MPS) image quality and reduce defect detection and quantitative accuracy. In this study, we developed a dual respiratory and cardiac gating system for a high-resolution fully stationary cardiac SPECT scanner in order to improve the image quality and defect detection. Respiratory motion was monitored using a compressive sensor pillow connected to a dual respiratory-cardiac gating box, which sends cardiac triggers only during end-expiration phases to the single cardiac trigger input on the SPECT scanners. The listmode data were rebinned retrospectively into end-expiration frames for respiratory motion reduction or eight cardiac gates only during end-expiration phases to compensate for both respiratory and cardiac motions. The proposed method was first validated on a motion phantom in the presence and absence of multiple perfusion defects, and then applied on 11 patient studies with and without perfusion defects. In the normal phantom studies, the end-expiration gated SPECT (EXG-SPECT) reduced respiratory motion blur and increased myocardium to blood pool contrast by 51.2% as compared to the ungated images. The proposed method also yielded an average of 11.2% increase in myocardium to defect contrast as compared to the ungated images in the phantom studies with perfusion defects. In the patient studies, EXG-SPECT significantly improved the myocardium to blood pool contrast (p < 0.005) by 24% on average as compared to the ungated images, and led to improved perfusion uniformity across segments on polar maps for normal patients. For a patient with defect, EXG-SPECT improved the defect contrast and definition. The dual respiratory-cardiac gating further reduced the blurring effect, increased the myocardium to blood pool contrast significantly by 36% (p < 0.05) compared to EXG-SPECT, and further improved defect characteristics and visualization of fine structures at the expense of increased noise on

  5. End-expiration Respiratory Gating for a High Resolution Stationary Cardiac SPECT system

    PubMed Central

    Chan, Chung; Harris, Mark; Le, Max; Biondi, James; Grobshtein, Yariv; Liu, Yi-Hwa; Sinusas, Albert J.; Liu, Chi

    2014-01-01

    Respiratory and cardiac motions can degrade myocardial perfusion SPECT (MPS) image quality and reduce defect detection and quantitative accuracy. In this study, we developed a dual-respiratory and cardiac gating system for a high resolution fully stationary cardiac SPECT scanner in order to improve the image quality and defect detection. Respiratory motion was monitored using a compressive sensor pillow connected to a dual respiratory-cardiac gating box, which sends cardiac triggers only during end-expiration phases to the single cardiac trigger input on the SPECT scanners. The listmode data were rebinned retrospectively into end-expiration frames for respiratory motion reduction or 8 cardiac gates only during end-expiration phases to compensate for both respiratory and cardiac motions. The proposed method was first validated on a motion phantom in the presence and absence of multiple perfusion defects, and then applied on 11 patient studies with and without perfusion defects. In the normal phantom studies, the end-expiration gated SPECT (EXG-SPECT) reduced respiratory motion blur and increased myocardium to blood pool contrast by 51.2% as compared to the ungated images. The proposed method also yielded an average of 11.2% increase in myocardium to defect contrast as compared to the ungated images in the phantom studies with perfusion defects. In the patient studies, EXG-SPECT significantly improved the myocardium to blood pool contrast (p<0.005) by 24% on average as compared to the ungated images, and led to improved perfusion uniformity across segments on polar maps for normal patients. For a patient with defect, EXG-SPECT improved the defect contrast and definition. The dual respiratory-cardiac gating further reduced the blurring effect, increased the myocardium to blood pool contrast significantly by 36% (p<0.05) compared to EXG SPECT, and further improved defect characteristics and visualization of fine structures at the expense of increased noise on the

  6. Agreement between bovine respiratory disease scoring systems for pre-weaned dairy calves.

    PubMed

    Aly, Sharif S; Love, William J; Williams, Deniece R; Lehenbauer, Terry W; Van Eenennaam, Alison; Drake, Christiana; Kass, Philip H; Farver, Thomas B

    2014-12-01

    Clinical scoring systems have been proposed for respiratory disease diagnosis in calves, including the Wisconsin (WI) system (McGuirk in 2008) which uses five clinical signs, each partitioned into four levels of severity. Recently, we developed the California (CA) bovine respiratory disease (BRD) scoring system requiring less calf handling and consisting of six clinical signs, each classified as normal or abnormal. The objective of this study was to estimate the on-farm agreement between the WI and the CA scoring systems. A total of 100 calves were enrolled on a CA dairy and assessed for BRD case status using the two scoring systems simultaneously. The Kappa coefficient of agreement between these two systems was estimated to be 0.85, which indicated excellent agreement beyond chance. The simpler design and reduced calf handling required by the CA BRD scoring system may make it advantageous for on-farm use. PMID:25424381

  7. Endogenous excitatory drive to the respiratory system in rapid eye movement sleep in cats

    PubMed Central

    Orem, John; Lovering, Andrew T; Dunin-Barkowski, Witali; Vidruk, Edward H

    2000-01-01

    A putative endogenous excitatory drive to the respiratory system in rapid eye movement (REM) sleep may explain many characteristics of breathing in that state, e.g. its irregularity and variable ventilatory responses to chemical stimuli. This drive is hypothetical, and determinations of its existence and character are complicated by control of the respiratory system by the oscillator and its feedback mechanisms. In the present study, endogenous drive was studied during apnoea caused by mechanical hyperventilation. We reasoned that if there was a REM-dependent drive to the respiratory system, then respiratory activity should emerge out of the background apnoea as a manifestation of the drive. Diaphragmatic muscle or medullary respiratory neuronal activity was studied in five intact, unanaesthetized adult cats who were either mechanically hyperventilated or breathed spontaneously in more than 100 REM sleep periods. Diaphragmatic activity emerged out of a background apnoea caused by mechanical hyperventilation an average of 34 s after the onset of REM sleep. Emergent activity occurred in 60 % of 10 s epochs in REM sleep and the amount of activity per unit time averaged approximately 40 % of eupnoeic activity. The activity occurred in episodes and was poorly related to pontogeniculo-occipital waves. At low CO2 levels, this activity was non-rhythmic. At higher CO2 levels (less than 0.5 % below eupnoeic end-tidal percentage CO2 levels in non-REM (NREM) sleep), activity became rhythmic. Medullary respiratory neurons were recorded in one of the five animals. Nineteen of twenty-seven medullary respiratory neurons were excited in REM sleep during apnoea. Excited neurons included inspiratory, expiratory and phase-spanning neurons. Excitation began about 43 s after the onset of REM sleep. Activity increased from an average of 6 impulses s−1 in NREM sleep to 15.5 impulses s−1 in REM sleep. Neuronal activity was non-rhythmic at low CO2 levels and became rhythmic when levels

  8. A computer-controlled pump and realistic anthropomorphic respiratory phantom for validating image-guided systems

    NASA Astrophysics Data System (ADS)

    Lin, Ralph; Wilson, Emmanuel; Tang, Jonathan; Stoianovici, Dan; Cleary, Kevin

    2007-03-01

    The development of image-guided interventions requires validation studies to evaluate new protocols. So far, these validation studies have been limited to animal models and to software and physical phantoms that simulate respiratory motion but cannot accommodate needle punctures in a realistic manner. We have built a computer-controlled pump that drives an anthropomorphic respiratory phantom for simulating natural breathing patterns. This pump consists of a power supply, a motion controller with servo amplifier, linear actuator, and custom fabricated pump assembly. By generating several sample waveforms, we were able to simulate typical breathing patterns. Using this pump, we were able to produce chest wall movements similar to typical chest wall movements observed in humans. This system has potential applications for evaluating new respiratory compensation algorithms and may facilitate improved testing of image-guided protocols under realistic interventional conditions.

  9. [The evolution of the human species: a long journey for the respiratory system].

    PubMed

    Gea, Joaquim

    2008-05-01

    Evolution has involved important changes in hominids, particularly in relation to the process of encephalization and the transition to bipedalism. Some of these changes involved structures related to the respiratory system and altered its functional behavior. Changes affecting the relationship between the skull and the spinal column, together with an improved laryngeal structure (allowing vocalization), resulted in a soft and elongated oropharynx, with part of the tongue integrated into its anterior wall, and thus in an increased tendency towards upper airway collapse during sleep. Vertebral bodies moved inwards into the thorax, which became slightly shorter and went from a bell-shaped appearance to that of a flatter barrel-shaped one. This resulted in respiratory muscle mechanics that were more efficient for upright posture. The pulmonary ventilation and perfusion gradients moved from a dorsoventral to a craniocaudal axis, while the structural organization of the respiratory muscles underwent only minor changes. PMID:18448018

  10. An internet-based system for home monitoring of respiratory muscle disorders.

    PubMed

    Silva Junior, Evert P; Esteves, Guilherme P; Faria, Alvaro C D; Melo, Pedro L

    2010-01-01

    Home telemonitoring is of great interest in respiratory medicine where large numbers of people have long term conditions. We developed a telemedicine instrument for home monitoring of patients with disturbed respiratory muscles. The instrument measures the maximum inspiratory pressure (Pimax), the inspiratory time constant (τ(i)) and connects to the Internet through TCP/IP protocol. The instrument was evaluated by means of a comparative analysis in 18 normal individuals and 15 COPD patients. In close agreement with the pathophysiology, a reduction in Pimax (p < 0.0001) and an increase in τ(i) (p < 0.001) was observed in COPD patients. We concluded that the developed system could be a useful tool for the evaluation of inspiratory muscle and for the implementation of telemedicine services, contributing to reduce the costs of the assistance offered to patients with respiratory diseases. PMID:21096291

  11. Development and Application of a Miniaturised Sensor System for Respiratory Investigations (MAP-RSS)

    NASA Astrophysics Data System (ADS)

    Hoffmann, U.; Drager, T.; Baumann, R.; Fasoulas, S.

    2008-06-01

    The project supported by the European Space Agency (ESA) in the frame of the "Microgravity Application Promotion Programe (MAP)" deals with the development and application of a new respiratory sensor system (RSS) for human respiratory investigations. Eight institutions, including three Industrial partners from different areas, combine their expertise by focusing on two selected applications in the field of ergospirometric exercise testing and lung function diagnostics with subsequent medication. The main goals of this project are to develop miniaturized oxygen and carbon dioxide sensors, to use their capability for simultaneous detection of total flow rates, to integrate them into a mask for the in-situ measurement of respiratory parameters, and to perform first qualification tests. For many manned space missions, and especially on the International Space Station, there is a need for a small, light-weight, portable, potentially body-mounted, metabolic gas analyzer with which periodic fitness or scientific evaluations could be performed by the astronauts.

  12. From Head to Toe: Respiratory, Circulatory, and Skeletal Systems. Book 3.

    ERIC Educational Resources Information Center

    Wiebe, Arthur, Ed.; And Others

    Designed to supplement curricular programs dealing with the human body, this booklet offers an activity-based, student-oriented approach for middle school teachers and students. Twelve activities focus on principles and skills related to the respiratory, circulatory, and skeletal systems. Each activity consists of student sheets and a teacher's…

  13. Preliminary results of a miniaturized respiratory sensor system used under hypergravity conditions up to 9 gz

    NASA Astrophysics Data System (ADS)

    Guenther, A.; Baumann, R.; Meyer, C.; Schmiel, T.; Nehring, M.; Tajmar, M.

    2013-12-01

    Respiratory gas analyses are used to explore the influence of increased gravity on the physiology of breathing. Due to the mass, size and intricacy of standard measurement systems, previous studies were limited to a maximum acceleration of + 5 gz (head-to-foot direction). Furthermore, no in situ mainstream measurements of oxygen and carbon dioxide concentration were possible under hypergravity conditions so far. This paper shows a first study which demonstrates a respiratory sensor system developed at the Institute for Aerospace Engineering at TU Dresden. This system is suitable for an in situ measurement of respiratory changes up to + 9 gz (maximum acceleration of jet pilots) and therefore provides a possibility for detailed physiological analyses in future. Three jet pilots were equipped with this system and accelerated under a defined profile up to 7, 8 and + 9 gz. The breathing air flow, oxygen and carbon dioxide concentration were recorded with our miniaturized solid state electrolyte gas sensors, which are also described in this paper. The analysed data show significant changes of the measured respiratory parameters depending on the G-level, the acceleration rate (G-rate of onset [g s-1]) and the examination time.

  14. Bilingual Skills Training Program. Barbering/Cosmetology. Module 9.0: Respiratory System.

    ERIC Educational Resources Information Center

    Northern New Mexico Community Coll., El Rito.

    This module on the respiratory system is the ninth of ten (CE 028 308-318) in the barbering/cosmetology course of a bilingual skills training program. (A Vocabulary Development Workbook for modules 6-10 is available as CE 028 313.) The course is designed to furnish theoretical and laboratory experiences. Module objectives are for students to…

  15. SU-D-17A-07: Development and Evaluation of a Prototype Ultrasonography Respiratory Monitoring System for 4DCT Reconstruction

    SciTech Connect

    Yan, P; Cheng, S; Chao, C; Jain, A

    2014-06-01

    Purpose: Respiratory motion artifacts are commonly seen in the abdominal and thoracic CT images. A Real-time Position Management (RPM) system is integrated with CT simulator using abdominal surface as a surrogate for tracking the patient respiratory motion. The respiratory-correlated four-dimensional computed tomography (4DCT) is then reconstructed by GE advantage software. However, there are still artifacts due to inaccurate respiratory motion detecting and sorting methods. We developed an Ultrasonography Respiration Monitoring (URM) system which can directly monitor diaphragm motion to detect respiratory cycles. We also developed a new 4DCT sorting and motion estimation method to reduce the respiratory motion artifacts. The new 4DCT system was compared with RPM and the GE 4DCT system. Methods: Imaging from a GE CT scanner was simultaneously correlated with both the RPM and URM to detect respiratory motion. A radiation detector, Blackcat GM-10, recorded the X-ray on/off and synchronized with URM. The diaphragm images were acquired with Ultrasonix RP system. The respiratory wave was derived from diaphragm images and synchronized with CT scanner. A more precise peaks and valleys detection tool was developed and compared with RPM. The motion is estimated for the slices which are not in the predefined respiratory phases by using block matching and optical flow method. The CT slices were then sorted into different phases and reconstructed, compared with the images reconstructed from GE Advantage software using respiratory wave produced from RPM system. Results: The 4DCT images were reconstructed for eight patients. The discontinuity at the diaphragm level due to an inaccurate identification of phases by the RPM was significantly improved by URM system. Conclusion: Our URM 4DCT system was evaluated and compared with RPM and GE 4DCT system. The new system is user friendly and able to reduce motion artifacts. It also has the potential to monitor organ motion during

  16. Implementation of a video-based respiratory gating system for radiation therapy

    NASA Astrophysics Data System (ADS)

    Ramsey, Chester Ray

    In order to increase the effectiveness of radiotherapy in lung cancer treatment, a method must be developed to further increase tumor dose while further minimizing the dose to healthy lung tissue. In this work, a respiratory gated radiation therapy program is established at the Thompson Cancer Survival Center for the treatment lung cancer. A commercially available gating system is used to selectively deliver absorbed dose to moving target volumes during time intervals when the target volume is within the intended region. Although respiratory gating has been used in other applications, such as MRI and CT, free breathing gating has never before been applied to conventional radiotherapy. In this work, techniques are developed for the first time for the implementation of free breathing respiratory gated radiation therapy. In the first phase of this study, the clinical efficacy of the procedure is justified for the treatment of lung, liver, and pancreatic cancers. In the second phase, the stability and reproducibility of the gating hardware are evaluated. This includes an evaluation of the dosimetric stability of the linear accelerator. The consistency of the gating circuit is tested for rapid beam on and off conditions. In addition, a dynamic test phantom is designed and built that simulates respiration in order to test the gating system. In the third phase, monthly and annual quality assurance programs are developed for the respiratory gating system to insure that the entire system is operating correctly. In the final phase, the clinical efficiency and practicality of this respiratory gating is addressed. In addition, patient specific quality assurance (QA) procedures are developed to ensure that the correct dose is delivered safely.

  17. Simple gas chromatographic system for analysis of microbial respiratory gases

    NASA Technical Reports Server (NTRS)

    Carle, G. C.

    1972-01-01

    Dual column ambient temperature system, consisting of pair of capillary columns, microbead thermistor detector and micro gas-sampling valve, is used in remote life-detection equipment for space experiments. Performance outweighs advantage gained by utilizing single-column systems to reduce weight, conserve carrier gas and operate at lower power levels.

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

    PubMed

    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. PMID:26296628

  19. A programmable system for acquisition and reduction of respiratory physiological data.

    PubMed

    Jenkins, J S; Valcke, C P; Ward, D S

    1989-01-01

    A portable software package (TIDAL--Tools for Intelligent Data Acquisition in the Laboratory) for acquiring and analyzing respiratory physiological data is described. TIDAL supports flow-, volume-, and concentration-measuring devices, and any other instruments that produce linear analog outputs. The system allows users to specify the names and types of channels to be sampled, and the calculations involved in reducing samples to breath-to-breath values. The specification of channels and calculations is given in EDL, an Experiment Description Language designed for respiratory physiology. EDL comprises a set of internal functions (primitives) which can be combined into arbitrarily complex expressions. To simplify EDL programming, TIDAL includes a macro processor and a standard macro library; the library contains definitions for a wide variety of respiratory variables. Examples are inspiratory and expiratory times and total volumes, mean inspired and expired gas volumes and concentrations, and end-tidal concentrations. Variables that are derived from these primary data, such as respiratory quotient, are also easily specified. TIDAL is written entirely in the C programming language, with special attention to portable coding practices. The code is organized in a modular structure that eases porting to multiple hardware/compiler/operating system environments. PMID:2919814

  20. Evidence and control of bifurcations in a respiratory system

    SciTech Connect

    Goldin, Matías A. Mindlin, Gabriel B.

    2013-12-15

    We studied the pressure patterns used by domestic canaries in the production of birdsong. Acoustically different sound elements (“syllables”) were generated by qualitatively different pressure gestures. We found that some ubiquitous transitions between syllables can be interpreted as bifurcations of a low dimensional dynamical system. We interpreted these results as evidence supporting a model in which different timescales interact nonlinearly.

  1. A breath sampling system assessing the influence of respiratory rate on exhaled breath composition.

    PubMed

    Lomonaco, T; Salvo, P; Ghimenti, S; Biagini, D; Bellagambi, F; Fuoco, R; Di Francesco, F

    2015-08-01

    This work presents a computerized system to monitor mouth pressure, tidal volume, exhaled airflow, respiration rate and end-tidal partial pressure of CO2 during breath collection. The system was used to investigate the effect of different respiratory rates on the volatile organic compounds (VOCs) concentrations in exhaled breath. For this purpose, VOCs with well-defined biochemical pathways and different chemical and physical properties were selected as biomarkers related to metabolism (acetone and isopropyl alcohol), cholesterol synthesis (isoprene) and intestinal microflora activity (ethanol). Mixed breath was collected from a nominally healthy volunteer in resting conditions by filling a Nalophan bag. The subject followed a regimented breathing pattern at different respiratory rates (10, 30 and 50 breaths per minute). Results highlight that ventilation pattern strongly influences the concentration of the selected compounds. The proposed system allows exhaled breath to be collected also in patients showing dyspnea such as in case of chronic heart failure, asthma and pulmonary diseases. PMID:26738056

  2. A Respiratory Movement Monitoring System Using Fiber-Grating Vision Sensor for Diagnosing Sleep Apnea Syndrome

    NASA Astrophysics Data System (ADS)

    Takemura, Yasuhiro; Sato, Jun-Ya; Nakajima, Masato

    2005-01-01

    A non-restrictive and non-contact respiratory movement monitoring system that finds the boundary between chest and abdomen automatically and detects the vertical movement of each part of the body separately is proposed. The system uses a fiber-grating vision sensor technique and the boundary position detection is carried out by calculating the centers of gravity of upward moving and downward moving sampling points, respectively. In the experiment to evaluate the ability to detect the respiratory movement signals of each part and to discriminate between obstructive and central apneas, detected signals of the two parts and their total clearly showed the peculiarities of obstructive and central apnea. The cross talk between the two categories classified automatically according to several rules that reflect the peculiarities was ≤ 15%. This result is sufficient for discriminating central sleep apnea syndrome from obstructive sleep apnea syndrome and indicates that the system is promising as screening equipment. Society of Japan

  3. An integrated mathematical model of the cardiovascular and respiratory systems.

    PubMed

    Trenhago, Paulo Roberto; Fernandes, Luciano Gonçalves; Müller, Lucas Omar; Blanco, Pablo Javier; Feijóo, Raúl Antonino

    2016-01-01

    This study presents a lumped model for the human cardiorespiratory system. Specifically, we incorporate a sophisticated gas dissociation and transport system to a fully integrated cardiovascular and pulmonary model. The model provides physiologically consistent predictions in terms of hemodynamic variables such as pressure, flow rate, gas partial pressures, and pH. We perform numerical simulations to evaluate the behavior of the partial pressures of oxygen and carbon dioxide in different vascular and pulmonary compartments. For this, we design the rest condition with low oxygen requirements and carbon dioxide production and exercise conditions with high oxygen demand and carbon dioxide production. Furthermore, model sensitivity to more relevant model parameters is studied. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26198626

  4. The usage of the Boussignac continuous positive airway pressure system in acute respiratory failure.

    PubMed

    Wong, D T; Tam, A D; Van Zundert, T C R V

    2013-05-01

    Traditionally, continuous positive airway pressure (CPAP) and bilevel positive airway pressure (BiPAP) devices have been used to treat patients in acute respiratory failure. However they require an electric power source, are relatively large in size, and may be difficult to use in prehospital settings. The recently introduced Boussignac CPAP system is capable of delivering 10 cmH2O of CPAP, is compact, portable and requires only an oxygen source. This paper reviews the efficacy of using Boussignac CPAP as a treatment for acute respiratory failure in both prehospital and hospital settings. All studies mainly focused on patients treated for cardiogenic pulmonary edema. In the prehospital setting, Boussigac CPAP significantly improved respiratory parameters and oxygenation from baseline values. In the emergency department setting, Boussignac CPAP was more effective than standard oxygen delivery and just as effective as BiPAP in improving patient oxygenation and respiration. In one study, implementing Boussignac CPAP reduced intubation rate and hospital stay. Most hospital staff found Boussignac CPAP easy to use and complication rates were low. Boussigac CPAP is a useful device in the treatment of patients with acute respiratory failure, especially in the prehospital setting. PMID:23419338

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

    NASA Astrophysics Data System (ADS)

    Saatci, Esra; Akan, Aydin

    2010-12-01

    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.

  6. A novel simulator for mechanical ventilation in newborns: MEchatronic REspiratory System SImulator for Neonatal Applications.

    PubMed

    Baldoli, Ilaria; Cuttano, Armando; Scaramuzzo, Rosa T; Tognarelli, Selene; Ciantelli, Massimiliano; Cecchi, Francesca; Gentile, Marzia; Sigali, Emilio; Laschi, Cecilia; Ghirri, Paolo; Menciassi, Arianna; Dario, Paolo; Boldrini, Antonio

    2015-08-01

    Respiratory problems are among the main causes of mortality for preterm newborns with pulmonary diseases; mechanical ventilation provides standard care, but long-term complications are still largely reported. In this framework, continuous medical education is mandatory to correctly manage assistance devices. However, commercially available neonatal respiratory simulators are rarely suitable for representing anatomical and physiological conditions; a step toward high-fidelity simulation, therefore, is essential for nurses and neonatologists to acquire the practice needed without any risk. An innovative multi-compartmental infant respirator simulator based on a five-lobe model was developed to reproduce different physio-pathological conditions in infants and to simulate many different kinds of clinical scenarios. The work consisted of three phases: (1) a theoretical study and modeling phase, (2) a prototyping phase, and (3) testing of the simulation software during training courses. The neonatal pulmonary simulator produced allows the replication and evaluation of different mechanical ventilation modalities in infants suffering from many different kinds of respiratory physio-pathological conditions. In particular, the system provides variable compliances for each lobe in an independent manner and different resistance levels for the airway branches; moreover, it allows the trainer to simulate both autonomous and mechanically assisted respiratory cycles in newborns. The developed and tested simulator is a significant contribution to the field of medical simulation in neonatology, as it makes it possible to choose the best ventilation strategy and to perform fully aware management of ventilation parameters. PMID:26238790

  7. Quiz Making Activities Using the Multi-Mouse Quiz System in an Elementary School

    ERIC Educational Resources Information Center

    Zhou, Juan; Mori, Mikihiko; Ueda, Hiroshi; Kita, Hajime

    2013-01-01

    The Multi-Mouse Quiz System is an application used to treat quizzes in a classroom or other learning environment. The system comprises the Multi Mouse Quiz (MMQ) and MMQEditor. The MMQ is an application of Single Display Groupware (SDG), which enables multiple users to answer quizzes by connecting several mice to an ordinary computer. The…

  8. Respiratory acidosis

    MedlinePlus

    Ventilatory failure; Respiratory failure; Acidosis - respiratory ... Causes of respiratory acidosis include: Diseases of the airways (such as asthma and chronic obstructive lung disease ) Diseases of the chest ( ...

  9. Evaluation of integrated respiratory gating systems on a Novalis Tx system.

    PubMed

    Chang, Zheng; Liu, Tonghai; Cai, Jing; Chen, Qing; Wang, Zhiheng; Yin, Fang-Fang

    2011-01-01

    The purpose of this study was to investigate the accuracy of motion tracking and radiation delivery control of integrated gating systems on a Novalis Tx system. The study was performed on a Novalis Tx system, which is equipped with Varian Real-time Position Management (RPM) system, and BrainLAB ExacTrac gating systems. In this study, the two systems were assessed on accuracy of both motion tracking and radiation delivery control. To evaluate motion tracking, two artificial motion profiles and five patients' respiratory profiles were used. The motion trajectories acquired by the two gating systems were compared against the references. To assess radiation delivery control, time delays were measured using a single-exposure method. More specifically, radiation is delivered with a 4 mm diameter cone within the phase range of 10%-45% for the BrainLAB ExacTrac system, and within the phase range of 0%-25% for the Varian RPM system during expiration, each for three times. Radiochromic films were used to record the radiation exposures and to calculate the time delays. In the work, the discrepancies were quantified using the parameters of mean and standard deviation (SD). Pearson's product-moment correlational analysis was used to test correlation of the data, which is quantified using a parameter of r. The trajectory profiles acquired by the gating systems show good agreement with those reference profiles. A quantitative analysis shows that the average mean discrepancies between BrainLAB ExacTrac system and known references are 1.5 mm and 1.9 mm for artificial and patient profiles, with the maximum motion amplitude of 28.0 mm. As for the Varian RPM system, the corresponding average mean discrepancies are 1.1 mm and 1.7 mm for artificial and patient profiles. With the proposed single-exposure method, the time delays are found to be 0.20 ± 0.03 seconds and 0.09 ± 0.01 seconds for BrainLAB ExacTrac and Varian RPM systems, respectively. The results indicate the systems can

  10. [SOME CLINICAL AND CYTOKINE FEATURES OF THE CLINICAL COURSE OF RECURRENT RESPIRATORY SYSTEM DISEASES IN CHILDREN WITH THE TOXOCARIASIS INVASION].

    PubMed

    Dralova, A; Usachova, E

    2015-12-01

    The aim of the present study was to analyze clinical and cytokine features of recurrent respiratory system diseases in children with toxocariasis. 50 children aged 1 to 17 years (mean age - 10±5 years) with recurrent current of respiratory system disorders were studied. During the survey such clinical manifestations of the respiratory system disorders as obstructive bronchitis (50%), bronchial asthma (30%), pneumonia (10%) and laryngotracheitis (10%) have been revealed. Statistical analysis of the results was performed using the software package STATISTICA 6.1 (SNANSOFT). We have shown that the disorders of respiratory system in case of toxocariasis invasion often occur with severe intoxication and bronchial obstruction syndromes, temperature reaction, respiratory insufficiency and hepatomegaly. A prolonged course of the disease has been noted. "Inflammatory" indicators of general blood analysis, such as leukocytosis and increased of ESR have been recorded in patients with respiratory system disorders in children with T.canis infection significantly more often, significant "allergic" laboratory changes were in the form of eosinophilia. High average levels of pro-inflammatory IL-6, as well as low levels of IL 5 have been determined in children suffering from the respiratory system disorders and with toxocariasis invasion in the anamnesis. The obtained findings require further study. PMID:26719552

  11. Effects of volatile substance abuse on the respiratory system in adolescents

    PubMed Central

    2011-01-01

    Aim Inhalant abuse is a prevalent and often overlooked form of substance abuse in adolescents. Chronic inhalant abuse can damage respiratory, cardiac, renal, hepatic, and neurologic systems. This study aims to determine the physiologic effects of inhaling solvents on the respiratory functions. Methods The general health status of the subjects was assessed by history taking, physical examination and a questionnaire which was designed to show the severity of respiratory symptoms. Spirometry, ventilation/perfusion scintigraphy, and high resolution computed tomography (HRCT) were performed to assess pulmonary functions and anatomy. Results Thirty-one male volatile substance abusers and 19 control subjects were included in the study. The mean age of onset of inhalant use was 14.6 ± 2.2 (9-18) years and duration of drug use was 3.7 ± 1.7 years. The most common respiratory symptoms in volatile substance abusers were nasal congestion (45.2%), sputum (38.7%), exercise intolerance (32.3%) and cough (22.6%). Results of spirometric studies showed 12 (41.4%) subjects with low FVC values < 80% of predicted, indicative of restrictive ventilatory pattern in the study group. Although the difference was not statistically significant, restrictive ventilatory pattern was higher in the study group. There was no statistically significant correlation between restrictive ventilatory pattern and the age of onset/duration/frequency of inhalant abuse, respiratory symptoms and scintigraphic abnormalities. Subjects who had restrictive pattern in their pulmonary function tests were more likely to have abnormal findings at HRCT (p < 0.01). Conclusion This study has shown a positive correlation between volatile substance abuse and the development of restrictive ventilatory pattern, but more comprehensive studies are needed for more precise conclusions. PMID:22958270

  12. A Wearable Respiratory Biofeedback System Based on Generalized Body Sensor Network

    PubMed Central

    Liu, Guan-Zheng; Huang, Bang-Yu

    2011-01-01

    Abstract Wearable medical devices have enabled unobtrusive monitoring of vital signs and emerging biofeedback services in a pervasive manner. This article describes a wearable respiratory biofeedback system based on a generalized body sensor network (BSN) platform. The compact BSN platform was tailored for the strong requirements of overall system optimizations. A waist-worn biofeedback device was designed using the BSN. Extensive bench tests have shown that the generalized BSN worked as intended. In-situ experiments with 22 subjects indicated that the biofeedback device was discreet, easy to wear, and capable of offering wearable respiratory trainings. Pilot studies on wearable training patterns and resultant heart rate variability suggested that paced respirations at abdominal level and with identical inhaling/exhaling ratio were more appropriate for decreasing sympathetic arousal and increasing parasympathetic activities. PMID:21545293

  13. Mouse Vocal Communication System: Are Ultrasounds Learned or Innate?

    ERIC Educational Resources Information Center

    Arriaga, Gustavo; Jarvis, Erich D.

    2013-01-01

    Mouse ultrasonic vocalizations (USVs) are often used as behavioral readouts of internal states, to measure effects of social and pharmacological manipulations, and for behavioral phenotyping of mouse models for neuropsychiatric and neurodegenerative disorders. However, little is known about the neurobiological mechanisms of rodent USV production.…

  14. Oscillatory mechanics of the respiratory system in ozone-exposed rats

    SciTech Connect

    Kotlikoff, M.I.; Jackson, A.C.; Watson, J.W.

    1984-01-01

    The respiratory system impedance of tracheostomized cardiorespiratory disease-free Sprague-Dawley rats was measured from 20 to 90 Hz at constant flow amplitudes in 10 rats exposed to 0.64 ppm (UV) ozone for 7 days, and eight rats exposed to the same level of ozone for 20 days. This data was compared with respiratory system impedence spectra of 24 normal rats obtained in the same manner. When compared with control, the real part (effective resistance) was significantly different at several frequencies in the 7-day group (P < 0.05), and group means were higher at all frequencies. The 20-day group showed no significant differences in effective resistance. The imaginary part (effective reactance) was significantly lower at higher frequencies (f > 36) in both exposure groups (P < 0.05). When the impedance curves for each individual were fit to a lumped six-parameter model, and the parameters were compared, only the peripheral resistance parameter of the 7-day group was significantly different from control (P < 0.05). We conclude that ozone exposure at this level causes changes in respiratory system impedance, that these changes consist primarily of decreased reactances at higher frequencies, and that at 7 days these changes can be modeled by an increase in peripheral resistance.

  15. Upper respiratory tract (image)

    MedlinePlus

    The major passages and structures of the upper respiratory tract include the nose or nostrils, nasal cavity, mouth, throat (pharynx), and voice box (larynx). The respiratory system is lined with a mucous membrane that ...

  16. MOUSE (MODULAR ORIENTED UNCERTAINTY SYSTEM): A COMPUTERIZED UNCERTAINTY ANALYSIS SYSTEM. OPERATIONAL MANUAL.

    EPA Science Inventory

    MOUSE (Modular Oriented Uncertainty SystEm) deals with the problem of uncertainties in models that consist of one or more algebraic equations. It was especially designed for use by those with little or no knowledge of computer languages or programming. It is compact (and thus can...

  17. A method of calculating total respiratory system compliance from resonant frequency: validity in a rabbit model.

    PubMed

    Schulze, A; Schaller, P; Dinger, J; Winkler, U; Gmyrek, D

    1990-12-01

    Ten anesthetized, tracheotomized, adult rabbits were used to test the validity of a method for calculation of total respiratory system compliance from resonant frequency (Cr). Reference values were obtained during constant flow inflation of the relaxed respiratory system by dividing the volume gain by the related difference in pressure at the airway opening (inflation method compliance, Ci). The animals were connected to a new type of servo-controlled infant ventilator. Besides volume-controlled mechanical ventilation at constant inspiratory flow rate and intermittent mandatory ventilation, there is a negative ventilator resistance mode integrated in this device for resistive unloading (Schulze A, Schaller P, Gehrhardt B, Mädler H-J, Gmyrek D: Pediatr Res 28:79-82, 1990). To measure resonant frequency (fr), the respiratory system was totally unloaded for a short period by a negative ventilator resistance exceeding the combined resistances of the endotracheal tube and airways. This evoked a continuous oscillation at fr. By analogy with electrical circuit theory, Cr was calculated according to C = 1/(4 pi 2.I.fr2) where C is compliance and I is inertance. The inertance of the endotracheal tube is given and that of the bronchial tree was ignored assuming a much greater total cross-sectional area and therefore much lower inertance when compared with the endotracheal tube. Three pairs of Ci - Cr values were obtained from each animal: 1) during intact respiratory muscle activity; 2) after pancuronium relaxation, and 3) after surfactant depletion by saline washout.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2284157

  18. Kinetics of drug selection systems in mouse embryonic stem cells

    PubMed Central

    2013-01-01

    Background Stable expression of transgenes is an important technique to analyze gene function. Various drug resistance genes, such as neo, pac, hph, zeo, bsd, and hisD, have been equally used as selection markers to isolate a transfectant without considering their dose-dependent characters. Results We quantitatively measured the variation of transgene expression levels in mouse embryonic stem (mES) cells, using a series of bi-cistronic expression vectors that contain Egfp expression cassette linked to each drug resistant gene via IRES with titration of the selective drugs, and found that the transgene expression levels achieved in each system with this vector design are in order, in which pac and zeo show sharp selection of transfectants with homogenously high expression levels. We also showed the importance of the choice of the drug selection system in gene-trap or gene targeting according to this order. Conclusions The results of the present study clearly demonstrated that an appropriate choice of the drug resistance gene(s) is critical for a proper design of the experimental strategy. PMID:23919313

  19. MEchatronic REspiratory System SImulator for Neonatal Applications (MERESSINA) project: a novel bioengineering goal

    PubMed Central

    Scaramuzzo, Rosa T; Ciantelli, Massimiliano; Baldoli, Ilaria; Bellanti, Lisa; Gentile, Marzia; Cecchi, Francesca; Sigali, Emilio; Tognarelli, Selene; Ghirri, Paolo; Mazzoleni, Stefano; Menciassi, Arianna; Cuttano, Armando; Boldrini, Antonio; Laschi, Cecilia; Dario, Paolo

    2013-01-01

    Respiratory function is mandatory for extrauterine life, but is sometimes impaired in newborns due to prematurity, congenital malformations, or acquired pathologies. Mechanical ventilation is standard care, but long-term complications, such as bronchopulmonary dysplasia, are still largely reported. Therefore, continuous medical education is mandatory to correctly manage devices for assistance. Commercially available breathing function simulators are rarely suitable for the anatomical and physiological realities. The aim of this study is to develop a high-fidelity mechatronic simulator of neonatal airways and lungs for staff training and mechanical ventilator testing. The project is divided into three different phases: (1) a review study on respiratory physiology and pathophysiology and on already available single and multi-compartment models; (2) the prototyping phase; and (3) the on-field system validation. PMID:23966804

  20. Respiratory motion prediction by using the adaptive neuro fuzzy inference system (ANFIS)

    NASA Astrophysics Data System (ADS)

    Kakar, Manish; Nyström, Håkan; Rye Aarup, Lasse; Jakobi Nøttrup, Trine; Rune Olsen, Dag

    2005-10-01

    The quality of radiation therapy delivered for treating cancer patients is related to set-up errors and organ motion. Due to the margins needed to ensure adequate target coverage, many breast cancer patients have been shown to develop late side effects such as pneumonitis and cardiac damage. Breathing-adapted radiation therapy offers the potential for precise radiation dose delivery to a moving target and thereby reduces the side effects substantially. However, the basic requirement for breathing-adapted radiation therapy is to track and predict the target as precisely as possible. Recent studies have addressed the problem of organ motion prediction by using different methods including artificial neural network and model based approaches. In this study, we propose to use a hybrid intelligent system called ANFIS (the adaptive neuro fuzzy inference system) for predicting respiratory motion in breast cancer patients. In ANFIS, we combine both the learning capabilities of a neural network and reasoning capabilities of fuzzy logic in order to give enhanced prediction capabilities, as compared to using a single methodology alone. After training ANFIS and checking for prediction accuracy on 11 breast cancer patients, it was found that the RMSE (root-mean-square error) can be reduced to sub-millimetre accuracy over a period of 20 s provided the patient is assisted with coaching. The average RMSE for the un-coached patients was 35% of the respiratory amplitude and for the coached patients 6% of the respiratory amplitude.

  1. Respiratory System

    MedlinePlus

    ... exchange between the capillaries and alveoli. CO2 is carbon dioxide, and O2 is oxygen. Airways The airways are ... rich air to your lungs. They also carry carbon dioxide, a waste gas, out of your lungs. The ...

  2. Postnatal Development of the Mouse Enteric Nervous System.

    PubMed

    Foong, Jaime Pei Pei

    2016-01-01

    Owing to over three decades of research, we now have a good understanding of the genetic and molecular control of enteric nervous system (ENS) development during embryonic and prenatal stages. On the other hand, it has only just become clear that a substantial process of ENS maturation occurs after birth (Hao et al. 2013a). During postnatal stages, in addition to genetic influences, ENS development is also potentially affected by the external environment. Thus it is possible that manipulating certain environmental factors could help prevent or reduce motility disorders. However the genetic and environmental factors that regulate postnatal ENS development remain unknown. Researchers have used a variety of animal models that are easy to manipulate genetically or experimentally, and have short gestational periods, to understand the development of the ENS. Notably, due to the availability of mouse models for several human enteric neuropathies, many studies have used the mature and developing murine ENS as a model. Here, I will discuss recent advances in knowledge about postnatal development of the murine ENS, and highlight future directions for this emerging research field. PMID:27379641

  3. On the Respiratory Mechanics Measured by Forced Oscillation Technique in Patients with Systemic Sclerosis

    PubMed Central

    Miranda, Ingrid Almeida; Dias Faria, Alvaro Camilo; Lopes, Agnaldo José; Jansen, José Manoel; Lopes de Melo, Pedro

    2013-01-01

    Background Pulmonary complications are the most common cause of death and morbidity in systemic sclerosis (SSc). The forced oscillation technique (FOT) offers a simple and detailed approach to investigate the mechanical properties of the respiratory system. We hypothesized that SSc may introduce changes in the resistive and reactive properties of the respiratory system, and that FOT may help the diagnosis of these abnormalities. Methodology/Principal Findings We tested these hypotheses in controls (n = 30) and patients with abnormalities classified using spirometry (n = 52) and pulmonary volumes (n = 29). Resistive data were interpreted with the zero-intercept resistance (Ri) and the slope of the resistance (S) as a function of frequency. Reactance changes were evaluated by the mean reactance between 4 and 32 Hz (Xm) and the dynamic compliance (Crs,dyn). The mechanical load was evaluated using the absolute value of the impedance in 4 Hz (Z4Hz). A compartmental model was used to obtain central (R) and peripheral (Rp) resistances, and alveolar compliance (C). The clinical usefulness was evaluated by investigating the area under the receiver operating characteristic curve (AUC). The presence of expiratory flow limitation (EFL) was also evaluated. For the groups classified using spirometry, SSc resulted in increased values in Ri, R, Rp and Z4Hz (p<0.003) and reductions in Crs,dyn, C and Xm (p<0.004). Z4Hz, C and Crs,dyn exhibited a high diagnostic accuracy (AUC>0.90). In groups classified by pulmonary volume, SSc resulted in reductions in S, Xm, C and Crs,dyn (p<0.01). Xm, C and Crs,dyn exhibited adequate diagnostic accuracy (AUC>0.80). It was also observed that EFL is not common in patients with SSc. Conclusions/Significance This study provides evidence that the respiratory resistance and reactance are changed in SSc. This analysis provides a useful description that is of particular significance for understanding respiratory pathophysiology and to ease the

  4. Particle deposition due to turbulent diffusion in the upper respiratory system

    NASA Technical Reports Server (NTRS)

    Hamill, P.

    1979-01-01

    Aerosol deposition in the upper respiratory system (trachea to segmental bronchi) is considered and the importance of turbulent diffusion as a deposition mechanism is evaluated. It is demonstrated that for large particles (diameter greater than about 5 microns), turbulent diffusion is the dominant deposition mechanism in the trachea. Conditions under which turbulent diffusion may be important in successive generations of the pulmonary system are determined. The probability of particle deposition is compared with probabilities of deposition, as determined by the equations generally used in regional deposition models. The analysis is theoretical; no new experimental data is presented.

  5. Color structured light system of chest wall motion measurement for respiratory volume evaluation

    NASA Astrophysics Data System (ADS)

    Chen, Huijun; Cheng, Yuan; Liu, Dongdong; Zhang, Xiaodong; Zhang, Jue; Que, Chengli; Wang, Guangfa; Fang, Jing

    2010-03-01

    We present a structured light system to dynamically measure human chest wall motion for respiratory volume estimation. Based on a projection of an encoded color pattern and a few active markers attached to the trunk, respiratory volumes are obtained by evaluating the 3-D topographic changes of the chest wall in an anatomically consistent measuring region during respiration. Three measuring setups are established: a single-sided illuminating-recording setup for standing posture, an inclined single-sided setup for supine posture, and a double-sided setup for standing posture. Results are compared with the pneumotachography and show good agreement in volume estimations [correlation coefficient: R>0.99 (P<0.001) for all setups]. The isovolume tests present small variations of the obtained volume during the isovolume maneuver (standard deviation<0.085 L for all setups). After validation by the isovolume test, an investigation of a patient with pleural effusion using the proposed method shows pulmonary functional differences between the diseased and the contralateral sides of the thorax, and subsequent improvement of this imbalance after drainage. These results demonstrate the proposed optical method is capable of not only whole respiratory volume evaluation with high accuracy, but also regional pulmonary function assessment in different chest wall behaviors, with the advantage of whole-field measurement.

  6. Intermittent hypoxia promotes recovery of respiratory motor function in spinal cord-injured mice depleted of serotonin in the central nervous system.

    PubMed

    Komnenov, Dragana; Solarewicz, Julia Z; Afzal, Fareeza; Nantwi, Kwaku D; Kuhn, Donald M; Mateika, Jason H

    2016-08-01

    We examined the effect of repeated daily exposure to intermittent hypoxia (IH) on the recovery of respiratory and limb motor function in mice genetically depleted of central nervous system serotonin. Electroencephalography, diaphragm activity, ventilation, core body temperature, and limb mobility were measured in spontaneously breathing wild-type (Tph2(+/+)) and tryptophan hydroxylase 2 knockout (Tph2(-/-)) mice. Following a C2 hemisection, the mice were exposed daily to IH (i.e., twelve 4-min episodes of 10% oxygen interspersed with 4-min normoxic periods followed by a 90-min end-recovery period) or normoxia (i.e., sham protocol, 21% oxygen) for 10 consecutive days. Diaphragm activity recovered to prehemisection levels in the Tph2(+/+) and Tph2(-/-) mice following exposure to IH but not normoxia [Tph2(+/+) 1.3 ± 0.2 (SE) vs. 0.3 ± 0.2; Tph2(-/-) 1.06 ± 0.1 vs. 0.3 ± 0.1, standardized to prehemisection values, P < 0.01]. Likewise, recovery of tidal volume and breathing frequency was evident, although breathing frequency values did not return to prehemisection levels within the time frame of the protocol. Partial recovery of limb motor function was also evident 2 wk after spinal cord hemisection. However, recovery was not dependent on IH or the presence of serotonin in the central nervous system. We conclude that IH promotes recovery of respiratory function but not basic motor tasks. Moreover, we conclude that spontaneous or treatment-induced recovery of respiratory and motor limb function is not dependent on serotonin in the central nervous system in a mouse model of spinal cord injury. PMID:27402561

  7. [Respiratory system of Pichia guilliermondii yeasts with different levels of flavinogenesis].

    PubMed

    Zviagil'skaia, R A; Fedorovich, D V; Shavlovskiĭ, G M

    1978-01-01

    The yeast Pichia guilliermondii was grown on media with different content of iron and its respiration system was studied. When the yeast was cultivated on a complete medium, its respiratory chain operated at the maximum rate in the exponential growth phase, i. e. all the three points of phosphorylation were involved; cytochrome oxidase was the only terminal oxidase. When the growth was decelerated and at the stationary phase, the alternative autooxidable cyanide-resistant pathway inhibited with salicyl hydroxamate partly functioned. Iron deficiency in the medium resulted in a two-three-fold decrease in the content of total and non-hemin iron in the cells, changes in the character and rate of growth, a decrease in the biomass yield, a high rate of flavinogenesis, a slight decrease in the respiration activity, though no drastic changes in the respiration system occurred. This system is represented, as in the case of cells grown on a complete medium, by a typical cytochrome system and an alternative autooxidable pathway. The absence of principal differences in the respiration systems of normal and iron-deficient cells, as well as the operation of the first point of coupling in flavinogenic cells, makes it doubtful that Fenh-proteins of the first segment of the respiratory chain are involved in the regulation of flavinogenesis. PMID:745565

  8. Telemedicine system for the care of patients with neuromuscular disease and chronic respiratory failure

    PubMed Central

    Morete, Emilio; González, Francisco

    2014-01-01

    Introduction Neuromuscular diseases cause a number of limitations which may be improved by using a telemedicine system. These include functional impairment and dependence associated with muscle weakness, the insidious development of respiratory failure and episodes of exacerbation. Material and methods The present study involved three patients with severe neuromuscular disease, chronic respiratory failure and long-term mechanical ventilation, who were followed up using a telemedicine platform. The telemedicine system is based on videoconferencing and telemonitoring of cardiorespiratory variables (oxygen saturation, heart rate, blood pressure and electrocardiogram). Two different protocols were followed depending on whether the patient condition was stable or unstable. Results Over a period of 5 years, we analyzed a series of variables including use of the system, patient satisfaction and clinical impact. Overall we performed 290 videoconference sessions, 269 short monitoring oximetry measurements and 110 blood pressure measurements. With respect to the clinical impact, after enrolment in the telemedicine program, the total number of hospital admissions fell from 18 to 3. Conclusions Our findings indicate that the system was user friendly for patients and care givers. Patient satisfaction scores were acceptable. The telemedicine system was effective for the home treatment of three patients with severe neuromuscular diseases and reduced the need for hospital admissions. PMID:25395959

  9. MIMO Radar System for Respiratory Monitoring Using Tx and Rx Modulation with M-Sequence Codes

    NASA Astrophysics Data System (ADS)

    Miwa, Takashi; Ogiwara, Shun; Yamakoshi, Yoshiki

    The importance of respiratory monitoring systems during sleep have increased due to early diagnosis of sleep apnea syndrome (SAS) in the home. This paper presents a simple respiratory monitoring system suitable for home use having 3D ranging of targets. The range resolution and azimuth resolution are obtained by a stepped frequency transmitting signal and MIMO arrays with preferred pair M-sequence codes doubly modulating in transmission and reception, respectively. Due to the use of these codes, Gold sequence codes corresponding to all the antenna combinations are equivalently modulated in receiver. The signal to interchannel interference ratio of the reconstructed image is evaluated by numerical simulations. The results of experiments on a developed prototype 3D-MIMO radar system show that this system can extract only the motion of respiration of a human subject 2m apart from a metallic rotatable reflector. Moreover, it is found that this system can successfully measure the respiration information of sleeping human subjects for 96.6 percent of the whole measurement time except for instances of large posture change.

  10. Optimization of the mammalian respiratory system: symmorphosis versus single species adaptation.

    PubMed

    Jones, J H

    1998-05-01

    Taylor and Weibel's principle of symmorphosis hypothesized optimal design of the mammalian respiratory system, with no excess structure relative to its maximal O2 flux, VO2max. Although they found symmorphosis not to be a general principle of design, it might apply to a highly adapted aerobic athlete, e.g. the Thoroughbred racehorse. Using a mathematical model based on empirical data of the equine O2 transport system at normoxic VO2max, the fraction of the total limitation to O2 flux contributed by each of the respiratory transport steps is calculated as either the fractional change (F) in VO2max for a 1% change in each component, or as the fraction of total O2 pressure drop (R(int)) across each component at VO2max. When calculated as F, alveolar ventilation (VA) and pulmonary diffusing capacity (DLO2) are major limiting factors, circulatory convection (Q) is nearly as limiting, and peripheral tissue diffusing capacity (DTO2) is only one-third as important. When calculated as R(int), DLO2 is the major factor, VA and DTO2 contribute significantly, and Q is smallest. These patterns contrast with analogous studies in humans, in which Q is the single major limiting factor. The results suggest that strong selection for aerobic power in horses has maximized the malleable components of their respiratory systems until the least malleable structure, the lungs, has become a major limitation to O2 flux. Symmorphosis cannot determine if such a design is or is not optimized, as every system falls on a continuous distribution of relative optimization among species. However, the concept of symmorphosis is useful for establishing a framework within which a single species can be compared with a quantitatively defined hypothesis of optimal animal design, and compared with other species according to those criteria. PMID:9787782

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

    NASA Technical Reports Server (NTRS)

    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.

  12. In vivo-CT system with respiratory and cardiac gating using synchrotron radiation

    NASA Astrophysics Data System (ADS)

    Sera, Toshihiro; Yokota, Hideo; Fujisaki, Kazuhiro; Fukasaku, Kazuaki; Uesugi, Kentaro; Yagi, Naoto; Himeno, Ryutaro

    2007-03-01

    The interest in using small animal models of human disease has produced a need to design a CT system at a microscopic level comparable to that achievable in a clinical CT in human. In this study, we developed a high-resolution in vivo-CT system with respiratory and cardiac gating using synchrotron radiation. The system was constructed in BL20B2 at SPring-8. SPring-8 is the third generation synchrotron radiation source in Hyogo, Japan, and prefers much higher flux X-ray than a laboratory X-ray source. Another advantage of synchrotron monochromatic CT is the minimalization of beam hardening effects, which pose serious problems when using white X-rays. Since the X-ray beam from the synchrotron source is parallel, each horizontal line corresponds to a slice position along the rotation axis. Multiple slices are easily obtained in one rotation (3D-CT). For in vivo scanning, the X-ray mechanical shutter and CCD electrical shutter were synchronized with an airway pressure (respiratory) and electrocardiographic (ECG) signal. Synchronization reduced the motion artifacts caused by respiration and heart beats, markedly improving visualization of the edges of the heart, ribs and diaphragm. In particular, small airways (diameter > 300 μm) and cerebral blood vessels were visualized clearly. This system is very useful for evaluating lung physiology and cardiovascular mechanics in vivo.

  13. [Basic types of respiratory system structure in insect egg envelopes, and genes controlling their formation].

    PubMed

    Omelina, E S; Baricheva, É M; Fedorova, E V

    2012-01-01

    Insects is a taxon surprisingly rich with species and varieties, and its representatives are considered as the most fitted and "evolutionary successful" living things. Insects are distinguished by diversity and abundance of adaptations to environmental conditions, representatives of this class inhabit different ecological niches, they can be found practically in every corner of the Earth and, in particular, in close adjacency to man. Among them are those who man benefits from and those who man struggles against. This determines man's interest in studying peculiarities of their development as well as adaptations formed by them in the course of evolution to become more viable. In the paper, data are presented on morphological structure of respiratory systems in insect egg envelopes that ensure respiration process of developing embryo. Variability of these systems and their dependence on environmental conditions are demonstrated for different insect species. The information about genes controlling development of respiratory systems in fruit fly eggs is brought together, and occurrence of evolutionary conservative genes participating in development of such systems in other insect species is ascertained. PMID:22834166

  14. [Use of spirometry in the evaluation of the cardiovascular and respiratory system in mitral valve prosthesis].

    PubMed

    Bykorez, V A; Rasputiak, O V

    1993-01-01

    Before the operation, in 103 patients with the defects of the right and left atrioventricular valves, echocardiography and spiro-ergometry were performed. Their performance permitted to reveal latent myocardial incompetence in these patients. Changes in the indices of external respiration and gas exchange at a level of the threshold standard load can serve as objective criteria for assessment of reserve resources of the cardiovascular and respiratory systems and prognosis of the development of acute cardiac failure at the shortest period after the mitral valve replacement. PMID:8139185

  15. Acute respiratory distress syndrome due to systemic lupus erythematosus with hemophagocytic syndrome: an autopsy report.

    PubMed

    Kaneko, Kazuma; Matsuda, Masayuki; Sekijima, Yoshiki; Hosoda, Waki; Gono, Takahisa; Hoshi, Kenichi; Shimojo, Hisashi; Ikeda, Shu-ichi

    2005-04-01

    This report concerns a patient with systemic lupus erythematosus (SLE) who died of acute respiratory distress syndrome (ARDS) 1 day after the onset of pulmonary symptoms. Autopsy demonstrated severe hemophagocytosis in the bone marrow and histopathology indicating a marked increase in vascular permeability in both lungs and kidneys. In this patient, active SLE and associated hemophagocytic syndrome may have induced an increase in the production of inflammatory cytokines, which immediately induced ARDS. Since fatal ARDS can occur as a life-threatening complication of SLE, careful observation is necessary, particularly when there are clinical findings suggestive of associated hemophagocytic syndrome. PMID:15338452

  16. Fluorescence molecular imaging system with a novel mouse surface extraction method and a rotary scanning scheme

    NASA Astrophysics Data System (ADS)

    Zhao, Yue; Zhu, Dianwen; Baikejiang, Reheman; Li, Changqing

    2015-03-01

    We have developed a new fluorescence molecular tomography (FMT) imaging system, in which we utilized a phase shifting method to extract the mouse surface geometry optically and a rotary laser scanning approach to excite fluorescence molecules and acquire fluorescent measurements on the whole mouse body. Nine fringe patterns with a phase shifting of 2π/9 are projected onto the mouse surface by a projector. The fringe patterns are captured using a webcam to calculate a phase map that is converted to the geometry of the mouse surface with our algorithms. We used a DigiWarp approach to warp a finite element mesh of a standard digital mouse to the measured mouse surface thus the tedious and time-consuming procedure from a point cloud to mesh is avoided. Experimental results indicated that the proposed method is accurate with errors less than 0.5 mm. In the FMT imaging system, the mouse is placed inside a conical mirror and scanned with a line pattern laser that is mounted on a rotation stage. After being reflected by the conical mirror, the emitted fluorescence photons travel through central hole of the rotation stage and the band pass filters in a motorized filter wheel, and are collected by a CCD camera. Phantom experimental results of the proposed new FMT imaging system can reconstruct the target accurately.

  17. The Apoe(-/-) mouse model: a suitable model to study cardiovascular and respiratory diseases in the context of cigarette smoke exposure and harm reduction.

    PubMed

    Lo Sasso, Giuseppe; Schlage, Walter K; Boué, Stéphanie; Veljkovic, Emilija; Peitsch, Manuel C; Hoeng, Julia

    2016-01-01

    Atherosclerosis-prone apolipoprotein E-deficient (Apoe(-/-)) mice display poor lipoprotein clearance with subsequent accumulation of cholesterol ester-enriched particles in the blood, which promote the development of atherosclerotic plaques. Therefore, the Apoe(-/-) mouse model is well established for the study of human atherosclerosis. The systemic proinflammatory status of Apoe(-/-) mice also makes them good candidates for studying chronic obstructive pulmonary disease, characterized by pulmonary inflammation, airway obstruction, and emphysema, and which shares several risk factors with cardiovascular diseases, including smoking. Herein, we review the results from published studies using Apoe(-/-) mice, with a particular focus on work conducted in the context of cigarette smoke inhalation studies. The findings from these studies highlight the suitability of this animal model for researching the effects of cigarette smoking on atherosclerosis and emphysema. PMID:27207171

  18. The Role and Immunobiology of Eosinophils in the Respiratory System: a Comprehensive Review.

    PubMed

    Eng, Stephanie S; DeFelice, Magee L

    2016-04-01

    The eosinophil is a fully delineated granulocyte that disseminates throughout the bloodstream to end-organs after complete maturation in the bone marrow. While the presence of eosinophils is not uncommon even in healthy individuals, these granulocytes play a central role in inflammation and allergic processes. Normally appearing in smaller numbers, higher levels of eosinophils in the peripheral blood or certain tissues typically signal a pathologic process. Eosinophils confer a beneficial effect on the host by enhancing immunity against molds and viruses. However, tissue-specific elevation of eosinophils, particularly in the respiratory system, can cause a variety of short-term symptoms and may lead to long-term sequelae. Eosinophils often play a role in more commonly encountered disease processes, such as asthma and allergic responses in the upper respiratory tract. They are also integral in the pathology of less common diseases including eosinophilic pneumonia, allergic bronchopulmonary aspergillosis, hypersensitivity pneumonitis, and drug reaction with eosinophilia and systemic symptoms. They can be seen in neoplastic disorders or occupational exposures as well. The involvement of eosinophils in pulmonary disease processes can affect the method of diagnosis and the selection of treatment modalities. By analyzing the complex interaction between the eosinophil and its environment, which includes signaling molecules and tissues, different therapies have been discovered and created in order to target disease processes at a cellular level. Innovative treatments such as mepolizumab and benralizumab will be discussed. The purpose of this article is to further explore the topic of eosinophilic presence, activity, and pathology in the respiratory tract, as well as discuss current and future treatment options through a detailed literature review. PMID:26797962

  19. SU-E-J-190: Development of Abdominal Compression & Respiratory Guiding System Using Gas Pressure Sensor

    SciTech Connect

    Kim, T; Kim, D; Kang, S; Cho, M; Kim, K; Shin, D; Suh, T; Kim, S

    2015-06-15

    Purpose: Abdominal compression is known to be effective but, often makes external-marker-based monitoring of breathing motion not feasible. In this study, we developed and evaluated a system that enables both abdominal compression and monitoring of residual abdominal motion simultaneously. The system can also provide visual-biofeedback capability. Methods: The system developed consists of a compression belt, an abdominal motion monitoring sensor (gas pressure sensor) and a visual biofeedback device. The compression belt was designed to be able to compress the frontal side of the abdomen. The pressure level of the belt is controlled by air volume and monitored in real time using the gas pressure sensor. The system displays not only the real-time monitoring curve but also a guiding respiration model (e.g., a breath hold or shallow breathing curve) simultaneously on the head mounted display to help patients keep their breathing pattern as consistent as possible. Three healthy volunteers were enrolled in this pilot study and respiratory signals (pressure variations) were obtained both with and without effective abdominal compression to investigate the feasibility of the developed system. Two guidance patterns, breath hold and shallow breathing, were tested. Results: All volunteers showed smaller abdominal motion with compression (about 40% amplitude reduction compared to without compression). However, the system was able to monitor residual abdominal motion for all volunteers. Even under abdominal compression, in addition, it was possible to make the subjects successfully follow the guide patterns using the visual biofeedback system. Conclusion: The developed abdominal compression & respiratory guiding system was feasible for residual abdominal motion management. It is considered that the system can be used for a respiratory motion involved radiation therapy while maintaining the merit of abdominal compression. This work was supported by the Radiation Technology R

  20. All systems GO for understanding mouse gene function

    PubMed Central

    Holmes, Chris; Brown, Steve DM

    2004-01-01

    It is widely supposed that the tissue specificity of gene expression indicates gene function. Now, an extensive analysis of gene expression in the mouse reveals that quantitative measurement of expression levels in different tissues can contribute powerfully to the prediction of gene function. PMID:15610553

  1. Respiratory alkalosis

    MedlinePlus

    Alkalosis - respiratory ... leads to shortness of breath can also cause respiratory alkalosis (such as pulmonary embolism and asthma). ... Treatment is aimed at the condition that causes respiratory alkalosis. Breathing into a paper bag -- or using ...

  2. Deposition of naphthalene and tetradecane vapors in models of the human respiratory system.

    PubMed

    Zhang, Zhe; Kleinstreuer, Clement

    2011-01-01

    Jet-propulsion fuel (particularly JP-8) is currently being used worldwide, exposing especially Air Force personnel and people living near airfields to JP-8 vapors and aerosols during aircraft fueling, maintenance operations, and/or cold starts. JP-8 is a complex mixture containing >200, mostly toxic, aliphatic and aromatic hydrocarbon compounds of which tetradecane and naphthalene were chosen as two representative chemical markers for computer simulations. Thus, transport and deposition of naphthalene and tetradecane vapors have been simulated in models of the human respiratory system. The inspiratory deposition data were analyzed in terms of regional deposition fractions (DFs) and deposition enhancement factors (DEF). The vapor depositions are affected by vapor properties (e.g. diffusivity), airway geometric features, breathing patterns, inspiratory flow rates, as well as airway-wall absorption parameter. Specifically, the respiratory uptake of vapors is greatly influenced by the degree of airway-wall absorption. For example, being an almost insoluble species in the mucus layer, the deposition of tetradecane vapor is nearly zero in the extrathoracic and tracheobronchial (TB) airways, that is, the DF is <1%. The remaining vapors may penetrate further and deposit in the alveolar airways. The DF of tetradecane vapors during inhalation in the alveolar region can range from 7% to 24%, depending on breathing waveform, inhalation rate, and thickness of the mucus layer. In contrast, naphthalene vapor almost completely deposits in the extrathoracic and TB airways and hardly moves downstream and deposits in the respiratory zone. The DFs of naphthalene vapor in the extrathoracic airways from nasal/oral to trachea under normal breathing conditions (Q = 15-60 L/min) are about 12-34%, although they are about 66-87% in the TB airways. In addition, the variation of breathing routes (say, from nasal breathing to oral breathing) may influence the vapor deposition in the

  3. Pseudorandom signals to estimate apparent transfer and coherence functions of nonlinear systems: applications to respiratory mechanics.

    PubMed

    Suki, B; Lutchen, K R

    1992-11-01

    There is an increasing need in physiology to estimate nonparametric linear transfer functions from data originating from biological systems which are invariably nonlinear. For pseudorandom (PRN) input stimuli, we derive general expressions for the apparent transfer (Z) and coherence (gamma 2) functions of nonlinear systems that can be represented by a Volterra series. It is shown that in the case of PRN signals in which the frequency components are integer multiples of other components the estimates of Z are seriously biased due to harmonic distortion and crosstalk among frequency components of the input. When the PRN signal includes components that are not integer multiples of other components harmonic distortion is avoided, but not necessarily cross talk. Here the estimates of Z remain poor without a noticeable influence on gamma 2. To avoid the problems associated with harmonic distortions and minimize the influence of crosstalk, a family of pseudorandom signals is proposed which are especially suited for the estimation of Z and gamma 2 in mechanical measurements of physiological systems at low frequencies. The components in the signals cannot be reproduced as linear combinations of two or more frequency components of the input. In a second-order system, this completely eliminates the bias, while in higher-order, but not strongly nonlinear systems, the interactions among the components are reduced to a level that the response can be considered as if it was measured with independent sine waves of an equivalent amplitude. It is also shown that the values of gamma 2 are not appropriate to assess linearity of the system. The theory is supported by simulation results and experimental examples brought from the field of respiratory mechanics by comparing the input impedance of the respiratory system of a dog measured with various PRN signals. PMID:1487277

  4. Immunohistochemical techniques and their applications in the histopathology of the respiratory system.

    PubMed Central

    Linnoila, I; Petrusz, P

    1984-01-01

    Subsequent to the first report in the 1940s on incubation of tissue sections with fluorescein-conjugated antibodies for localization of antigens, a great number of modifications were introduced to improve the validity of immunohistochemistry which has become a growingly popular tool. The use of immunoenzymatic techniques eliminates the need for expensive fluorescence microscopy equipment, the lack of permanency of preparations and the lack of electron density required in ultrastructural localization of antigens. Regardless of the technique, it is also important to choose a correct fixation which allows the proper preservation of antigens and morphology and the penetration of antibodies through the entire thickness of the preparation. A variety of immunohistochemical techniques have been applied to study several components of the lung, such as collagen, surface active material, lung specific antigens, and enzymes and the detection of tumor markers, immunoglobulins and infectious agents in the respiratory system which is reviewed. The large surface area and the multiplicity of cell types provided by the respiratory tract epithelium of humans for exposure to microbial as well as toxic substances in the environment make this organ system very vulnerable but a good early indicator of adverse health effects. Immunohistochemistry provides valuable information complementary to the immunochemical and biochemical characterization of this barrier. Images FIGURE 2. FIGURE 3. FIGURE 3. FIGURE 4. FIGURE 4. FIGURE 5. PMID:6090113

  5. [Influences of chest deformation by upper abdominal retractor on respiratory system impedance during abdominal surgery].

    PubMed

    Oka, T; Ozawa, Y; Sato, J

    1999-02-01

    The present study was carried out to clarify the effects of chest deformation by upper abdominal retractor on respiratory system impedance during abdominal surgery. We measured the impedances of respiratory system (RS), lung, and chest wall (CW) in nine anesthetized paralyzed subjects employing a pseudorandom noise forced volume oscillation technique. These measurements were performed before and after the lifting chest wall by upper abdominal retractor. The effects of chest deformation was significant on the impedances of RS, lung, while no discernible effect was found in CW impedance. Lifting chest wall decreased RS resistance which was totally accounted for by the decrease in lung resistance, whereas the lifting did not affect reactance in either RS or lung. The mathematical modeling showed the significant lifting effect on the resistance of the parenchyma. In conclusion, change in RS mechanics produced by chest deformation by upper abdominal retractor is dominated in lung but not in CW. Among the lung mechanical components, parenchyma is the primary site of the lifting effect. PMID:10087819

  6. Efficient reactivation of latent herpes simplex virus from mouse central nervous system tissues.

    PubMed

    Chen, Shih-Heng; Yao, Hui-Wen; Huang, Wen-Yen; Hsu, Kuei-Sen; Lei, Huan-Yao; Shiau, Ai-Li; Chen, Shun-Hua

    2006-12-01

    For decades, numerous ex vivo studies have documented that latent herpes simplex virus (HSV) reactivates efficiently from ganglia, but rarely from the central nervous systems (CNS), of mice when assayed by mincing tissues before explant culture, despite the presence of viral genomes in both sites. Here we show that 88% of mouse brain stems reactivated latent virus when they were dissociated into cell suspensions before ex vivo explant culture. The efficient reactivation of HSV from the mouse CNS was demonstrated with more than one viral strain, viral serotype, and mouse strain, further indicating that the CNS can be an authentic latency site for HSV with the potential to cause recurrent disease. PMID:17005636

  7. Development of a microspectrophotometer system for monitoring the redox reactions of respiratory pigments

    NASA Astrophysics Data System (ADS)

    Kavanagh, Karen Y.; Walsh, James E.; Murphy, J.; Harmey, M.; Farrell, M. A.; Hardimann, O.; Perryman, R.

    1997-05-01

    The continuing demand for non-invasive tools for use in clinical diagnosis has created the need for flexible and innovative optical systems which satisfy current requirements. We report the development of a microspectrophotometer system for use on mitochondrial respiratory pigments. This novel optical fiber set-up uses visible spectrophotometry to monitor the reduction of mitochondrial electron carriers. Preliminary data is presented for the reduction of cytochrome-c by two methods. In the first, cytochrome-c was reduced in isolation using sodium dithionite. The second was an in-vivo simulation of the reduction of cytochrome-c using the mitochondrial extract from rat liver. The key features of the system are; front end adaptability, high sensitivity and fast scanning capabilities which are essential for the rapid biological reactions which are observed.

  8. [Association of fatty acid metabolism with systemic inflammatory response in chronic respiratory diseases].

    PubMed

    Denisenko, Y K; Novgorodtseva, T P; Zhukova, N V; Antonuk, M V; Lobanova, E G; Kalinina, E P

    2016-03-01

    We examined composition of plasma non-esterified fatty acids (NFAs), erythrocyte fatty acids, levels of eicosanoids in patients with asthma and chronic obstructive pulmonary disease (COPD) with different type of the inflammatory response. The results of our study show that asthma and COPD in remission are associated with changes in the composition NFAs of plasma, FA of erythrocytes, level eicosanoid despite the difference in the regulation of immunological mechanisms of systemic inflammation. These changes are characterized by excessive production of arachidonic acid (20:4n-6) and cyclooxygenase and lipoxygenase metabolites (thromboxane B2, leukotriene B4) and deficiency of their functional antagonist, eicosapentaenoic acid (20:5n-3). The recognized association between altered fatty acid composition and disorders of the immune mechanisms of regulation of systemic inflammation in COPD and asthma demonstrated the important role of fatty acids and their metabolites in persistence of inflammatory processes in diseases of the respiratory system in the condition of remission. PMID:27420629

  9. Oxidative Stress and Respiratory System: Pharmacological and Clinical Reappraisal of N-Acetylcysteine

    PubMed Central

    Santus, Pierachille; Corsico, Angelo; Solidoro, Paolo; Braido, Fulvio; Di Marco, Fabiano

    2014-01-01

    The large surface area for gas exchange makes the respiratory system particularly susceptible to oxidative stress-mediated injury. Both endogenous and exogenous pro-oxidants (e.g. cigarette smoke) trigger activation of leukocytes and host defenses. These mechanisms interact in a “multilevel cycle” responsible for the control of the oxidant/antioxidant homeostasis. Several studies have demonstrated the presence of increased oxidative stress and decreased antioxidants (e.g. reduced glutathione [GSH]) in subjects with chronic obstructive pulmonary disease (COPD), but the contribution of oxidative stress to the pathophysiology of COPD is generally only minimally discussed. The aim of this review was to provide a comprehensive overview of the role of oxidative stress in the pathogenesis of respiratory diseases, particularly COPD, and to examine the available clinical and experimental evidence on the use of the antioxidant N-acetylcysteine (NAC), a precursor of GSH, as an adjunct to standard therapy for the treatment of COPD. The proposed concept of “multilevel cycle” helps understand the relationship between respiratory diseases and oxidative stress, thus clarifying the rationale for using NAC in COPD. Until recently, antioxidant drugs such as NAC have been regarded only as mucolytic agents. Nevertheless, several clinical trials indicate that NAC may reduce the rate of COPD exacerbations and improve small airways function. The most plausible explanation for the beneficial effects observed in patients with COPD treated with NAC lies in the mucolytic and antioxidant effects of this drug. Modulation of bronchial inflammation by NAC may further account for these favorable clinical results. PMID:24787454

  10. Respiratory Impairment and Systemic Inflammation in Cedar Asthmatics Removed from Exposure

    PubMed Central

    Carlsten, Chris; Dybuncio, Anne; Pui, Mandy M.; Chan-Yeung, Moira

    2013-01-01

    Background Prior research has shown that removing occupational asthmatics from exposure does not routinely lead to significant improvements in respiratory impairment. These studies were of limited duration and factors determining recovery remain obscure. Our objective was to evaluate residual respiratory impairment and associated sputum and blood biomarkers in subjects with Western red cedar asthma after exposure cessation. Methods Subjects previously diagnosed with cedar asthma, and removed from exposure to cedar dust for at least one year, were recruited. Subjects completed a questionnaire and spirometry. PC20 (methacholine concentration that produces 20% fall in FEV1 (forced expiratory volume at 1 second)) sputum cellularity and select Th1/Th2 (T helper cells 1 and 2) cytokine concentrations in peripheral blood were determined. The asthma impairment class was determined and multivariate analyses were performed to determine its relationship with sputum cell counts and serum cytokines. Results 40 non-smoking males (mean age 62) were examined at a mean interval of 25 years from cedar asthma diagnosis and 17 years from last cedar exposure. 40% were in impairment class 2/3. On average, the PC20 had increased by 2.0 mg/ml; the FEV1 decreased by 1.5 L, with greater decrease in those with greater impairment. Higher impairment was associated with serum interferon-gamma (mean = 1.3 pg/ml in class 2/3 versus 0.62 pg/ml in class 0/1, p = 0.04), mainly due to the FEV1 component (correlation with interferon-gamma = −0.46, p = 0.005). Conclusion Years after exposure cessation, patients with Western red cedar asthma have persistent airflow obstruction and respiratory impairment, associated with systemic inflammation. PMID:23468925

  11. Technical and dosimetric aspects of respiratory gating using a pressure-sensor motion monitoring system

    SciTech Connect

    Li, X. Allen; Stepaniak, Christopher; Gore, Elizabeth

    2006-01-15

    This work introduces a gating technique that uses 4DCT to determine gating parameters and to plan gated treatment, and employs a Siemens linear accelerator to deliver the gated treatment. Because of technology incompatibility, the 4DCT scanner (LightSpeed, GE) and the Siemens accelerator require two different motion-monitoring systems. The motion monitoring system (AZ-773V, Anzai Med.) used for the gated delivery utilizes a pressure sensor to detect the external respiratory motion (pressure change) in real time. Another system (RPM, Varian) used for the 4DCT scanner (LightSpeed, GE) is based on an infrared camera to detect motion of external markers. These two motion monitoring systems (RPM and Anzai systems) were found to correlate well with each other. The depth doses and profile measured for gated delivery (with a duty cycle of 25% or 50%) were found to agree within 1.0% with those measured for ungated delivery, indicating that gating did not significantly alter beam characteristics. The measurement verified also that the MU linearity and beam output remained unchanged (within 0.3%). A practical method of using 4DCT to plan a gated treatment was developed. The duty cycle for either phase or amplitude gating can be determined based on 4DCT with consideration of set-up error and delivery efficiency. The close-loop measurement involving the entire gating process (imaging, planning, and delivery) showed that the measured isodose distributions agreed with those intended, validating the accuracy and reliability of the gating technique. Based these observations, we conclude that the gating technique introduced in this work, integrating Siemens linear accelerator and Anzai pressure sensor device with GE/Varian RPM 4DCT, is reliable and effective, and it can be used clinically to account for respiratory motion during radiation therapy.

  12. The effects of centrally injected arachidonic acid on respiratory system: Involvement of cyclooxygenase to thromboxane signaling pathway.

    PubMed

    Erkan, Leman Gizem; Guvenc, Gokcen; Altinbas, Burcin; Niaz, Nasir; Yalcin, Murat

    2016-05-01

    Arachidonic acid (AA) is a polyunsaturated fatty acid that is present in the phospholipids of the cell membranes of the body and is abundant in the brain. Exogenously administered AA has been shown to affect brain metabolism and to exhibit cardiovascular and neuroendocrine actions. However, little is known regarding its respiratory actions and/or central mechanism of its respiratory effects. Therefore, the present study was designed to investigate the possible effects of centrally injected AA on respiratory system and the mediation of the central cyclooxygenase (COX) to thromboxane A2 (TXA2) signaling pathway on AA-induced respiratory effects in anaesthetized rats. Intracerebroventricular (i.c.v.) administration of AA induced dose- and time-dependent increase in tidal volume, respiratory rates and respiratory minute ventilation and also caused an increase in partial oxygen pressure (pO2) and decrease in partial carbon dioxide pressure (pCO2) in male anaesthetized Spraque Dawley rats. I.c.v. pretreatment with ibuprofen, a non-selective COX inhibitor, completely blocked the hyperventilation and blood gases changes induced by AA. In addition, central pretreatment with different doses of furegrelate, a TXA2 synthesis inhibitor, also partially prevented AA-evoked hyperventilation and blood gases effects. These data explicitly show that centrally administered AA induces hyperventilation with increasing pO2 and decreasing pCO2 levels which are mediated by the activation of central COX to TXA2 signaling pathway. PMID:26767978

  13. CONSTANT-PHASE DESCRIPTIONS OF CANINE LUNG, CHEST WALL, AND TOTAL RESPIRATORY SYSTEM VISCOELASTICITY: EFFECTS OF DISTENDING PRESSURE

    PubMed Central

    Kaczka, David W.; Smallwood, Jennifer L.

    2012-01-01

    The dynamic mechanical properties of the respiratory system reflect the ensemble behavior of its constituent structural elements. This study assessed the appropriateness of constant-phase descriptions of respiratory tissue viscoelasticity at various distending pressures. We measured the mechanical input impedance (Z) of the lungs, chest wall and total respiratory system in twelve dogs at mean airway pressures from 5 to 30 cmH2O. Each Z was fitted with a constant-phase model which provided estimates tissue damping (G), elastance (H), and hysteresivity (η = G/H). Both G and H sharply increased with increasing distending pressure for the lungs and chest wall, while η attained a minimum near 15-20 cm H2O. Model fitting errors for the lungs and total respiratory system increased for distending pressures greater than 20 cm H2O, indicating that constant-phase descriptions of parenchymal and respiratory system viscoelasticty may be inappropriate at volumes closer to total lung capacity. Such behavior may reflect alterations in load distribution across various parenchymal stress-bearing elements. PMID:22691447

  14. Effect of a botanical composition, UP446, on respiratory, cardiovascular and central nervous systems in beagle dogs and rats.

    PubMed

    Yimam, Mesfin; Lee, Young Chul; Jia, Qi

    2016-06-01

    Extensive safety evaluation of UP446, a botanical composition comprised of standardized extracts from roots of Scutellaria baicalensis and heartwoods of Acacia catechu, has been reported previously. Here we carried out additional studies to assess the effect of UP446 on respiratory, cardiovascular and central nervous (CNS) systems. A Functional observational battery (FOB) and whole body plethysmography system in rats and implanted telemetry in dogs were utilized to evaluate the potential CNS, respiratory and cardiovascular toxicity, respectively. UP446 was administered orally at dose levels of 800, 2000 and 5000 mg/kg to SpragueDawley rats and at 4 ascending dose levels (0, 250, 500 and 1000 mg/kg) to beagle dogs. No abnormal effects were observed on the cage side, open field, hand held, and sensori-motor observations suggestive of toxicity in respiratory, cardiovascular and central nervous (CNS) systems. Rectal temperatures were comparable for each treatment groups. Similarly, respiratory rate, tidal volume and minute volume were unaffected by any of the treatment groups. No UP446 related changes were observed on blood pressure, heart rate and electrocardiogram in beagle dogs at dose levels of 250, 500 and 1000 mg/kg. Some minor incidental, non-dose correlated changes were observed in the FOB assessment. These data suggest that UP446 has minimal or no pharmaco-toxicological effect on the respiratory, cardiovascular and central nervous systems. PMID:27012374

  15. Significant upregulation of cytokine secretion from T helper type 9 and 17 cells in a NC/Nga mouse model of ambient chemical exposure-induced respiratory allergy.

    PubMed

    Nishino, Risako; Fukuyama, Tomoki; Watanabe, Yuko; Kurosawa, Yoshimi; Kosaka, Tadashi; Harada, Takanori

    2016-01-01

    It has been reported that ambient chemical exposure is closely associated with respiratory allergies. We attempted to develop an original protocol for detecting ambient chemical exposure-induced respiratory allergy in different strains of mice. In the process of comparing allergic potency of these mice, we observed that NC/Nga mice showed significant upregulation of respiratory allergic symptoms as well as specific type of cytokine secretions. The main purpose of this study was to investigate the mechanism underlying these phenomena in NC/Nga mice in comparison with BALB/c mice. For the model of respiratory allergy, female BALB/c and NC/Nga mice were sensitized and challenged with trimellitic anhydride. Clinical observation, IgE and immunocyte counts, and cytokine profile in the serum, lymph nodes, and bronchoalveolar lavage fluid were recorded. We also monitored the expression of genes encoding pro-inflammatory cytokines in the lung. We found that worsening of respiratory status was noted only in NC/Nga mice, whereas Th2 reactions were significantly increased in BALB/c mice compared with NC/Nga mice. In contrast, the levels of Th9 and Th17-derived cytokines in NC/Nga mice were significantly higher than those in BALB/c mice. Thus, Th9 and Th17 may be involved in the aggravation of respiratory allergic symptoms induced by ambient chemicals. PMID:27095298

  16. Fast evolution of urban ultrafine particles: Implications for deposition doses in the human respiratory system

    NASA Astrophysics Data System (ADS)

    Manigrasso, Maurizio; Avino, Pasquale

    2012-05-01

    The impact of ultrafine particles (diameters <100 nm) on human health has been addressed in many toxicological studies. It is therefore important to assess relevant respiratory exposure of the population. In this paper, aerosol number-size distribution was measured with 1 s time resolution, in a street canyon, in proximity to traffic, with the purpose of studying the fast evolution of UFP doses deposited in the respiratory system. Close to the traffic, nucleation particle concentrations increase within few seconds and decrease in tens of seconds. As a consequence, the exposure pattern, near to traffic, may be represented as a sequence of short-term peak exposures. The number of UFPs deposited for each tidal volume of air inhaled (instant UFP doses) rapidly reaches level of 107 particles, with maximum values for the alveolar interstitial region. For the correct estimate of short-term exposures, in scenarios involving proximity to traffic, it is therefore crucial to rely on aerosol measurements with a time resolution able to trace the fast evolution of aerosol from vehicle exhausts. When traffic levels drop, spike values of instant UFP doses are comparatively less frequent and the maxima of their size distributions shift from 10 to 20 nm (nucleation particles) to greater diameter (up to about 60 nm).

  17. Distribution and Respiratory Activity of Mycobacteria in Household Water System of Healthy Volunteers in Japan

    PubMed Central

    Ichijo, Tomoaki; Izumi, Yoko; Nakamoto, Sayuri; Yamaguchi, Nobuyasu; Nasu, Masao

    2014-01-01

    The primary infectious source of nontuberculous mycobacteria (NTM), which are known as opportunistic pathogens, appears to be environmental exposure, and it is important to reduce the frequency of exposure from environmental sources for preventing NTM infections. In order to achieve this, the distribution and respiratory activity of NTM in the environments must be clarified. In this study, we determined the abundance of mycobacteria and respiratory active mycobacteria in the household water system of healthy volunteers using quantitative PCR and a fluorescent staining method, because household water has been considered as one of the possible infectious sources. We chose healthy volunteer households in order to lessen the effect of possible residential contamination from an infected patient. We evaluated whether each sampling site (bathroom drain, kitchen drain, bath heater pipe and showerhead) have the potential to be the sources of NTM infections. Our results indicated that drains in the bathroom and kitchen sink are the niche for Mycobacterium spp. and M. avium cells were only detected in the bathtub inlet. Both physicochemical and biologic selective pressures may affect the preferred habitat of Mycobacterium spp. Regional differences also appear to exist as demonstrated by the presence (US) or absence (Japan) of Mycobacterium spp. on showerheads. Understanding of the country specific human activities and water usage will help to elucidate the infectious source and route of nontuberculous mycobacterial disease. PMID:25350137

  18. Enhancement of Aerosol Cisplatin Chemotherapy with Gene Therapy Expressing ABC10 protein in Respiratory System

    PubMed Central

    Hohenforst-Schmidt, Wolfgang; Zarogoulidis, Paul; Linsmeier, Bernd; Kioumis, Ioannis; Li, Qiang; Huang, Haidong; Sachpatzidou, Despoina; Lampaki, Sofia; Organtzis, John; Domvri, Kalliopi; Sakkas, Leonidas; Zachariadis, George A.; Archontas, Konstantinos N.; Kallianos, Anastasios; Rapti, Aggeliki; Yarmus, Lonny; Zarogoulidis, Konstantinos; Brachmann, Johannes

    2014-01-01

    Inhaled therapy for lung cancer is a local form of treatment. Currently inhaled non-specific cytotoxic agents have been evaluated as a future treatment for local disease control and distant metastasis control. There are few information regarding the influence of local transporters and gene expression of the respiratory epithelium to the absorption of administered drugs. In the current work we used adenoviral-type 5(dE1/E3) (Cytomegalovirus promoter) with human ABCA10 transgene (Ad-h-ABCA10) purchased from Vector Labs® in order to investigate whether gene therapy can be used as a pre-treatment to enhance the efficiency of inhaled cisplatin. We included the following groups to our work: a) control, b) aerosol vector, c) aerosol vector plus cisplatin, d) aerosol cisplatin, e) intratumoral cisplatin administration, f) intratumoral vector plus cisplatin administration. The results indicate that the aerosol cisplatin group had a long term survival with the intratumoral cisplatin group following. The enhancement of the ABCA family locally to the respiratory system prior to the aerosol cisplatin administration can be used safely and efficiently. Future treatment design of local therapies should include the investigation of local transporters and genes. PMID:24723977

  19. Respiratory dynamics of discontinuous gas exchange in the tracheal system of the desert locust, Schistocerca gregaria.

    PubMed

    Groenewald, Berlizé; Hetz, Stefan K; Chown, Steven L; Terblanche, John S

    2012-07-01

    Gas exchange dynamics in insects is of fundamental importance to understanding evolved variation in breathing patterns, such as discontinuous gas exchange cycles (DGCs). Most insects do not rely solely on diffusion for the exchange of respiratory gases but may also make use of respiratory movements (active ventilation) to supplement gas exchange at rest. However, their temporal dynamics have not been widely investigated. Here, intratracheal pressure, V(CO2) and body movements of the desert locust Schistocerca gregaria were measured simultaneously during the DGC and revealed several important aspects of gas exchange dynamics. First, S. gregaria employs two different ventilatory strategies, one involving dorso-ventral contractions and the other longitudinal telescoping movements. Second, although a true spiracular closed (C)-phase of the DGC could be identified by means of subatmospheric intratracheal pressure recordings, some CO(2) continued to be released. Third, strong pumping actions do not necessarily lead to CO(2) release and could be used to ensure mixing of gases in the closed tracheal system, or enhance water vapour reabsorption into the haemolymph from fluid-filled tracheole tips by increasing the hydrostatic pressure or forcing fluid into the haemocoel. Finally, this work showed that the C-phase of the DGC can occur at any pressure. These results provide further insights into the mechanistic basis of insect gas exchange. PMID:22675191

  20. Workshop to identify critical windows of exposure for children's health: immune and respiratory systems work group summary.

    PubMed Central

    Dietert, R R; Etzel, R A; Chen, D; Halonen, M; Holladay, S D; Jarabek, A M; Landreth, K; Peden, D B; Pinkerton, K; Smialowicz, R J; Zoetis, T

    2000-01-01

    Fetuses, infants, and juveniles (preadults) should not be considered simply "small adults" when it comes to toxicological risk. We present specific examples of developmental toxicants that are more toxic to children than to adults, focusing on effects on the immune and respiratory systems. We describe differences in both the pharmacokinetics of the developing immune and respiratory systems as well as changes in target organ sensitivities to toxicants. Differential windows of vulnerability during development are identified in the context of available animal models. We provide specific approaches to directly investigate differential windows of vulnerability. These approaches are based on fundamental developmental biology and the existence of discrete developmental processes within the immune and respiratory systems. The processes are likely to influence differential developmental susceptibility to toxicants, resulting in lifelong toxicological changes. We also provide a template for comparative research. Finally, we discuss the application of these data to risk assessment. PMID:10852848

  1. Effects of inhalation of beta 2-sympathicomimetic and anticholinergic agents on the impedance of the respiratory system in normal subjects.

    PubMed

    Wesseling, G; Vonk, H M; Wouters, E F

    1990-05-01

    Impedance measurement of the respiratory system by forced oscillations is a sensitive and accurate method to detect mechanical parameters, especially in normal subjects. The effects of inhalation of 0.2 mg of fenoterol and 0.02 mg of ipratropium bromide on the impedance of the respiratory system was studied in 20 healthy subjects in a frequency spectrum between 4 and 52 Hz. Both agents caused a statistically significant decrease in resistance (Rrs). Inhalation of fenoterol and ipratropium bromide caused a significant increase in reactance (Xrs). The decrease in Rrs was greater after inhalation of fenoterol than after ipratropium bromide. Fenoterol and ipratropium bromide caused qualitatively similar changes in Rrs and Xrs of the respiratory system. The changes in Rrs can be explained by dilation of the central airways. The changes in Xrs are supposed to be the result of an increase in the capacitance of the lungs. PMID:2139600

  2. Respiratory Distress

    NASA Technical Reports Server (NTRS)

    1976-01-01

    The University of Miami School of Medicine asked the Research Triangle Institute for assistance in improvising the negative pressure technique to relieve respiratory distress in infants. Marshall Space Flight Center and Johnson Space Center engineers adapted this idea to the lower-body negative-pressure system seals used during the Skylab missions. Some 20,000 babies succumb to respiratory distress in the U.S. each year, a condition in which lungs progressively lose their ability to oxygenate blood. Both positive and negative pressure techniques have been used - the first to force air into lungs, the second to keep infant's lungs expanded. Negative pressure around chest helps the baby expand his lungs and maintain proper volume of air. If doctors can keep the infant alive for four days, the missing substance in the lungs will usually form in sufficient quantity to permit normal breathing. The Skylab chamber and its leakproof seals were adapted for medical use.

  3. Comparison of visual biofeedback system with a guiding waveform and abdomen-chest motion self-control system for respiratory motion management

    PubMed Central

    Nakajima, Yujiro; Kadoya, Noriyuki; Kanai, Takayuki; Ito, Kengo; Sato, Kiyokazu; Dobashi, Suguru; Yamamoto, Takaya; Ishikawa, Yojiro; Matsushita, Haruo; Takeda, Ken; Jingu, Keiichi

    2016-01-01

    Irregular breathing can influence the outcome of 4D computed tomography imaging and cause artifacts. Visual biofeedback systems associated with a patient-specific guiding waveform are known to reduce respiratory irregularities. In Japan, abdomen and chest motion self-control devices (Abches) (representing simpler visual coaching techniques without a guiding waveform) are used instead; however, no studies have compared these two systems to date. Here, we evaluate the effectiveness of respiratory coaching in reducing respiratory irregularities by comparing two respiratory management systems. We collected data from 11 healthy volunteers. Bar and wave models were used as visual biofeedback systems. Abches consisted of a respiratory indicator indicating the end of each expiration and inspiration motion. Respiratory variations were quantified as root mean squared error (RMSE) of displacement and period of breathing cycles. All coaching techniques improved respiratory variation, compared with free-breathing. Displacement RMSEs were 1.43 ± 0.84, 1.22 ± 1.13, 1.21 ± 0.86 and 0.98 ± 0.47 mm for free-breathing, Abches, bar model and wave model, respectively. Period RMSEs were 0.48 ± 0.42, 0.33 ± 0.31, 0.23 ± 0.18 and 0.17 ± 0.05 s for free-breathing, Abches, bar model and wave model, respectively. The average reduction in displacement and period RMSE compared with the wave model were 27% and 47%, respectively. For variation in both displacement and period, wave model was superior to the other techniques. Our results showed that visual biofeedback combined with a wave model could potentially provide clinical benefits in respiratory management, although all techniques were able to reduce respiratory irregularities. PMID:26922090

  4. Faecal bile acids are natural ligands of the mouse accessory olfactory system.

    PubMed

    Doyle, Wayne I; Dinser, Jordan A; Cansler, Hillary L; Zhang, Xingjian; Dinh, Daniel D; Browder, Natasha S; Riddington, Ian M; Meeks, Julian P

    2016-01-01

    The accessory olfactory system (AOS) guides behaviours that are important for survival and reproduction, but understanding of AOS function is limited by a lack of identified natural ligands. Here we report that mouse faeces are a robust source of AOS chemosignals and identify bile acids as a class of natural AOS ligands. Single-unit electrophysiological recordings from accessory olfactory bulb neurons in ex vivo preparations show that AOS neurons are strongly and selectively activated by peripheral stimulation with mouse faecal extracts. Faecal extracts contain several unconjugated bile acids that cause concentration-dependent neuronal activity in the AOS. Many AOS neurons respond selectively to bile acids that are variably excreted in male and female mouse faeces, and others respond to bile acids absent in mouse faeces. These results identify faeces as a natural source of AOS information, and suggest that bile acids may be mammalian pheromones and kairomones. PMID:27324439

  5. Faecal bile acids are natural ligands of the mouse accessory olfactory system

    PubMed Central

    Doyle, Wayne I.; Dinser, Jordan A.; Cansler, Hillary L.; Zhang, Xingjian; Dinh, Daniel D.; Browder, Natasha S.; Riddington, Ian M.; Meeks, Julian P.

    2016-01-01

    The accessory olfactory system (AOS) guides behaviours that are important for survival and reproduction, but understanding of AOS function is limited by a lack of identified natural ligands. Here we report that mouse faeces are a robust source of AOS chemosignals and identify bile acids as a class of natural AOS ligands. Single-unit electrophysiological recordings from accessory olfactory bulb neurons in ex vivo preparations show that AOS neurons are strongly and selectively activated by peripheral stimulation with mouse faecal extracts. Faecal extracts contain several unconjugated bile acids that cause concentration-dependent neuronal activity in the AOS. Many AOS neurons respond selectively to bile acids that are variably excreted in male and female mouse faeces, and others respond to bile acids absent in mouse faeces. These results identify faeces as a natural source of AOS information, and suggest that bile acids may be mammalian pheromones and kairomones. PMID:27324439

  6. Systemic lupus erythematosus with distal renal tubular acidosis presenting as hypokalemic paralysis with respiratory failure.

    PubMed

    Koul, Parvaiz Ahmad; Wahid, Abdul; Shah, Bashir Ahmad

    2003-01-01

    An eighteen-year-old woman presented with hypokalemic respiratory failure. She was found to have distal renal tubular acidosis (dRTA) as the underlying cause for hypokalemia. This was treated successfully, and no apparent etiology for the dRTA was discovered. Three years later she presented with full-blown picture of systemic lupus erythematosus (SLE) together with features of persistent dRTA complicated, this time, with bilateral renal calculi and nephrocalcinosis. It is very likely that the dRTA was an early feature that preceded the other markers of SLE. The moral of this case is that patients with dRTA should be followed-up carefully as a primary cause for the dRTA may show up in-due-course and to monitor the treatment so as to prevent long-term complications of the RTA. PMID:18209445

  7. Adenosine transport systems on dissociated brain cells from mouse, guinea-pig, and rat

    SciTech Connect

    Johnston, M.E.; Geiger, J.D. )

    1990-09-01

    The kinetics and sodium dependence of adenosine transport were determined using an inhibitor-stop method on dissociated cell body preparations obtained from mouse, guinea-pig and rat brain. Transport affinity (KT) values for the high affinity adenosine transport systems KT(H) were significantly different between these three species; mean +/- SEM values were 0.34 +/- 0.1 in mouse, 0.9 +/- 0.2 in rat, and 1.5 +/- 0.5 microM in guinea-pig. The KT values for the low affinity transport system KT(L) were not different between the three species. Brain cells from rat displayed a significantly greater maximal capacity to accumulate (3H)adenosine (Vmax) than did mouse or guinea-pig for the high affinity system, or than did mouse for the low affinity system. When sodium chloride was replaced in the transport medium with choline chloride, the KT(H) values for guinea-pig and rat were both increased by approximately 100%; only in rat did the change reach statistical significance. The sodium-dependence of adenosine transport in mouse brain was clearly absent. The differences between KT(H) values in mouse and those in guinea-pig or rat were accentuated in the absence of sodium. The differences in kinetic values, ionic requirements, and pharmacological characteristics between adenosine transporters in CNS tissues of mouse, guinea-pig and rat may help account for some of the variability noted among species in terms of their physiological responses to adenosine.

  8. Bacterial Respiratory Tract Infections are Promoted by Systemic Hyperglycemia after Severe Burn Injury in Pediatric Patients

    PubMed Central

    Kraft, Robert; Herndon, David N; Mlcak, Ronald P; Finnerty, Celeste C; Cox, Robert A; Williams, Felicia N; Jeschke, Marc G

    2014-01-01

    Background Burn injuries are associated with hyperglycemia leading to increased incidence of infections with pneumonia being one of the most prominent and adverse complication. Recently, various studies in critically ill patients indicated that increased pulmonary glucose levels with airway/blood glucose threshold over 150 mg/dl lead to an overwhelming growth of bacteria in the broncho-pulmonary system, subsequently resulting in an increased risk of pulmonary infections. The aim of the present study was to determine whether a similar cutoff value exists for severely burned pediatric patients. Methods One-hundred six severely burned pediatric patients were enrolled in the study. Patients were divided in two groups: high (H) defined as daily average glucose levels >75% of LOS >150 mg/dl), and low (L) with daily average glucose levels >75% of the LOS <150 mg/dl). Incidences of pneumonia, atelectasis, and acute respiratory distress syndrome (ARDS) were assessed. Incidence of infections, sepsis, and respiratory parameters were recorded. Blood was analyzed for glucose and insulin levels. Statistical analysis was performed using Student’s t-test and chi-square test. Significance was set at p<0.05. Results Patient groups were similar in demographics and injury characteristics. Pneumonia in patients on the mechanical ventilation (L: 21% H: 32%) and off mechanical ventilation (L: 5% H: 15%), as well as ARDS were significantly higher in the high group (L: 3% H: 19%), p<0.05, while atelectasis was not different. Patients in the high group required significantly longer ventilation compared to low patients (p<0.05). Furthermore, incidence of infection and sepsis were significantly higher in the high group, p<0.05. Conclusion Our results indicate that systemic glucose levels over 150 mg/dl are associated with a higher incidence of pneumonia confirming the previous studies in critically ill patients. PMID:24074819

  9. Idiopathic scoliosis. Mechanical properties of the respiratory system and the ventilatory response to carbon dioxide.

    PubMed

    Kafer, E R

    1975-06-01

    The aims were to examine the effects of scoliosis (angle), and age on lung volumes, elastic properties of the respiratory system, and the ventilatory response to CO2. The mean age of the 55 patients was 25.4 plus or minus SEM 2.5 yr, and the mean angle was 80 plus or minus SEM 4.2. The mean plus or minus SEM percent predicted lung volumes were vital capacity (VC), 60.5 plus or minus 2.7; total lung capacity (TLC), 70,2 plus or minus 2.6; functional residual capacity (frc), 79.3 plus or minus 3.2; and residual volume (RV), 99.7 plus or minus 5.2. The correlation coefficients between the angle of scoliosis and each of the following were significant: TLC (-0.548), percent predicted TLC (-0.547), VC (-0.485), percent predicted VC (-0.523), FRC (-0.533), percent predicted FRC (-0.338), RV (-0.438), and percent predicted RV (-0.318). The mean compliance of the total respiratory system (Crs) was 0.049 litter/cm H2O plus or minus SEM 0.004, and the mean compliance of the chest wall (Ccw) was 0.080 liter/cm H2O plus or minus SEM 0.012. The Crs and Ccw were inversely proportional to the angle (r-0.620 and -0.721) and directly proportional to the height and the weight. The mean deltaV/deltaPco2 was 1.32 liter/min per mm Hg (SEM 0.171), and the mean deltaVt/deltaPco2 was 28.9 ml/mm Hg (SEM 3.64). The correlation coefficients between deltaV/deltaPco2 and the following were height, 0.499; VC, 0.792; TLC, 0.632; AND Crs, 0.520; and between the deltaTt/deltaPco2 and the following were height, 0.500; VC, 0.878; TLC, 0.802; and Crs, 0.590. We conclude that body size and the deformity were the determinants of the lung volumes and the mechanical properties of the respiratory system, and that these variables were the major factors in both the magnitude and pattern of the ventilatory response to CO2. The correlations between age and the mechanical properties of the respiratory sytem, deltaV/deltaPco2, and deltaVt/deltaPco2, were not significant, but the correlation coefficients between

  10. The organotelluride catalyst (PHTE)₂NQ prevents HOCl-induced systemic sclerosis in mouse.

    PubMed

    Marut, Wioleta K; Kavian, Niloufar; Servettaz, Amélie; Nicco, Carole; Ba, Lalla A; Doering, Mandy; Chéreau, Christiane; Jacob, Claus; Weill, Bernard; Batteux, Frédéric

    2012-04-01

    Systemic sclerosis (SSc) is a connective tissue disorder characterized by skin and visceral fibrosis, microvascular damage, and autoimmunity. HOCl-induced mouse SSc is a murine model that mimics the main features of the human disease, especially the activation and hyperproliferation rate of skin fibroblasts. We demonstrate here the efficiency of a tellurium-based catalyst 2,3-bis(phenyltellanyl)naphthoquinone ((PHTE)(2)NQ) in the treatment of murine SSc, through its selective cytotoxic effects on activated SSc skin fibroblasts. SSc mice treated with (PHTE)(2)NQ displayed a significant decrease in lung and skin fibrosis and in alpha-smooth muscle actin (α-SMA) expression in the skin compared with untreated mouse SSc animals. Serum concentrations of advanced oxidation protein products, nitrate, and anti-DNA topoisomerase I autoantibodies were increased in SSc mice, but were significantly reduced in SSc mice treated with (PHTE)(2)NQ. To assess the mechanism of action of (PHTE)(2)NQ, the cytotoxic effect of (PHTE)(2)NQ was compared in normal fibroblasts and in mouse SSc skin fibroblasts. ROS production is higher in mouse SSc fibroblasts than in normal fibroblasts, and was still increased by (PHTE)(2)NQ to reach a lethal threshold and kill mouse SSc fibroblasts. Therefore, the effectiveness of (PHTE)(2)NQ in the treatment of mouse SSc seems to be linked to the selective pro-oxidative and cytotoxic effects of (PHTE)(2)NQ on hyperproliferative fibroblasts. PMID:22277946

  11. An Ultrahigh Resolution SPECT System for I-125 Mouse Brain Imaging Studies

    PubMed Central

    Meng, L. J.; Fu, G.; Roy, E. J.; Suppe, B.; Chen, C. T.

    2009-01-01

    This paper presents some initial experimental results obtained with a dual-head prototype single photon emission microscope system (SPEM) that is dedicated to mouse brain studies using I-125 labeled radiotracers. In particular, this system will be used for in vivo tacking of radiolabeled T cells in mouse brain. This system is based on the use of the intensified electron multiplying charge-coupled device (I-EMCCD) camera that offers the combination of an excellent intrinsic spatial resolution, a good signal-to-noise ratio, a large active area and a reasonable detection efficiency over an energy range between 27–140keV. In this study, the dual-head SPEM system was evaluated using both resolution phantoms and a mouse with locally injected T cells labelled with I-125. It was demonstrated that for a relatively concentrated source object, the current dual-head SPEM system is capable of visualizing the tiny amount of radioactivity (~12 nCi) carried by a very small number (<1000) of T cells. The current SPEM system design allows four or six camera heads to be installed in a stationary system configuration that offers a doubled or tripled sensitivity at a spatial resolution similar to that obtained with the dualhead system. This development would provide a powerful tool for in vivo and non-invasive tracking of radiolabeled T cells in mouse brain and potentially for other rodent brain imaging studies. PMID:20161174

  12. Do individually ventilated cage systems generate a problem for genetic mouse model research?

    PubMed

    Logge, W; Kingham, J; Karl, T

    2014-09-01

    Technological developments over recent decades have produced a novel housing system for laboratory mice, so-called 'individually ventilated cage' (IVC) systems. IVCs present a cage environment which is different to conventional filter-top cages (FILTER). Nothing is known about the consequences of IVC housing on genetic mouse models, despite studies reporting IVC-mediated changes to the phenotypes of inbred mouse strains. Thus, in this study, we systematically compared the established behavioural phenotype of a validated mouse model for the schizophrenia risk gene neuregulin 1 (TM Nrg1 HET) kept in FILTER housing with Nrg1 mutant mice raised in IVC systems. We found that particular schizophrenia-relevant endophenotypes of TM Nrg1 HETs which had been established and widely published using FILTER housing were altered when mice were raised in IVC housing. IVCs diminished the schizophrenia-relevant prepulse inhibition deficit of Nrg1 mutant males. Furthermore, IVC housing had a sex-dependent moderate effect on the locomotive phenotype of Nrg1 mice across test paradigms. Behavioural effects of IVC housing were less prominent in female mice. Thus, transferring the breeding colony of mouse mutants from FILTER to IVC systems can shift disease-relevant behaviours and therefore challenge the face validity of these mice. Researchers facing an upgrade of their mouse breeding or holding facilities to IVC systems must be aware of the potential impact this upgrade might have on their genetic mouse models. Future publications should provide more details on the cage system used to allow appropriate data comparison across research sites. PMID:24920375

  13. The effect of centrally injected CDP-choline on respiratory system; involvement of phospholipase to thromboxane signaling pathway.

    PubMed

    Topuz, Bora B; Altinbas, Burcin; Yilmaz, Mustafa S; Saha, Sikha; Batten, Trevor F; Savci, Vahide; Yalcin, Murat

    2014-05-01

    CDP-choline is an endogenous metabolite in phosphatidylcholine biosynthesis. Exogenous administration of CDP-choline has been shown to affect brain metabolism and to exhibit cardiovascular, neuroendocrine neuroprotective actions. On the other hand, little is known regarding its respiratory actions and/or central mechanism of its respiratory effect. Therefore the current study was designed to investigate the possible effects of centrally injected CDP-choline on respiratory system and the mediation of the central cholinergic receptors and phospholipase to thromboxane signaling pathway on CDP-choline-induced respiratory effects in anaesthetized rats. Intracerebroventricularly (i.c.v.) administration of CDP-choline induced dose- and time-dependent increased respiratory rates, tidal volume and minute ventilation of male anaesthetized Spraque Dawley rats. İ.c.v. pretreatment with atropine failed to alter the hyperventilation responses to CDP-choline whereas mecamylamine, cholinergic nicotinic receptor antagonist, mepacrine, phospholipase A2 inhibitor, and neomycin phospholipase C inhibitor, blocked completely the hyperventilation induced by CDP-choline. In addition, central pretreatment with furegrelate, thromboxane A2 synthesis inhibitor, also partially blocked CDP-choline-evoked hyperventilation effects. These data show that centrally administered CDP-choline induces hyperventilation which is mediated by activation of central nicotinic receptors and phospholipase to thromboxane signaling pathway. PMID:24560778

  14. METHODS USED TO STUDY RESPIRATORY VIRUS INFECTION

    PubMed Central

    Flaño, Emilio; Jewell, Nancy A.; Durbin, Russell K.; Durbin, Joan E.

    2009-01-01

    This unit describes protocols for infecting the mouse respiratory tract, and assaying virus replication and host response in the lung. Respiratory infections are the leading cause of acute illness worldwide, affecting mostly infants and children in developing countries. The purpose of this unit is to provide the readers with a basic strategy and protocols to study the pathogenesis and immunology of respiratory virus infection using the mouse as an animal model. The procedures include: (i) basic techniques for mouse infection, tissue sampling and preservation, (ii) determination of viral titers, isolation and analysis of lymphocytes and dendritic cells using flow-cytometry, and (iii) lung histology, immunohistochemistry and in situ hybridization. PMID:19499505

  15. Influence of pneumoperitoneum and postural change on the cardiovascular and respiratory systems in dogs.

    PubMed

    Park, Young Tae; Okano, Shozo

    2015-10-01

    We investigated the influence of pneumoperitoneum#(PP) and postural change under inhalation anesthesia with isoflurane, which is routinely used in dogs, on the cardiovascular and respiratory systems. As test animals, 6 adult beagles were used. To induce anesthesia, atropine, butorphanol and propofol were intravenously injected. Anesthesia was maintained with 1.3 MAC (1.7%) isoflurane. The following were the experiment conditions: I:E ratio, 1:1.9; tidal air exchange, 20 ml/kg; and ventilation frequency, 14 times/min. Respiration was regulated so that the PaCO2 was approximately 35 to 40 mmHg before the start of the experiment. PP with CO2 (intraperitoneal pressure 15 mmHg) and a postural change (15°C) was performed during the experiment. As parameters of circulatory kinetics, heart rate (HR), mean aortic pressure (MAP), mean pulmonary arterial pressure (MPAP), central venous pressure (CVP), femoral venous pressure (FVP) and cardiac output (CO) were measured. As parameters of respiratory kinetics, airway pressure (PAW) and blood gas (BG) were measured. There were significant increases in HR, MAP, MPAP, CVP, FVP, CO, PAW and PaCO2 after PP in the horizontal position. There were significant increases in CVP, FVP, PAW and PaCO2 after PP in the Trendelenburg position. There were significant increases in the MPAP, CVP, FVP, PAW and PaCO2 after PP in the inverse Trendelenburg position. There was a significant difference in FVP after PP between the Trendelenburg position and inverse Trendelenburg position. The results of this experiment suggest that appropriate anesthesia control, such as changing the ventilation conditions after PP, is required for laparoscopic surgery under inhalation anesthesia with isoflurane. PMID:26027843

  16. Evaluation of a nasal/oral discriminate sampling system for capnographic respiratory monitoring.

    PubMed

    Derrick, S J; Waters, H; Kang, S W; Cwalina, T F; Simmons, W

    1993-10-01

    Although continuous end-tidal carbon dioxide (PETCO2 mmHg) measurements permit the earliest detection of alveolar hypoventilation, apnea and/or obstruction, technical difficulties have thus far precluded its reliable implementation in the spontaneously breathing patient with a natural (e.g., nonartificially secured) airway. Among the technical difficulties is the fact that conventional sampling devices do not take into account the possibility that breathing may take place primarily through either the nose or the mouth. As a result, the efficacy of a new nasal/oral discriminate sampling system (NODSS) was examined for capnographic observation of respiratory adequacy. NODSS is unique because it provides the opportunity to select simultaneous or discriminate collection of carbon dioxide exhaled through the nose and/or mouth. Twenty-four American Society of Anesthesiologists physical status I to IV patients (ages 30-88 years) were capnographically monitored in the postanesthesia care unit following general anesthesia for various surgical procedures. All patients were extubated and breathing spontaneously. Simultaneously, direct arterial carbon dioxide (PaCO2 mmHg) determinations were made using an indwelling radial artery catheter to determine their correlation with PETCO2 obtained by NODSS. A comparison between PaCO2 values and noninvasive nasal and/or oral PETCO2 obtained by NODSS showed a positive correlation (r value) of 0.602 to 0.849 when statistically analyzed by Pearson's product-moment correlation coefficient. There was no significant difference between the mean (PaCO2-PETCO2) gradient derived through nasal sampling, as compared to the mean gradient derived by oral sampling with this device (P > 0.05). Noninvasive capnographic monitoring by NODSS is a convenient, reliable, effective, and accurate alternative to direct arterial blood gas determination that may be used for the early detection of respiratory inadequacy in the spontaneously breathing patient who

  17. Multiple Roles and Interactions of Tbx4 and Tbx5 in Development of the Respiratory System

    PubMed Central

    Arora, Ripla; Metzger, Ross J.; Papaioannou, Virginia E.

    2012-01-01

    Normal development of the respiratory system is essential for survival and is regulated by multiple genes and signaling pathways. Both Tbx4 and Tbx5 are expressed throughout the mesenchyme of the developing lung and trachea; and, although multiple genes are known to be required in the epithelium, only Fgfs have been well studied in the mesenchyme. In this study, we investigated the roles of Tbx4 and Tbx5 in lung and trachea development using conditional mutant alleles and two different Cre recombinase transgenic lines. Loss of Tbx5 leads to a unilateral loss of lung bud specification and absence of tracheal specification in organ culture. Mutants deficient in Tbx4 and Tbx5 show severely reduced lung branching at mid-gestation. Concordant with this defect, the expression of mesenchymal markers Wnt2 and Fgf10, as well as Fgf10 target genes Bmp4 and Spry2, in the epithelium is downregulated. Lung branching undergoes arrest ex vivo when Tbx4 and Tbx5 are both completely lacking. Lung-specific Tbx4 heterozygous;Tbx5 conditional null mice die soon after birth due to respiratory distress. These pups have small lungs and show severe disruptions in tracheal/bronchial cartilage rings. Sox9, a master regulator of cartilage formation, is expressed in the trachea; but mesenchymal cells fail to condense and consequently do not develop cartilage normally at birth. Tbx4;Tbx5 double heterozygous mutants show decreased lung branching and fewer tracheal cartilage rings, suggesting a genetic interaction. Finally, we show that Tbx4 and Tbx5 interact with Fgf10 during the process of lung growth and branching but not during tracheal/bronchial cartilage development. PMID:22876201

  18. The transcriptome of mouse central nervous system myelin

    PubMed Central

    Thakurela, Sudhir; Garding, Angela; Jung, Ramona B.; Müller, Christina; Goebbels, Sandra; White, Robin; Werner, Hauke B.; Tiwari, Vijay K.

    2016-01-01

    Rapid nerve conduction in the CNS is facilitated by insulation of axons with myelin, a specialized oligodendroglial compartment distant from the cell body. Myelin is turned over and adapted throughout life; however, the molecular and cellular basis of myelin dynamics remains elusive. Here we performed a comprehensive transcriptome analysis (RNA-seq) of myelin biochemically purified from mouse brains at various ages and find a surprisingly large pool of transcripts enriched in myelin. Further computational analysis showed that the myelin transcriptome is closely related to the myelin proteome but clearly distinct from the transcriptomes of oligodendrocytes and brain tissues, suggesting a highly selective incorporation of mRNAs into the myelin compartment. The mRNA-pool in myelin displays maturation-dependent dynamic changes of composition, abundance, and functional associations; however ageing-dependent changes after 6 months were minor. We suggest that this transcript pool enables myelin turnover and the local adaptation of individual pre-existing myelin sheaths. PMID:27173133

  19. The transcriptome of mouse central nervous system myelin.

    PubMed

    Thakurela, Sudhir; Garding, Angela; Jung, Ramona B; Müller, Christina; Goebbels, Sandra; White, Robin; Werner, Hauke B; Tiwari, Vijay K

    2016-01-01

    Rapid nerve conduction in the CNS is facilitated by insulation of axons with myelin, a specialized oligodendroglial compartment distant from the cell body. Myelin is turned over and adapted throughout life; however, the molecular and cellular basis of myelin dynamics remains elusive. Here we performed a comprehensive transcriptome analysis (RNA-seq) of myelin biochemically purified from mouse brains at various ages and find a surprisingly large pool of transcripts enriched in myelin. Further computational analysis showed that the myelin transcriptome is closely related to the myelin proteome but clearly distinct from the transcriptomes of oligodendrocytes and brain tissues, suggesting a highly selective incorporation of mRNAs into the myelin compartment. The mRNA-pool in myelin displays maturation-dependent dynamic changes of composition, abundance, and functional associations; however ageing-dependent changes after 6 months were minor. We suggest that this transcript pool enables myelin turnover and the local adaptation of individual pre-existing myelin sheaths. PMID:27173133

  20. Illuminating Cancer Systems With Genetically-Engineered Mouse Models and Coupled Luciferase Reporters In Vivo

    PubMed Central

    Kocher, Brandon; Piwnica-Worms, David

    2013-01-01

    Bioluminescent imaging (BLI) is a powerful non-invasive tool that has dramatically accelerated the in vivo interrogation of cancer systems and longitudinal analysis of mouse models of cancer over the past decade. Various luciferase enzymes have been genetically engineered into mouse models (GEMMs) of cancer which permit investigation of cellular and molecular events associated with oncogenic transcription, post-transcriptional processing, protein-protein interactions, transformation and oncogene addiction in live cells and animals. Luciferase-coupled GEMMs ultimately serve as a non-invasive, repetitive, longitudinal, and physiological means by which cancer systems and therapeutic responses can be investigated accurately within the autochthonous context of a living animal. PMID:23585416

  1. Respiratory papillomas

    PubMed Central

    Alagusundaramoorthy, Sayee Sundar; Agrawal, Abhinav

    2016-01-01

    Papillomas are known to occur in the lower respiratory tract. They are however, rare compared to their occurrence in the upper respiratory tract. These are generally exophytic tumors in the more proximal upper airways however cases with more distal location with an inverted growth pattern have also been described in the literature. These can be solitary or multiple and multifocality associated with multiple papillomas in the upper respiratory/aerodigestive tract. The four major types of respiratory papillomas are (1) Recurrent respiratory papillomas, (2) solitary squamous papillomas, (3) solitary glandular papillomas, (4) mixed papillomas. We review the incidence, etiopathology, diagnosis, and possible treatment modalities and algorithms for these respiratory papillomas. PMID:27625447

  2. Research on curative effect of traditional Chinese medicine treating low-grade fever of children caused by respiratory system infection.

    PubMed

    Li, Xiangyun

    2015-07-01

    This study aims to explore the curative effect of traditional Chinese medicine treating low-grade fever of children caused by respiratory system infection. Sixty children who suffered low-grade fever caused by respiratory system infection were selected and divided into treatment group and control group randomly, each with 30 cases. Control group was treated with conventional methods including oxygen uptake, nebulization and anti-infection, etc, while treatment group was given boil-free granules of traditional Chinese medicine besides the treatment which control group received. Then clinical curative effect of two groups was compared. Results showed that 28 cases (93.3%) were cured in treatment group; while 21 cases (70.0%) were cured in control group. Compared with control group, the treatment group showed up better treatment efficiency and the difference between groups was of statistical significance (P<0.05). Comparison of results of two groups suggested that, traditional Chinese medicine granules has satisfactory curative effect in the treatment of low-grade fever of children caused by respiratory system infection; characterized by short treatment cycle and effective treatment effect, Chinese medicine granules in the combination with oxygen atomization inhalation is proved to be able to efficiently remit symptoms such as coughing, gasp and labored breathing, with outstanding curative effect in the treatment of low-grade fever of children caused by respiratory system infection, thus it is worthy of popularization and application clinically. PMID:26431646

  3. A system for continuous long-term measurement of respiratory gas exchange in ventilated patients.

    PubMed

    Guttmann, J; Krieg, N; Vogel, W M

    1987-01-01

    A system for continuous long-term measurement of respiratory gas exchange in ventilated patients is presented. The method is noninvasive and may be applied in a clinical setting over a period of several days without adversely affecting the patient's wellbeing. The set-up was designed exclusively as a research tool. It registers oxygen uptake and CO2 elimination at 5 min intervals; breath-averaged measurements are carried out every 30 s. Expired minute volume is measured with a pneumotachograph equipped with an automatic drift compensation. A newly developed gas mixer insures that the inspiratory oxygen concentration remains constant. Expired gases are analysed for O2 and CO2 concentrations by mass spectrometer. The effect of the compressible gas volume is eliminated by segregating the inspiratory gas from the expired gas. The basic accuracy of measurement of the method is +/- 2.5% for oxygen uptake and +/- 2.0% for CO2 elimination. This result is based on a comparison of the individual components of the system with standard methods. The system's time constant (t90) for changes in O2 and CO2 concentrations is about 50 s. Based on the results of a case study, we will discuss oxygen uptake, CO2 elimination and the oxygen uptake profile of a patient measured over a period of seven days. PMID:3120837

  4. Respiratory Failure

    MedlinePlus

    Respiratory failure happens when not enough oxygen passes from your lungs into your blood. Your body's organs, such ... brain, need oxygen-rich blood to work well. Respiratory failure also can happen if your lungs can't ...

  5. A low-cost telemetry system suitable for measuring mouse biopotentials.

    PubMed

    Lin, David C; Bucher, Brandon P; Davis, Howard P; Sprunger, Leslie K

    2008-03-01

    The ability to generate specific genetic mutations in mice is a powerful tool to study normal and pathophysiological function. In order to determine the effects of a mutation, measurement of physiological variables, such as biopotentials, is often necessary. However, such measurements can be particularly challenging to obtain from an awake, unrestrained mouse. The goal of this study was to design and implement a telemetry system suitable for recording biopotentials from a mouse. A battery-powered system was fabricated from commercially available electronic components mounted on a small circuit board. The frequency response of the system was measured over a range of frequencies and found suitable for recording biopotentials in mice and larger animals. We affixed the circuit board externally to a mouse and connected surface electrodes to measure electrocardiograms (ECG). The size and weight of the board did not disturb normal behavior over 30-60 min. Recorded ECGs had easily identifiable components relevant to physiological parameters and had a similar frequency spectrum compared to recordings obtained from a commercially available measurement system. In conclusion, the telemetry system was low-cost due to the availability of the components, straightforward to implement, and provided biopotential recordings suitable for measuring physiological parameters in an awake mouse. PMID:17403611

  6. Observations on gas exchange and element recycle within a gas-closed algal-mouse system

    NASA Technical Reports Server (NTRS)

    Smernoff, D. T.; Wharton, R. A., Jr.; Averner, M. M.

    1986-01-01

    Life support systems based on bioregeneration rely on the control and manipulation of organisms. Algae are potentially useful for a variety of Closed Ecological Life Support System (CELSS) functions including the revitalization of atmospheres, production of food and for nitrogen fixation. The results of experiments conducted with a gas-closed algal-mouse system designed to investigate gas exchange phenomena under varying algal environmental conditions, and the ability of algae to utilize oxidized mouse solid waste are reported. Inherent instabilities exist between the uptake and release of carbon dioxide (CO2) and oxygen (O2) by the mouse and algae in a gas-closed system. Variations in light intensity and cell density alter the photosynthetic rate of the algae and enable short-term steady-state concentrations of atmospheric CO2 and O2. Different nitrogen sources (urea and nitrate) result in different algal assimilatory quotients (AQ). Combinations of photosynthetic rate and AQ ratio manipulations were examined for their potential in stabilizing atmospheric gas concentrations in the gas-closed algal-mouse system.

  7. Evaluation of a lightweight protective-mask concept for Respiratory Protection System 21. Final report

    SciTech Connect

    Carpenter, T.J.

    1992-01-01

    In the event of combat where Nuclear, Biological, or Chemical (NBC) weapons could be presented, the soldier must be protected while being able to perform his mission. NBC protective equipment for individuals included both protection for the body and the head. However, this equipment causes disadvantages due to the physiological burden on the soldier, such as: Reduction in vision, both field of view and acuity; Degradation on communications, both speech and hearing capabilities; Increased heat load by containing body heat and preventing exposure to cooling air. The U.S. Army Chemical, Research, Development, and Engineering Center (CRDEC) is entering development of the next generation of respiratory protection (RESPO 21) to replace the current M40 series of protective masks. One of the system concepts is a lightweight protective mask (LPM) which utilizes a barrier film for both the facepiece and hood. This concept provides a lightweight, conformal mask design which can be rolled or folded into a very smal package. Concept studies have been competed for advanced seal designs, attachment systems, and electronics for this mask.

  8. Evolution of the respiratory system in nonavian theropods: evidence from rib and vertebral morphology.

    PubMed

    Schachner, Emma R; Lyson, Tyler R; Dodson, Peter

    2009-09-01

    Recent reports of region-specific vertebral pneumaticity in nonavian theropod dinosaurs have brought attention to the hypothesis that these animals possessed an avian-style respiratory system with flow-through ventilation. This study explores the thoracic rib and vertebral anatomy of Sinraptor, Allosaurus, Tyrannosaurus, and Deinonychus; four nonavian theropods that all show well-preserved thoracic vertebrae and ribs. Comparisons to the osteology and soft tissue anatomy of extant saurians provide new evidence supporting the hypothesis of flow-through ventilation in nonavian theropods. Analyses of diapophyseal and parapophyseal position and thoracic rib morphology suggest that most nonavian theropods possessed lungs that were deeply incised by the adjacent bicapitate thoracic ribs. This functionally constrains the lungs as rigid nonexpansive organs that were likely ventilated by accessory nonvascularized air sacs. The axial anatomy of this group also reveals that a crocodilian-like hepatic-piston lung would be functionally and biomechanically untenable. Taken together with the evidence that avian-like air sacs were present in basal theropods, these data lead us to conclude that an avian-style pulmonary system was likely a universal theropod trait. PMID:19711481

  9. Transmissibility of the monkeypox virus clades via respiratory transmission: investigation using the prairie dog-monkeypox virus challenge system.

    PubMed

    Hutson, Christina L; Gallardo-Romero, Nadia; Carroll, Darin S; Clemmons, Cody; Salzer, Johanna S; Nagy, Tamas; Hughes, Christine M; Olson, Victoria A; Karem, Kevin L; Damon, Inger K

    2013-01-01

    Monkeypox virus (MPXV) is endemic within Africa where it sporadically is reported to cause outbreaks of human disease. In 2003, an outbreak of human MPXV occurred in the US after the importation of infected African rodents. Since the eradication of smallpox (caused by an orthopoxvirus (OPXV) related to MPXV) and cessation of routine smallpox vaccination (with the live OPXV vaccinia), there is an increasing population of people susceptible to OPXV diseases. Previous studies have shown that the prairie dog MPXV model is a functional animal model for the study of systemic human OPXV illness. Studies with this model have demonstrated that infected animals are able to transmit the virus to naive animals through multiple routes of exposure causing subsequent infection, but were not able to prove that infected animals could transmit the virus exclusively via the respiratory route. Herein we used the model system to evaluate the hypothesis that the Congo Basin clade of MPXV is more easily transmitted, via respiratory route, than the West African clade. Using a small number of test animals, we show that transmission of viruses from each of the MPXV clade was minimal via respiratory transmission. However, transmissibility of the Congo Basin clade was slightly greater than West African MXPV clade (16.7% and 0% respectively). Based on these findings, respiratory transmission appears to be less efficient than those of previous studies assessing contact as a mechanism of transmission within the prairie dog MPXV animal model. PMID:23408990

  10. Reprogramming of mouse amniotic fluid cells using a PiggyBac transposon system.

    PubMed

    Bertin, E; Piccoli, M; Franzin, C; Nagy, A; Mileikovsky, M; De Coppi, P; Pozzobon, M

    2015-11-01

    Induced pluripotent stem (iPS) cells are generated from mouse and human somatic cells by forced expression of defined transcription factors using different methods. Amniotic fluid (AF) cells are easy to obtain from routinely scheduled procedures for prenatal diagnosis and iPS cells have been generated from human AF. Here, we generated iPS cells from mouse AF cells, using a non-viral-based approach constituted by the PiggyBac (PB) transposon system. All iPS cell lines obtained exhibited characteristics of pluripotent cells, including the ability to differentiate toward derivatives of all three germ layers in vitro and in vivo. PMID:26987920

  11. Development of the mouse vestibular system in the absence of gravity perception

    NASA Technical Reports Server (NTRS)

    Smith, Michael; Yuan Wang, Xiang; Wolgemuth, Debra J.; Murashov, Alexander K.

    2003-01-01

    The tilted mutant mouse, which lacks otoconia in the inner ear, was used to study development of the mouse vestibular system in the absence of gravity perception. Otoconia are dense particles composed of proteins and calcium carbonate crystals suspended in the gelatinous macular membrane. They enhance, and are largely responsible for, sensitivity to gravity. Morphometric analysis of the vestibular ganglion showed that the mutant developed more slowly than the normal controls, both in rate of development and cell number, particularly during the first week of post-natal development. The mutant ganglia also exhibited a reduction of cells during the first 6 days of post-natal development.

  12. DEVELOPMENT OF AN INTACT HEPATOCYTE ACTIVATION SYSTEM FOR ROUTINE USE WITH THE MOUSE LYMPHOMA ASSAY

    EPA Science Inventory

    The authors have developed a method for cocultivating primary rat hepatocytes with L5178Y/TK+/- 3.7.2C mouse lymphoma cells. The system should provide a means to simulate more closely in vivo metabolism compared to metabolism by liver homogenates, while still being useful for rou...

  13. Porcine reproductive and respiratory syndrome virus (PRRSV): pathogenesis and interaction with the immune System

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This review addresses important issues of porcine reproductive and respiratory syndrome virus (PRRSV) infection, immunity, pathogenesis and control. Worldwide PRRS is the most economically important infectious disease of pigs. We highlight the latest information on viral genome structure, pathogenic...

  14. Efficacy of a Low-Cost Bubble CPAP System in Treatment of Respiratory Distress in a Neonatal Ward in Malawi

    PubMed Central

    Kawaza, Kondwani; Machen, Heather E.; Brown, Jocelyn; Mwanza, Zondiwe; Iniguez, Suzanne; Gest, Al; Smith, E. O'Brian; Oden, Maria; Richards-Kortum, Rebecca R.; Molyneux, Elizabeth

    2014-01-01

    Background Respiratory failure is a leading cause of neonatal mortality in the developing world. Bubble continuous positive airway pressure (bCPAP) is a safe, effective intervention for infants with respiratory distress and is widely used in developed countries. Because of its high cost, bCPAP is not widely utilized in low-resource settings. We evaluated the performance of a new bCPAP system to treat severe respiratory distress in a low resource setting, comparing it to nasal oxygen therapy, the current standard of care. Methods We conducted a non-randomized convenience sample study to test the efficacy of a low-cost bCPAP system treating newborns with severe respiratory distress in the neonatal ward of Queen Elizabeth Central Hospital, in Blantyre, Malawi. Neonates weighing >1,000 g and presenting with severe respiratory distress who fulfilled inclusion criteria received nasal bCPAP if a device was available; if not, they received standard care. Clinical assessments were made during treatment and outcomes compared for the two groups. Findings 87 neonates (62 bCPAP, 25 controls) were recruited. Survival rate for neonates receiving bCPAP was 71.0% (44/62) compared with 44.0% (11/25) for controls. 65.5% (19/29) of very low birth weight neonates receiving bCPAP survived to discharge compared to 15.4% (1/13) of controls. 64.6% (31/48) of neonates with respiratory distress syndrome (RDS) receiving bCPAP survived to discharge, compared to 23.5% (4/17) of controls. 61.5% (16/26) of neonates with sepsis receiving bCPAP survived to discharge, while none of the seven neonates with sepsis in the control group survived. Interpretation Use of a low-cost bCPAP system to treat neonatal respiratory distress resulted in 27% absolute improvement in survival. The beneficial effect was greater for neonates with very low birth weight, RDS, or sepsis. Implementing appropriate bCPAP devices could reduce neonatal mortality in developing countries. PMID:24489715

  15. The human respiratory gate

    PubMed Central

    Eckberg, Dwain L

    2003-01-01

    Respiratory activity phasically alters membrane potentials of preganglionic vagal and sympathetic motoneurones and continuously modulates their responsiveness to stimulatory inputs. The most obvious manifestation of this ‘respiratory gating’ is respiratory sinus arrhythmia, the rhythmic fluctuations of electrocardiographic R–R intervals observed in healthy resting humans. Phasic autonomic motoneurone firing, reflecting the throughput of the system, depends importantly on the intensity of stimulatory inputs, such that when levels of stimulation are low (as with high arterial pressure and sympathetic activity, or low arterial pressure and vagal activity), respiratory fluctuations of sympathetic or vagal firing are also low. The respiratory gate has a finite capacity, and high levels of stimulation override the ability of respiration to gate autonomic responsiveness. Autonomic throughput also depends importantly on other factors, including especially, the frequency of breathing, the rate at which the gate opens and closes. Respiratory sinus arrhythmia is small at rapid, and large at slow breathing rates. The strong correlation between systolic pressure and R–R intervals at respiratory frequencies reflects the influence of respiration on these two measures, rather than arterial baroreflex physiology. A wide range of evidence suggests that respiratory activity gates the timing of autonomic motoneurone firing, but does not influence its tonic level. I propose that the most enduring significance of respiratory gating is its use as a precisely controlled experimental tool to tease out and better understand otherwise inaccessible human autonomic neurophysiological mechanisms. PMID:12626671

  16. The human respiratory gate

    NASA Technical Reports Server (NTRS)

    Eckberg, Dwain L.

    2003-01-01

    Respiratory activity phasically alters membrane potentials of preganglionic vagal and sympathetic motoneurones and continuously modulates their responsiveness to stimulatory inputs. The most obvious manifestation of this 'respiratory gating' is respiratory sinus arrhythmia, the rhythmic fluctuations of electrocardiographic R-R intervals observed in healthy resting humans. Phasic autonomic motoneurone firing, reflecting the throughput of the system, depends importantly on the intensity of stimulatory inputs, such that when levels of stimulation are low (as with high arterial pressure and sympathetic activity, or low arterial pressure and vagal activity), respiratory fluctuations of sympathetic or vagal firing are also low. The respiratory gate has a finite capacity, and high levels of stimulation override the ability of respiration to gate autonomic responsiveness. Autonomic throughput also depends importantly on other factors, including especially, the frequency of breathing, the rate at which the gate opens and closes. Respiratory sinus arrhythmia is small at rapid, and large at slow breathing rates. The strong correlation between systolic pressure and R-R intervals at respiratory frequencies reflects the influence of respiration on these two measures, rather than arterial baroreflex physiology. A wide range of evidence suggests that respiratory activity gates the timing of autonomic motoneurone firing, but does not influence its tonic level. I propose that the most enduring significance of respiratory gating is its use as a precisely controlled experimental tool to tease out and better understand otherwise inaccessible human autonomic neurophysiological mechanisms.

  17. Micromachined polymerase chain reaction system for multiple DNA amplification of upper respiratory tract infectious diseases.

    PubMed

    Liao, Chia-Sheng; Lee, Gwo-Bin; Wu, Jiunn-Jong; Chang, Chih-Ching; Hsieh, Tsung-Min; Huang, Fu-Chun; Luo, Ching-Hsing

    2005-01-15

    This paper presents a micro polymerase chain reaction (PCR) chip for the DNA-based diagnosis of microorganism genes and the detection of their corresponding antibiotic-resistant genes. The micro PCR chip comprises cheap biocompatible soda-lime glass substrates with integrated thin-film platinum resistors as heating/sensing elements, and is fabricated using micro-electro-mechanical-system (MEMS) techniques in a reliable batch-fabrication process. The heating and temperature sensing elements are made of the same material and are located inside the reaction chamber in order to ensure a uniform temperature distribution. This study performs the detection of several genes associated with upper respiratory tract infection microorganisms, i.e. Streptococcus pneumoniae, Haemopilus influenze, Staphylococcu aureus, Streptococcus pyogenes, and Neisseria meningitides, together with their corresponding antibiotic-resistant genes. The lower thermal inertia of the proposed micro PCR chip relative to conventional bench-top PCR systems enables a more rapid detection operation with reduced sample and reagent consumption. The experimental data reveal that the high heating and cooling rates of the system (20 and 10 degrees C/s, respectively) permit successful DNA amplification within 15 min. The micro PCR chip is also capable of performing multiple DNA amplification, i.e. the simultaneous duplication of multiple genes under different conditions in separate reaction wells. Compared with the large-scale PCR system, it is greatly advantageous for fast diagnosis of multiple infectious diseases. Multiplex PCR amplification of two DNA segments in the same well is also feasible using the proposed micro device. The developed micro PCR chip provides a crucial tool for genetic analysis, molecular biology, infectious disease detection, and many other biomedical applications. PMID:15590288

  18. A BDNF loop-domain mimetic acutely reverses spontaneous apneas and respiratory abnormalities during behavioral arousal in a mouse model of Rett syndrome

    PubMed Central

    Kron, Miriam; Lang, Min; Adams, Ian T.; Sceniak, Michael; Longo, Frank; Katz, David M.

    2014-01-01

    Reduced levels of brain-derived neurotrophic factor (BDNF) are thought to contribute to the pathophysiology of Rett syndrome (RTT), a severe neurodevelopmental disorder caused by loss-of-function mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2). In Mecp2 mutant mice, BDNF deficits have been associated with breathing abnormalities, a core feature of RTT, as well as with synaptic hyperexcitability within the brainstem respiratory network. Application of BDNF can reverse hyperexcitability in acute brainstem slices from Mecp2-null mice, suggesting that therapies targeting BDNF or its receptor, TrkB, could be effective at acute reversal of respiratory abnormalities in RTT. Therefore, we examined the ability of LM22A-4, a small-molecule BDNF loop-domain mimetic and TrkB partial agonist, to modulate synaptic excitability within respiratory cell groups in the brainstem nucleus tractus solitarius (nTS) and to acutely reverse abnormalities in breathing at rest and during behavioral arousal in Mecp2 mutants. Patch-clamp recordings in Mecp2-null brainstem slices demonstrated that LM22A-4 decreases excitability at primary afferent synapses in the nTS by reducing the amplitude of evoked excitatory postsynaptic currents and the frequency of spontaneous and miniature excitatory postsynaptic currents. In vivo, acute treatment of Mecp2-null and -heterozygous mutants with LM22A-4 completely eliminated spontaneous apneas in resting animals, without sedation. Moreover, we demonstrate that respiratory dysregulation during behavioral arousal, a feature of human RTT, is also reversed in Mecp2 mutants by acute treatment with LM22A-4. Together, these data support the hypothesis that reduced BDNF signaling and respiratory dysfunction in RTT are linked, and establish the proof-of-concept that treatment with a small-molecule structural mimetic of a BDNF loop domain and a TrkB partial agonist can acutely reverse abnormal breathing at rest and in response to behavioral arousal

  19. Occupational exposure to poultry dust and effects on the respiratory system in workers.

    PubMed

    Viegas, S; Faísca, V M; Dias, H; Clérigo, A; Carolino, E; Viegas, C

    2013-01-01

    Farmers are occupationally exposed to many respiratory hazards at work and display higher rates of asthma and respiratory symptoms than other workers. Dust is one of the components present in poultry production that increases risk of adverse respiratory disease occurrence. Dust originates from poultry residues, molds, and feathers and is biologically active as it contains microorganisms. Exposure to dust is known to produce a variety of clinical responses, including asthma, chronic bronchitis, chronic airways obstructive disease (COPD), allergic alveolitis, and organic dust toxic syndrome (ODTS). A study was developed to determine particle contamination in seven poultry farms and correlate this with prevalence rate of respiratory defects and record by means of a questionnaire the presence of clinical symptoms associated with asthma and other allergy diseases by European Community Respiratory Health Survey. Poultry farm dust contamination was found to contain higher concentrations of particulate matter (PM) PM5 and PM10. Prevalence rate of obstructive pulmonary disorders was higher in individuals with longer exposure regardless of smoking status. In addition, a high prevalence for asthmatic (42.5%) and nasal (51.1%) symptoms was noted in poultry workers. Data thus show that poultry farm workers are more prone to suffer from respiratory ailments and this may be attributed to higher concentrations of PM found in the dust. Intervention programs aimed at reducing exposure to dust will ameliorate occupational working conditions and enhance the health of workers. PMID:23514065

  20. Pathogenesis of H5N1 influenza virus infections in mice and ferret models differ between respiratory and digestive system exposure

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background. Epidemiological, clinical and laboratory data suggests H5N1 influenza viruses are transmitted through and predominantly affect the respiratory system of mammals. Some data suggests digestive system involvement. However, direct evidence of alimentary transmission and infection in mammal...

  1. Determining respiratory system resistance and reactance by impulse oscillometry in obese individuals

    PubMed Central

    de Albuquerque, Cláudio Gonçalves; de Andrade, Flávio Maciel Dias; Rocha, Marcus Aurélio de Almeida; de Oliveira, Alina Farias França; Ladosky, Waldemar; Victor, Edgar Guimarães; Rizzo, José Ângelo

    2015-01-01

    Objective: To evaluate peripheral respiratory system resistance and reactance (Rrs and Xrs, respectively) in obese individuals. Methods: We recruited 99 individuals, dividing them into four groups by body mass index (BMI): < 30.0 kg/m2 (control, n = 31); 30.0-39.9 kg/m2 (obesity, n = 13); 40.0-49.9 kg/m2 (severe obesity, n = 28); and ≥ 50.0 kg/m2 (morbid obesity, n = 13). Using impulse oscillometry, we measured total Rrs, central Rrs, and Xrs. Peripheral Rrs was calculated as the difference between total Rrs and central Rrs. All subjects also underwent spirometry. Results: Of the 99 individuals recruited, 14 were excluded because they failed to perform forced expiratory maneuvers correctly during spirometry. The individuals in the severe obesity and morbid obesity groups showed higher peripheral Rrs and lower Xrs in comparison with those in the two other groups. Conclusions: Having a BMI ≥ 40 kg/m2 was associated with a significant increase in peripheral Rrs and with a decrease in Xrs. PMID:26578133

  2. Influence of apnoeic oxygenation in respiratory and circulatory system under general anaesthesia.

    PubMed

    Kolettas, Alexander; Grosomanidis, Vasilis; Kolettas, Vasilis; Zarogoulidis, Paul; Tsakiridis, Kosmas; Katsikogiannis, Nikolaos; Tsiouda, Theodora; Kiougioumtzi, Ioanna; Machairiotis, Nikolaos; Drylis, Georgios; Kesisis, Georgios; Beleveslis, Thomas; Zarogoulidis, Konstantinos

    2014-03-01

    Apnoeic oxygenation is an alternative technique of oxygenation which is recommended in the consecutive oxygen administration with varying flows (2-10 lt/min) through a catheter which is positioned over the keel of the trachea. Apnoeic oxygenation maintains for a significant period of time the oxygenation of blood in breathless conditions. This technique was first applied in 1947 by Draper, Whitehead, and Spencer and it was studied sporadically by other inventors too. However, the international literature shows few studies that have examined closely apnoeic oxygenation and its effects on Hemodynamic image and the respiratory system of the human body. Recently they have begun to arise some studies which deal with the application of this technique in several conditions such as difficult tracheal intubation, ventilation of guinea pigs in campaign conditions where the oxygen supply is limited and calculable, the application of this technique in combination with the use of extracorporeal removal of carbon dioxide (CO2). All the above indicate, the clinical use of this technique. PMID:24672687

  3. Influence of apnoeic oxygenation in respiratory and circulatory system under general anaesthesia

    PubMed Central

    Kolettas, Alexander; Grosomanidis, Vasilis; Kolettas, Vasilis; Tsakiridis, Kosmas; Katsikogiannis, Nikolaos; Tsiouda, Theodora; Kiougioumtzi, Ioanna; Machairiotis, Nikolaos; Drylis, Georgios; Kesisis, Georgios; Beleveslis, Thomas; Zarogoulidis, Konstantinos

    2014-01-01

    Apnoeic oxygenation is an alternative technique of oxygenation which is recommended in the consecutive oxygen administration with varying flows (2-10 lt/min) through a catheter which is positioned over the keel of the trachea. Apnoeic oxygenation maintains for a significant period of time the oxygenation of blood in breathless conditions. This technique was first applied in 1947 by Draper, Whitehead, and Spencer and it was studied sporadically by other inventors too. However, the international literature shows few studies that have examined closely apnoeic oxygenation and its effects on Hemodynamic image and the respiratory system of the human body. Recently they have begun to arise some studies which deal with the application of this technique in several conditions such as difficult tracheal intubation, ventilation of guinea pigs in campaign conditions where the oxygen supply is limited and calculable, the application of this technique in combination with the use of extracorporeal removal of carbon dioxide (CO2). All the above indicate, the clinical use of this technique. PMID:24672687

  4. Respiratory sinus arrhythmia and auditory processing in autism: Modifiable deficits of an integrated social engagement system?

    PubMed Central

    Porges, Stephen W.; Macellaio, Matthew; Stanfill, Shannon D.; McCue, Kimberly; Lewis, Gregory F.; Harden, Emily R.; Handelman, Mika; Denver, John; Bazhenova, Olga V.; Heilman, Keri J.

    2012-01-01

    The current study evaluated processes underlying two common symptoms (i.e., state regulation problems and deficits in auditory processing) associated with a diagnosis of autism spectrum disorders. Although these symptoms have been treated in the literature as unrelated, when informed by the Polyvagal Theory, these symptoms may be viewed as the predictable consequences of depressed neural regulation of an integrated social engagement system, in which there is down regulation of neural influences to the heart (i.e., via the vagus) and to the middle ear muscles (i.e., via the facial and trigeminal cranial nerves). Respiratory sinus arrhythmia (RSA) and heart period were monitored to evaluate state regulation during a baseline and two auditory processing tasks (i.e., the SCAN tests for Filtered Words and Competing Words), which were used to evaluate auditory processing performance. Children with a diagnosis of autism spectrum disorders (ASD) were contrasted with aged matched typically developing children. The current study identified three features that distinguished the ASD group from a group of typical developing children: 1) baseline RSA, 2) direction of RSA reactivity, and 3) auditory processing performance. In the ASD group, the pattern of change in RSA during the attention demanding SCAN tests moderated the relation between performance on the Competing Words test and IQ. In addition, in a subset of ASD participants, auditory processing performance improved and RSA increased following an intervention designed to improve auditory processing. PMID:23201146

  5. MOUSE SKIN TUMORS AND HUMAN LUNG CANCER: RELATIONSHIPS WITH COMPLEX ENVIRONMENTAL EMISSIONS

    EPA Science Inventory

    Historically, mouse skin tumorigenesis has been used to evaluate the tumorigenic effects of complex mixtures including human respiratory carcinogens. his study examines the quantitative relationships between tumor induction in SENCAR mouse skin and the induction of respiratory ca...

  6. Clinical Accuracy of the Respiratory Tumor Tracking System of the CyberKnife: Assessment by Analysis of Log Files

    SciTech Connect

    Hoogeman, Mischa Prevost, Jean-Briac; Nuyttens, Joost; Poell, Johan; Levendag, Peter; Heijmen, Ben

    2009-05-01

    Purpose: To quantify the clinical accuracy of the respiratory motion tracking system of the CyberKnife treatment device. Methods and Materials: Data in log files of 44 lung cancer patients treated with tumor tracking were analyzed. Errors in the correlation model, which relates the internal target motion with the external breathing motion, were quantified. The correlation model error was compared with the geometric error obtained when no respiratory tracking was used. Errors in the prediction method were calculated by subtracting the predicted position from the actual measured position after 192.5 ms (the time lag to prediction in our current system). The prediction error was also measured for a time lag of 115 ms and a new prediction method. Results: The mean correlation model errors were less than 0.3 mm. Standard deviations describing intrafraction variations around the whole-fraction mean error were 0.2 to 1.9 mm for cranio-caudal, 0.1 to 1.9 mm for left-right, and 0.2 to 2.5 mm for anterior-posterior directions. Without the use of respiratory tracking, these variations would have been 0.2 to 8.1 mm, 0.2 to 5.5 mm, and 0.2 to 4.4 mm. The overall mean prediction error was small (0.0 {+-} 0.0 mm) for all directions. The intrafraction standard deviation ranged from 0.0 to 2.9 mm for a time delay of 192.5 ms but was halved by using the new prediction method. Conclusions: Analyses of the log files of real clinical cases have shown that the geometric error caused by respiratory motion is substantially reduced by the application of respiratory motion tracking.

  7. Atmosphere stabilization and element recycle in an experimental mouse-algal system

    NASA Technical Reports Server (NTRS)

    Smernoff, David T.

    1986-01-01

    Life support systems based on bioregeneration rely on the control and manipulation of organisms. Experiments conducted with a gas-closed mouse-algal system designed to investigate principles of photosynthetic gas exchange focus primarily on observing gas exchange phenomena under varying algal environmental conditions and secondarily on studying element cycling through compartments of the experimental system. Inherent instabilities exit between the uptake and release of carbon dioxide CO2 and oxygen O2 by the mouse and algae. Variations in light intensity and cell density alter the photosynthetic rate of the algae and enable maintenance of physiologic concentrations of CO2 and O2. Different nitrogen sources (urea and nitrate) result in different algal assimilatory quotients (AQ). Combinations of photosynthetic rate and AQ ratio manipulations have been examined for their potential in stabilizing atmospheric gas concentrations in the gas-closed algal-mouse system. Elemental mass balances through the experimental systems compartments are being studied with the concurrent development of a mathematical simulation model. Element cycling experiments include quantification of elemental flows through system compartments and wet oxidation of system waste materials for use as an algal nutrient source. Oxidized waste products demonstrate inhibitory properties although dilution has been shown to allow normal growth.

  8. Physiological and pathophysiological interactions between the respiratory central pattern generator and the sympathetic nervous system.

    PubMed

    Molkov, Yaroslav I; Zoccal, Daniel B; Baekey, David M; Abdala, Ana P L; Machado, Benedito H; Dick, Thomas E; Paton, Julian F R; Rybak, Ilya A

    2014-01-01

    Respiratory modulation seen in the sympathetic nerve activity (SNA) implies that the respiratory and sympathetic networks interact. During hypertension elicited by chronic intermittent hypoxia (CIH), the SNA displays an enhanced respiratory modulation reflecting strengthened interactions between the networks. In this chapter, we review a series of experimental and modeling studies that help elucidate possible mechanisms of sympatho-respiratory coupling. We conclude that this coupling significantly contributes to both the sympathetic baroreflex and the augmented sympathetic activity after exposure to CIH. This conclusion is based on the following findings. (1) Baroreceptor activation results in perturbation of the respiratory pattern via transient activation of postinspiratory neurons in the Bötzinger complex (BötC). The same BötC neurons are involved in the respiratory modulation of SNA, and hence provide an additional pathway for the sympathetic baroreflex. (2) Under hypercapnia, phasic activation of abdominal motor nerves (AbN) is accompanied by synchronous discharges in SNA due to the common source of this rhythmic activity in the retrotrapezoid nucleus (RTN). CIH conditioning increases the CO2 sensitivity of central chemoreceptors in the RTN which results in the emergence of AbN and SNA discharges under normocapnic conditions similar to those observed during hypercapnia in naïve animals. Thus, respiratory-sympathetic interactions play an important role in defining sympathetic output and significantly contribute to the sympathetic activity and hypertension under certain physiological or pathophysiological conditions, and the theoretical framework presented may be instrumental in understanding of malfunctioning control of sympathetic activity in a variety of disease states. PMID:25194190

  9. Fate of inhaled monoclonal antibodies after the deposition of aerosolized particles in the respiratory system.

    PubMed

    Guilleminault, L; Azzopardi, N; Arnoult, C; Sobilo, J; Hervé, V; Montharu, J; Guillon, A; Andres, C; Herault, O; Le Pape, A; Diot, P; Lemarié, E; Paintaud, G; Gouilleux-Gruart, V; Heuzé-Vourc'h, N

    2014-12-28

    Monoclonal antibodies (mAbs) are usually delivered systemically, but only a small proportion of the drug reaches the lung after intravenous injection. The inhalation route is an attractive alternative for the local delivery of mAbs to treat lung diseases, potentially improving tissue concentration and exposure to the drug while limiting passage into the bloodstream and adverse effects. Several studies have shown that the delivery of mAbs or mAb-derived biopharmaceuticals via the airways is feasible and efficient, but little is known about the fate of inhaled mAbs after the deposition of aerosolized particles in the respiratory system. We used cetuximab, an anti-EGFR antibody, as our study model and showed that, after its delivery via the airways, this mAb accumulated rapidly in normal and cancerous tissues in the lung, at concentrations twice those achieved after intravenous delivery, for early time points. The spatial distribution of cetuximab within the tumor was heterogeneous, as reported after i.v. injection. Pharmacokinetic (PK) analyses were carried out in both mice and macaques and showed aerosolized cetuximab bioavailability to be lower and elimination times shorter in macaques than in mice. Using transgenic mice, we showed that FcRn, a key receptor involved in mAb distribution and PK, was likely to make a greater contribution to cetuximab recycling than to the transcytosis of this mAb in the airways. Our results indicate that the inhalation route is potentially useful for the treatment of both acute and chronic lung diseases, to boost and ensure the sustained accumulation of mAbs within the lungs, while limiting their passage into the bloodstream. PMID:25451545

  10. Reductions in the variations of respiration signals for respiratory-gated radiotherapy when using the video-coaching respiration guiding system

    NASA Astrophysics Data System (ADS)

    Lee, Hyun Jeong; Yea, Ji Woon; Oh, Se An

    2015-07-01

    Respiratory-gated radiation therapy (RGRT) has been used to minimize the dose to normal tissue in lung-cancer radiotherapy. The present research aims to improve the regularity of respiration in RGRT by using a video-coached respiration guiding system. In the study, 16 patients with lung cancer were evaluated. The respiration signals of the patients were measured by using a realtime position management (RPM) respiratory gating system (Varian, USA), and the patients were trained using the video-coaching respiration guiding system. The patients performed free breathing and guided breathing, and the respiratory cycles were acquired for ~5 min. Then, Microsoft Excel 2010 software was used to calculate the mean and the standard deviation for each phase. The standard deviation was computed in order to analyze the improvement in the respiratory regularity with respect to the period and the displacement. The standard deviation of the guided breathing decreased to 48.8% in the inhale peak and 24.2% in the exhale peak compared with the values for the free breathing of patient 6. The standard deviation of the respiratory cycle was found to be decreased when using the respiratory guiding system. The respiratory regularity was significantly improved when using the video-coaching respiration guiding system. Therefore, the system is useful for improving the accuracy and the efficiency of RGRT.

  11. A model for gas and nutrient exchange in the chorionic vasculature system of the mouse placenta

    NASA Astrophysics Data System (ADS)

    Mirbod, Parisa; Sled, John

    2015-11-01

    The aim of this study is to develop an analytical model for the oxygen and nutrient transport from the umbilical cord to the small villous capillaries. The nutrient and carbon dioxide removal from the fetal cotyledons in the mouse placental system has also been considered. This model describes the mass transfer between the fetal and the maternal red blood cells in the chorionic arterial vasculature system. The model reveals the detail fetal vasculature system and its geometry and the precise mechanisms of mass transfer through the placenta. The dimensions of the villous capillaries, the total length of the villous trees, the total villi surface area, and the total resistance to mass transport in the fetal villous trees has also been defined. This is the first effort to explain the reason why there are at least 7 lobules in the mouse placenta from the fluid dynamics point of view.

  12. The estrogen receptor fusion system in mouse models: a reversible switch.

    PubMed

    Whitfield, Jonathan; Littlewood, Trevor; Evan, Gerard I; Soucek, Laura

    2015-03-01

    Reversible regulatory mouse models have significantly contributed to our understanding of normal tissue and cancer biology, providing the opportunity to temporally control initiation, progression, and evolution of physiological and pathological events. The tamoxifen inducible system, one of the best-characterized "reversible switch" models, has a number of beneficial features. In this system, the hormone-binding domain of the mammalian estrogen receptor is used as a heterologous regulatory domain. Upon ligand binding, the receptor is released from its inhibitory complex and the fusion protein becomes functional. We summarize the advantages and drawbacks of the system, describe several mouse models that rely on it, and discuss potential improvements that could render it even more useful and versatile. PMID:25734072

  13. [Respiratory behavior].

    PubMed

    Gallego, J; Gaultier, C

    2000-02-01

    The notion of respiratory behaviour is grounded, among other approaches, on studies of neuronal mechanisms of voluntary breathing, clinical data, conditioning experiments and respiratory sensations. The interactions between cortical centres of voluntary breathing and respiratory neurones in the brain stem are poorly understood: voluntary control operates through the direct action of corticomotor centres on respiratory motoneurones; however these cortical structures may directly act on bulbopontine centres, and therefore indirectly on respiratory motoneurones. Recordings in animals of brain stem neuronal activity, brain imaging in humans, and transcortical stimulation of the diaphragm in humans and in animal models support either one or the other hypothesis. The mutual independence of the automatic and the voluntary controls of breathing appears in patients with impaired bulbopontine automatism and operational voluntary control (Central Congenital Hypoventilation Syndrome), and in patients with the reverse impairment (locked-in syndrome). Finally, recent studies in humans and animals show that classical conditioning affects respiratory control and sensations. PMID:10756555

  14. Editing of mouse and human immunoglobulin genes by CRISPR-Cas9 system

    PubMed Central

    Cheong, Taek-Chin; Compagno, Mara; Chiarle, Roberto

    2016-01-01

    Applications of the CRISPR-Cas9 system to edit the genome have widely expanded to include DNA gene knock-out, deletions, chromosomal rearrangements, RNA editing and genome-wide screenings. Here we show the application of CRISPR-Cas9 technology to edit the mouse and human immunoglobulin (Ig) genes. By delivering Cas9 and guide-RNA (gRNA) with retro- or lenti-virus to IgM+ mouse B cells and hybridomas, we induce class-switch recombination (CSR) of the IgH chain to the desired subclass. Similarly, we induce CSR in all human B cell lines tested with high efficiency to targeted IgH subclass. Finally, we engineer mouse hybridomas to secrete Fab′ fragments instead of the whole Ig. Our results indicate that Ig genes in mouse and human cells can be edited to obtain any desired IgH switching helpful to study the biology of normal and lymphoma B cells. We also propose applications that could transform the technology of antibody production. PMID:26956543

  15. Editing of mouse and human immunoglobulin genes by CRISPR-Cas9 system.

    PubMed

    Cheong, Taek-Chin; Compagno, Mara; Chiarle, Roberto

    2016-01-01

    Applications of the CRISPR-Cas9 system to edit the genome have widely expanded to include DNA gene knock-out, deletions, chromosomal rearrangements, RNA editing and genome-wide screenings. Here we show the application of CRISPR-Cas9 technology to edit the mouse and human immunoglobulin (Ig) genes. By delivering Cas9 and guide-RNA (gRNA) with retro- or lenti-virus to IgM(+) mouse B cells and hybridomas, we induce class-switch recombination (CSR) of the IgH chain to the desired subclass. Similarly, we induce CSR in all human B cell lines tested with high efficiency to targeted IgH subclass. Finally, we engineer mouse hybridomas to secrete Fab' fragments instead of the whole Ig. Our results indicate that Ig genes in mouse and human cells can be edited to obtain any desired IgH switching helpful to study the biology of normal and lymphoma B cells. We also propose applications that could transform the technology of antibody production. PMID:26956543

  16. Respiratory failure in diabetic ketoacidosis

    PubMed Central

    Konstantinov, Nikifor K; Rohrscheib, Mark; Agaba, Emmanuel I; Dorin, Richard I; Murata, Glen H; Tzamaloukas, Antonios H

    2015-01-01

    Respiratory failure complicating the course of diabetic ketoacidosis (DKA) is a source of increased morbidity and mortality. Detection of respiratory failure in DKA requires focused clinical monitoring, careful interpretation of arterial blood gases, and investigation for conditions that can affect adversely the respiration. Conditions that compromise respiratory function caused by DKA can be detected at presentation but are usually more prevalent during treatment. These conditions include deficits of potassium, magnesium and phosphate and hydrostatic or non-hydrostatic pulmonary edema. Conditions not caused by DKA that can worsen respiratory function under the added stress of DKA include infections of the respiratory system, pre-existing respiratory or neuromuscular disease and miscellaneous other conditions. Prompt recognition and management of the conditions that can lead to respiratory failure in DKA may prevent respiratory failure and improve mortality from DKA. PMID:26240698

  17. Respiratory failure in diabetic ketoacidosis.

    PubMed

    Konstantinov, Nikifor K; Rohrscheib, Mark; Agaba, Emmanuel I; Dorin, Richard I; Murata, Glen H; Tzamaloukas, Antonios H

    2015-07-25

    Respiratory failure complicating the course of diabetic ketoacidosis (DKA) is a source of increased morbidity and mortality. Detection of respiratory failure in DKA requires focused clinical monitoring, careful interpretation of arterial blood gases, and investigation for conditions that can affect adversely the respiration. Conditions that compromise respiratory function caused by DKA can be detected at presentation but are usually more prevalent during treatment. These conditions include deficits of potassium, magnesium and phosphate and hydrostatic or non-hydrostatic pulmonary edema. Conditions not caused by DKA that can worsen respiratory function under the added stress of DKA include infections of the respiratory system, pre-existing respiratory or neuromuscular disease and miscellaneous other conditions. Prompt recognition and management of the conditions that can lead to respiratory failure in DKA may prevent respiratory failure and improve mortality from DKA. PMID:26240698

  18. Respiratory Homeostasis and Exploitation of the Immune System for Lung Cancer Vaccines

    PubMed Central

    Yagui-Beltrán, Adam; Coussens, Lisa M; Jablons, David M

    2011-01-01

    Lung cancer is the leading cause of all cancer deaths in the US. The international scientific and clinical community has made significant advances toward understanding specific molecular mechanisms underlying lung carcinogenesis; however, despite these insights and advances in surgery and chemoradiotherapy, the prognosis for non-small-cell lung cancer (NSCLC) remains poor. Nonetheless, significant effort is being focused on advancing translational research evaluating the efficacy of novel targeted therapeutic strategies for lung cancer. Illustrative examples of this include antagonists of the epidermal growth factor receptor (EGFR), tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib, and a diverse assortment of anti-angiogenic compounds targeting growth factors and/or their receptors that regulate tumor-associated angiogenic programs. In addition, with the increased awareness of the significant role chronically activated leukocytes play as potentiators of solid-tumor development, the role of innate and adaptive immune cells as regulators of lung carcinogenesis is being examined. While some of these studies are examining how novel therapeutic strategies may enhance the efficacy of lung cancer vaccines, others are evaluating the intrinsic characteristics of the immune response to lung cancer in order to identify rate-limiting molecular and/or cellular programs to target with novel anticancer therapeutics. In this article, we explore important aspects of the immune system and its role in regulating normal respiratory homeostasis compared with the immune response accompanying development of lung cancer. These hallmarks are then discussed in the context of recent efforts to develop lung cancer vaccines, where we have highlighted important concepts that must be taken into consideration for future development of novel therapeutic strategies and clinical trials assessing their efficacy. PMID:22368692

  19. A Chimeric Virus-Mouse Model System for Evaluating the Function and Inhibition of Papain-Like Proteases of Emerging Coronaviruses

    PubMed Central

    Deng, Xufang; Agnihothram, Sudhakar; Mielech, Anna M.; Nichols, Daniel B.; Wilson, Michael W.; StJohn, Sarah E.; Larsen, Scott D.; Mesecar, Andrew D.; Lenschow, Deborah J.; Baric, Ralph S.

    2014-01-01

    ABSTRACT To combat emerging coronaviruses, developing safe and efficient platforms to evaluate viral protease activities and the efficacy of protease inhibitors is a high priority. Here, we exploit a biosafety level 2 (BSL-2) chimeric Sindbis virus system to evaluate protease activities and the efficacy of inhibitors directed against the papain-like protease (PLpro) of severe acute respiratory syndrome coronavirus (SARS-CoV), a biosafety level 3 (BSL-3) pathogen. We engineered Sindbis virus to coexpress PLpro and a substrate, murine interferon-stimulated gene 15 (ISG15), and found that PLpro mediates removal of ISG15 (deISGylation) from cellular proteins. Mutation of the catalytic cysteine residue of PLpro or addition of a PLpro inhibitor blocked deISGylation in virus-infected cells. Thus, deISGylation is a marker of PLpro activity. Infection of alpha/beta interferon receptor knockout (IFNAR−/−) mice with these chimeric viruses revealed that PLpro deISGylation activity removed ISG15-mediated protection during viral infection. Importantly, administration of a PLpro inhibitor protected these mice from lethal infection, demonstrating the efficacy of a coronavirus protease inhibitor in a mouse model. However, this PLpro inhibitor was not sufficient to protect the mice from lethal infection with SARS-CoV MA15, suggesting that further optimization of the delivery and stability of PLpro inhibitors is needed. We extended the chimeric-virus platform to evaluate the papain-like protease/deISGylating activity of Middle East respiratory syndrome coronavirus (MERS-CoV) to provide a small-animal model to evaluate PLpro inhibitors of this recently emerged pathogen. This platform has the potential to be universally adaptable to other viral and cellular enzymes that have deISGylating activities. IMPORTANCE Evaluating viral protease inhibitors in a small-animal model is a critical step in the path toward antiviral drug development. We modified a biosafety level 2 chimeric virus

  20. Systemic neutrophil activation in a mouse model of ischemic stroke and reperfusion.

    PubMed

    Morrison, Helena; McKee, Dana; Ritter, Leslie

    2011-04-01

    As a natural response to injury and disease, neutrophils activate, adhere to the microvasculature, migrate into brain tissue, and release toxic substances such as reactive oxygen species and proteases. This neutrophil response occurs when blood flow is returned to brain tissue (reperfusion) after ischemic stroke. Thus, the presence of activated systemic neutrophils increases the potential for tissue injury during reperfusion after ischemic stroke. Although experiments in rat models suggest that activated neutrophils play a pivotal role in cerebral ischemia reperfusion injury, little is known about systemic neutrophil activation during reperfusion following ischemic stroke in a mouse model. The purpose of this study was to characterize systemic leukocyte responses and neutrophil CD11b expression 15-min and 24-hr post-reperfusion in a mouse model of ischemic stroke. The intraluminal filament method of transient middle cerebral artery occlusion (tMCAO) with reperfusion or a sham procedure was performed in male C57Bl/6 mice. Automated leukocyte counts and manual white blood cell (WBC) differential counts were measured. Flow cytometry was used to assess systemic neutrophil surface CD11b expression. The data suggest that the damaging potential of systemic neutrophil activation begins as early as 15 min and remains evident at 24 hr after the initiation of reperfusion. In addition, because transgenic mouse models, bred on a C57Bl/6 background, are increasingly used to elucidate single mechanisms of reperfusion injury after ischemic stroke, findings from this study are foundational for future investigations examining the damaging potential of neutrophil responses post-reperfusion after ischemic stroke in genetically altered mouse models within this background strain. PMID:21044968

  1. A Novel, Real-Time, In Vivo Mouse Retinal Imaging System

    PubMed Central

    Butler, Mark C.; Sullivan, Jack M.

    2015-01-01

    Purpose To develop an efficient, low-cost instrument for robust real-time imaging of the mouse retina in vivo, and assess system capabilities by evaluating various animal models. Methods Following multiple disappointing attempts to visualize the mouse retina during a subretinal injection using commercially available systems, we identified the key limitation to be inadequate illumination due to off axis illumination and poor optical train optimization. Therefore, we designed a paraxial illumination system for Greenough-type stereo dissecting microscope incorporating an optimized optical launch and an efficiently coupled fiber optic delivery system. Excitation and emission filters control spectral bandwidth. A color coupled-charged device (CCD) camera is coupled to the microscope for image capture. Although, field of view (FOV) is constrained by the small pupil aperture, the high optical power of the mouse eye, and the long working distance (needed for surgical manipulations), these limitations can be compensated by eye positioning in order to observe the entire retina. Results The retinal imaging system delivers an adjustable narrow beam to the dilated pupil with minimal vignetting. The optic nerve, vasculature, and posterior pole are crisply visualized and the entire retina can be observed through eye positioning. Normal and degenerative retinal phenotypes can be followed over time. Subretinal or intraocular injection procedures are followed in real time. Real-time, intravenous fluorescein angiography for the live mouse has been achieved. Conclusions A novel device is established for real-time viewing and image capture of the small animal retina during subretinal injections for preclinical gene therapy studies. PMID:26551329

  2. Integrative database management for mouse development: systems and concepts.

    PubMed

    Singh, Amar V; Rouchka, Eric C; Rempala, Greg A; Bastian, Caleb D; Knudsen, Thomas B

    2007-03-01

    Cells in the developing embryo must integrate complex signals from the genome and environment to make decisions about their behavior or fate. The ability to understand the fundamental biology of the decision-making process, and how these decisions may go awry during abnormal development, requires a systems biology paradigm. Presently, the ability to build models with predictive capability in birth defects research is constrained by an incomplete understanding of the fundamental parameters underlying embryonic susceptibility, sensitivity, and vulnerability. Key developmental milestones must be parameterized in terms of system structure and dynamics, the relevant control methods, and the overall design logic of metabolic and regulatory networks. High-content data from genome-based studies provide some comprehensive coverage of these operational processes but a key research challenge is data integration. Analysis can be facilitated by data management resources and software to reveal the structure and function of bionetwork motifs potentially associated with an altered developmental phenotype. Borrowing from applied mathematics and artificial intelligence, we conceptualize a system that can help address the new challenges posed by the transformation of birth defects research into a data-driven science. PMID:17539026

  3. Minocycline suppresses morphine-induced respiratory depression, suppresses morphine-induced reward, and enhances systemic morphine-induced analgesia

    PubMed Central

    Hutchinson, Mark R.; Northcutt, Alexis L.; Chao, Lindsey W.; Kearney, Jeffrey J.; Zhang, Yingning; Berkelhammer, Debra L.; Loram, Lisa C.; Rozeske, Robert R.; Bland, Sondra T.; Maier, Steven F.; Gleeson, Todd T.; Watkins, Linda R.

    2008-01-01

    Recent data suggest that opioids can activate immune-like cells of the central nervous system (glia). This opioid-induced glial activation is associated with decreased analgesia, owing to the release of proinflammatory mediators. Here we examine in rats whether the putative microglial inhibitor, minocycline, may affect morphine-induced respiratory depression and/or morphine-induced reward (conditioned place preference). Systemic co-administration of minocycline significantly attenuated morphine-induced reductions in tidal volume, minute volume, inspiratory force and expiratory force, but did not affect morphine-induced reductions in respiratory rate. Minocycline attenuation of respiratory depression was also paralleled with significant attenuation by minocycline of morphine-induced reductions in blood oxygen saturation. Minocycline also attenuated morphine conditioned place preference. Minocycline did not simply reduce all actions of morphine, as morphine analgesia was significantly potentiated by minocycline co-administration. Lastly, morphine dose-dependently increased cyclooxygenase-1 gene expression in a rat microglial cell line, an effect that was dose-dependently blocked by minocycline. Together, these data support that morphine can directly activate microglia in a minocycline-suppressible manner and suggest a pivotal role for minocycline-sensitive processes in the mechanisms of morphine-induced respiration depression, reward, and pain modulation. PMID:18706994

  4. Amla Enhances Mitochondrial Spare Respiratory Capacity by Increasing Mitochondrial Biogenesis and Antioxidant Systems in a Murine Skeletal Muscle Cell Line

    PubMed Central

    Yamamoto, Hirotaka; Morino, Katsutaro; Mengistu, Lemecha; Ishibashi, Taishi; Kiriyama, Kohei; Ikami, Takao; Maegawa, Hiroshi

    2016-01-01

    Amla is one of the most important plants in Indian traditional medicine and has been shown to improve various age-related disorders while decreasing oxidative stress. Mitochondrial dysfunction is a proposed cause of aging through elevated oxidative stress. In this study, we investigated the effects of Amla on mitochondrial function in C2C12 myotubes, a murine skeletal muscle cell model with abundant mitochondria. Based on cell flux analysis, treatment with an extract of Amla fruit enhanced mitochondrial spare respiratory capacity, which enables cells to overcome various stresses. To further explore the mechanisms underlying these effects on mitochondrial function, we analyzed mitochondrial biogenesis and antioxidant systems, both proposed regulators of mitochondrial spare respiratory capacity. We found that Amla treatment stimulated both systems accompanied by AMPK and Nrf2 activation. Furthermore, we found that Amla treatment exhibited cytoprotective effects and lowered reactive oxygen species (ROS) levels in cells subjected to t-BHP-induced oxidative stress. These effects were accompanied by increased oxygen consumption, suggesting that Amla protected cells against oxidative stress by using enhanced spare respiratory capacity to produce more energy. Thus we identified protective effects of Amla, involving activation of mitochondrial function, which potentially explain its various effects on age-related disorders. PMID:27340504

  5. Vanadium Inhalation in a Mouse Model for the Understanding of Air-Suspended Particle Systemic Repercussion

    PubMed Central

    Fortoul, T. I.; Rodriguez-Lara, V.; Gonzalez-Villalva, A.; Rojas-Lemus, M.; Cano-Gutierrez, G.; Ustarroz-Cano, M.; Colin-Barenque, L.; Montaño, L. F.; García-Pelez, I.; Bizarro-Nevares, P.; Lopez-Valdez, N.; Falcon-Rodriguez, C. I.; Jimenez-Martínez, R. S.; Ruiz-Guerrero, M. L.; López-Zepeda, L. S.; Morales-Rivero, A.; Muñiz-Rivera-Cambas, A.

    2011-01-01

    There is an increased concern about the health effects that air-suspended particles have on human health which have been dissected in animal models. Using CD-1 mouse, we explore the effects that vanadium inhalation produce in different tissues and organs. Our findings support the systemic effects of air pollution. In this paper, we describe our findings in different organs in our conditions and contrast our results with the literature. PMID:21716674

  6. Behavioral Assessment of the Aging Mouse Vestibular System

    PubMed Central

    Tung, Victoria W. K.; Burton, Thomas J.; Dababneh, Edward; Quail, Stephanie L.; Camp, Aaron J.

    2014-01-01

    Age related decline in balance performance is associated with deteriorating muscle strength, motor coordination and vestibular function. While a number of studies show changes in balance phenotype with age in rodents, very few isolate the vestibular contribution to balance under either normal conditions or during senescence. We use two standard behavioral tests to characterize the balance performance of mice at defined age points over the lifespan: the rotarod test and the inclined balance beam test. Importantly though, a custom built rotator is also used to stimulate the vestibular system of mice (without inducing overt signs of motion sickness). These two tests have been used to show that changes in vestibular mediated-balance performance are present over the murine lifespan. Preliminary results show that both the rotarod test and the modified balance beam test can be used to identify changes in balance performance during aging as an alternative to more difficult and invasive techniques such as vestibulo-ocular (VOR) measurements. PMID:25045963

  7. Inferring cortical function in the mouse visual system through large-scale systems neuroscience.

    PubMed

    Hawrylycz, Michael; Anastassiou, Costas; Arkhipov, Anton; Berg, Jim; Buice, Michael; Cain, Nicholas; Gouwens, Nathan W; Gratiy, Sergey; Iyer, Ramakrishnan; Lee, Jung Hoon; Mihalas, Stefan; Mitelut, Catalin; Olsen, Shawn; Reid, R Clay; Teeter, Corinne; de Vries, Saskia; Waters, Jack; Zeng, Hongkui; Koch, Christof

    2016-07-01

    The scientific mission of the Project MindScope is to understand neocortex, the part of the mammalian brain that gives rise to perception, memory, intelligence, and consciousness. We seek to quantitatively evaluate the hypothesis that neocortex is a relatively homogeneous tissue, with smaller functional modules that perform a common computational function replicated across regions. We here focus on the mouse as a mammalian model organism with genetics, physiology, and behavior that can be readily studied and manipulated in the laboratory. We seek to describe the operation of cortical circuitry at the computational level by comprehensively cataloging and characterizing its cellular building blocks along with their dynamics and their cell type-specific connectivities. The project is also building large-scale experimental platforms (i.e., brain observatories) to record the activity of large populations of cortical neurons in behaving mice subject to visual stimuli. A primary goal is to understand the series of operations from visual input in the retina to behavior by observing and modeling the physical transformations of signals in the corticothalamic system. We here focus on the contribution that computer modeling and theory make to this long-term effort. PMID:27382147

  8. Inferring cortical function in the mouse visual system through large-scale systems neuroscience

    PubMed Central

    Hawrylycz, Michael; Anastassiou, Costas; Arkhipov, Anton; Berg, Jim; Buice, Michael; Cain, Nicholas; Gouwens, Nathan W.; Gratiy, Sergey; Iyer, Ramakrishnan; Lee, Jung Hoon; Mihalas, Stefan; Mitelut, Catalin; Olsen, Shawn; Reid, R. Clay; Teeter, Corinne; de Vries, Saskia; Waters, Jack; Zeng, Hongkui; Koch, Christof

    2016-01-01

    The scientific mission of the Project MindScope is to understand neocortex, the part of the mammalian brain that gives rise to perception, memory, intelligence, and consciousness. We seek to quantitatively evaluate the hypothesis that neocortex is a relatively homogeneous tissue, with smaller functional modules that perform a common computational function replicated across regions. We here focus on the mouse as a mammalian model organism with genetics, physiology, and behavior that can be readily studied and manipulated in the laboratory. We seek to describe the operation of cortical circuitry at the computational level by comprehensively cataloging and characterizing its cellular building blocks along with their dynamics and their cell type-specific connectivities. The project is also building large-scale experimental platforms (i.e., brain observatories) to record the activity of large populations of cortical neurons in behaving mice subject to visual stimuli. A primary goal is to understand the series of operations from visual input in the retina to behavior by observing and modeling the physical transformations of signals in the corticothalamic system. We here focus on the contribution that computer modeling and theory make to this long-term effort. PMID:27382147

  9. Assessing particle and fiber toxicology in the respiratory system: the stereology toolbox.

    PubMed

    Brandenberger, Christina; Ochs, Matthias; Mühlfeld, Christian

    2015-01-01

    The inhalation of airborne particles can lead to pathological changes in the respiratory tract. For this reason, toxicology studies on effects of inhalable particles and fibers often include an assessment of histopathological alterations in the upper respiratory tract, the trachea and/or the lungs. Conventional pathological evaluations are usually performed by scoring histological lesions in order to obtain "quantitative" information and an estimation of the severity of the lesion. This approach not only comprises a potential subjective bias, depending on the examiner's judgment, but also conveys the risk that mild alterations escape the investigator's eye. The most accurate way of obtaining unbiased quantitative information about three-dimensional (3D) features of tissues, cells, or organelles from two-dimensional physical or optical sections is by means of stereology, the gold standard of image-based morphometry. Nevertheless, it can be challenging to express histopathological changes by morphometric parameters such as volume, surface, length or number only. In this review we therefore provide an overview on different histopathological lesions in the respiratory tract associated with particle and fiber toxicology and on how to apply stereological methods in order to correctly quantify and interpret histological lesions in the respiratory tract. The article further aims at pointing out common pitfalls in quantitative histopathology and at providing some suggestions on how respiratory toxicology can be improved by stereology. Thus, we hope that this article will stimulate scientists in particle and fiber toxicology research to implement stereological techniques in their studies, thereby promoting an unbiased 3D assessment of pathological lesions associated with particle exposure. PMID:26521139

  10. Multiparametric and semiquantitative scoring systems for the evaluation of mouse model histopathology - a systematic review

    PubMed Central

    2013-01-01

    Background Histopathology has initially been and is still used to diagnose infectious, degenerative or neoplastic diseases in humans or animals. In addition to qualitative diagnoses semiquantitative scoring of a lesion`s magnitude on an ordinal scale is a commonly demanded task for histopathologists. Multiparametric, semiquantitative scoring systems for mouse models histopathology are a common approach to handle these questions and to include histopathologic information in biomedical research. Results Inclusion criteria for scoring systems were a first description of a multiparametric, semiquantiative scoring systems which comprehensibly describe an approach to evaluate morphologic lesion. A comprehensive literature search using these criteria identified 153 originally designed semiquantitative scoring systems for the analysis of morphologic changes in mouse models covering almost all organs systems and a wide variety of disease models. Of these, colitis, experimental autoimmune encephalitis, lupus nephritis and collagen induced osteoarthritis colitis were the disease models with the largest number of different scoring systems. Closer analysis of the identified scoring systems revealed a lack of a rationale for the selection of the scoring parameters or a correlation between scoring parameter value and the magnitude of the clinical symptoms in most studies. Conclusion Although a decision for a particular scoring system is clearly dependent on the respective scientific question this review gives an overview on currently available systems and may therefore allow for a better choice for the respective project. PMID:23800279

  11. Epithelial morphogenesis: the mouse eye as a model system.

    PubMed

    Chauhan, Bharesh; Plageman, Timothy; Lou, Ming; Lang, Richard

    2015-01-01

    Morphogenesis is the developmental process by which tissues and organs acquire the shape that is critical to their function. Here, we review recent advances in our understanding of the mechanisms that drive morphogenesis in the developing eye. These investigations have shown that regulation of the actin cytoskeleton is central to shaping the presumptive lens and retinal epithelia that are the major components of the eye. Regulation of the actin cytoskeleton is mediated by Rho family GTPases, by signaling pathways and indirectly, by transcription factors that govern the expression of critical genes. Changes in the actin cytoskeleton can shape cells through the generation of filopodia (that, in the eye, connect adjacent epithelia) or through apical constriction, a process that produces a wedge-shaped cell. We have also learned that one tissue can influence the shape of an adjacent one, probably by direct force transmission, in a process we term inductive morphogenesis. Though these mechanisms of morphogenesis have been identified using the eye as a model system, they are likely to apply broadly where epithelia influence the shape of organs during development. PMID:25662266

  12. Culturing Mouse Cardiac Valves in the Miniature Tissue Culture System.

    PubMed

    Kruithof, Boudewijn P T; Lieber, Samuel C; Kruithof-de Julio, Marianna; Gaussin, Vincian; Goumans, Marie José

    2015-01-01

    Heart valve disease is a major burden in the Western world and no effective treatment is available. This is mainly due to a lack of knowledge of the molecular, cellular and mechanical mechanisms underlying the maintenance and/or loss of the valvular structure. Current models used to study valvular biology include in vitro cultures of valvular endothelial and interstitial cells. Although, in vitro culturing models provide both cellular and molecular mechanisms, the mechanisms involved in the 3D-organization of the valve remain unclear. While in vivo models have provided insight into the molecular mechanisms underlying valvular development, insight into adult valvular biology is still elusive. In order to be able to study the regulation of the valvular 3D-organization on tissue, cellular and molecular levels, we have developed the Miniature Tissue Culture System. In this ex vivo flow model the mitral or the aortic valve is cultured in its natural position in the heart. The natural configuration and composition of the leaflet are maintained allowing the most natural response of the valvular cells to stimuli. The valves remain viable and are responsive to changing environmental conditions. This MTCS may provide advantages on studying questions including but not limited to, how does the 3D organization affect valvular biology, what factors affect 3D organization of the valve, and which network of signaling pathways regulates the 3D organization of the valve. PMID:26555276

  13. Atmosphere behavior in gas-closed mouse-algal systems - An experimental and modelling study

    NASA Technical Reports Server (NTRS)

    Averner, M. M.; Moore, B., III; Bartholomew, I.; Wharton, R.

    1984-01-01

    A NASA-sponsored research program initiated using mathematical modelling and laboratory experimentation aimed at examining the gas-exchange characteristics of artificial animal/plant systems closed to the ambient atmosphere is studied. The development of control techniques and management strategies for maintaining the atmospheric levels of carbon dioxide and oxygen at physiological levels is considered. A mathematical model simulating the behavior of a gas-closed mouse-algal system under varying environmental conditions is described. To verify and validate the model simulations, an analytical system with which algal growth and gas exchange characteristics can be manipulated and measured is designed, fabricated, and tested. The preliminary results are presented.

  14. The expression pattern of Follistatin-like 1 in mouse central nervous system development.

    PubMed

    Yang, Yang; Liu, Junhua; Mao, Huihua; Hu, Yu-An; Yan, Yan; Zhao, Chunjie

    2009-10-01

    Follistatin-like 1 (Fstl1), also named TSC-36 (TGF-beta-stimulated clone 36), was first cloned from the mouse osteoblastic MC3T3-E1 cell line and can be up-regulated by TGF-beta. To better study the function of Fstl1 during the development of the mouse central nervous system (CNS), we examined Fstl1 expression in the developing mouse CNS, in detail, by in situ hybridization. Our results show that Fstl1 is strongly expressed in the telencephalon, diencephalon, brainstem, limbic system and spinal cord. In the telencephalon, Fstl1 positive cells are mainly located in the ventricular zone (VZ) and the subventricular zone (SVZ); a relatively weak signal was observed in layers II and III of the neocortex at postnatal stages. Fstl1 expression is robust in the developing hippocampus and persists to P20. In the developing diencephalon and hindbrain, abundant Fstl1 signals were also detected in nuclei including the medial habenular nucleus, the medial dorsal nucleus, the cochlear nuclei and so on. In addition, a strong expression of Fstl1 was detected in the thalamencephalic signal center, as well as in the olfactory cortex from E14.5 to P0. Meanwhile, Fstl1 was expressed in the septal area and the cingulate gyrus of the limbic system after birth. A high level of expression was also observed in the ventral horn of the spinal cord. These results indicate that Fstl1 may play an important role during CNS development in the mouse. PMID:19595790

  15. Prenatal diazepam exposure alters respiratory control system and GABAA and adenosine receptor gene expression in newborn rats.

    PubMed

    Picard, Nathalie; Guénin, Stéphanie; Perrin, Yolande; Hilaire, Gérard; Larnicol, Nicole

    2008-07-01

    In experimental animals, prenatal diazepam exposure has clearly been associated with behavioral disturbances. Its impact on newborn breathing has not been documented despite potential deleterious consequences for later brain development. We addressed this issue in neonatal rats (0-2 d) born from dams, which consumed 2 mg/kg/d diazepam via drinking fluid throughout gestation. In vivo, prenatal diazepam exposure significantly altered the normoxic-breathing pattern, lowering breathing frequency (105 vs. 125 breaths/min) and increasing tidal volume (16.2 vs. 12.7 mL/kg), and the ventilatory response to hypoxia, inducing an immediate and marked decrease in tidal volume (-30%) absent in controls. In vitro, prenatal diazepam exposure significantly increased the respiratory-like frequency produced by pontomedullary and medullary preparations (+38% and +19%, respectively) and altered the respiratory-like response to application of nonoxygenated superfusate. Both in vivo and in vitro, the recovery from oxygen deprivation challenges was delayed by prenatal diazepam exposure. Finally, real-time PCR showed that prenatal diazepam exposure affected mRNA levels of alpha1 and alpha2 GABAA receptor subunits and of A1 and A2A adenosine receptors in the brainstem. These mRNA changes, which are region-specific, suggest that prenatal diazepam exposure interferes with developmental events whose impact on the respiratory system maturation deserves further studies. PMID:18360306

  16. The Impact of Sugar Cane–Burning Emissions on the Respiratory System of Children and the Elderly

    PubMed Central

    Cançado, José E.D.; Saldiva, Paulo H.N.; Pereira, Luiz A.A.; Lara, Luciene B.L.S.; Artaxo, Paulo; Martinelli, Luiz A.; Arbex, Marcos A.; Zanobetti, Antonella; Braga, Alfesio L.F.

    2006-01-01

    We analyzed the influence of emissions from burning sugar cane on the respiratory system during almost 1 year in the city of Piracicaba in southeast Brazil. From April 1997 through March 1998, samples of inhalable particles were collected, separated into fine and coarse particulate mode, and analyzed for black carbon and tracer elements. At the same time, we examined daily records of children (< 13 years of age) and elderly people (> 64 years of age) admitted to the hospital because of respiratory diseases. Generalized linear models were adopted with natural cubic splines to control for season and linear terms to control for weather. Analyses were carried out for the entire period, as well as for burning and nonburning periods. Additional models were built using three factors obtained from factor analysis instead of particles or tracer elements. Increases of 10.2 μg/m3 in particles ≥ 2.5 μm/m3 aerodynamic diameter (PM2.5) and 42.9 μg/m3 in PM10 were associated with increases of 21.4% [95% confidence interval (CI), 4.3–38.5] and 31.03% (95% CI, 1.25–60.21) in child and elderly respiratory hospital admissions, respectively. When we compared periods, the effects during the burning period were much higher than the effects during nonburning period. Elements generated from sugar cane burning (factor 1) were those most associated with both child and elderly respiratory admissions. Our results show the adverse impact of sugar cane burning emissions on the health of the population, reinforcing the need for public efforts to reduce and eventually eliminate this source of air pollution. PMID:16675427

  17. A novel sex determination system in a close relative of the house mouse

    PubMed Central

    Veyrunes, Frederic; Chevret, Pascale; Catalan, Josette; Castiglia, Riccardo; Watson, Johan; Dobigny, Gauthier; Robinson, Terence J.; Britton-Davidian, Janice

    2010-01-01

    Therian mammals have an extremely conserved XX/XY sex determination system. A limited number of mammal species have, however, evolved to escape convention and present aberrant sex chromosome complements. In this study, we identified a new case of atypical sex determination in the African pygmy mouse Mus minutoides, a close evolutionary relative of the house mouse. The pygmy mouse is characterized by a very high proportion of XY females (74%, n = 27) from geographically widespread Southern and Eastern African populations. Sequencing of the high mobility group domain of the mammalian sex determining gene Sry, and karyological analyses using fluorescence in situ hybridization and G-banding data, suggest that the sex reversal is most probably not owing to a mutation of Sry, but rather to a chromosomal rearrangement on the X chromosome. In effect, two morphologically different X chromosomes were identified, one of which, designated X*, is invariably associated with sex-reversed females. The asterisk designates the still unknown mutation converting X*Y individuals into females. Although relatively still unexplored, such an atypical sex chromosome system offers a unique opportunity to unravel new genetic interactions involved in the initiation of sex determination in mammals. PMID:20007182

  18. Linking susceptibility genes and pathogenesis mechanisms using mouse models of systemic lupus erythematosus

    PubMed Central

    Crampton, Steve P.; Morawski, Peter A.; Bolland, Silvia

    2014-01-01

    Systemic lupus erythematosus (SLE) represents a challenging autoimmune disease from a clinical perspective because of its varied forms of presentation. Although broad-spectrum steroids remain the standard treatment for SLE, they have many side effects and only provide temporary relief from the symptoms of the disease. Thus, gaining a deeper understanding of the genetic traits and biological pathways that confer susceptibility to SLE will help in the design of more targeted and effective therapeutics. Both human genome-wide association studies (GWAS) and investigations using a variety of mouse models of SLE have been valuable for the identification of the genes and pathways involved in pathogenesis. In this Review, we link human susceptibility genes for SLE with biological pathways characterized in mouse models of lupus, and discuss how the mechanistic insights gained could advance drug discovery for the disease. PMID:25147296

  19. Feeding behavior as an early predictor of bovine respiratory disease in North American feedlot systems.

    PubMed

    Wolfger, B; Schwartzkopf-Genswein, K S; Barkema, H W; Pajor, E A; Levy, M; Orsel, K

    2015-01-01

    Bovine respiratory disease (BRD), which can cause substantial losses for feedlot operations, is often difficult to detect based solely on visual observations. The objectives of the current study were to determine a BRD case identification based on clinical and laboratory parameters and assess the value of feeding behavior for early detection of BRD. Auction-derived, mixed-breed beef steers (n = 213) with an average arrival weight of 294 kg were placed at a southern Alberta commercial feedlot equipped with an automated feed bunk monitoring system. Feeding behavior was recorded continuously (1-s intervals) for 5 wk after arrival and summarized into meals. Meals were defined as feeding events that were interrupted by less than 300 s nonfeeding. Meal intake (g) and meal time (min) were further summarized into daily mean, minimum, maximum, and sum and, together with frequency of meals per day, were fit into a discrete survival time analysis with a conditional log-log link. Feedlot staff visually evaluated (pen-checked) health status twice daily. Within 35 d after arrival, 76% (n = 165) of the steers had 1 or more clinical signs of BRD (reluctance to move, crusted nose, nasal or ocular discharge, drooped ears or head, and gaunt appearance). Whereas 41 blood samples could not be processed due to immediate freezing, for 124 of these steers, complete and differential blood cell count, total serum protein, plasma fibrinogen, serum concentration of haptoglobin (HP), and serum amyloid A (SAA) were determined. The disease definition for BRD was a rectal temperature ≥ 40.0°C, at least 2 clinical signs of BRD, and HP > 0.15 mg/mL. It was noteworthy that 94% of the 124 steers identified by the feedlot staff with clinical signs of BRD had HP > 0.15 mg/mL. An increase in mean meal intake, frequency, and mean inter-meal interval was associated with a decreased hazard for developing BRD 7 d before visual identification (P < 0.001). Furthermore, increased mean mealtime, frequency

  20. A Support System for Mouse Operations Using Eye-Gaze Input

    NASA Astrophysics Data System (ADS)

    Abe, Kiyohiko; Nakayama, Yasuhiro; Ohi, Shoichi; Ohyama, Minoru

    We have developed an eye-gaze input system for people with severe physical disabilities, such as amyotrophic lateral sclerosis (ALS) patients. This system utilizes a personal computer and a home video camera to detect eye-gaze under natural light. The system detects both vertical and horizontal eye-gaze by simple image analysis, and does not require special image processing units or sensors. Our conventional eye-gaze input system can detect horizontal eye-gaze with a high degree of accuracy. However, it can only classify vertical eye-gaze into 3 directions (up, middle and down). In this paper, we propose a new method for vertical eye-gaze detection. This method utilizes the limbus tracking method for vertical eye-gaze detection. Therefore our new eye-gaze input system can detect the two-dimension coordinates of user's gazing point. By using this method, we develop a new support system for mouse operation. This system can move the mouse cursor to user's gazing point.

  1. Central neural mechanisms of progesterone action: application to the respiratory system.

    PubMed

    Bayliss, D A; Millhorn, D E

    1992-08-01

    Around the turn of the century, it was recognized that women hyperventilate during the luteal phase of the menstrual cycle and during pregnancy. Although a causative role for the steroid hormone progesterone in this hyperventilation was suggested as early as the 1940s, there has been no clear indication as to the mechanism by which it produces its respiratory effects. In contrast, much mechanistic information has been obtained over the same period about a different effect of progesterone, i.e., the facilitation of reproductive behaviors. In this case, the bulk of the evidence supports the hypothesis that progesterone acts via a genomic mechanism with characteristics not unlike those predicted by classic models for steroid hormone action. We recently, therefore, undertook a series of experiments to test predictions of those same models with reference to the respiratory effects of progesterone. Here we highlight the results of those studies; as background to and precedent for our experiments, we briefly review previous work in which effects of progesterone on respiration and reproductive behaviors have been studied. Our results indicate that the respiratory response to progesterone is mediated at hypothalamic sites through an estrogen- (E2) dependent progesterone receptor- (PR) mediated mechanism requiring RNA and protein synthesis, i.e., gene expression. The E2 dependence of the respiratory response to progesterone is likely a consequence of the demonstrated induction of PR mRNA and PR in hypothalamic neurons by E2. In short, we found that neural mechanisms underlying the stimulation of respiration by progesterone were similar to those mediating its reproductive effects. PMID:1399957

  2. Development and Function of the Mouse Vestibular System in the Absence of Gravity Perception

    NASA Technical Reports Server (NTRS)

    Wolgemuth, Debra J.

    2005-01-01

    The hypothesis that was tested in this research was that the absence of gravity perception, such as would occur in space, would affect the development and function of the vestibular and central nervous systems. Further, we postulated that these effects would be more significant at specific stages of post-natal development of the animal. We also proposed the use of molecular genetic approaches that would provide important information as to the hierarchy of gene function during the development and subsequent function of the vestibular system. The tilted (tlt) mutant mouse has been characterized as lacking the ability to provide sensory input to the gravity receptors. The tlt/tlt mutant mice were a particularly attractive model for the study of vestibular function since the primary defect was limited to the receptor part of the vestibular system, and there were no detectable abnormal phenotypes in other organ systems. The goal of the proposed studies was to assess immediate and delayed effects of the lack of gravity perception on the vestibular system. Particular attention was paid to characterizing primarily affected periods of vestibular morphogenesis, and to identifying downstream genetic pathways that are altered in the CNS of the tlt/tlt mutant mouse. The specific aims were: (1) to characterize the postnatal morphogenesis of the CNS in the tlt mutant mouse, using detailed morphometric analysis of isolated vestibular ganglia and brain tissue at different stages of postnatal development and assessment of apoptotic cell death; (2) to examine the expression of selected genes implicated by mutational analysis to be important in vestibular development or function by in situ hybridization or immunohistochemistry in the mutant mice; and (3) to identify other genes involved in vestibular development and function, using differential cloning strategies to isolate genes whose expression is changed in the mutant versus normal vestibular system.

  3. An Automated Mouse Tail Vascular Access System by Vision and Pressure Feedback

    PubMed Central

    Chang, Yen-Chi; Berry-Pusey, Brittany; Yasin, Rashid; Vu, Nam; Maraglia, Brandon; Chatziioannou, Arion X.; Tsao, Tsu-Chin

    2015-01-01

    This paper develops an automated vascular access system (A-VAS) with novel vision-based vein and needle detection methods and real-time pressure feedback for murine drug delivery. Mouse tail vein injection is a routine but critical step for preclinical imaging applications. Due to the small vein diameter and external disturbances such as tail hair, pigmentation, and scales, identifying vein location is difficult and manual injections usually result in poor repeatability. To improve the injection accuracy, consistency, safety, and processing time, A-VAS was developed to overcome difficulties in vein detection noise rejection, robustness in needle tracking, and visual servoing integration with the mechatronics system. PMID:26478693

  4. Pointright: a system to redirect mouse and keyboard control among multiple machines

    DOEpatents

    Johanson, Bradley E.; Winograd, Terry A.; Hutchins, Gregory M.

    2008-09-30

    The present invention provides a software system, PointRight, that allows for smooth and effortless control of pointing and input devices among multiple displays. With PointRight, a single free-floating mouse and keyboard can be used to control multiple screens. When the cursor reaches the edge of a screen it seamlessly moves to the adjacent screen and keyboard control is simultaneously redirected to the appropriate machine. Laptops may also redirect their keyboard and pointing device, and multiple pointers are supported simultaneously. The system automatically reconfigures itself as displays go on, go off, or change the machine they display.

  5. Molecular and neuronal homology between the olfactory systems of zebrafish and mouse.

    PubMed

    Saraiva, Luis R; Ahuja, Gaurav; Ivandic, Ivan; Syed, Adnan S; Marioni, John C; Korsching, Sigrun I; Logan, Darren W

    2015-01-01

    Studies of the two major olfactory organs of rodents, the olfactory mucosa (OM) and the vomeronasal organ (VNO), unraveled the molecular basis of smell in vertebrates. However, some vertebrates lack a VNO. Here we generated and analyzed the olfactory transcriptome of the zebrafish and compared it to the olfactory transcriptomes of mouse to investigate the evolutionary and molecular relationship between single and dual olfactory systems. Our analyses revealed a high degree of molecular conservation, with orthologs of mouse olfactory cell-specific markers and all but one of their chemosensory receptor classes expressed in the single zebrafish olfactory organ. Zebrafish chemosensory receptor genes are expressed across a large dynamic range and their RNA abundance correlates positively with the number of neurons expressing that RNA. Thus we estimate the relative proportions of neuronal sub-types expressing different chemosensory receptors. Receptor repertoire size drives the absolute abundance of different classes of neurons, but we find similar underlying patterns in both species. Finally, we identified novel marker genes that characterize rare neuronal populations in both mouse and zebrafish. In sum, we find that the molecular and cellular mechanisms underpinning olfaction in teleosts and mammals are similar despite 430 million years of evolutionary divergence. PMID:26108469

  6. Molecular and neuronal homology between the olfactory systems of zebrafish and mouse

    PubMed Central

    Saraiva, Luis R.; Ahuja, Gaurav; Ivandic, Ivan; Syed, Adnan S.; Marioni, John C.; Korsching, Sigrun I.; Logan, Darren W.

    2015-01-01

    Studies of the two major olfactory organs of rodents, the olfactory mucosa (OM) and the vomeronasal organ (VNO), unraveled the molecular basis of smell in vertebrates. However, some vertebrates lack a VNO. Here we generated and analyzed the olfactory transcriptome of the zebrafish and compared it to the olfactory transcriptomes of mouse to investigate the evolutionary and molecular relationship between single and dual olfactory systems. Our analyses revealed a high degree of molecular conservation, with orthologs of mouse olfactory cell-specific markers and all but one of their chemosensory receptor classes expressed in the single zebrafish olfactory organ. Zebrafish chemosensory receptor genes are expressed across a large dynamic range and their RNA abundance correlates positively with the number of neurons expressing that RNA. Thus we estimate the relative proportions of neuronal sub-types expressing different chemosensory receptors. Receptor repertoire size drives the absolute abundance of different classes of neurons, but we find similar underlying patterns in both species. Finally, we identified novel marker genes that characterize rare neuronal populations in both mouse and zebrafish. In sum, we find that the molecular and cellular mechanisms underpinning olfaction in teleosts and mammals are similar despite 430 million years of evolutionary divergence. PMID:26108469

  7. Respiratory acidosis

    MedlinePlus

    ... when the lungs cannot remove all of the carbon dioxide the body produces. This causes body fluids, especially ... Acute respiratory acidosis is a condition in which carbon dioxide builds up very quickly, before the kidneys can ...

  8. Evaluating respiratory patient disability.

    PubMed

    Ruiz Manzano, Juan; Alfageme Michavila, Inmaculada; Chiner Vives, Eusebi; Martínez González, Cristina

    2012-08-01

    The evaluation of the disabilities of patients with respiratory disease is regulated by the Spanish Ministry of Labor and Social Security, as are disabilities of any other type. We believe, however, that in respiratory pathologies this evaluation is especially complicated because, as they are chronic processes, they inter-relate with other systems. Furthermore, they tend to have occasional exacerbations; therefore, normal periods may alternate with other periods of important functional limitations. The present document arises from the desire of SEPAR to update this topic and to respond to the requests of respiratory disease patient associations who have asked us to do so. In this paper, we analyze the current situation of work disability legislation as well as the determination of degrees and percentages, including the current criteria for assigning disabilities due to respiratory tract deficiencies. Lastly, we propose work guidelines that would improve the existing scenario and outline this evaluation for specific pathologies. PMID:22341300

  9. Respiratory chain supercomplexes.

    PubMed

    Schägger, H

    2001-01-01

    Respiratory chain supercomplexes have been isolated from mammalian and yeast mitochondria, and bacterial membranes. Functional roles of respiratory chain supercomplexes are catalytic enhancement, substrate channelling, and stabilization of complex I by complex III in mammalian cells. Bacterial supercomplexes are characterized by their relatively high detergent-stability compared to yeast or mammalian supercomplexes that are stable to sonication. The mobility of substrate cytochrome c increases in the order bacterial, yeast, and mammalian respiratory chain. In bacterial supercomplexes, the electron transfer between complexes III and IV involves movement of the mobile head of a tightly bound cytochrome c, whereas the yeast S. cerevisiae seems to use substrate channelling of a mobile cytochrome c, and mammalian respiratory chains have been described to use a cytochrome c pool. Dimeric ATP synthase seems to be specific for mitochondrial OXPHOS systems. Monomeric complex V was found in Acetobacterium woodii and Paracoccus denitrificans. PMID:11798023

  10. MicroCT Morphometry Analysis of Mouse Cancellous Bone: Intra- and Inter-system Reproducibility

    PubMed Central

    Verdelis, K.; Lukashova, L.; Atti, E.; Mayer-Kuckuk, P.; Peterson, M.G.E.; Tetradis, S.; Boskey, A.L.; van der Meulen, M.C.H.

    2012-01-01

    The agreement between measurements and the relative performance reproducibility among different microcomputed tomography (microCT) systems, especially at voxel sizes close to the limit of the instruments, is not known. To compare this reproducibility 3D morphometric analyses of mouse cancellous bone from distal femoral epiphyses were performed using three different ex vivo microCT systems: GE eXplore Locus SP, Scanco μCT35 and Skyscan 1172. Scans were completed in triplicate at 12μm and 8μm voxel sizes and morphometry measurements, from which relative values and dependence on voxel size were examined. Global and individual visually assessed thresholds were compared. Variability from repeated scans at 12μm voxel size was also examined. Bone volume fraction and trabecular separation values were similar, while values for relative bone surface, trabecular thickness and number varied significantly across the three systems. The greatest differences were measured in trabecular thickness (up to 236%) and number (up to 218%). The relative dependence of measurements on voxel size was highly variable for the trabecular number (from 0% to 20% relative difference between measurements from 12μm and 8μm voxel size scans, depending on the system). The intra-system reproducibility of all trabecular measurements was also highly variable across the systems and improved for BV/TV in all the systems when a smaller voxel size was used. It improved using a smaller voxel size in all the other parameters examined for the Scanco system, but not consistently so for the GE or the Skyscan system. Our results indicate trabecular morphometry measurements should not be directly compared across microCT systems. In addition, the conditions, including voxel size, for trabecular morphometry studies in mouse bone should be chosen based on the specific microCT system and the measurements of main interest. PMID:21621659

  11. Self-Calibrating Respiratory-Flowmeter Combination

    NASA Technical Reports Server (NTRS)

    Westenskow, Dwayne R.; Orr, Joseph A.

    1990-01-01

    Dual flowmeters ensure accuracy over full range of human respiratory flow rates. System for measurement of respiratory flow employs two flowmeters; one compensates for deficiencies of other. Combination yields easily calibrated system accurate over wide range of gas flow.

  12. Cystic Fibrosis (CF) Respiratory Screen: Sputum

    MedlinePlus

    ... Cystic Fibrosis (CF) Chloride Sweat Test Lungs and Respiratory System Cystic Fibrosis: Diet and Nutrition Cystic Fibrosis Cystic Fibrosis: Diet and Nutrition Lungs and Respiratory System Contact Us Print Resources Send to a friend ...

  13. The influence of boundary conditions to the flow through model of upper part of human respiratory system

    NASA Astrophysics Data System (ADS)

    Elcner, Jakub; Chovancova, Michaela; Jicha, Miroslav

    2014-03-01

    Respiratory system represents relatively large system of gradually branching channels which can be hardly solved by numerical simulations. Nowadays, research in this area is focused to solve problems in selected parts of respiratory tract rather than whole system. This simplification comes with problem of accurate assessment of boundary conditions on model geometry. Geometry used on Department of Thermomechanics and Environmental Engineering on Brno University of Technology consists of mouth cavity, larynx, trachea and bronchial tree up to seventh generation of branching. This article is focused on comparison of two different settings of boundary conditions steady inspiration during light activity regime. First set of boundary conditions represents commonly used setting with zero pressure resistance on outlet from the model and second method deals with more realistic assumption, where incomplete 3D geometry is coupled with the rest of bronchial tree described by 1D equations and also correlated by the amount of air, which flows in specific lung lobe. The article observed differences in individual mass flow through the model branches under different conditions and its influence on the flow structures.

  14. Validity of Outcome Prediction Scoring Systems in Korean Patients with Severe Adult Respiratory Distress Syndrome Receiving Extracorporeal Membrane Oxygenation Therapy

    PubMed Central

    2016-01-01

    Recently, several prognostic scoring systems for patients with severe acute respiratory distress syndrome (ARDS) requiring extracorporeal membrane oxygenation (ECMO) have been published. The aim of this study was to validate the established scoring systems for outcome prediction in Korean patients. We retrospectively reviewed the data of 50 patients on ECMO therapy in our center from 2012 to 2014. A calculation of outcome prediction scoring tools was performed and the comparison across various models was conducted. In our study, the overall hospital survival was 46% and successful weaning rate was 58%. The Predicting Death for Severe ARDS on V-V ECMO (PRESERVE) score showed good discrimination of mortality prediction for patients on ECMO with AUC of 0.80 (95% CI 0.66-0.90). The respiratory extracorporeal membrane oxygenation survival prediction (RESP) score and simplified acute physiology score (SAPS) II score also showed fair prediction ability with AUC of 0.79 (95% CI 0.65-0.89) and AUC of 0.78 (95% CI 0.64-0.88), respectively. However, the ECMOnet score failed to predict mortality with AUC of 0.51 (95% CI 0.37-0.66). When evaluating the predictive accuracy according to optimal cut-off point of each scoring system, RESP score had a best specificity of 91.3% and 66.7% of sensitivity, respectively. This study supports the clinical usefulness of the prognostic scoring tools for severe ARDS with ECMO therapy when applying to the Korean patients receiving ECMO. PMID:27247503

  15. Validity of Outcome Prediction Scoring Systems in Korean Patients with Severe Adult Respiratory Distress Syndrome Receiving Extracorporeal Membrane Oxygenation Therapy.

    PubMed

    Lee, Seunghyun; Yeo, Hye Ju; Yoon, Seong Hoon; Lee, Seung Eun; Cho, Woo Hyun; Jeon, Doo Soo; Kim, Yun Seong; Son, Bong Soo; Kim, Do Hyung

    2016-06-01

    Recently, several prognostic scoring systems for patients with severe acute respiratory distress syndrome (ARDS) requiring extracorporeal membrane oxygenation (ECMO) have been published. The aim of this study was to validate the established scoring systems for outcome prediction in Korean patients. We retrospectively reviewed the data of 50 patients on ECMO therapy in our center from 2012 to 2014. A calculation of outcome prediction scoring tools was performed and the comparison across various models was conducted. In our study, the overall hospital survival was 46% and successful weaning rate was 58%. The Predicting Death for Severe ARDS on V-V ECMO (PRESERVE) score showed good discrimination of mortality prediction for patients on ECMO with AUC of 0.80 (95% CI 0.66-0.90). The respiratory extracorporeal membrane oxygenation survival prediction (RESP) score and simplified acute physiology score (SAPS) II score also showed fair prediction ability with AUC of 0.79 (95% CI 0.65-0.89) and AUC of 0.78 (95% CI 0.64-0.88), respectively. However, the ECMOnet score failed to predict mortality with AUC of 0.51 (95% CI 0.37-0.66). When evaluating the predictive accuracy according to optimal cut-off point of each scoring system, RESP score had a best specificity of 91.3% and 66.7% of sensitivity, respectively. This study supports the clinical usefulness of the prognostic scoring tools for severe ARDS with ECMO therapy when applying to the Korean patients receiving ECMO. PMID:27247503

  16. Moderate local and systemic respiratory syncytial virus-specific T-cell responses upon mild or subclinical RSV infection.

    PubMed

    de Waal, L; Koopman, L P; van Benten, I J; Brandenburg, A H; Mulder, P G H; de Swart, R L; Fokkens, W J; Neijens, H J; Osterhaus, A D M E

    2003-06-01

    Respiratory syncytial virus (RSV) infections are a major cause of severe respiratory disease in infants. It has been shown that there is an increased frequency of childhood wheezing in ex-bronchiolitic preteen children. This was postulated to be mediated by a vigorous virus-specific Th2 response influencing the further development of the immune system. Little is known about the possible role of the immune response to clinically mild RSV infections in this respect. We have studied the RSV-specific cellular immune response in infants with a laboratory-confirmed RSV upper respiratory tract infection (URTI; n = 13, mean age 12 months, range 2-22 months) in comparison with infants with non-RSV mediated URTI (n = 9, mean age 9.3 months, range 4-18 months) or infants with severe RSV bronchiolitis (n = 11, mean age 2.3 months, range 1-6 months). RSV-specific cytokine-producing cells were enumerated using the ELISPOT method in peripheral blood mononuclear cells and nasal brush T-cells, collected during the acute and convalescent phase of the infection. Mixed Th1 (IFN-gamma) and Th2 (IL-4 and IL-13) responses were detected in all three groups. Frequencies of RSV-specific T-cells were lower in both URTI groups than in the RSV bronchiolitis group, and not significantly different between the RSV URTI and the non-RSV URTI group. The absence of vigorous virus-specific Th2 responses upon mild RSV infection does not support the hypothesis that these infections influence the development of the immune system and that they predispose for the development of atopic disease. PMID:12696123

  17. Evaluation of a Decision Support System for Obstructive Sleep Apnea with Nonlinear Analysis of Respiratory Signals

    PubMed Central

    Kaimakamis, Evangelos; Tsara, Venetia; Bratsas, Charalambos; Sichletidis, Lazaros; Karvounis, Charalambos; Maglaveras, Nikolaos

    2016-01-01

    Introduction Obstructive Sleep Apnea (OSA) is a common sleep disorder requiring the time/money consuming polysomnography for diagnosis. Alternative methods for initial evaluation are sought. Our aim was the prediction of Apnea-Hypopnea Index (AHI) in patients potentially suffering from OSA based on nonlinear analysis of respiratory biosignals during sleep, a method that is related to the pathophysiology of the disorder. Materials and Methods Patients referred to a Sleep Unit (135) underwent full polysomnography. Three nonlinear indices (Largest Lyapunov Exponent, Detrended Fluctuation Analysis and Approximate Entropy) extracted from two biosignals (airflow from a nasal cannula, thoracic movement) and one linear derived from Oxygen saturation provided input to a data mining application with contemporary classification algorithms for the creation of predictive models for AHI. Results A linear regression model presented a correlation coefficient of 0.77 in predicting AHI. With a cutoff value of AHI = 8, the sensitivity and specificity were 93% and 71.4% in discrimination between patients and normal subjects. The decision tree for the discrimination between patients and normal had sensitivity and specificity of 91% and 60%, respectively. Certain obtained nonlinear values correlated significantly with commonly accepted physiological parameters of people suffering from OSA. Discussion We developed a predictive model for the presence/severity of OSA using a simple linear equation and additional decision trees with nonlinear features extracted from 3 respiratory recordings. The accuracy of the methodology is high and the findings provide insight to the underlying pathophysiology of the syndrome. Conclusions Reliable predictions of OSA are possible using linear and nonlinear indices from only 3 respiratory signals during sleep. The proposed models could lead to a better study of the pathophysiology of OSA and facilitate initial evaluation/follow up of suspected patients OSA

  18. Respiratory Allergies: A General Overview of Remedies, Delivery Systems, and the Need to Progress

    PubMed Central

    Colombo, Giselda; Celenza, Cinzia

    2014-01-01

    The spread of respiratory allergies is increasing in parallel with the alarm of the scientific community. Evidently, our knowledge of the onset mechanisms of these diseases and, as a consequence, of the available remedies is inadequate. This review provides a brief, general description of current therapeutic resources and the state of research with regard to both drugs and medical devices in order to highlight their limits and the urgent need for progress. Increasing the amount of basic biochemical research will improve our knowledge of such onset mechanisms and the potential efficacy of therapeutic preparations. PMID:25006500

  19. Minimally invasive microendoscopy system for in vivo functional imaging of deep nuclei in the mouse brain

    PubMed Central

    Bocarsly, Miriam E.; Jiang, Wan-chen; Wang, Chen; Dudman, Joshua T.; Ji, Na; Aponte, Yeka

    2015-01-01

    The ability to image neurons anywhere in the mammalian brain is a major goal of optical microscopy. Here we describe a minimally invasive microendoscopy system for studying the morphology and function of neurons at depth. Utilizing a guide cannula with an ultrathin wall, we demonstrated in vivo two-photon fluorescence imaging of deeply buried nuclei such as the striatum (2.5 mm depth), substantia nigra (4.4 mm depth) and lateral hypothalamus (5.0 mm depth) in mouse brain. We reported, for the first time, the observation of neuronal activity with subcellular resolution in the lateral hypothalamus and substantia nigra of head-fixed awake mice. PMID:26601017

  20. Severe acute respiratory syndrome-coronavirus infection in aged nonhuman primates is associated with modulated pulmonary and systemic immune responses

    PubMed Central

    2014-01-01

    Background Many respiratory viruses disproportionately impact the elderly. Likewise, advanced age correlated with more adverse disease outcomes following severe acute respiratory syndrome coronavirus (SARS-CoV) infection in humans. We used an aged African green monkey SARS-CoV infection model to better understand age-related mechanisms of increased susceptibility to viral respiratory infections. Nonhuman primates are critical translational models for such research given their similarities to humans in immune-ageing as well as lung structure. Results Significant age- and infection-dependent differences were observed in both systemic and mucosal immune compartments. Peripheral lymphocytes, specifically CD8 T and B cells were significantly lower in aged monkeys pre- and post- SARS-CoV infection, while neutrophil and monocyte numbers were not impacted by age or infection status. Serum proinflammatory cytokines were similar in both age groups, whereas significantly lower levels of IL-1beta, IL-18, IL-6, IL-12 and IL-15 were detected in the lungs of SARS-CoV-infected aged monkeys at either 5 or 10 days post infection. Total lung leukocyte numbers and relative frequency of CD8 T cells, B cells, macrophages and dendritic cells were greatly reduced in the aged host during SARS-CoV infection, despite high levels of chemoattractants for many of these cells in the aged lung. Dendritic cells and monocytes/macrophages showed age-dependent differences in activation and chemokine receptor profiles, while the CD8 T cell and B cell responses were significantly reduced in the aged host. In examination of viral titers, significantly higher levels of SARS-CoV were detected in the nasal swabs early, at day 1 post infection, in aged as compared to juvenile monkeys, but virus levels were only slightly higher in aged animals by day 3. Although there was a trend of higher titers in respiratory tissues at day 5 post infection, this did not reach statistical significance and virus was

  1. Respiratory dysfunction associated with traumatic injury to the central nervous system.

    PubMed

    Slack, R S; Shucart, W

    1994-12-01

    Pulmonary dysfunction is a common complication of head trauma and spinal cord injury. Abnormal breathing patterns reflect the influence of altered neural integration. Early arterial hypoxemia can result from ventilation-perfusion mismatching, microatelectasis, aspiration, fat embolism, or the development of the adult respiratory distress syndrome. Significant changes in lung volumes, ventilation, and gas exchange can occur in spinal cord injury as a result of the loss of diaphramatic or intercostal muscle function. Recruitment of accessory respiratory muscles plays an important role in stabilizing the rib cage and improving expiratory function. Strength training improves expiratory muscle function in quadriplegics and should be continued indefinitely. Most importantly, survival of patients with CNS injuries improves with meticulous and vigorous pulmonary hygiene. The pulmonary hygiene program should include regular changes in the patient's position, assisted coughing and deep breathing exercises, incentive spirometer, bronchodilators, fiberoptic bronchoscopy when indicated, and frequent monitoring of pulmonary mechanics. Long-term survival of the patient with head trauma or spinal cord injury is correlated to successful weaning from mechanical ventilation. Various forms of mechanical ventilator support can be adopted for the patient's ventilatory needs, and many patients will achieve some degree of freedom from mechanical ventilation. Newer ventilatory assist devices that do not require tracheostomy should be considered. PMID:7867288

  2. Smoking status in parents of children hospitalized with a diagnosis of respiratory system disorders.

    PubMed

    Cinar, Nursan; Dede, Cemile; Cevahir, Reyhan; Sevimli, Döndü

    2010-11-01

    The purpose of this study was to investigate the relationship between the statuses of hospitalized children with diagnosis of respiratory tract disease with cigarette use in the parents. This descriptive study was conducted in a Gowerment Hospital in the Sakarya city center in Turkey between June 2007 and June 2008. The inclusion criterion was willingness of families with children hospitalized due to diagnosis of respiratory disease to participate in the study. Data were collected from 345 parents using the questionnaire prepared by researchers. In our study parental smoking was observed in 42.3% of fathers, 7.8% mothers and for 20.9% both parents were smoking. It was found that the hospitalization rates were more than two times higher in children diagnosed with pneumonia and bronchitis and three times higher in children hospitalized for asthma whose parents smoke at home compared to those whose parents are non-smokers. Health care professionals who take care of children need to discuss the harmful effects of smoking and the importance of reducing childhood exposure to secondhand smoke; parents should be educated and encouraged not to smoke. PMID:21108615

  3. New insight into the evolution of the vertebrate respiratory system and the discovery of unidirectional airflow in iguana lungs

    PubMed Central

    Cieri, Robert L.; Craven, Brent A.; Schachner, Emma R.; Farmer, C. G.

    2014-01-01

    The generally accepted framework for the evolution of a key feature of the avian respiratory system, unidirectional airflow, is that it is an adaptation for efficiency of gas exchange and expanded aerobic capacities, and therefore it has historically been viewed as important to the ability of birds to fly and to maintain an endothermic metabolism. This pattern of flow has been presumed to arise from specific features of the respiratory system, such as an enclosed intrapulmonary bronchus and parabronchi. Here we show unidirectional airflow in the green iguana, a lizard with a strikingly different natural history from that of birds and lacking these anatomical features. This discovery indicates a paradigm shift is needed. The selective drivers of the trait, its date of origin, and the fundamental aerodynamic mechanisms by which unidirectional flow arises must be reassessed to be congruent with the natural history of this lineage. Unidirectional flow may serve functions other than expanded aerobic capacity; it may have been present in the ancestral diapsid; and it can occur in structurally simple lungs. PMID:25404314

  4. [Characteristics of the respiratory chain and the oxidative phosphorylation system of mitochondria in the flavinogenic Eremothecium ashbyii strain].

    PubMed

    Zviagil'skaia, R A; Korosteleva, N L; Mironov, V A

    1976-01-01

    Tightly coupled mitochondria were isolated from cells of the flavinogenic strain of Eremothecium ashbyii collected during the logarithmic and stationary growth phases. The composition of the respiratory chain and characteristics of the energy coupling system are described. The mitochondria show a wide spectrum of metabolic activity and oxidize Krebs cycle compenents and exogenous NADH. The terminal segment of the respiratory chain is represented by a typical cytochrome system. The mitochondria of the ascomycete collected during the logarithmic growth phase are characterized by a relatively high content of cytochromes b and c, a high rate of oxidation of NAD-dependent substrates, the presence of lower homologues of ubiquinone, UQ6 and UQ7, and extremely high sensitivity of respiration to the action of antimycin A, low content of a component sensitive to rotenone, contrasting with the operation of all three sites of phosphorylation. Transition to the stationary growth phase is accompanied with a decrease in the rate of oxidation of all substrates studied and a declined effectiveness of oxidative phosphorylation. The data obtained are discussed in relation to the ability of the cells for "overproduction" of flavins. PMID:187903

  5. New insight into the evolution of the vertebrate respiratory system and the discovery of unidirectional airflow in iguana lungs.

    PubMed

    Cieri, Robert L; Craven, Brent A; Schachner, Emma R; Farmer, C G

    2014-12-01

    The generally accepted framework for the evolution of a key feature of the avian respiratory system, unidirectional airflow, is that it is an adaptation for efficiency of gas exchange and expanded aerobic capacities, and therefore it has historically been viewed as important to the ability of birds to fly and to maintain an endothermic metabolism. This pattern of flow has been presumed to arise from specific features of the respiratory system, such as an enclosed intrapulmonary bronchus and parabronchi. Here we show unidirectional airflow in the green iguana, a lizard with a strikingly different natural history from that of birds and lacking these anatomical features. This discovery indicates a paradigm shift is needed. The selective drivers of the trait, its date of origin, and the fundamental aerodynamic mechanisms by which unidirectional flow arises must be reassessed to be congruent with the natural history of this lineage. Unidirectional flow may serve functions other than expanded aerobic capacity; it may have been present in the ancestral diapsid; and it can occur in structurally simple lungs. PMID:25404314

  6. Single and combined effects of air pollutants on circulatory and respiratory system-related mortality in Belgrade, Serbia.

    PubMed

    Stojić, Svetlana Stanišić; Stanišić, Nemanja; Stojić, Andreja; Šoštarić, Andrej

    2016-01-01

    The aim of this study was to investigate the association between short- and long-term exposure to particulate matter (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), and soot and mortality attributed to circulatory and respiratory diseases in Belgrade area (Serbia). The analyzed data set comprised results of regular pollutant monitoring and corresponding administrative records on frequency of daily mortality in the period 2009-2014. Nonlinear exposure-response dependencies and delayed effects of temperature were examined by means of distributed lag nonlinear models. The air pollutant loadings and circulatory system-related death rates in Belgrade area are among the highest in Europe. Data demonstrated that excess risk of death with short-term exposure to elevated concentrations of PM10, SO2, and soot was not significant, whereas marked effect size estimates for exposure over 90 d preceding mortality were found. The influence of chronic exposure was shown to be greater for respiratory than circulatory system-related mortality. When stratified by age and gender, higher risk was noted for male individuals below the age of 65 years. PMID:26699658

  7. Fertilization of Mouse Gametes in Vitro Using a Digital Microfluidic System.

    PubMed

    Huang, Hong-Yuan; Shen, Hsien-Hua; Chung, Lung-Yuan; Chung, Yu-Hsiang; Chen, Chih-Chen; Hsu, Chia-Hsien; Fan, Shih-Kang; Yao, Da-Jeng

    2015-12-01

    We demonstrated in vitro fertilization (IVF) using a digital microfluidic (DMF) system, so-called electrowetting on dielectric (EWOD). The DMF device was proved to be biocompatible and the DMF manipulation of a droplet was harmless to the embryos. This DMF platform was then used for the fertilization of mouse gametes in vitro and for embryo dynamic culture based on a dispersed droplet form. Development of the embryos was instantaneously recorded by a time-lapse microscope in an incubator. Our results indicated that increasing the number of sperms for IVF would raise the rate of fertilization. However, the excess of sperms in the 10 μL culture medium would more easily make the embryo dead during cell culture. Dynamic culture powered with EWOD can manipulate a single droplet containing mouse embryos and culture to the eight-cell stage. The fertilization rate of IVF demonstrated by DMF system was 34.8%, and about 25% inseminated embryos dynamically cultured on a DMF chip developed into an eight-cell stage. The results indicate that the DMF system has the potential for application in assisted reproductive technology. PMID:26529769

  8. Successful management of acute respiratory failure in an Idiopathic Pulmonary Fibrosis patient using an extracorporeal carbon dioxide removal system.

    PubMed

    Vianello, Andrea; Arcaro, Giovanna; Paladini, Luciana; Iovino, Silvia

    2016-01-01

    Patients with Idiopathic Pulmonary Fibrosis (IPF) requiring Invasive Mechanical Ventilation (IMV) following unsuccessful treatment with Non-Invasive Ventilation (NIV) have a high mortality rate. IMV is, moreover, an independent predictor of poor outcome during the post-transplantation period in patients on waiting lists for Lung Transplantation (LT). Here we describe the successful management of an IPF patient with acute respiratory failure (ARF) using a pump-assisted veno-venous system for extracorporeal CO2 removal (ECCO2R) (ProLUNG® system) as an alternative to endotracheal intubation (ETI) following NIV failure. Given this positive experience, further studies are warranted focusing on the ECCO2R system's tolerability, safety, and efficacy in patients with IPF and severe ARF in whom NIV alone is ineffective. PMID:27537725

  9. Investigation of the flow-field in the upper respiratory system when wearing N95 filtering facepiece respirator.

    PubMed

    Zhang, Xiaotie; Li, Hui; Shen, Shengnan; Cai, Mang

    2016-05-01

    This article presents a reverse modeling of the headform when wearing a filtering facepiece respirator (FFR) and a computational fluid dynamics (CFD) simulation based on the modeling. The whole model containing the upper respiratory airway, headform, and FFR was directly recorded by computed tomography (CT) scanning, and a medical contrast medium was used to make the FFR "visible." The FFR was normally worn by the subject during CT scanning so that the actual deformation of both the FFR and the face muscles during contact can be objectively conserved. The reverse modeling approach was introduced to rebuild the geometric model and convert it into a CFD solvable model. In this model, we conducted a transient numerical simulation of air flow containing carbon dioxide, thermal dynamics, and pressure and wall shear stress distribution in the respiratory system taking into consideration an individual wearing a FFR. The breathing cycle was described as a time-dependent profile of the air velocity through the respiratory airway. The result shows that wearing the N95 FFR results in CO2 accumulation, an increase in temperature and pressure elevation inside the FFR cavity. The volume fraction of CO2 reaches 1.2% after 7 breathing cycles and then is maintained at 3.04% on average. The wearers re-inhale excessive CO2 in every breathing cycle from the FFR cavity. The air temperature in the FFR cavity increases rapidly at first and then stays close to the exhaled temperature. Compared to not wearing an FFR, wearers have to increase approximately 90 Pa more pressure to keep the same breathing flow rate of 30.54 L/min after wearing an FFR. The nasal vestibule bears more wall shear stress than any other area in the airway. PMID:26653154

  10. Effect of Delta-9-Tetrahydrocannabinol on Mouse Resistance to Systemic Candida albicans Infection

    PubMed Central

    Blumstein, Gideon W.; Parsa, Arya; Park, Anthony K.; McDowell, Beverly L. P.; Arroyo-Mendoza, Melissa; Girguis, Marie; Adler-Moore, Jill P.; Olson, Jon; Buckley, Nancy E.

    2014-01-01

    Delta-9-tetrahydrocannabinol (Δ9-THC), the psychoactive component of marijuana, is known to suppress the immune responses to bacterial, viral and protozoan infections, but its effects on fungal infections have not been studied. Therefore, we investigated the effects of chronic Δ9-THC treatment on mouse resistance to systemic Candida albicans (C. albicans) infection. To determine the outcome of chronic Δ9-THC treatment on primary, acute systemic candidiasis, c57BL/6 mice were given vehicle or Δ9-THC (16 mg/kg) in vehicle on days 1–4, 8–11 and 15–18. On day 19, mice were infected with 5×105 C. albicans. We also determined the effect of chronic Δ9-THC (4–64 mg/kg) treatment on mice infected with a non-lethal dose of 7.5×104 C. albicans on day 2, followed by a higher challenge with 5×105 C. albicans on day 19. Mouse resistance to the infection was assessed by survival and tissue fungal load. Serum cytokine levels were determine to evaluate the immune responses. In the acute infection, chronic Δ9-THC treatment had no effect on mouse survival or tissue fungal load when compared to vehicle treated mice. However, Δ9-THC significantly suppressed IL-12p70 and IL-12p40 as well as marginally suppressed IL-17 versus vehicle treated mice. In comparison, when mice were given a secondary yeast infection, Δ9-THC significantly decreased survival, increased tissue fungal burden and suppressed serum IFN-γ and IL-12p40 levels compared to vehicle treated mice. The data showed that chronic Δ9-THC treatment decreased the efficacy of the memory immune response to candida infection, which correlated with a decrease in IFN-γ that was only observed after the secondary candida challenge. PMID:25057822

  11. The effects of positive end-expiratory pressure on respiratory system mechanics and hemodynamics in postoperative cardiac surgery patients.

    PubMed

    Auler, J O; Carmona, M J; Barbas, C V; Saldiva, P H; Malbouisson, L M

    2000-01-01

    We prospectively evaluated the effects of positive end-expiratory pressure (PEEP) on the respiratory mechanical properties and hemodynamics of 10 postoperative adult cardiac patients undergoing mechanical ventilation while still anesthetized and paralyzed. The respiratory mechanics was evaluated by the inflation inspiratory occlusion method and hemodynamics by conventional methods. Each patient was randomized to a different level of PEEP (5, 10 and 15 cmH2O), while zero end-expiratory pressure (ZEEP) was established as control. PEEP of 15-min duration was applied at 20-min intervals. The frequency dependence of resistance and the viscoelastic properties and elastance of the respiratory system were evaluated together with hemodynamic and respiratory indexes. We observed a significant decrease in total airway resistance (13.12 +/- 0.79 cmH2O l-1 s-1 at ZEEP, 11.94 +/- 0.55 cmH2O l-1 s-1 (P<0.0197) at 5 cmH2O of PEEP, 11.42 +/- 0.71 cmH2O l-1 s-1 (P<0.0255) at 10 cmH2O of PEEP, and 10.32 +/- 0.57 cmH2O l-1 s-1 (P<0.0002) at 15 cmH2O of PEEP). The elastance (Ers; cmH2O/l) was not significantly modified by PEEP from zero (23.49 +/- 1.21) to 5 cmH2O (21.89 +/- 0.70). However, a significant decrease (P<0.0003) at 10 cmH2O PEEP (18.86 +/- 1.13), as well as (P<0.0001) at 15 cmH2O (18.41 +/- 0.82) was observed after PEEP application. Volume dependence of viscoelastic properties showed a slight but not significant tendency to increase with PEEP. The significant decreases in cardiac index (l min-1 m-2) due to PEEP increments (3.90 +/- 0.22 at ZEEP, 3.43 +/- 0.17 (P<0. 0260) at 5 cmH2O of PEEP, 3.31 +/- 0.22 (P<0.0260) at 10 cmH2O of PEEP, and 3.10 +/- 0.22 (P<0.0113) at 15 cmH2O of PEEP) were compensated for by an increase in arterial oxygen content owing to shunt fraction reduction (%) from 22.26 +/- 2.28 at ZEEP to 11.66 +/- 1.24 at PEEP of 15 cmH2O (P<0.0007). We conclude that increments in PEEP resulted in a reduction of both airway resistance and respiratory elastance

  12. Features preferred in-identification system based on computer mouse movements

    NASA Astrophysics Data System (ADS)

    Jašek, Roman; Kolařík, Martin

    2016-06-01

    Biometric identification systems build features, which describe people, using various data. Usually it is not known which of features could be chosen, and a dedicated process called a feature selection is applied to resolve this uncertainty. The relevant features, that are selected with this process, then describe the people in the system as well as possible. It is likely that the relevancy of selected features also mean that these features describe the important things in the measured behavior and that they partly reveal how the behavior works. This paper uses this idea and evaluates results of many runs of feature selection runs in a system, that identifies people using their moving a computer mouse. It has been found that the most frequently selected features repeat between runs, and that these features describe the similar things of the movements.

  13. [Effects of chromium compounds on the respiratory system. 5. Long term inhalation of chromic acid mist in electroplating by C57BL female mice and recapitulation of our experimental studies].

    PubMed

    Adachi, S

    1987-01-01

    Long term inhalation of CrO3 mist by C57BL mice The effects of the chromic acid mist used in electroplating on the respiratory system of C57BL mice (female; n = 43) were examined histopathologically after exposure for 12 months to the mist (1.81 mgCr/m3-120 min, twice a week). Among the 23 mice sacrificed at 12 months after the first exposure, three cases of perforation in the nasal septs, a case of proliferative change of the tracheal epithelium, nine cases of emphysema and four of adenomatous metaplasia of the lungs were observed on antopsy. Among the 20 mice which were sacrificed six months after the last exposure, the same changes as the 12-month exposure group were also observed in the nasal septum, trachea and lungs, but papillomas observed in the nasal epithelia of six mice and adenoma in the lung of a mouse were new findings not seen in the 12-month exposure group. These results suggest that, in view of the low incidence of spontaneous lung tumor in C57BL mice, inhalation of chromic acid mist in electroplating might be a risk factor of lung cancer. Additionally, the occurrence of papillomas in the nasal epithelium demonstrates the need of directing attention to the possible development of cancer of the upper respiratory tract in chromium electroplating workers. Recapitulation on our experimental studies Upon completion of our five reports on the effects of chromium compounds on the respiratory system, a recapitulation of our experimental studies was made and compared with the findings of a number of reports on chromium. It was experimentally and epidemiologically confirmed that hexavalent chromium compounds act as carcinogens and cause specific biological effects on the respiratory system. These characteristics of hexavalent compounds might be attributable to the strong oxidizing potency and/or high permeability through the cell membrane. Furthermore, hexavalent compounds might be entirely different in biological action from trivalent compounds which are

  14. Contribution of a Cyanide-insensitive Alternate Respiratory System to Increases in Formamide Hydro-lyase Activity and to Growth in Stemphylium loti in Vitro1

    PubMed Central

    Rissler, Jane F.; Millar, Roy L.

    1977-01-01

    Stemphylium loti, a pathogen of a cyanogenic plant, possesses a cyanide-insensitive alternate respiratory pathway. In the absence of cytochrome inhibitors, the alternate system had only a minor role in respiration. When S. loti was grown in medium amended with antimycin to block the cytochrome chain, the alternate system accounted for the total oxygen consumption associated with respiration. The contribution of the alternate respiratory system to increases in formamide hydro-lyase (FHL) activity and to growth in S. loti in vitro was assessed. FHL, induced by cyanide, converts cyanide to nontoxic formamide and is partially responsible for the tolerance of S. loti to high concentrations of cyanide in vitro. When the cytochromes were blocked and the cyanide-insensitive respiratory pathway accounted for 100% of the oxygen uptake associated with respiration, FHL activity, but not changes in dry weight, was positively correlated with activity of the alternate pathway. As the alternate pathway activity decreased with increasing concentrations of salicylhydroxamic acid, the level of FHL activity correspondingly decreased. The alternate respiratory system may provide for increases in FHL activity but not for growth. S. loti appears to have two mechanisms for cyanide tolerance in vitro: cyanide-insensitive respiration and FHL activity. The initial activity of FHL for detoxification of cyanide may depend on the alternate respiratory pathway when the cytochromes of the electron transport chain are blocked. PMID:16660201

  15. A primary culture system of mouse thick ascending limb cells with preserved function and uromodulin processing.

    PubMed

    Glaudemans, Bob; Terryn, Sara; Gölz, Nadine; Brunati, Martina; Cattaneo, Angela; Bachi, Angela; Al-Qusairi, Lama; Ziegler, Urs; Staub, Olivier; Rampoldi, Luca; Devuyst, Olivier

    2014-02-01

    The epithelial cells lining the thick ascending limb (TAL) of the loop of Henle perform essential transport processes and secrete uromodulin, the most abundant protein in normal urine. The lack of differentiated cell culture systems has hampered studies of TAL functions. Here, we report a method to generate differentiated primary cultures of TAL cells, developed from microdissected tubules obtained in mouse kidneys. The TAL tubules cultured on permeable filters formed polarized confluent monolayers in ∼12 days. The TAL cells remain differentiated and express functional markers such as uromodulin, NKCC2, and ROMK at the apical membrane. Electrophysiological measurements on primary TAL monolayers showed a lumen-positive transepithelial potential (+9.4 ± 0.8 mV/cm(2)) and transepithelial resistance similar to that recorded in vivo. The transepithelial potential is abolished by apical bumetanide and in primary cultures obtained from ROMK knockout mice. The processing, maturation and apical secretion of uromodulin by primary TAL cells is identical to that observed in vivo. The primary TAL cells respond appropriately to hypoxia, hypertonicity, and stimulation by desmopressin, and they can be transfected. The establishment of this primary culture system will allow the investigation of TAL cells obtained from genetically modified mouse models, providing a critical tool for understanding the role of that segment in health and disease. PMID:23887378

  16. Dog and mouse: toward a balanced view of the mammalian olfactory system.

    PubMed

    Barrios, Arthur W; Sánchez-Quinteiro, Pablo; Salazar, Ignacio

    2014-01-01

    Although the most intensively studied mammalian olfactory system is that of the mouse, in which olfactory chemical cues of one kind or another are detected in four different nasal areas [the main olfactory epithelium (MOE), the septal organ (SO), Grüneberg's ganglion, and the sensory epithelium of the vomeronasal organ (VNO)], the extraordinarily sensitive olfactory system of the dog is also an important model that is increasingly used, for example in genomic studies of species evolution. Here we describe the topography and extent of the main olfactory and vomeronasal sensory epithelia of the dog, and we report finding no structures equivalent to the Grüneberg ganglion and SO of the mouse. Since we examined adults, newborns, and fetuses we conclude that these latter structures are absent in dogs, possibly as the result of regression or involution. The absence of a vomeronasal component based on VR2 receptors suggests that the VNO may be undergoing a similar involutionary process. PMID:25309347

  17. A linear, time-varying simulation of the respiratory tract system

    SciTech Connect

    Hernandez, O.

    1992-11-01

    These results show that regional deposition efficiencies of inhaled particles are highly dependent on the level of physical activity in all the spectrum of thermodynamic and aerodynamic aerosol particle sizes; also it was shown that for particles in the aerodynamic size range, the values of regional deposition efficiencies at the inner regions of the lung are highly dependent on age. In addition, the shape of regional deposition efficiency curves as a function of particle size have a similar behavior for all ages; thus, any variation of the airway geometry and respiratory physiological parameters such as tidal volumes and breathing frequencies due to age difference do not cause a change in the fundamental mechanisms of deposition. Thus, for all the cases of physical activity and age dependency, the deposition of ultrafine aerosol particles is highly enhanced by diffusive processes in all regions of the respiratory tract, and for very large aerosol size particles this behavior is repeated again due to impaction and sedimentation mechanisms. Although the results presented at this work, are the result of computer simulations based on different sources of experimental data, the structure of the computer simulation code BIODEP is flexible enough to the acquisition of any kind of new experimental information in terms of biokinetic analysis and regional deposition parameters. In addition, since the design of BIODEP was intended for easy access to the users, then with exception of the subroutine DIVPAG, at this moment, the modular design of BIODEP using FORTRAN 77 allows the implementation of all the subroutines of BIODEP to be used in a interactive mode with any microcomputer.

  18. Closed system respirometry may underestimate tissue gas exchange and bias the respiratory exchange ratio (RER).

    PubMed

    Malte, Christian Lind; Nørgaard, Simon; Wang, Tobias

    2016-02-01

    Closed respirometry is a commonly used method to measure gas exchange in animals due to its apparent simplicity. Typically, the rates of O2 uptake and CO2 excretion (VO2 and VCO2, respectively) are assumed to be in steady state, such that the measured rates of gas exchange equal those at tissue level. In other words, the respiratory gas exchange ratio (RER) is assumed to equal the respiratory quotient (RQ). However, because the gas concentrations change progressively during closure, the animal inspires air with a progressively increasing CO2 concentration and decreasing O2 concentration. These changes will eventually affect gas exchange causing the O2 and CO2 stores within the animal to change. Because of the higher solubility/capacitance of CO2 in the tissues of the body, VCO2 will be more affected than VO2, and we hypothesize therefore that RER will become progressively underestimated as closure time is prolonged. This hypothesis was addressed by a combination of experimental studies involving closed respirometry on ball pythons (Python regius) as well as mathematical models of gas exchange. We show that increased closed duration of the respirometer reduces RER by up to 13%, and these findings may explain previous reports of RER values being below 0.7. Our model reveals that the maximally possible reduction in RER is determined by the storage capacity of the body for CO2 (product of size and specific capacitance) relative to the respirometer storage capacity. Furthermore, modeling also shows that pronounced ventilatory and circulatory response to hypercapnia can alleviate the reduction in RER. PMID:26523499

  19. Visualizing Viral Dissemination in the Mouse Nervous System, Using a Green Fluorescent Protein-Expressing Borna Disease Virus Vector▿

    PubMed Central

    Ackermann, Andreas; Guelzow, Timo; Staeheli, Peter; Schneider, Urs; Heimrich, Bernd

    2010-01-01

    Borna disease virus (BDV) frequently persists in the brain of infected animals. To analyze viral dissemination in the mouse nervous system, we generated a mouse-adapted virus that expresses green fluorescent protein (GFP). This viral vector supported GFP expression for up to 150 days and possessed an extraordinary staining capacity, visualizing complete dendritic arbors as well as individual axonal fibers of infected neurons. GFP-positive cells were first detected in cortical areas from where the virus disseminated through the entire central nervous system (CNS). Late in infection, GFP expression was found in the sciatic nerve, demonstrating viral spread from the central to the peripheral nervous system. PMID:20219925

  20. Implantable Self-Powered Low-Level Laser Cure System for Mouse Embryonic Osteoblasts' Proliferation and Differentiation.

    PubMed

    Tang, Wei; Tian, Jingjing; Zheng, Qiang; Yan, Lin; Wang, Jiangxue; Li, Zhou; Wang, Zhong Lin

    2015-08-25

    Bone remodeling or orthodontic treatment is usually a long-term process. It is highly desirable to speed up the process for effective medical treatment. In this work, a self-powered low-level laser cure system for osteogenesis is developed using the power generated by the triboelectric nanogenerator. It is found that the system significantly accelerated the mouse embryonic osteoblasts' proliferation and differentiation, which is essential for bone and tooth healing. The system is further demonstrated to be driven by a living creature's motions, such as human walking or a mouse's breathing, suggesting its practical use as a portable or implantable clinical cure for bone remodeling or orthodontic treatment. PMID:26161869

  1. Temperature control of a microspectrophotometer system for monitoring the redox reactions of respiratory pigments in small volumes

    NASA Astrophysics Data System (ADS)

    Kavanagh, Karen Y.; Walsh, James E.; Murphy, J.; Harmey, M.; Farrell, M. A.; Hardimann, O.; Perryman, R.

    1998-05-01

    We report the development of a microspectrophotometer system for use on micro samples of mitochondrial respiratory pigments. A novel optical fiber set-up uses visible spectrophotometry to monitor the reduction of mitochondrial electron carriers. Data is presented for the reduction of cytochrome-c and for the effect of temperature on the levels of complex II/III activity from the mitochondria of rat liver. This in-vivo simulation of the reduction of cytochrome-c can be observed using a fiber optic probe which requires less than twenty (mu) l of sample for analysis. The key features of the system are: front end adaptability, high sensitivity and fast multispectral acquisition which are essential for the biological reactions which are observed.

  2. Mouse Curve Biometrics

    SciTech Connect

    Schulz, Douglas A.

    2007-10-08

    A biometric system suitable for validating user identity using only mouse movements and no specialized equipment is presented. Mouse curves (mouse movements with little or no pause between them) are individually classied and used to develop classication histograms, which are representative of an individual's typical mouse use. These classication histograms can then be compared to validate identity. This classication approach is suitable for providing continuous identity validation during an entire user session.

  3. Management of Respiratory Failure.

    PubMed

    Singh Lamba, Tejpreet; Sharara, Rihab Saeed; Leap, Jennifer; Singh, Anil C

    2016-01-01

    The management of acute respiratory failure varies according to the etiology. A clear understanding of physiology of respiration and pathophysiological mechanisms of respiratory failure is mandatory for managing these patients. The extent of abnormality in arterial blood gas values is a result of the balance between the severity of disease and the degree of compensation by cardiopulmonary system. Normal blood gases do not mean that there is an absence of disease because the homeostatic system can compensate. However, an abnormal arterial blood gas value reflects uncompensated disease that might be life threatening. PMID:26919671

  4. Stability of the human respiratory control system. I. Analysis of a two-dimensional delay state-space model.

    PubMed

    Batzel, J J; Tran, H T

    2000-07-01

    A number of mathematical models of the human respiratory control system have been developed since 1940 to study a wide range of features of this complex system. Among them, periodic breathing (including Cheyne-Stokes respiration and apneustic breathing) is a collection of regular but involuntary breathing patterns that have important medical implications. The hypothesis that periodic breathing is the result of delay in the feedback signals to the respiratory control system has been studied since the work of Grodins et al. in the early 1950's [12]. The purpose of this paper is to study the stability characteristics of a feedback control system of five differential equations with delays in both the state and control variables presented by Khoo et al. [17] in 1991 for modeling human respiration. The paper is divided in two parts. Part I studies a simplified mathematical model of two nonlinear state equations modeling arterial partial pressures of O2 and CO2 and a peripheral controller. Analysis was done on this model to illuminate the effect of delay on the stability. It shows that delay dependent stability is affected by the controller gain, compartmental volumes and the manner in which changes in the ventilation rate is produced (i.e., by deeper breathing or faster breathing). In addition, numerical simulations were performed to validate analytical results. Part II extends the model in Part I to include both peripheral and central controllers. This, however, necessitates the introduction of a third state equation modeling CO2 levels in the brain. In addition to analytical studies on delay dependent stability, it shows that the decreased cardiac output (and hence increased delay) resulting from the congestive heart condition can induce instability at certain control gain levels. These analytical results were also confirmed by numerical simulations. PMID:10958415

  5. Stability of the human respiratory control system. II. Analysis of a three-dimensional delay state-space model.

    PubMed

    Batzel, J J; Tran, H T

    2000-07-01

    A number of mathematical models of the human respiratory control system have been developed since 1940 to study a wide range of features of this complex system. Among them, periodic breathing (including Cheyne-Stokes respiration and apneustic breathing) is a collection of regular but involuntary breathing patterns that have important medical implications. The hypothesis that periodic breathing is the result of delay in the feedback signals to the respiratory control system has been studied since the work of Grodins et al. in the early 1950's [1]. The purpose of this paper is to study the stability characteristics of a feedback control system of five differential equations with delays in both the state and control variables presented by Khoo et al. [4] in 1991 for modeling human respiration. The paper is divided in two parts. Part I studies a simplified mathematical model of two nonlinear state equations modeling arterial partial pressures of O2 and CO2 and a peripheral controller. Analysis was done on this model to illuminate the effect of delay on the stability. It shows that delay dependent stability is affected by the controller gain, compartmental volumes and the manner in which changes in the ventilation rate is produced (i.e., by deeper breathing or faster breathing). In addition, numerical simulations were performed to validate analytical results. Part II extends the model in Part I to include both peripheral and central controllers. This, however, necessitates the introduction of a third state equation modeling CO2 levels in the brain. In addition to analytical studies on delay dependent stability, it shows that the decreased cardiac output (and hence increased delay) resulting from the congestive heart condition can induce instability at certain control gain levels. These analytical results were also confirmed by numerical simulations. PMID:10958416

  6. Investigations of the Cardiovascular and Respiratory Systems on Board the International Space Station: Experiments Puls and Pneumocard

    NASA Astrophysics Data System (ADS)

    Baranov, V. M.; Baevsky, R. M.; Drescher, J.; Tank, J.

    parameters describing the results of the function of these systems like heart rate, arterial pressure, cardiac output, or breathing frequency, concentration of O2 and CO2 , etc. Missing significant changes of these parameters during weightlessness supports the hypothesis that adaptational and compensatory mechanisms are sufficient and guarantee cardiovascular homeostasis under changing environmental conditions. characteristic changes of the vegetative balance and of the activity of different regulatory elements at the brainstem and subcortical level. This changes guaranteed the adaptation to long term weightlessness. However, it remains unclear to what extent the different levels are involved. Moreover, the criteria describing the efficacy of cardiorespiratory interaction for the different functional states are not defined yet. The investigation of this problems is highly relevant in order to improve the medical control, especially if considering that the disruption of regulatory systems mostly precedes dangerous destruction of homeostasis. cardiovascular and respiratory function on Board the International Space Station (ISS) aiming to obtain new insights into the interaction between different regulatory elements. "Puls" is measures ECG, photoplethysmogram (PPG), and the pneumotachogram (PTG). The ECG is used to measure time series of R-R intervals and to analyse HRV. PPG is used to define the pulse wave velocity, phases of the cardiac cycle, and an estimate of the filling of finger vessels. The variability of these parameters is also calculated and compared to HRV. The analysis of the PTG allows to describe the interaction of the regulatory parameters of the cardiovascular and respiratory systems. Hence, an important feature of the experiment "Puls" is the investigation of regulatory mechanisms rather than of cardiovascular homeostasis. cardiography) and left ventricular contractility (seismocardiography) will be obtained. This expansion is of major importance

  7. Respiratory Failure

    MedlinePlus

    ... from inhaling smoke or harmful fumes Treatment for respiratory failure depends on whether the condition is acute (short-term) or chronic (ongoing) and how severe it is. It also depends on the underlying cause. You may receive oxygen therapy and other treatment to help you breathe. NIH: ...

  8. The Effects of Leucine, Zinc, and Chromium Supplements on Inflammatory Events of the Respiratory System in Type 2 Diabetic Rats

    PubMed Central

    Kolahian, Saeed; Sadri, Hassan; Shahbazfar, Amir Ali; Amani, Morvarid; Mazadeh, Anis; Mirani, Mehdi

    2015-01-01

    Diabetes mellitus is a major cause of serious micro- and macrovascular diseases that affect nearly every system in the body, including the respiratory system. Non-enzymatic protein glycation due to hyperglycaemic stress has fundamental implications due to the large capillary network and amount of connective tissue in the lung. The current study was designed to determine whether leucine, zinc, and chromium supplementations influence the function and histological structure of the respiratory tract in a rat model of type 2 diabetes. Seventy-seven rats were divided into eleven groups, consisting of 7 animals each. One group served as negative control and insulin and glibenclamide were used as positive control drugs. Thus, eight groups received the nutritional supplements alone or in combination with each other. Nutritional supplements and glibenclamide were added to the drinking water and neutral protamine Hagedorn insulin was subcutaneously injected during the 4 weeks of treatment period. The induction of type 2 diabetes in the rats caused an infiltration of mononuclear cells and edema in the submucosa of the trachea and lung, severe fibrosis around the vessels and airways, and perivascular and peribronchial infiltration of inflammatory cells and fibrin. In the diabetic group, the total inflammation score and Reid index significantly increased. Diabetes induction significantly reduced the total antioxidant status and elevated the lipid peroxidation products in the serum, lung lavage and lung tissue of the diabetic animals. Treatment with nutritional supplements significantly decreased the histopathological changes and inflammatory indices in the diabetic animals. Supplementation of diabetic rats with leucine, zinc, and chromium, alone and in combination, significantly increased the total antioxidant status and lipid peroxidation level in the diabetic animals. The nutritional supplements improved the enzymatic antioxidant activity of catalase, glutathione peroxidase

  9. The Effects of Leucine, Zinc, and Chromium Supplements on Inflammatory Events of the Respiratory System in Type 2 Diabetic Rats.

    PubMed

    Kolahian, Saeed; Sadri, Hassan; Shahbazfar, Amir Ali; Amani, Morvarid; Mazadeh, Anis; Mirani, Mehdi

    2015-01-01

    Diabetes mellitus is a major cause of serious micro- and macrovascular diseases that affect nearly every system in the body, including the respiratory system. Non-enzymatic protein glycation due to hyperglycaemic stress has fundamental implications due to the large capillary network and amount of connective tissue in the lung. The current study was designed to determine whether leucine, zinc, and chromium supplementations influence the function and histological structure of the respiratory tract in a rat model of type 2 diabetes. Seventy-seven rats were divided into eleven groups, consisting of 7 animals each. One group served as negative control and insulin and glibenclamide were used as positive control drugs. Thus, eight groups received the nutritional supplements alone or in combination with each other. Nutritional supplements and glibenclamide were added to the drinking water and neutral protamine Hagedorn insulin was subcutaneously injected during the 4 weeks of treatment period. The induction of type 2 diabetes in the rats caused an infiltration of mononuclear cells and edema in the submucosa of the trachea and lung, severe fibrosis around the vessels and airways, and perivascular and peribronchial infiltration of inflammatory cells and fibrin. In the diabetic group, the total inflammation score and Reid index significantly increased. Diabetes induction significantly reduced the total antioxidant status and elevated the lipid peroxidation products in the serum, lung lavage and lung tissue of the diabetic animals. Treatment with nutritional supplements significantly decreased the histopathological changes and inflammatory indices in the diabetic animals. Supplementation of diabetic rats with leucine, zinc, and chromium, alone and in combination, significantly increased the total antioxidant status and lipid peroxidation level in the diabetic animals. The nutritional supplements improved the enzymatic antioxidant activity of catalase, glutathione peroxidase

  10. A microbial clock provides an accurate estimate of the postmortem interval in a mouse model system

    PubMed Central

    Metcalf, Jessica L; Wegener Parfrey, Laura; Gonzalez, Antonio; Lauber, Christian L; Knights, Dan; Ackermann, Gail; Humphrey, Gregory C; Gebert, Matthew J; Van Treuren, Will; Berg-Lyons, Donna; Keepers, Kyle; Guo, Yan; Bullard, James; Fierer, Noah; Carter, David O; Knight, Rob

    2013-01-01

    Establishing the time since death is critical in every death investigation, yet existing techniques are susceptible to a range of errors and biases. For example, forensic entomology is widely used to assess the postmortem interval (PMI), but errors can range from days to months. Microbes may provide a novel method for estimating PMI that avoids many of these limitations. Here we show that postmortem microbial community changes are dramatic, measurable, and repeatable in a mouse model system, allowing PMI to be estimated within approximately 3 days over 48 days. Our results provide a detailed understanding of bacterial and microbial eukaryotic ecology within a decomposing corpse system and suggest that microbial community data can be developed into a forensic tool for estimating PMI. DOI: http://dx.doi.org/10.7554/eLife.01104.001 PMID:24137541

  11. Defining Functional Gene-Circuit Interfaces in the Mouse Nervous System

    PubMed Central

    Soden, Marta E.; Gore, Bryan B.; Zweifel, Larry S.

    2013-01-01

    Complexity in the nervous system is established by developmental genetic programs, maintained by differential genetic profiles, and sculpted by experiential and environmental influence over gene expression. Determining how specific genes define neuronal phenotypes, shape circuit connectivity, and regulate circuit function is essential for understanding how the brain processes information, directs behavior, and adapts to changing environments. Mouse genetics has contributed greatly to current percepts of gene-circuit interfaces in behavior, but considerable work remains. Large-scale initiatives to map gene expression and connectivity in the brain, together with advanced techniques in molecular genetics, now allow detailed exploration of the genetic basis of nervous system function at the level of specific circuit connections. In this review, we highlight several key advances for defining the function of specific genes within a neural network. PMID:24007626

  12. Mustard vesicants alter expression of the endocannabinoid system in mouse skin.

    PubMed

    Wohlman, Irene M; Composto, Gabriella M; Heck, Diane E; Heindel, Ned D; Lacey, C Jeffrey; Guillon, Christophe D; Casillas, Robert P; Croutch, Claire R; Gerecke, Donald R; Laskin, Debra L; Joseph, Laurie B; Laskin, Jeffrey D

    2016-07-15

    Vesicants including sulfur mustard (SM) and nitrogen mustard (NM) are bifunctional alkylating agents that cause skin inflammation, edema and blistering. This is associated with alterations in keratinocyte growth and differentiation. Endogenous cannabinoids, including N-arachidonoylethanolamine (anandamide, AEA) and 2-arachidonoyl glycerol (2-AG), are important in regulating inflammation, keratinocyte proliferation and wound healing. Their activity is mediated by binding to cannabinoid receptors 1 and 2 (CB1 and CB2), as well as peroxisome proliferator-activated receptor alpha (PPARα). Levels of endocannabinoids are regulated by fatty acid amide hydrolase (FAAH). We found that CB1, CB2, PPARα and FAAH were all constitutively expressed in mouse epidermis and dermal appendages. Topical administration of NM or SM, at concentrations that induce tissue injury, resulted in upregulation of FAAH, CB1, CB2 and PPARα, a response that persisted throughout the wound healing process. Inhibitors of FAAH including a novel class of vanillyl alcohol carbamates were found to be highly effective in suppressing vesicant-induced inflammation in mouse skin. Taken together, these data indicate that the endocannabinoid system is important in regulating skin homeostasis and that inhibitors of FAAH may be useful as medical countermeasures against vesicants. PMID:27125198

  13. Gastrointestinal cancer studies in the human to nude mouse heterotransplant system.

    PubMed

    Schmidt, M; Deschner, E E; Thaler, H T; Clements, L; Good, R A

    1977-05-01

    Human gastrointestinal cancer xenografts were established in the nude mouse. Grafts were accomplished with gastric adenocarcinomas, gastric leiomyosarcoma, histiocytic lymphoma of the stomach and gallbladder, pancreatic tumors, colonic cancers and cell lines of duodenal (HUTU-80) and pancreatic (HS-766-T) cancers, melanoma (SK-Mel-5), and murine metastasizing Lewis lung carcinoma. The rate of successful xenografting of these tumors varied from virtually 100% with colon and duodenal cancer, 50% for a pancreatic cancer (P-1), to only 17% for gastric adenocarcinoma. Pancreas and colon adenocarcinomas have been maintained by successive xenotransplantation over 16 and 19 months, respectively. Human xenografts retained morphological identity with tissues of origin through several transplant generations and shared some of their ultrastructural characteristics but did not metastasize. Rodent xenografts, of heterogenous origin were characterized by differences in the duration of the latent period and in the rate of their initial development as described by the average doubling times and average slopes (B) of their growth curves. Differences between B of the Lewis lung carcinoma and all of the human xenografts and between B of a pancreatic adenocarcinoma and three other neoplasms were significant (P less than 0.05 to 0.04). Labeling indices determined for 14 cancer transplants were in the range of previously reported data for similar neoplasms in patients or other xenograft systems. These findings suggest that the nude mouse model can be used to evaluate endogenous properties of gastrointestinal cancers and their responses to exogenous agents. PMID:321290

  14. Robust axonal regeneration occurs in the injured CAST/Ei mouse central nervous system

    PubMed Central

    Omura, Takao; Omura, Kumiko; Tedeschi, Andrea; Riva, Priscilla; Painter, Michio W; Rojas, Leticia; Martin, Joshua; Lisi, Véronique; Huebner, Eric A; Latremoliere, Alban; Yin, Yuqin; Barrett, Lee; Singh, Bhagat; Lee, Stella; Crisman, Tom; Gao, Fuying; Li, Songlin; Kapur, Kush; Geschwind, Daniel H; Kosik, Kenneth S; Coppola, Giovanni; He, Zhigang; Carmichael, S Thomas; Benowitz, Larry I; Costigan, Michael; Woolf, Clifford J

    2015-01-01

    SUMMARY Axon regeneration in the central nervous system (CNS) requires reactivating injured neurons’ intrinsic growth state and enabling growth in an inhibitory environment. Using an inbred mouse neuronal phenotypic screen, we find that CAST/Ei mouse adult dorsal root ganglion neurons extend axons more on CNS myelin than the other eight strains tested, especially when pre-injured. Injury-primed CAST/Ei neurons also regenerate markedly in the spinal cord and optic nerve more than those from C57BL/6 mice and show greater spouting following ischemic stroke. Heritability estimates indicate that extended growth in CAST/Ei neurons on myelin is genetically determined, and two whole-genome expression screens yield the Activin transcript Inhba as most correlated with this ability. Inhibition of Activin signaling in CAST/Ei mice diminishes their CNS regenerative capacity whereas its activation in C57BL/6 animals boosts regeneration. This screen demonstrates that mammalian CNS regeneration can occur and reveals a molecular pathway that contributes to this ability. PMID:26004914

  15. Systems Biology-Based Identification of Mycobacterium tuberculosis Persistence Genes in Mouse Lungs

    PubMed Central

    Dutta, Noton K.; Bandyopadhyay, Nirmalya; Veeramani, Balaji; Lamichhane, Gyanu; Karakousis, Petros C.; Bader, Joel S.

    2014-01-01

    ABSTRACT Identifying Mycobacterium tuberculosis persistence genes is important for developing novel drugs to shorten the duration of tuberculosis (TB) treatment. We developed computational algorithms that predict M. tuberculosis genes required for long-term survival in mouse lungs. As the input, we used high-throughput M. tuberculosis mutant library screen data, mycobacterial global transcriptional profiles in mice and macrophages, and functional interaction networks. We selected 57 unique, genetically defined mutants (18 previously tested and 39 untested) to assess the predictive power of this approach in the murine model of TB infection. We observed a 6-fold enrichment in the predicted set of M. tuberculosis genes required for persistence in mouse lungs relative to randomly selected mutant pools. Our results also allowed us to reclassify several genes as required for M. tuberculosis persistence in vivo. Finally, the new results implicated additional high-priority candidate genes for testing. Experimental validation of computational predictions demonstrates the power of this systems biology approach for elucidating M. tuberculosis persistence genes. PMID:24549847

  16. Vegfr3-CreER (T2) mouse, a new genetic tool for targeting the lymphatic system.

    PubMed

    Martinez-Corral, Ines; Stanczuk, Lukas; Frye, Maike; Ulvmar, Maria Helena; Diéguez-Hurtado, Rodrigo; Olmeda, David; Makinen, Taija; Ortega, Sagrario

    2016-07-01

    The lymphatic system is essential in many physiological and pathological processes. Still, much remains to be known about the molecular mechanisms that control its development and function and how to modulate them therapeutically. The study of these mechanisms will benefit from better controlled genetic mouse models targeting specifically lymphatic endothelial cells. Among the genes expressed predominantly in lymphatic endothelium, Vegfr3 was the first one identified and is still considered to be one of the best lymphatic markers and a key regulator of the lymphatic system. Here, we report the generation of a Vegfr3-CreER (T2) knockin mouse by gene targeting in embryonic stem cells. This mouse expresses the tamoxifen-inducible CreER(T2) recombinase under the endogenous transcriptional control of the Vegfr3 gene without altering its physiological expression or regulation. The Vegfr3-CreER (T2) allele drives efficient recombination of floxed sequences upon tamoxifen administration specifically in Vegfr3-expressing cells, both in vitro, in primary lymphatic endothelial cells, and in vivo, at different stages of mouse embryonic development and postnatal life. Thus, our Vegfr3-CreER (T2) mouse constitutes a new powerful genetic tool for lineage tracing analysis and for conditional gene manipulation in the lymphatic endothelium that will contribute to improve our current understanding of this system. PMID:26993803

  17. Respiratory Home Health Care

    MedlinePlus

    ... Healthy Living > Living With Lung Disease > Respiratory Home Health Care Font: Aerosol Delivery Oxygen Resources Immunizations Pollution Nutrition ... Disease Articles written by Respiratory Experts Respiratory Home Health Care Respiratory care at home can contribute to improved ...

  18. Functional respiratory imaging to assess the interaction between systemic roflumilast and inhaled ICS/LABA/LAMA

    PubMed Central

    Vos, Wim; Hajian, Bita; De Backer, Jan; Van Holsbeke, Cedric; Vinchurkar, Samir; Claes, Rita; Hufkens, Annemie; Parizel, Paul M; Bedert, Lieven; De Backer, Wilfried

    2016-01-01

    Background Patients with COPD show a significant reduction of the lobar hyperinflation at the functional residual capacity level in the patients who improved >120 mL in forced expiratory volume in 1 second (FEV1) after 6 months of treatment with roflumilast in addition to inhaled corticosteroids (ICSs)/long-acting beta-2 agonists (LABAs)/long-acting muscarinic antagonists (LAMAs). Methods Functional respiratory imaging was used to quantify lobar hyperinflation, blood vessel density, ventilation, aerosol deposition, and bronchodilation. To investigate the exact mode of action of roflumilast, correlations between lobar and global measures have been tested using a mixed-model approach with nested random factors and Pearson correlation, respectively. Results The reduction in lobar hyperinflation appears to be associated with a larger blood vessel density in the respective lobes (t=−2.154, P=0.040); lobes with a higher percentage of blood vessels reduce more in hyperinflation in the responder group. Subsequently, it can be observed that lobes that reduce in hyperinflation after treatment are better ventilated (t=−5.368, P<0.001). Functional respiratory imaging (FRI)-based aerosol deposition showed that enhanced ventilation leads to more peripheral particle deposition of ICS/LABA/LAMA in the better-ventilated areas (t=2.407, P=0.024). Finally, the study showed that areas receiving more particles have increased FRI-based bronchodilation (t=2.564, P=0.017), leading to an increase in FEV1 (R=0.348, P=0.029). Conclusion The study demonstrated that orally administered roflumilast supports the reduction of regional hyperinflation in areas previously undertreated by inhalation medication. The local reduction in hyperinflation induces a redistribution of ventilation and aerosol deposition, leading to enhanced efficacy of the concomitant ICS/LABA/LAMA therapy. FRI appears to be a sensitive tool to describe the mode of action of novel compounds in chronic obstructive pulmonary

  19. The immunostimulating complex (ISCOM) is an efficient mucosal delivery system for respiratory syncytial virus (RSV) envelope antigens inducing high local and systemic antibody responses

    PubMed Central

    Hu, K-F; Elvander, M; Merza, M; Åkerblom, L; Brandenburg, A; Morein, B

    1998-01-01

    ISCOM is an efficient mucosal delivery system for RSV envelope proteins as measured by antibody responses in respiratory tract secretions and in sera of mice following two intranasal (i.n.) administrations. Intranasally administered RSV ISCOMs induced high levels of IgA antibodies both in the upper respiratory tract and in the lungs. In the lungs, a prominent and long-lasting IgA response was recorded, which still persisted 22 weeks after the second i.n. immunization when the experiment ended. Subcutaneous (s.c.) immunization only induced low IgA titres in the upper respiratory tract and no measurable response to RSV was found in the lungs. Differences were also noticed in serum between the i.n. and s.c. modes of immunization. ISCOMs given intranasally induced earlier, higher and longer lasting IgM and IgG1 serum anti-RSV antibody responses than those induced by the s.c. mode of administration. A low serum IgE response was only detectable at 2 weeks after i.n. immunization with ISCOMs and after s.c. immunization with an inactivated virus, but no IgE response was detectable after s.c. injection of ISCOMs. The serum IgA response was more pronounced following s.c. injection of inactivated virus than after i.n. application of ISCOMs, and a clear-cut booster effect was obtained with a second immunization. Virtually no serum IgA response was detected after the s.c. administration of ISCOMs. In conclusion, the high immune responses induced by RSV ISCOMs in the respiratory tract and serum after i.n. administration indicate prominent mucosal delivery and adjuvant properties of the ISCOMs, warranting further studies. PMID:9717973

  20. [Comparative effects of terbutaline sulphate and ipratropium bromide on the respiratory system (author's transl)].

    PubMed

    Villate Navarro, J I; Sobradillo Peña, V; Atxotequi Iaraoligoitia, V; Salaverri Nalda, A; Orive Martínez, C

    1980-04-10

    Bronchodilator action of two pharmacologically different drugs have been compared. Ipratropium bromide (Sch 1000) is a synthetic atropine derivative and terbutaline sulphate is a beta-stimulating agent. Twelve asthmatic patients and eight patients with chronic bronquitis received terbutaline 0.50 mg. and ipratropium 0.04 mg by aerosol inhalation. Both drugs were given at random on a consecutive-day schedule. All patients were clinically stable before treatment (basal FEV/VC less than 60 percent). Total lung capacity (TLC) forced expiratory volume (FEV), SRaw, and V'/V curves before and at 15, 60, 120, and 240 minutes after the produce administration were registered. Presence of side-effects was also checked. An intensive bronchodilator action was observed either after inhalation of ipratropium bromide or terbutaline, but statistical studies showed no significant differences between both drugs in relation to intensity and duration of their actions. Sch 1000 caused similar bronchodilator effects in all cases; a more intense effect in patients with chronic bronchitis could not be noticed. Evaluation of V'/V curve, and especially its relation to a same pulmonary volume, pointed out that both drugs act upon small respiratory airways. Advance side-effects were not present. PMID:6446008

  1. Secretion of the respiratory syncytial virus fusion protein from insect cells using the baculovirus expression system.

    PubMed

    Tan, Boon-Huan; Brown, Gaie; Sugrue, Richard J

    2007-01-01

    Sequences derived from the respiratory syncytial virus (RSV) fusion (F) protein were expressed in insect cells as recombinant glutathione-S-transferase (GST)-tagged proteins. The sequence covering the F2 subunit (GST-F2), and a truncated form of the F protein in which the transmembrane domain was removed (GST-F2/F1), were cloned into the baculovirus pAcSecG2T secretory vector. These virus sequences also had the endogenous virus signal sequence removed and replaced with a signal sequence derived from the baculovirus gp67 glycoprotein, which was present in pAcSecG2T. The recombinant RSV glycoproteins were successfully detected in expressing cells by immunofluorescence assay and in the tissue culture medium by western blot analysis. The secreted recombinant GST-F2/F1 protein was further analysed using glycosidases. Our results showed that the GST-F2/F1 protein were sensitive to peptide:N-glycosidase F (PNGase F) treatment, but not to Endoglycosidase H (EndoH) treatment. This indicates that the secreted recombinant proteins were modified by the addition of mature N-linked glycan chains. PMID:17502677

  2. Effects of ozone on the respiratory health, allergic sensitization, and cellular immune system in children

    SciTech Connect

    Zwick, H.; Popp, W.; Wagner, C.; Reiser, K.; Schmoeger, J.B.; Boeck, A.H.; Herkner, K.; Radunsky, K. )

    1991-11-01

    To investigate the lasting effects of high ozone concentrations under environmental conditions, we examined the respiratory health, pulmonary function, bronchial hyperresponsiveness to methacholine, allergic sensitization, and lymphocyte subpopulations of 10- to 14-yr-old children. A total of 218 children recruited from an area with high ozone concentrations (Group A) were tested against 281 children coming from an area with low ozone concentrations (Group B). As to subjective complaints, categorized as 'usually cough with or without phlegm,' 'breathlessness,' and 'susceptibility to chest colds,' there was no difference between the two groups. The lung function parameters were similar, but in Group A subjects' bronchial hyperresponsiveness occurred more frequently and was found to be more severe than in Group B (29.4 versus 19.9%, p less than 0.02; PD20 2,100 {plus minus} 87 versus 2,350 {plus minus} 58 micrograms, p less than 0.05). In both groups the number of children who had been suffering from allergic diseases and sensitization to aeroallergens, found by means of the skin test, was the same. Comparison of the total IgE levels showed no difference at all between the two groups. As far as the white blood cells are concerned, the total and differential cell count was the same, whereas lymphocyte subpopulations showed readily recognizable changes.

  3. Early-life Exposure to Widespread Environmental Toxicants and Health Risk: A Focus on the Immune and Respiratory Systems.

    PubMed

    Cao, Junjun; Xu, Xijin; Hylkema, Machteld N; Zeng, Eddy Y; Sly, Peter D; Suk, William A; Bergman, Åke; Huo, Xia

    2016-01-01

    Evidence has accumulated that exposure to widespread environmental toxicants, such as heavy metals, persistent organic pollutants, and tobacco smoke adversely affect fetal development and organ maturation, even after birth. The developing immune and respiratory systems are more sensitive to environmental toxicants due to their long-term physical development, starting from the early embryonic stage and persisting into early postnatal life, which requires complex signaling pathways that control proliferation and differentiation of highly heterogeneous cell types. In this review, we summarize the effect of early-life exposure to several widespread environmental toxicants on immune and lung development before and after birth, including the effects on immune cell counts, baseline characteristics of cell-mediated and humoral immunity, and alteration of lung structure and function in offspring. We also review evidence supporting the association between early-life exposure to environmental toxicants and risk for immune-related diseases and lung dysfunction in offspring in later life. PMID:27325070

  4. Massive Systemic Air Embolism during Extracorporeal Membrane Oxygenation Support of a Neonate with Acute Respiratory Distress Syndrome after Cardiac Surgery

    PubMed Central

    Timpa, Joseph G.; O’Meara, Carlisle; McILwain, R. Britt; Dabal, Robert J.; Alten, Jeffrey A.

    2011-01-01

    Abstract: Extracorporeal membrane oxygenation (ECMO) is universally accepted as a potential lifesaving therapy for neonates suffering severe cardiorespiratory failure, with survival reported as 81% weaning off ECMO and 69% to hospital discharge in this population. Although ECMO may reduce mortality in certain neonatal patients, it is associated with significant complications. Air in the circuit complicates 4.9% of neonatal ECMO runs, and it is crucial that all ECMO caregivers are trained in the prevention of air embolism and possess the knowledge necessary to efficiently identify and remove air from the ECMO circuit to prevent life threatening consequences. We present a fatal case of neonatal systemic air embolism leading to massive entrainment of air into the ECMO venous return cannula of a neonatal patient with acute respiratory distress syndrome following repair of obstructed total anomalous pulmonary venous connection. We describe the pathophysiology and presentation of this rare condition and the importance of early recognition, due to its high mortality rate. PMID:21848179

  5. Acid particles and the tracheobronchial region of the respiratory system. An irritation-signaling model for possible health effects

    SciTech Connect

    Hattis, D.; Wasson, J.M.; Page, G.S.; Stern, B.; Franklin, C.A.

    1987-09-01

    This paper explores some detailed mechanistic hypotheses for the possible action of acid particles on the tracheobronchial region of the human respiratory system. Because of the buffering capacity and volume of mucus produced per day it appears doubtful that ordinary ambient exposures to acid particles could markedly change the overall pH of tracheobronchial mucus considered as a whole. However, it is possible that individual acidic particles could contain enough acid to deliver localized irritant signals that could be the triggers for enhanced mucus secretion and cell division in sensitive portions of the bronchial tree, and thereby contribute to the processes involved in chronic bronchitis. Depending on the exact pH depression required for a signal to be perceived by the tracheobronchial epithelium, the acid content of the incoming particles per unit weight, and the effect of neutralization by ammonia in the upper respiratory tract, the minimum size of an acidic particle required to deliver a perceptible signal might range from about 0.4 to 0.7 microns for portions of the epithelium that are frequently swept by 4-micron mucus droplets. Since particle number per unit weight declines dramatically with increasing particle size, the most potent fraction of particles in terms of signals delivered per /sup +/g/m/sup 3/ is likely to be just above the minimum size that is needed to produce an effective signal. The model developed here makes predictions of the relative potency of particles of different size and acid delivery capacity that could be tested in both experimental animal systems and human epidemiological studies.

  6. Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system.

    PubMed

    Marques, Sueli; Zeisel, Amit; Codeluppi, Simone; van Bruggen, David; Mendanha Falcão, Ana; Xiao, Lin; Li, Huiliang; Häring, Martin; Hochgerner, Hannah; Romanov, Roman A; Gyllborg, Daniel; Muñoz-Manchado, Ana B; La Manno, Gioele; Lönnerberg, Peter; Floriddia, Elisa M; Rezayee, Fatemah; Ernfors, Patrik; Arenas, Ernest; Hjerling-Leffler, Jens; Harkany, Tibor; Richardson, William D; Linnarsson, Sten; Castelo-Branco, Gonçalo

    2016-06-10

    Oligodendrocytes have been considered as a functionally homogeneous population in the central nervous system (CNS). We performed single-cell RNA sequencing on 5072 cells of the oligodendrocyte lineage from 10 regions of the mouse juvenile and adult CNS. Thirteen distinct populations were identified, 12 of which represent a continuum from Pdgfra(+) oligodendrocyte precursor cells (OPCs) to distinct mature oligodendrocytes. Initial stages of differentiation were similar across the juvenile CNS, whereas subsets of mature oligodendrocytes were enriched in specific regions in the adult brain. Newly formed oligodendrocytes were detected in the adult CNS and were responsive to complex motor learning. A second Pdgfra(+) population, distinct from OPCs, was found along vessels. Our study reveals the dynamics of oligodendrocyte differentiation and maturation, uncoupling them at a transcriptional level and highlighting oligodendrocyte heterogeneity in the CNS. PMID:27284195

  7. Cutting edge: Mouse NAIP1 detects the type III secretion system needle protein.

    PubMed

    Rayamajhi, Manira; Zak, Daniel E; Chavarria-Smith, Joseph; Vance, Russell E; Miao, Edward A

    2013-10-15

    The NAIP/NLRC4 inflammasomes activate caspase-1 in response to bacterial type III secretion systems (T3SSs). Inadvertent injection of the T3SS rod protein and flagellin into the cytosol is detected through murine NAIP2 and NAIP5/6, respectively. In this study, we identify the agonist for the orphan murine NAIP1 receptor as the T3SS needle protein. NAIP1 is poorly expressed in resting mouse bone marrow-derived macrophages; however, priming with polyinosinic-polycytidylic acid induces it and confers needle protein sensitivity. Further, overexpression of NAIP1 in immortalized bone marrow-derived macrophages by retroviral transduction enabled needle detection. In contrast, peritoneal cavity macrophages basally express NAIP1 and respond to needle protein robustly, independent of priming. Human macrophages are known to express only one NAIP gene, which detects the needle protein, but not rod or flagellin. Thus, murine NAIP1 is functionally analogous to human NAIP. PMID:24043898

  8. The effect of tumor location and respiratory function on tumor movement estimated by real-time tracking radiotherapy (RTRT) system

    SciTech Connect

    Onimaru, Rikiya; Shirato, Hiroki . E-mail: hshirato@radi.med.hokudai.ac.jp; Fujino, Masaharu; Suzuki, Keishiro; Yamazaki, Kouichi; Nishimura, Masaharu; Dosaka-Akita, Hirotoshi; Miyasaka, Kazuo

    2005-09-01

    Purpose: The effects of tumor location and pulmonary function on the motion of fiducial markers near lung tumors were evaluated to deduce simple guidelines for determining the internal margin in radiotherapy without fiducial markers. Methods and Materials: Pooled data collected by a real-time tumor-tracking radiotherapy system on 42 markers in 39 patients were analyzed. The pulmonary functions of all patients were assessed before radiotherapy. Using chest X-ray film, the position of the marker was expressed relative to the geometry of the unilateral lung. Posterior location meant the area of the posterior half of the lung in a lateral chest X-ray film, and caudal location meant the caudal half of the chest X-ray film; these categories were determined by measuring the distance between the marker and anatomic landmarks, including the apex, costophrenic angle, midline of spinal canal, lateral, anterior, and posterior boundary of the lung. Results: Before the radiotherapy, 18 patients had obstructive respiratory dysfunction (ratio of forced expiratory volume in 1 s to forced vital capacity [FEV{sub 1.0}/FVC] <70), 5 patients had constrictive dysfunction (percent vital capacity [%VC] <80), and 3 had mixed dysfunction. Means of FEV{sub 1.0}/FVC and %VC were 97.0% and 66.5%, respectively. Median tumor movements in the x (left-right), y (anteroposterior), and z (craniocaudal) directions were 1.1 mm, 2.3 mm, and 5.4 mm, respectively. There was no significant correlation between respiratory function and magnitude of marker movement in any direction. Median marker movement in the z direction was 2.6 mm for the cranial location and 11.8 mm for the caudal location, respectively (p < 0.001). Median movement in the z direction was 11.8 mm for posterior location and 3.4 mm for anterior location, respectively (p < 0.01). Conclusions: Simple measurement of the relative location on plain chest X-ray film was related, but respiratory function test was not related, to the craniocaudal

  9. A Mouse Model for Pathogen-induced Chronic Inflammation at Local and Systemic Sites

    PubMed Central

    Slocum, Connie S.; Weinberg, Ellen O.; Hua, Ning; Gudino, Cynthia V.; Hamilton, James A.; Genco, Caroline A.

    2014-01-01

    Chronic inflammation is a major driver of pathological tissue damage and a unifying characteristic of many chronic diseases in humans including neoplastic, autoimmune, and chronic inflammatory diseases. Emerging evidence implicates pathogen-induced chronic inflammation in the development and progression of chronic diseases with a wide variety of clinical manifestations. Due to the complex and multifactorial etiology of chronic disease, designing experiments for proof of causality and the establishment of mechanistic links is nearly impossible in humans. An advantage of using animal models is that both genetic and environmental factors that may influence the course of a particular disease can be controlled. Thus, designing relevant animal models of infection represents a key step in identifying host and pathogen specific mechanisms that contribute to chronic inflammation. Here we describe a mouse model of pathogen-induced chronic inflammation at local and systemic sites following infection with the oral pathogen Porphyromonas gingivalis, a bacterium closely associated with human periodontal disease. Oral infection of specific-pathogen free mice induces a local inflammatory response resulting in destruction of tooth supporting alveolar bone, a hallmark of periodontal disease. In an established mouse model of atherosclerosis, infection with P. gingivalis accelerates inflammatory plaque deposition within the aortic sinus and innominate artery, accompanied by activation of the vascular endothelium, an increased immune cell infiltrate, and elevated expression of inflammatory mediators within lesions. We detail methodologies for the assessment of inflammation at local and systemic sites. The use of transgenic mice and defined bacterial mutants makes this model particularly suitable for identifying both host and microbial factors involved in the initiation, progression, and outcome of disease. Additionally, the model can be used to screen for novel therapeutic strategies

  10. A novel method for somatic transgenesis of the mouse prostate using the Sleeping Beauty transposon system

    PubMed Central

    Hammer, Kimberly D.P.; Alsop, Jim; Buresh-Stiemke, Rita A.; Frantskevich, Katsiaryna; Malinowski, Rita; Roethe, Laura; Powers, Ginny L; Marker, Paul C.

    2014-01-01

    BACKGROUND In vivo ectopic gene expression is a common approach for prostate research through the use of transgenes in germline transgenic mice. For some other organs, somatic transgenesis with the Sleeping Beauty transposon system has allowed in vivo ectopic gene expression with higher throughput and lower cost than germline transgenic approaches. METHODS Mouse e16 urogenital sinuses (UGSs) were co-injected with plasmids expressing the Sleeping Beauty transposase and plasmids with control or activated BRAF expressing transposons. Following electroporation, the transduced UGSs were grown as allografts in mouse hosts for 8 weeks, and the resulting allografts were evaluated for several endpoints. RESULTS Transposon-transduced UGS allografts developed into prostatic tissue with normal tissue structure and cellular differentiation. Integration of transposon vectors into the genomes of transduced allografts was confirmed using linker-mediated PCR, sequencing, and in situ PCR. Transduction of UGS allografts with transposons expressing activated BRAF resulted in ectopic BRAF expression that was detectable at both the mRNA and protein levels. Prostatic ducts over-expressing activated BRAF also had ectopic activation of the ERK1/2 mitogen activated kinases and increased epithelial cell proliferation. CONCLUSIONS The Sleeping Beauty transposon system can be used to achieve somatic transgenesis of prostatic allografts. This new method for achieving ectopic gene expression in the prostate will complement other existing approaches such as ectopic gene expression in cell lines and in germline transgenic mice. Advantages of this new approach include preservation of stromal-epithelial interactions not possible with cell lines, and higher throughput and lower cost than traditional germline transgenic approaches. PMID:24647932

  11. MONICA: a compact, portable dual gamma camera system for mouse whole-body imaging

    SciTech Connect

    Choyke, Peter L; Xia, Wenze; Seidel, Jurgen; Kakareka, John W; Pohida, Thomas J; Milenic, Diane E; Proffitt, James; Majewski, Stan; Weisenberger, Andrew G; Green, Michael V

    2010-04-01

    Introduction We describe a compact, portable dual-gamma camera system (named "MONICA" for MObile Nuclear Imaging CAmeras) for visualizing and analyzing the whole-body biodistribution of putative diagnostic and therapeutic single photon emitting radiotracers in animals the size of mice. Methods Two identical, miniature pixelated NaI(Tl) gamma cameras were fabricated and installed ?looking up? through the tabletop of a compact portable cart. Mice are placed directly on the tabletop for imaging. Camera imaging performance was evaluated with phantoms and field performance was evaluated in a weeklong In-111 imaging study performed in a mouse tumor xenograft model. Results Tc-99m performance measurements, using a photopeak energy window of 140 keV?10%, yielded the following results: spatial resolution (FWHM at 1 cm), 2.2 mm; sensitivity, 149 cps (counts per seconds)/MBq (5.5 cps/μCi); energy resolution (FWHM, full width at half maximum), 10.8%; count rate linearity (count rate vs. activity), r2=0.99 for 0?185 MBq (0?5 mCi) in the field of view (FOV); spatial uniformity, <3% count rate variation across the FOV. Tumor and whole-body distributions of the In-111 agent were well visualized in all animals in 5-min images acquired throughout the 168-h study period. Conclusion Performance measurements indicate that MONICA is well suited to whole-body single photon mouse imaging. The field study suggests that inter-device communications and user-oriented interfaces included in the MONICA design facilitate use of the system in practice. We believe that MONICA may be particularly useful early in the (cancer) drug development cycle where basic whole-body biodistribution data can direct future development of the agent under study and where logistical factors, e.g., limited imaging space, portability and, potentially, cost are important.

  12. Orexin, cardio-respiratory function, and hypertension

    PubMed Central

    Li, Aihua; Nattie, Eugene

    2014-01-01

    In this review we focus on the role of orexin in cardio-respiratory functions and its potential link to hypertension. (1) Orexin, cardiovascular function, and hypertension. In normal rats, central administration of orexin can induce significant increases in arterial blood pressure (ABP) and sympathetic nerve activity (SNA), which can be blocked by orexin receptor antagonists. In spontaneously hypertensive rats (SHRs), antagonizing orexin receptors can significantly lower blood pressure under anesthetized or conscious conditions. (2) Orexin, respiratory function, and central chemoreception. The prepro-orexin knockout mouse has a significantly attenuated ventilatory CO2 chemoreflex, and in normal rats, central application of orexin stimulates breathing while blocking orexin receptors decreases the ventilatory CO2 chemoreflex. Interestingly, SHRs have a significantly increased ventilatory CO2 chemoreflex relative to normotensive WKY rats and blocking both orexin receptors can normalize this exaggerated response. (3) Orexin, central chemoreception, and hypertension. SHRs have higher ABP and SNA along with an enhanced ventilatory CO2 chemoreflex. Treating SHRs by blocking both orexin receptors with oral administration of an antagonist, almorexant (Almxt), can normalize the CO2 chemoreflex and significantly lower ABP and SNA. We interpret these results to suggest that the orexin system participates in the pathogenesis and maintenance of high blood pressure in SHRs, and the central chemoreflex may be a causal link to the increased SNA and ABP in SHRs. Modulation of the orexin system could be a potential target in treating some forms of hypertension. PMID:24574958

  13. Comparison of Respiratory Disease Prevalence among Voluntary Monitoring Systems for Pig Health and Welfare in the UK

    PubMed Central

    Eze, J. I.; Correia-Gomes, C.; Borobia-Belsué, J.; Tucker, A. W.; Sparrow, D.; Strachan, D. W.; Gunn, G. J.

    2015-01-01

    Surveillance of animal diseases provides information essential for the protection of animal health and ultimately public health. The voluntary pig health schemes, implemented in the United Kingdom, are integrated systems which capture information on different macroscopic disease conditions detected in slaughtered pigs. Many of these conditions have been associated with a reduction in performance traits and consequent increases in production costs. The schemes are the Wholesome Pigs Scotland in Scotland, the BPEX Pig Health Scheme in England and Wales and the Pig Regen Ltd. health and welfare checks done in Northern Ireland. This report set out to compare the prevalence of four respiratory conditions (enzootic pneumonia-like lesions, pleurisy, pleuropneumonia lesions and abscesses in the lung) assessed by these three Pig Health Schemes. The seasonal variations and year trends associated with the conditions in each scheme are presented. The paper also highlights the differences in prevalence for each condition across these schemes and areas where further research is needed. A general increase in the prevalence of enzootic pneumonia like lesions was observed in Scotland, England and Wales since 2009, while a general decrease was observed in Northern Ireland over the years of the scheme. Pleurisy prevalence has increased since 2010 in all three schemes, whilst pleuropneumonia has been decreasing. Prevalence of abscesses in the lung has decreased in England, Wales and Northern Ireland but has increased in Scotland. This analysis highlights the value of surveillance schemes based on abattoir pathology monitoring of four respiratory lesions. The outputs at scheme level have significant value as indicators of endemic and emerging disease, and for producers and herd veterinarians in planning and evaluating herd health control programs when comparing individual farm results with national averages. PMID:26020635

  14. Evaluation of an air-filtration system for preventing aerosol transmission of Porcine reproductive and respiratory syndrome virus

    PubMed Central

    2005-01-01

    Abstract The purpose of this study was to evaluate the ability of a commercial air-filtration system to reduce aerosol transmission of Porcine reproductive and respiratory syndrome virus (PRRSV). The system consisted of a pre-filter and 2 filters with EU8 and EU13 ratings. In each of 4 trials, 5 PRRSV-infected donor pigs and 1 naïve recipient pig (each 25 kg) were housed in opposing chambers connected by a 1.3-m-long duct. The system filtered air entering 1 recipient-pig chamber (filtered facility) from the donor- chamber but not a 2nd recipient-pig chamber (nonfiltered facility). The donor pigs had been experimentally infected with PRRSV MN-184, an isolate previously documented to be shed at a high frequency in contagious aerosols. On days 3 to 7 after infection of the donors, the 2 groups were housed in their respective chambers for 6 h and then in separate facilities, where samples were collected for testing by polymerase chain reaction and enzyme-linked immunosorbent assay over 14 d. Aerosol transmission was observed in 6 of the 20 replicates in the nonfiltered facility, whereas all pigs remained PRRSV-negative in the filtered facility; the difference was significant at P < 0.01. Thus, under the conditions of this study, the air-filtration system evaluated appeared to be highly effective at reducing aerosol transmission of PRRSV. PMID:16479728

  15. Global gene expression profiling in infants with acute respiratory syncytial virus broncholitis demonstrates systemic activation of interferon signaling networks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Respiratory syncytial virus (RSV) is a leading cause of pediatric lower respiratory tract infections and has a high impact on pediatric emergency department utilization. Variation in host response may influence the pathogenesis and disease severity. We evaluated global gene expression profiles to be...

  16. T-cell-mediated clearance of mouse hepatitis virus strain JHM from the central nervous system.

    PubMed Central

    Sussman, M A; Shubin, R A; Kyuwa, S; Stohlman, S A

    1989-01-01

    Clearance of the neurotropic JHM strain of mouse hepatitis virus from the central nervous system was examined by the transfer of spleen cells from immunized donors. A T cell with the surface phenotype of Thy1.2+ CD4+ CD8- asialo-GM1+ Mac-1- was found to be necessary for viral clearance. The surface phenotype and adherence to nylon wool suggest that these cells are activated helper-inducer T cells. Adoptive transfer to congenic histocompatibility strains demonstrated the necessity for compatibility at the D locus of the major histocompatibility complex. The expression of the CD4 surface marker and the requirement for major histocompatibility complex class I were further studied by the transfer of cells to recipients treated with anti-CD4 or anti-CD8 monoclonal antibodies. Treatment of recipients with either the anti-CD8 or the anti-CD4 antibodies inhibited virus clearance from the central nervous system. This suggests that the CD4+ cell acts as a helper and that virus is cleared from the central nervous system. This suggests that the CD4+ cell acts as a helper and that virus is cleared from the central nervous system by CD8+ cells that recognize viral antigen in the context of the H-2Db gene product. PMID:2542613

  17. Respiratory Systems of Dental Technicians Negatively Affected during 5 Years of Follow-Up

    PubMed Central

    Bozkurt, Nurgül; Yurdasal, Belkıs; Bozkurt, Ali İhsan; Yılmaz, Özlem; Tekin, Mahmut

    2016-01-01

    volume in one second (FEV1). While restrictive disorder was found 25% in the first PFT evaluations, this ratio increased to 31% in the second PFT. When the radiological results were considered, 62% of the first X-ray results were found to be normal but this ratio decreased to 18% in 2013. While reticular/reticulonodular opacities were found in 11% of cases in 2008, it increased to 30% in 2013. Seven technicians were diagnosed with pneumoconiosis (5.6%). Conclusion: Respiratory tracts of the technicians were negatively affected during the five year period. The number of pneumoconiosis cases (5.6%) shows that it is necessary to adopt comprehensive work health and safety precautions for laboratories. PMID:27606139

  18. Systemic combined melatonin-mitochondria treatment improves acute respiratory distress syndrome in the rat.

    PubMed

    Sun, Cheuk-Kwan; Lee, Fan-Yen; Kao, Ying-Hsien; Chiang, Hsin-Ju; Sung, Pei-Hsun; Tsai, Tzu-Hsien; Lin, Yu-Chun; Leu, Steve; Wu, Ying-Chung; Lu, Hung-I; Chen, Yung-Lung; Chung, Sheng-Ying; Su, Hong-Lin; Yip, Hon-Kan

    2015-03-01

    Despite high in-hospital mortality associated with acute respiratory distress syndrome (ARDS), there is no effective therapeutic strategy. We tested the hypothesis that combined melatonin-mitochondria treatment ameliorates 100% oxygen-induced ARDS in rats. Adult male Sprague-Dawley rats (n = 40) were equally categorized into normal controls, ARDS, ARDS-melatonin, ARDS with intravenous liver-derived mitochondria (1500 μg per rat 6 hr after ARDS induction), and ARDS receiving combined melatonin-mitochondria. The results showed that 22 hr after ARDS induction, oxygen saturation (saO2 ) was lowest in the ARDS group and highest in normal controls, significantly lower in ARDS-melatonin and ARDS-mitochondria than in combined melatonin-mitochondria group, and significantly lower in ARDS-mitochondria than in ARDS-melatonin group. Conversely, right ventricular systolic blood pressure and lung weight showed an opposite pattern compared with saO2 among all groups (all P < 0.001). Histological integrity of alveolar sacs showed a pattern identical to saO2 , whereas lung crowding score exhibited an opposite pattern (all P < 0.001). Albumin level and inflammatory cells (MPO+, CD40+, CD11b/c+) from bronchoalveolar lavage fluid showed a pattern opposite to saO2 (all P < 0.001). Protein expression of indices of inflammation (MMP-9, TNF-α, NF-κB), oxidative stress (oxidized protein, NO-1, NOX-2, NOX-4), apoptosis (mitochondrial Bax, cleaved caspase-3, and PARP), fibrosis (Smad3, TGF-β), mitochondrial damage (cytochrome C), and DNA damage (γ-H2AX+) exhibited an opposite pattern compared to saO2 in all groups, whereas protein (HO-1, NQO-1, GR, GPx) and cellular (HO-1+) expressions of antioxidants exhibited a progressively increased pattern from normal controls to ARDS combined melatonin-mitochondria group (all P < 0.001). In conclusion, combined melatonin-mitochondrial was superior to either treatment alone in attenuating ARDS in this rat model. PMID:25491480

  19. Combining Healthcare-Based and Participatory Approaches to Surveillance: Trends in Diarrheal and Respiratory Conditions Collected by a Mobile Phone System by Community Health Workers in Rural Nepal

    PubMed Central

    2016-01-01

    Background Surveillance systems are increasingly relying upon community-based or crowd-sourced data to complement traditional facilities-based data sources. Data collected by community health workers during the routine course of care could combine the early warning power of community-based data collection with the predictability and diagnostic regularity of facility data. These data could inform public health responses to epidemics and spatially-clustered endemic diseases. Here, we analyze data collected on a daily basis by community health workers during the routine course of clinical care in rural Nepal. We evaluate if such community-based surveillance systems can capture temporal trends in diarrheal diseases and acute respiratory infections. Methods During the course of their clinical activities from January to December 2013, community health workers recorded healthcare encounters using mobile phones. In parallel, we accessed condition-specific admissions from 2011–2013 in the hospital from which the community health program was based. We compared diarrhea and acute respiratory infection rates from both the hospital and the community, and assigned three categories of local disease activity (low, medium, and high) to each week in each village cluster with categories determined by tertiles. We compared condition-specific mean hospital rates across categories using ANOVA to assess concordance between hospital and community-collected data. Results There were 2,710 cases of diarrhea and 373 cases of acute respiratory infection reported by community health workers during the one-year study period. At the hospital, the average weekly incidence of diarrhea and acute respiratory infections over the three-year period was 1.8 and 3.9 cases respectively per 1,000 people in each village cluster. In the community, the average weekly rate of diarrhea and acute respiratory infections was 2.7 and 0.5 cases respectively per 1,000 people. Both diarrhea and acute respiratory

  20. Informatics center for mouse genomics: the dissection of complex traits of the nervous system.

    PubMed

    Rosen, Glenn D; La Porte, Nathan T; Diechtiareff, Boris; Pung, Christopher J; Nissanov, Jonathan; Gustafson, Carl; Bertrand, Louise; Gefen, Smadar; Fan, Yingli; Tretiak, Oleh J; Manly, Kenneth F; Park, Melburn R; Williams, Alexander G; Connolly, Michael T; Capra, John A; Williams, Robert W

    2003-01-01

    In recent years, there has been an explosion in the number of tools and techniques available to researchers interested in exploring the genetic basis of all aspects of central nervous system (CNS) development and function. Here, we exploit a powerful new reductionist approach to explore the genetic basis of the very significant structural and molecular differences between the brains of different strains of mice, called either complex trait or quantitative trait loci (QTL) analysis. Our specific focus has been to provide universal access over the web to tools for the genetic dissection of complex traits of the CNS--tools that allow researchers to map genes that modulate phenotypes at a variety of levels ranging from the molecular all the way to the anatomy of the entire brain. Our website, The Mouse Brain Library (MBL; http://mbl.org) is comprised of four interrelated components that are designed to support this goal: The Brain Library, iScope, Neurocartographer, and WebQTL. The centerpiece of the MBL is an image database of histologically prepared museum-quality slides representing nearly 2000 mice from over 120 strains--a library suitable for stereologic analysis of regional volume. The iScope provides fast access to the entire slide collection using streaming video technology, enabling neuroscientists to acquire high-magnification images of any CNS region for any of the mice in the MBL. Neurocartographer provides automatic segmentation of images from the MBL by warping precisely delineated boundaries from a 3D atlas of the mouse brain. Finally, WebQTL provides statistical and graphical analysis of linkage between phenotypes and genotypes. PMID:15043219

  1. A comparative study of experimental mouse models of central nervous system demyelination.

    PubMed

    Dumitrascu, O M; Mott, K R; Ghiasi, H

    2014-06-01

    Several mouse models of multiple sclerosis (MS) are now available. We have established a mouse model, in which ocular infection with a recombinant HSV-1 that expresses murine interleukin (IL)-2 constitutively (HSV-IL-2) causes central nervous system demyelination in different strains of mice. This model differs from most other models, in which it represents a mixture of viral and immune triggers. In the present study, we directly compared MOG35-55, MBP35-47 and PLP190-209 models of experimental autoimmune encephalitis with our HSV-IL-2-induced MS model. Mice with HSV-IL-2- and myelin oligodendrocyte glycoprotein (MOG)-induced demyelinating diseases demonstrated a similar pattern and distribution of demyelination in their brain, spinal cord (SC) and optic nerves (ONs). In contrast, no demyelination was detected in the ONs of myelin basic protein (MBP)- and proteolipid protein (PLP)-injected mice. Interferon-β (IFN-β) injections significantly reduced demyelination in brains of all groups, in the SCs of the MOG and MBP groups, and completely blocked it in the SCs of the PLP and HSV-IL-2 groups as well as in ONs of MOG and HSV-IL-2 groups. In contrast to IFN-β treatment, IL-12p70 protected the HSV-IL-2 group from demyelination, whereas IL-4 was not effective at all in preventing demyelination. MOG-injected mice showed clinical signs of paralysis and disease-related mortality, whereas mice in the other treatment groups did not. Collectively, the results indicate that the HSV-IL-2 model and the MOG model complement each other and, together, provide unique insights into the heterogeneity of human MS. PMID:24718267

  2. The Potent Respiratory System of Osedax mucofloris (Siboglinidae, Annelida) - A Prerequisite for the Origin of Bone-Eating Osedax?

    PubMed Central

    Huusgaard, Randi S.; Vismann, Bent; Kühl, Michael; Macnaugton, Martin; Colmander, Veronica; Rouse, Greg W.; Glover, Adrian G.; Dahlgren, Thomas; Worsaae, Katrine

    2012-01-01

    Members of the conspicuous bone-eating genus, Osedax, are widely distributed on whale falls in the Pacific and Atlantic Oceans. These gutless annelids contain endosymbiotic heterotrophic bacteria in a branching root system embedded in the bones of vertebrates, whereas a trunk and anterior palps extend into the surrounding water. The unique life style within a bone environment is challenged by the high bacterial activity on, and within, the bone matrix possibly causing O2 depletion, and build-up of potentially toxic sulphide. We measured the O2 distribution around embedded Osedax and showed that the bone microenvironment is anoxic. Morphological studies showed that ventilation mechanisms in Osedax are restricted to the anterior palps, which are optimized for high O2 uptake by possessing a large surface area, large surface to volume ratio, and short diffusion distances. The blood vascular system comprises large vessels in the trunk, which facilitate an ample supply of oxygenated blood from the anterior crown to a highly vascularised root structure. Respirometry studies of O. mucofloris showed a high O2 consumption that exceeded the average O2 consumption of a broad line of resting annelids without endosymbionts. We regard this combination of features of the respiratory system of O. mucofloris as an adaptation to their unique nutrition strategy with roots embedded in anoxic bones and elevated O2 demand due to aerobic heterotrophic endosymbionts. PMID:22558289

  3. MARS: a mouse atlas registration system based on a planar x-ray projector and an optical camera

    NASA Astrophysics Data System (ADS)

    Wang, Hongkai; Stout, David B.; Taschereau, Richard; Gu, Zheng; Vu, Nam T.; Prout, David L.; Chatziioannou, Arion F.

    2012-10-01

    This paper introduces a mouse atlas registration system (MARS), composed of a stationary top-view x-ray projector and a side-view optical camera, coupled to a mouse atlas registration algorithm. This system uses the x-ray and optical images to guide a fully automatic co-registration of a mouse atlas with each subject, in order to provide anatomical reference for small animal molecular imaging systems such as positron emission tomography (PET). To facilitate the registration, a statistical atlas that accounts for inter-subject anatomical variations was constructed based on 83 organ-labeled mouse micro-computed tomography (CT) images. The statistical shape model and conditional Gaussian model techniques were used to register the atlas with the x-ray image and optical photo. The accuracy of the atlas registration was evaluated by comparing the registered atlas with the organ-labeled micro-CT images of the test subjects. The results showed excellent registration accuracy of the whole-body region, and good accuracy for the brain, liver, heart, lungs and kidneys. In its implementation, the MARS was integrated with a preclinical PET scanner to deliver combined PET/MARS imaging, and to facilitate atlas-assisted analysis of the preclinical PET images.

  4. The transcobalamin receptor knockout mouse: a model for vitamin B12 deficiency in the central nervous system

    PubMed Central

    Lai, Shao-Chiang; Nakayama, Yasumi; Sequeira, Jeffrey M.; Wlodarczyk, Bogdan J.; Cabrera, Robert M.; Finnell, Richard H.; Bottiglieri, Teodoro; Quadros, Edward V.

    2013-01-01

    The membrane receptor (TCblR/CD320) for transcobalamin (TC)-bound cobalamin (Cbl) facilitates the cellular uptake of Cbl. A genetically modified mouse model involving ablation of the CD320 gene was generated to study the effects on cobalamin homeostasis. The nonlethal nature of this knockout and the lack of systemic cobalamin deficiency point to other mechanisms for cellular Cbl uptake in the mouse. However, severe cobalamin depletion in the central nervous system (CNS) after birth (P<0.01) indicates that TCblR is the only receptor responsible for Cbl uptake in the CNS. Metabolic Cbl deficiency in the brain was evident from the increased methylmalonic acid (P<0.01–0.04), homocysteine (P<0.01), cystathionine (P<0.01), and the decreased S-adenosylmethionine/S-adenosyl homocysteine ratio (P<0.01). The CNS pathology of Cbl deficiency seen in humans may not manifest in this mouse model; however, it does provide a model with which to evaluate metabolic pathways and genes affected.—Lai, S.-C., Nakayama, Y., Sequeira, J. M., Wlodarczyk, B. J., Cabrera, R. M., Finnell, R. H., Bottiglieri, T., Quadros, E. V. The transcobalamin receptor knockout mouse: a model for vitamin B12 deficiency in the central nervous system. PMID:23430977

  5. Mapping of the mouse olfactory system with manganese-enhanced magnetic resonance imaging and diffusion tensor imaging.

    PubMed

    Gutman, David A; Magnuson, Matthew; Majeed, Waqas; Keifer, Orion P; Davis, Michael; Ressler, Kerry J; Keilholz, Shella

    2013-03-01

    As the power of studying mouse genetics and behavior advances, research tools to examine systems level connectivity in the mouse are critically needed. In this study, we compared statistical mapping of the olfactory system in adult mice using manganese-enhanced MRI (MEMRI) and diffusion tensor imaging (DTI) with probabilistic tractography. The primary goal was to determine whether these complementary techniques can determine mouse olfactory bulb (OB) connectivity consistent with known anatomical connections. For MEMRI, 3D T1-weighted images were acquired before and after bilateral nasal administration of MnCl(2) solution. Concomitantly, high-resolution diffusion-tensor images were obtained ex vivo from a second group of mice and processed with a probabilistic tractography algorithm originating in the OB. Incidence maps were created by co-registering and overlaying data from the two scan modalities. The resulting maps clearly show pathways between the OB and amygdala, piriform cortex, caudate putamen, and olfactory cortex in both the DTI and MEMRI techniques that are consistent with the known anatomical connections. These data demonstrate that MEMRI and DTI are complementary, high-resolution neuroimaging tools that can be applied to mouse genetic models of olfactory and limbic system connectivity. PMID:22527121

  6. Mouse embryo motion and embryonic development from the 2-cell to blastocyst stage using mechanical vibration systems.

    PubMed

    Asano, Yuka; Matsuura, Koji

    2014-06-01

    We investigated the effect of mechanical stimuli on mouse embryonic development from the 2-cell to blastocyst stage to evaluate physical factors affecting embryonic development. Shear stress (SS) applied to embryos using two mechanical vibration systems (MVSs) was calculated by observing microscopic images of moving embryos during mechanical vibration (MV). The MVSs did not induce any motion of the medium and the diffusion rate using MVSs was the same as that under static conditions. Three days of culture using MVS did not improve embryonic development. MVS transmitted MV power more efficiently to embryos than other systems and resulted in a significant decrease in development to the morula or blastocyst stage after 2 days. Comparison of the results of embryo culture using dynamic culture systems demonstrated that macroscopic diffusion of secreted materials contributes to improved development of mouse embryos to the blastocyst stage. These results also suggest that the threshold of SS and MV to induce negative effects for mouse embryos at stages earlier than the blastocyst may be lower than that for the blastocyst, and that mouse embryos are more sensitive to physical and chemical stimuli than human or pig embryos because of their thinner zona pellucida. PMID:23697534

  7. Type II fuzzy systems for amyloid plaque segmentation in transgenic mouse brains for Alzheimer's disease quantification

    NASA Astrophysics Data System (ADS)

    Khademi, April; Hosseinzadeh, Danoush

    2014-03-01

    Alzheimer's disease (AD) is the most common form of dementia in the elderly characterized by extracellular deposition of amyloid plaques (AP). Using animal models, AP loads have been manually measured from histological specimens to understand disease etiology, as well as response to treatment. Due to the manual nature of these approaches, obtaining the AP load is labourious, subjective and error prone. Automated algorithms can be designed to alleviate these challenges by objectively segmenting AP. In this paper, we focus on the development of a novel algorithm for AP segmentation based on robust preprocessing and a Type II fuzzy system. Type II fuzzy systems are much more advantageous over the traditional Type I fuzzy systems, since ambiguity in the membership function may be modeled and exploited to generate excellent segmentation results. The ambiguity in the membership function is defined as an adaptively changing parameter that is tuned based on the local contrast characteristics of the image. Using transgenic mouse brains with AP ground truth, validation studies were carried out showing a high degree of overlap and low degree of oversegmentation (0.8233 and 0.0917, respectively). The results highlight that such a framework is able to handle plaques of various types (diffuse, punctate), plaques with varying Aβ concentrations as well as intensity variation caused by treatment effects or staining variability.

  8. The use of a generalized reconstruction by inversion of coupled systems (GRICS) approach for generic respiratory motion correction in PET/MR imaging.

    PubMed

    Fayad, Hadi; Odille, Freddy; Schmidt, Holger; Würslin, Christian; Küstner, Thomas; Feblinger, Jacques; Visvikis, Dimitris

    2015-03-21

    Respiratory motion is a source of artifacts in multimodality imaging such as PET/MR. Solutions include retrospective or prospective gating. They have however found limited use in clinical practice, since their increased overall acquisition duration to maintain overall image quality. More elaborate methods consist of using 4D MR datasets to extract spatial deformations in order to correct for the respiratory motion in PET. The main drawbacks of such approaches is the relatively long acquisition times associated with 4D MR imaging which is often incompatible with clinical PET/MR protocols. The objective of this work was to overcome these limitations by exploiting a generalized reconstruction by inversion of coupled systems (GRICS) approach. The methodology is based on a joint estimation of motion during the MR image reconstruction process, providing internal structure motion and associated deformation matrices for retrospective use in PET respiratory motion correction. This method was first validated on four MR volunteers and two PET/MR patient datasets by comparing GRICS generated MR images to 4D MR series obtained by retrospective gating. In a second step 4D PET datasets corresponding to acquired 4D MR images were simulated using the GATE Monte Carlo simulation platform. GRICS generated deformation matrices were subsequently used to correct respiratory motion in comparison to the 4D MR image based deformations both for the simulated and the two 4D PET/MR patient datasets. Results confirm that GRICS synchronized MR images correlate well with the acquired 4D MR series. Similarly, the use of GRICS for respiratory motion correction allows an equivalent percentage improvement on lesion contrast, position and size, considering the PET simulated tumors as well as PET real tumors. This work demonstrates the potential interest of using GRICS for PET respiratory motion correction in combined PET/MR using shorter duration acquisitions without the need for 4D MRI and

  9. The use of a generalized reconstruction by inversion of coupled systems (GRICS) approach for generic respiratory motion correction in PET/MR imaging

    NASA Astrophysics Data System (ADS)

    Fayad, Hadi; Odille, Freddy; Schmidt, Holger; Würslin, Christian; Küstner, Thomas; Feblinger, Jacques; Visvikis, Dimitris

    2015-03-01

    Respiratory motion is a source of artifacts in multimodality imaging such as PET/MR. Solutions include retrospective or prospective gating. They have however found limited use in clinical practice, since their increased overall acquisition duration to maintain overall image quality. More elaborate methods consist of using 4D MR datasets to extract spatial deformations in order to correct for the respiratory motion in PET. The main drawbacks of such approaches is the relatively long acquisition times associated with 4D MR imaging which is often incompatible with clinical PET/MR protocols. The objective of this work was to overcome these limitations by exploiting a generalized reconstruction by inversion of coupled systems (GRICS) approach. The methodology is based on a joint estimation of motion during the MR image reconstruction process, providing internal structure motion and associated deformation matrices for retrospective use in PET respiratory motion correction. This method was first validated on four MR volunteers and two PET/MR patient datasets by comparing GRICS generated MR images to 4D MR series obtained by retrospective gating. In a second step 4D PET datasets corresponding to acquired 4D MR images were simulated using the GATE Monte Carlo simulation platform. GRICS generated deformation matrices were subsequently used to correct respiratory motion in comparison to the 4D MR image based deformations both for the simulated and the two 4D PET/MR patient datasets. Results confirm that GRICS synchronized MR images correlate well with the acquired 4D MR series. Similarly, the use of GRICS for respiratory motion correction allows an equivalent percentage improvement on lesion contrast, position and size, considering the PET simulated tumors as well as PET real tumors. This work demonstrates the potential interest of using GRICS for PET respiratory motion correction in combined PET/MR using shorter duration acquisitions without the need for 4D MRI and

  10. Establishment of a specific cell death induction system in Bombyx mori by a transgene with the conserved apoptotic regulator, mouse Bcl-2-associated X protein (mouse Bax).

    PubMed

    Sumitani, M; Sakurai, T; Kasashima, K; Kobayashi, S; Uchino, K; Kanzaki, R; Tamura, T; Sezutsu, H

    2015-12-01

    The induction of apoptosis in vivo is a useful tool for investigating the functions and importance of particular tissues. B-cell leukaemia/lymphoma 2-associated X protein (Bax) functions as a pro-apoptotic factor and induces apoptosis in several organisms. The Bax-mediated apoptotic system is widely conserved from Caenorhabditis elegans to humans. In order to establish a tissue-specific cell death system in the domestic silkworm, Bombyx mori, we constructed a transgenic silkworm that overexpressed mouse Bax (mBax) in particular tissues by the Gal4-upstream activation sequence system. We found that the expression of mBax induced specific cell death in the silk gland, fat body and sensory cells. Fragmentation of genomic DNA was observed in the fat body, which expressed mBax, thereby supporting apoptotic cell death in this tissue. Using this system, we also demonstrated that specific cell death in sensory cells attenuated the response to the sex pheromone bombykol. These results show that we successfully established a tissue-specific cell death system in vivo that enabled specific deficiencies in particular tissues. The inducible cell death system may provide useful means for industrial applications of the silkworm and possible utilization for other species. PMID:26426866

  11. Local and systemic antibody response to bovine respiratory syncytial virus infection and reinfection in calves with and without maternal antibodies.

    PubMed

    Kimman, T G; Westenbrink, F; Schreuder, B E; Straver, P J

    1987-06-01

    Enzyme-linked immunosorbent assays for the detection of immunoglobulin M (IgM), IgA, IgG1, and IgG2 antibodies against bovine respiratory syncytial virus (BRSV) were used to measure antibody responses of calves after experimental or natural infection with BRSV. Serially collected sera, lung lavage samples, nasal and eye secretions, and feces were tested for the presence of these antibodies. Lung lavage fluids and nasal secretions were further examined for the presence of virus. After experimental infection of 3- to 4-week-old, colostrum-deprived (seronegative) calves, the virus was detected from days 3 to 8 post-initial inoculation day (PID). An immune response was first detected 8 to 10 days PID, when BRSV-specific IgM and IgA appeared nearly simultaneously in serum, secretions, and feces. BRSV-specific IgG1 appeared only in serum on days 13 to 17 PID, and IgG2 was first detected in sera from 1 to 3 months PID. Specific IgM and IgA were detectable in the different samples for various periods. In the respiratory and eye secretions, IgA usually remained detectable for long periods, that is, for up to 3.5 months or longer. In lung lavage samples, BRSV-specific IgG1 was only incidentally demonstrated and appeared to be blood derived. The immune response of a 5-month-old calf strongly resembled that of the 3- to 4-week-old calves (feces excepted), indicating that an age effect on the immune response to BRSV is unlikely. After experimental infection of colostrum-fed, seropositive calves, both local and systemic antibody responses were largely or totally suppressed. The degree of suppression seemed to be related to the level of preinoculation virus-specific serum IgG1. Of all isotypes, IgM was least affected. Colostrum-fed animals shed virus in about equal amounts and for the same length of time as colostrum-deprived calves. Clinical signs were mild in both groups. After reinfection, no virus shedding was detected in either colostrum-deprived or colostrum-fed calves. In

  12. Internal validation of a telemedical system for monitoring patients with chronic respiratory diseases.

    PubMed

    Jablonski, I; Glomb, G; Guszkowski, T; Kasprzak, B; Pekala, J; Polak, A G; Stepien, A F; Swierczynski, Z; Mroczka, J

    2010-01-01

    One of the most promising and innovative developments in medicine are telemedical systems. The system PulmoTel 2010 and its internal validation are presented, focusing on the system architecture, hardware, software and communication solutions. PulmoTel 2010 consists of a distant server managing users and medical devices, as well as data transmission, processing, storage and presentation. The server cooperates with home units used by patients, capable of performing lung function tests. All the elements communicate via the Internet, however other media, as wire and mobile telephony, can be additionally applied in regions with a less developed infrastructure. Internal validation of the system was performed using data generated by application simulating features of a home unit. It demonstrated an appropriate operation of the overall system and fulfillment of the main objectives of the project. PMID:21096156

  13. Dysrhythmias of the respiratory oscillator

    NASA Astrophysics Data System (ADS)

    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

  14. Immunomodulator plasmid projected by systems biology as a candidate for the development of adjunctive therapy for respiratory syncytial virus infection.

    PubMed

    Vargas, José Eduardo; de Souza, Ana Paula Duarte; Porto, Bárbara Nery; Fazolo, Tiago; Mayer, Fabiana Quoos; Pitrez, Paulo Márcio; Stein, Renato Tetelbom

    2016-03-01

    An imbalance in Th1/Th2 cytokine immune response has been described to influence the pathogenesis of respiratory syncytial virus (RSV) acute bronchiolitis and the severity of infection. Th2-driven response has been well described under first RSV vaccine (formalin-inactivated RSV vaccine antigens) and replicated in some conditions for RSV-infected mice, in which a Th2-dependent lung eosinophilia increases illness severity, accompanied of tissue damage. Currently, several prototypes of RSV vaccine are being tested, but there is no vaccine available so far. The advance of bioinformatics can help to solve this issue. Systems biology approaches based on network topological analysis may help to identify new genes in order to direct Th1 immune response during RSV challenge. For this purpose, network centrality analyses from high-throughput experiments were performed in order to select major genes enrolled in each T-helper immune response. Thus, genes termed Hub (B) and bottlenecks (H), which control the flow of biological information (Th1 or Th2 immune response, in this case) within the network, would be identified. As these genes possess high potential to promote Th1 immune response, they could be cloned under regulation of specific promoters in a plasmid, which will be available as a gene-transfer adjunctive to vaccines. Th1 immune response potentiated by our strategy may contribute to accelerate Th1/Th2 shift from neonatal immune system, which might favor protective immunity against RSV infection and reduce lung damage. PMID:26601594

  15. A robust and high-throughput Cre reporting and characterization system for the whole mouse brain

    PubMed Central

    Madisen, Linda; Zwingman, Theresa A.; Sunkin, Susan M.; Oh, Seung Wook; Zariwala, Hatim A.; Gu, Hong; Ng, Lydia L.; Palmiter, Richard D.; Hawrylycz, Michael J.; Jones, Allan R.; Lein, Ed S.; Zeng, Hongkui

    2009-01-01

    The Cre/lox system is widely used in mice to achieve cell-type-specific gene expression. However, a strong and universal responding system to express genes under Cre control is still lacking. We have generated a set of Cre reporter mice with strong, ubiquitous expression of fluorescent proteins of different spectra. The robust native fluorescence of these reporters enables direct visualization of fine dendritic structures and axonal projections of the labeled neurons, which is useful in mapping neuronal circuitry, imaging and tracking specific cell populations in vivo. Using these reporters and a high-throughput in situ hybridization platform, we are systematically profiling Cre-directed gene expression throughout the mouse brain in a number of Cre-driver lines, including novel Cre lines targeting different cell types in the cortex. Our expression data are displayed in a public online database to help researchers assess the utility of various Cre-driver lines for cell-type-specific genetic manipulation. PMID:20023653

  16. Pannexin-1 expression in developing mouse nervous system: new evidence for expression in sensory ganglia.

    PubMed

    Raslan, Abdulrahman; Hainz, Nadine; Beckmann, Anja; Tschernig, Thomas; Meier, Carola

    2016-04-01

    Pannexin1 (Panx1) is one of three members of the pannexin protein family. The expression of Panx1 mRNA has been extensively investigated from late embryonic to adult stages. In contrast, expression during early embryonic development is largely unknown. Our aim is to examine the temporal and spatial expression of Panx1 in mouse embryonic development by focusing on embryonic days (E) 9.5 to 12.5. Whole embryos are investigated in order to provide a comprehensive survey. Analyses were performed at the mRNA level by using reverse transcription plus the polymerase chain reaction and whole-mount in situ hybridization. Panx1 mRNA was detected in the heads and bodies of embryos at all developmental stages investigated (E9.5, E10.5, E11.5, E12.5). In particular, the nervous system expressed Panx1 at an early time point. Interestingly, Panx1 expression was found in afferent ganglia of the cranial nerves and spinal cord. This finding is of particular interest in the context of neuropathic pain and other Panx1-related neurological disorders. Our study shows, for the first time, that Panx1 is expressed in the central and peripheral nervous system during early developmental stages. The consequences of Panx1 deficiency or inhibition in a number of experimental paradigms might therefore be predicated on changes during early development. PMID:26453396

  17. Distribution of EphA5 receptor protein in the developing and adult mouse nervous system

    PubMed Central

    Cooper, Margaret A.; Crockett, David P.; Nowakowski, Richard S.; Gale, Nicholas W.; Zhou, Renping

    2009-01-01

    The EphA5 receptor tyrosine kinase plays key roles in axon guidance during development. However, the presence of EphA5 protein in the nervous system has not been fully characterized. To better examine EphA5 localization, mutant mice, in which the EphA5 cytoplasmic domain was replaced with β-galactosidase, were analyzed for both temporal and regional changes in the distribution of EphA5 protein in the developing and adult nervous system. During embryonic development, high levels of EphA5 protein were found in the retina, olfactory bulb, cerebral neocortex, hippocampus, pretectum, tectum, cranial nerve nuclei, and the spinal cord. Variations in intensity were observed as development proceeded. Staining of pretectal nuclei, tectal nuclei, and other areas of the mesencephalon became more diffuse after maturity whereas the cerebral neocortex gained more robust intensity. In the adult, receptor protein continued to be detected in many areas including the olfactory nuclei, neocortex, piriform cortex, induseum griseum, hippocampus, thalamus, amygdala, hypothalamus and septum. In addition, EphA5 protein was found in the claustrum, stria terminalis, barrel cortex, striatal patches, and along discrete axon tracts within the corpus callosum of the adult. These observations suggest that EphA5 function is not limited to the developing mouse brain and may play a role in synaptic plasticity in the adult. PMID:19326470

  18. Systemic anti-VEGF treatment strongly reduces skin inflammation in a mouse model of psoriasis.

    PubMed

    Schonthaler, Helia B; Huggenberger, Reto; Wculek, Stefanie K; Detmar, Michael; Wagner, Erwin F

    2009-12-15

    Although(,) vascular remodeling is a hallmark of many chronic inflammatory disorders such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis, anti-vascular strategies to treat these conditions have received little attention to date. We investigated the anti-inflammatory activity of systemic blockade of VEGF-A by the inhibitory monoclonal antibody G6-31, employing a therapeutic trial in a mouse model of psoriasis. Simultaneous deletion of JunB and c-Jun (DKO*) in the epidermis of adult mice leads to a psoriasis-like phenotype with hyper- and parakeratosis and increased subepidermal vascularization. Moreover, an inflammatory infiltrate and elevated levels of cytokines/chemokines including TNFalpha, IL-1alpha/beta, IL-6, and the innate immune mediators IL-22, IL-23, IL-23R, and IL-12p40 are detected. Here we show that anti-VEGF antibody treatment of mice already displaying disease symptoms resulted in an overall improvement of the psoriatic lesions leading to a reduction in the number of blood vessels and a significant decrease in the size of dermal blood and lymphatic vessels. Importantly, anti-VEGF-treated mice showed a pronounced reduction of inflammatory cells within the dermis and a normalization of epidermal differentiation. These results demonstrate that systemic blockade of VEGF by an inhibitory antibody might be used to treat patients who have inflammatory skin disorders such as psoriasis. PMID:19995970

  19. Hippocampal Damage in Mouse and Human Forms of Systemic Autoimmune Disease

    PubMed Central

    Ballok, David A.; Woulfe, John; Sur, Monalisa; Cyr, Michael; Sakic, Boris

    2006-01-01

    Systemic lupus erythematosus (SLE) is frequently accompanied by neuropsychiatric (NP) and cognitive deficits of unknown etiology. By using autoimmune MRL-lpr mice as an animal model of NP-SLE, we examine the relationship between autoimmunity, hippocampal damage, and behavioral dysfunction. Fluoro Jade B (FJB) staining and anti-ubiquitin (anti-Ub) immunocytochemistry were used to assess neuronal damage in young (asymptomatic) and aged (diseased) mice, while spontaneous alternation behavior (SAB) was used to estimate the severity of hippocampal dysfunction. The causal relationship between autoimmunity and neuropathology was tested by prolonged administration of the immunosuppressive drug cyclophosphamide (CY). In comparison to congenic MRL +/+ controls, SAB acquisition rates and performance in the “reversal” trial were impaired in diseased MRL-lpr mice, suggesting limited use of the spatial learning strategy. FJB-positive neurons and anti-Ub particles were frequent in the CA3 region. Conversely, CY treatment attenuated the SAB deficit and overall FJB staining. Similarly to mouse brain, the hippocampus from a patient who died from NP-SLE showed reduced neuronal density in the CA3 region and dentate gyrus, as well as increased FJB positivity in these regions. Gliosis and neuronal loss were observed in the gray matter, and T lymphocytes and stromal calcifications were common in the choroid plexus. Taken together, these results suggest that systemic autoimmunity induces significant hippocampal damage, which may underlie affective and cognitive deficits in NP-SLE. PMID:15301441

  20. Analysis of Different Promoter Systems for Efficient Transgene Expression in Mouse Embryonic Stem Cell Lines

    PubMed Central

    Chung, Sangmi; Andersson, Therese; Sonntag, Kai-C.; Björklund, Lars; Isacson, Ole; Kim, Kwang-Soo

    2008-01-01

    Mouse embryonic stem (ES) cells are derived from the inner cell mass of the preimplantation embryo and have the developmental capacity to generate all cell types of the body. Combined with efficient genetic manipulation and in vitro differentiation procedures, ES cells are a useful system for the molecular analysis of developmental pathways. We analyzed and compared the transcriptional activities of a cellular polypeptide chain elongation factor 1 alpha (EF), a cellular-virus hybrid (cytomegalo-virus [CMV] immediate early enhancer fused to chicken β-actin [CBA]), and a viral CMV promoter system in two ES cell lines. When transiently transfected, the EF and CBA promoters robustly drove reporter gene expression, while the CMV promoter was inactive. We also demonstrated that the EF and CBA promoters effectively drove gene expression in different stages of cell development: naïve ES cells, embryoid bodies (EBs), and neuronal precursor cells. In contrast, the CMV promoter did not have transcriptional activity in either ES cells or EB but had significant activity once ES cells differentiated into neuronal precursors. Our data show that individual promoters have different abilities to express reporter gene expression in the ES and other cell types tested. PMID:11897870

  1. Growth Arrest Specific 1 (GAS1) Is Abundantly Expressed in the Adult Mouse Central Nervous System

    PubMed Central

    Zarco, Natanael; Bautista, Elizabeth; Cuéllar, Manola; Vergara, Paula; Flores-Rodriguez, Paola; Aguilar-Roblero, Raúl

    2013-01-01

    Growth arrest specific 1 (GAS1) is a pleiotropic protein that induces apoptosis and cell arrest in different tumors, but it is also involved in the development of the nervous system and other tissues and organs. This dual ability is likely caused by its capacity to interact both by inhibiting the intracellular signaling cascade induced by glial cell-line derived neurotrophic factor and by facilitating the activity of the sonic hedgehog pathway. The presence of GAS1 mRNA has been described in adult mouse brain, and here we corroborated this observation. We then proceeded to determine the distribution of the protein in the adult central nervous system (CNS). We detected, by western blot analysis, expression of GAS1 in olfactory bulb, caudate-putamen, cerebral cortex, hippocampus, mesencephalon, medulla oblongata, cerebellum, and cervical spinal cord. To more carefully map the expression of GAS1, we performed double-label immunohistochemistry and noticed expression of GAS1 in neurons in all brain areas examined. We also observed expression of GAS1 in astroglial cells, albeit the pattern of expression was more restricted than that seen in neurons. Briefly, in the present article, we report the widespread distribution and cellular localization of the GAS1 native protein in adult mammalian CNS. PMID:23813868

  2. Exploring membrane respiratory chains.

    PubMed

    Marreiros, Bruno C; Calisto, Filipa; Castro, Paulo J; Duarte, Afonso M; Sena, Filipa V; Silva, Andreia F; Sousa, Filipe M; Teixeira, Miguel; Refojo, Patrícia N; Pereira, Manuela M

    2016-08-01

    Acquisition of energy is central to life. In addition to the synthesis of ATP, organisms need energy for the establishment and maintenance of a transmembrane difference in electrochemical potential, in order to import and export metabolites or to their motility. The membrane potential is established by a variety of membrane bound respiratory complexes. In this work we explored the diversity of membrane respiratory chains and the presence of the different enzyme complexes in the several phyla of life. We performed taxonomic profiles of the several membrane bound respiratory proteins and complexes evaluating the presence of their respective coding genes in all species deposited in KEGG database. We evaluated 26 quinone reductases, 5 quinol:electron carriers oxidoreductases and 18 terminal electron acceptor reductases. We further included in the analyses enzymes performing redox or decarboxylation driven ion translocation, ATP synthase and transhydrogenase and we also investigated the electron carriers that perform functional connection between the membrane complexes, quinones or soluble proteins. Our results bring a novel, broad and integrated perspective of membrane bound respiratory complexes and thus of the several energetic metabolisms of living systems. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi. PMID:27044012

  3. Respiratory Muscle Plasticity

    PubMed Central

    Gransee, Heather M.; Mantilla, Carlos B.; Sieck, Gary C.

    2014-01-01

    Muscle plasticity is defined as the ability of a given muscle to alter its structural and functional properties in accordance with the environmental conditions imposed on it. As such, respiratory muscle is in a constant state of remodeling, and the basis of muscle’s plasticity is its ability to change protein expression and resultant protein balance in response to varying environmental conditions. Here, we will describe the changes of respiratory muscle imposed by extrinsic changes in mechanical load, activity, and innervation. Although there is a large body of literature on the structural and functional plasticity of respiratory muscles, we are only beginning to understand the molecular-scale protein changes that contribute to protein balance. We will give an overview of key mechanisms regulating protein synthesis and protein degradation, as well as the complex interactions between them. We suggest future application of a systems biology approach that would develop a mathematical model of protein balance and greatly improve treatments in a variety of clinical settings related to maintaining both muscle mass and optimal contractile function of respiratory muscles. PMID:23798306

  4. [Respiratory complications after transfusion].

    PubMed

    Bernasinski, M; Mertes, P-M; Carlier, M; Dupont, H; Girard, M; Gette, S; Just, B; Malinovsky, J-M

    2014-05-01

    Respiratory complications of blood transfusion have several possible causes. Transfusion-Associated Circulatory Overload (TACO) is often the first mentioned. Transfusion-Related Acute Lung Injury (TRALI), better defined since the consensus conference of Toronto in 2004, is rarely mentioned. French incidence is low. Non-hemolytic febrile reactions, allergies, infections and pulmonary embolism are also reported. The objective of this work was to determine the statistical importance of the different respiratory complications of blood transfusion. This work was conducted retrospectively on transfusion accidents in six health centers in Champagne-Ardenne, reported to Hemovigilance between 2000 and 2009 and having respiratory symptoms. The analysis of data was conducted by an expert committee. Eighty-three cases of respiratory complications are found (316,864 blood products). We have counted 26 TACO, 12 TRALI (only 6 cases were identified in the original investigation of Hemovigilance), 18 non-hemolytic febrile reactions, 16 cases of allergies, 5 transfusions transmitted bacterial infections and 2 pulmonary embolisms. Six new TRALI were diagnosed previously labeled TACO for 2 of them, allergy and infection in 2 other cases and diagnosis considered unknown for the last 2. Our study found an incidence of TRALI 2 times higher than that reported previously. Interpretation of the data by a multidisciplinary committee amended 20% of diagnoses. This study shows the imperfections of our system for reporting accidents of blood transfusion when a single observer analyses the medical records. PMID:24814817

  5. The natural organosulfur compound dipropyltetrasulfide prevents HOCl-induced systemic sclerosis in the mouse

    PubMed Central

    2013-01-01

    Introduction The aim of this study was to test the naturally occurring organosulfur compound dipropyltetrasulfide (DPTTS), found in plants, which has antibiotic and anticancer properties, as a treatment for HOCl-induced systemic sclerosis in the mouse. Methods The prooxidative, antiproliferative, and cytotoxic effects of DPTTS were evaluated ex vivo on fibroblasts from normal and HOCl mice. In vivo, the antifibrotic and immunomodulating properties of DPTTS were evaluated in the skin and lungs of HOCl mice. Results H2O2 production was higher in fibroblasts derived from HOCl mice than in normal fibroblasts (P < 0.05). DPTTS did not increase H2O2 production in normal fibroblasts, but DPTTS dose-dependently increased H2O2 production in HOCl fibroblasts (P < 0.001 with 40 μM DPTTS). Because H2O2 reached a lethal threshold in cells from HOCl mice, the antiproliferative, cytotoxic, and proapoptotic effects of DPTTS were significantly higher in HOCl fibroblasts than for normal fibroblasts. In vivo, DPTTS decreased dermal thickness (P < 0.001), collagen content in skin (P < 0.01) and lungs (P < 0.05), αSMA (P < 0.01) and pSMAD2/3 (P < 0.01) expression in skin, formation of advanced oxidation protein products and anti-DNA topoisomerase-1 antibodies in serum (P < 0.05) versus untreated HOCl mice. Moreover, in HOCl mice, DPTTS reduced splenic B-cell counts (P < 0.01), the proliferative rates of B-splenocytes stimulated by lipopolysaccharide (P < 0.05), and T-splenocytes stimulated by anti-CD3/CD28 mAb (P < 0.001). Ex vivo, it also reduced the production of IL-4 and IL-13 by activated T cells (P < 0.05 in both cases). Conclusions The natural organosulfur compound DPTTS prevents skin and lung fibrosis in the mouse through the selective killing of diseased fibroblasts and its immunomodulating properties. DPTTS may be a potential treatment for systemic sclerosis. PMID:24286210

  6. Differences in Pathogenesis for Salmonella enterica serovar Typhimurium in the Mouse Versus the Swine Model Identify Bacterial Gene Products Required for Systemic but not Gastrointestinal Disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Over the last several decades, the mouse model of Typhoid fever has been an extremely productive model to investigate Salmonella enterica serovar Typhimurium pathogenesis. The mouse is the paradigm for investigating systemic disease due to infection by Salmonella; however, the swine model of gastro...

  7. Evaluation of the Mitochondrial Respiratory Chain and Oxidative Phosphorylation System Using Yeast Models of OXPHOS Deficiencies

    PubMed Central

    Fontanesi, Flavia; Diaz, Francisca; Barrientos, Antoni

    2009-01-01

    The oxidative phosphorylation (OXPHOS) system consists of five multimeric complexes embedded in the mitochondrial inner membrane. They work in concert to drive the aerobic synthesis of ATP. Mitochondrial and nuclear DNA mutations affecting the accumulation and function of these enzymes are the most common cause of mitochondrial diseases and have also been associated with neurodegeneration and aging. Several approaches for the assessment of the OXPHOS system enzymes have been developed. Based on the methods described elsewhere, we present here the creation and study of yeast models of mitochondrial OXPHOS deficiencies. PMID:19806592

  8. An endocannabinoid system is present in the mouse olfactory epithelium but does not modulate olfaction

    PubMed Central

    Hutch, Chelsea; Hillard, Cecilia J.; Jia, Cuihong; Hegg, Colleen C.

    2015-01-01

    Endocannabinoids modulate a diverse array of functions including progenitor cell proliferation in the central nervous system, and odorant detection and food intake in the mammalian central olfactory system and larval Xenopus laevis peripheral olfactory system. However, the presence and role of endocannabinoids in the peripheral olfactory epithelium has not been examined in mammals. We found the presence of cannabinoid type 1 (CB1) and cannabinoid type 2 (CB2) receptor protein and mRNA in the olfactory epithelium. Using either immunohistochemistry or calcium imaging we localized CB1 receptors on neurons, glia like sustentacular cells, microvillous cells and progenitor-like basal cells. To examine the role of endocannabinoids, CB1 and CB2 receptor deficient (CB1−/−/CB2−/−) mice were used. The endocannabinoid 2-arachidonylglycerol (2-AG) was present at high levels in both C57BL/6 wildtype and CB1−/−/CB2−/− mice. 2-AG synthetic and degradative enzymes are expressed in wildtype mice. A small but significant decrease in basal cell and olfactory sensory neuron numbers was observed in CB1−/−/CB2−/− mice compared to wildtype mice. The decrease in olfactory sensory neurons did not translate to impairment in olfactory-mediated behaviors assessed by the buried food test and habituation/dishabituation test. Collectively, these data indicate the presence of an endocannabinoid system in the mouse olfactory epithelium. However, unlike in tadpoles, endocannabinoids do not modulate olfaction. Further investigation on the role of endocannabinoids in progenitor cell function in the olfactory epithelium is warranted. PMID:26037800

  9. Immune System Modifications Induced in a Mouse Model of Chronic Exposure to (90)Sr.

    PubMed

    Synhaeve, Nicholas; Musilli, Stefania; Stefani, Johanna; Nicolas, Nour; Delissen, Olivia; Dublineau, Isabelle; Bertho, Jean-Marc

    2016-03-01

    Strontium 90 ((90)Sr) remains in the environment long after a major nuclear disaster occurs. As a result, populations living on contaminated land are potentially exposed to daily ingesting of low quantities of (90)Sr. The potential long-term health effects of such chronic contamination are unknown. In this study, we used a mouse model to evaluate the effects of (90)Sr ingestion on the immune system, the animals were chronically exposed to (90)Sr in drinking water at a concentration of 20 kBq/l, for a daily ingestion of 80-100 Bq/day. This resulted in a reduced number of CD19(+) B lymphocytes in the bone marrow and spleen in steady-state conditions. In contrast, the results from a vaccine experiment performed as a functional test of the immune system showed that in response to T-dependent antigens, there was a reduction in IgG specific to tetanus toxin (TT), a balanced Th1/Th2 response inducer antigen, but not to keyhole limpet hemocyanin (KLH), a strong Th2 response inducer antigen. This was accompanied by a reduction in Th1 cells in the spleen, consistent with the observed reduction in specific IgG concentration. The precise mechanisms by which (90)Sr acts on the immune system remain to be elucidated. However, our results suggest that (90)Sr ingestion may be responsible for some of the reported effects of internal contamination on the immune system in civilian populations exposed to the Chernobyl fallout. PMID:26930377

  10. Acute Radiation Syndrome Severity Score System in Mouse Total-Body Irradiation Model.

    PubMed

    Ossetrova, Natalia I; Ney, Patrick H; Condliffe, Donald P; Krasnopolsky, Katya; Hieber, Kevin P

    2016-08-01

    Radiation accidents or terrorist attacks can result in serious consequences for the civilian population and for military personnel responding to such emergencies. The early medical management situation requires quantitative indications for early initiation of cytokine therapy in individuals exposed to life-threatening radiation doses and effective triage tools for first responders in mass-casualty radiological incidents. Previously established animal (Mus musculus, Macaca mulatta) total-body irradiation (γ-exposure) models have evaluated a panel of radiation-responsive proteins that, together with peripheral blood cell counts, create a multiparametic dose-predictive algorithm with a threshold for detection of ~1 Gy from 1 to 7 d after exposure as well as demonstrate the acute radiation syndrome severity score systems created similar to the Medical Treatment Protocols for Radiation Accident Victims developed by Fliedner and colleagues. The authors present a further demonstration of the acute radiation sickness severity score system in a mouse (CD2F1, males) TBI model (1-14 Gy, Co γ-rays at 0.6 Gy min) based on multiple biodosimetric endpoints. This includes the acute radiation sickness severity Observational Grading System, survival rate, weight changes, temperature, peripheral blood cell counts and radiation-responsive protein expression profile: Flt-3 ligand, interleukin 6, granulocyte-colony stimulating factor, thrombopoietin, erythropoietin, and serum amyloid A. Results show that use of the multiple-parameter severity score system facilitates identification of animals requiring enhanced monitoring after irradiation and that proteomics are a complementary approach to conventional biodosimetry for early assessment of radiation exposure, enhancing accuracy and discrimination index for acute radiation sickness response categories and early prediction of outcome. PMID:27356057

  11. Contribution of Bordetella bronchiseptica Type III secretion system to respiratory disease in swine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: The type III secretion system (TTSS) of gram negative bacteria allows injection of effector proteins directly into the cytosol of eukaryotic cells. Previous studies have demonstrated that the B. bronchiseptica TTSS plays a role in the persistent bacterial colonization of the trachea of m...

  12. Pharmacological interference with the glucocorticoid system influences symptoms and lifespan in a mouse model of Rett syndrome.

    PubMed

    Braun, Sebastian; Kottwitz, Denise; Nuber, Ulrike A

    2012-04-15

    Rett syndrome (RTT) is caused by loss-of-function mutations in the X-linked gene MECP2 coding for methyl CpG-binding protein 2 (MeCP2). This protein can act as transcriptional repressor, and we showed in a previous study that glucocorticoid-inducible genes are up-regulated in an RTT mouse model and that these genes are direct MeCP2 targets. Here, we report that pharmacological intervention with the glucocorticoid system has an impact on the symptoms and lifespan in an RTT mouse model. Our data support a functional implication of the stress hormone system in RTT and suggest this hormone system as potential therapeutic target. PMID:22186023

  13. [Effects of histamine on the pressure-volume curve of the respiratory system in the guinea pig].

    PubMed

    Clerici, C; Macquin, I; Lhoste, F; Atlan, G; Harf, A

    1985-01-01

    Intravenous infusion of histamine has been shown to constrict smooth muscle of alveolar ducts. In this study, we have assessed the effects of a prolonged infusion of histamine to obtain a steady state response on quasistatic pressure-volume curves (P-V curves) together with the changes in dynamic compliance (Cdyn) and conductance (G) of the respiratory system. Increasing doses of histamine were given in order to obtain the dose-response characteristics of the changes in Cdyn, G and P-V curves. In nine anesthetized guinea-pigs under mechanical ventilation, administration of histamine resulted in a fall in Cdyn and G with a decrease of 50% of initial value approximately for 150 ng X kg-1 X s-1 of histamine. Modifications of the P-V curves were characterized by a decrease in the maximal volume, and an increase in the hysteresis of the P-V loop due to the downward displacement of the inflation limb. With infusion of histamine, there was a large decrease of quasi-static compliance which appeared to account for most of the decrease in dynamic compliance. Such changes in P-V curves can be related both to a closure of alveolar ducts and to an alteration of lung distensibility. Comparison of the dose-response curves for the different parameters indicated that Cdyn and G reflect, at least in part, events occurring in the periphery of the lung. PMID:4041662

  14. Twin-arginine translocation system (tat) mutants of Salmonella are attenuated due to envelope defects, not respiratory defects.

    PubMed

    Craig, Maureen; Sadik, Adam Y; Golubeva, Yekaterina A; Tidhar, Avital; Slauch, James M

    2013-09-01

    The twin-arginine translocation system (Tat) transports folded proteins across the cytoplasmic membrane and is critical to virulence in Salmonella and other pathogens. Experimental and bioinformatic data indicate that 30 proteins are exported via Tat in Salmonella Typhimurium. However, there are no data linking specific Tat substrates with virulence. We inactivated every Tat-exported protein and determined the virulence phenotype of mutant strains. Although a tat mutant is highly attenuated, no single Tat-exported substrate accounts for this virulence phenotype. Rather, the attenuation is due primarily to envelope defects caused by failure to translocate three Tat substrates, the N-acetylmuramoyl-l-alanine amidases, AmiA and AmiC, and the cell division protein, SufI. Strikingly, neither the amiA amiC nor the sufI mutations alone conferred any virulence defect. Although AmiC and SufI have previously been localized to the divisome, the synthetic phenotypes observed are the first to suggest functional overlap. Many Tat substrates are involved in anaerobic respiration, but we show that a mutant completely deficient in anaerobic respiration retains full virulence in both the oral and systemic phases of infection. Similarly, an obligately aerobic mutant is fully virulent. These results suggest that in the classic mouse model of infection, S. Typhimurium is replicating only in aerobic environments. PMID:23822642

  15. Twin-arginine Translocation System (tat) Mutants of Salmonella are Attenuated Due to Envelope Defects, not Respiratory Defects

    PubMed Central

    Craig, Maureen; Sadik, Adam Y.; Golubeva, Yekaterina A.; Tidhar, Avital; Slauch, James M.

    2013-01-01

    Summary The twin-arginine translocation system (Tat) transports folded proteins across the cytoplasmic membrane and is critical to virulence in Salmonella and other pathogens. Experimental and bioinformatic data indicate that 30 proteins are exported via Tat in Salmonella Typhimurium. However, there are no data linking specific Tat substrates with virulence. We inactivated every Tat-exported protein and determined the virulence phenotype of mutant strains. Though a tat mutant is highly attenuated, no single Tat-exported substrate accounts for this virulence phenotype. Rather, the attenuation is due primarily to envelope defects caused by failure to translocate three Tat substrates, the N-acetylmuramoyl-L-alanine amidases, AmiA and AmiC, and the cell division protein, SufI. Strikingly, neither the amiA amiC nor the sufI mutations alone conferred any virulence defect. Although AmiC and SufI have previously been localized to the divisome, the synthetic phenotypes observed are the first to suggest functional overlap. Many Tat substrates are involved in anaerobic respiration, but we show that a mutant completely deficient in anaerobic respiration retains full virulence in both the oral and systemic phases of infection. Similarly, an obligately aerobic mutant is fully virulent. These results suggest that in the classic mouse model of infection, S. Typhimurium is replicating only in aerobic environments. PMID:23822642

  16. Design of a Miniature Tissue Culture System to Culture Mouse Heart Valves

    PubMed Central

    Lieber, Samuel C.; Kruithof, Boudewijn P. T.; Aubry, Nadine; Vatner, Stephen F.; Gaussin, Vinciane

    2010-01-01

    Valvular heart disease is a leading cause of morbidity and mortality in adults but little is known about the underlying etiology. A better understanding of the genetic and hemodynamic mechanisms involved in growth and remodeling of heart valves during physiological and pathological conditions is needed for a better understanding of valvular heart disease. Here, we report the design of a miniature tissue culture system (MTCS) that allows the culture of mitral valves from perinatal to adult mice. The design of the MTCS is novel in that fine positioning and cannulation can be conducted with hearts of different sizes (perinatal to adult). Perfusion of the heart and hence, culture of the mitral valve in its natural position, occurs in a hydraulically sealed culture bath environment. Using the MTCS, we successfully cultured the mitral valve of adult mouse hearts for 3 days. Histological analysis indicated that the cultured valves remained viable and their extracellular matrix organization was similar to age-matched native valves. Gene expression could also be modified in cultured valves by perfusion with medium containing beta-galactosidase-expressing adenovirus. Thus, the MTCS is a new tool to study the genetic and hemodynamic mechanisms underlying the three-dimensional organization of the heart valves, which could provide insights in the pathology of valvular heart disease and be used in animal models for the development of tissue-engineered heart valves. PMID:20099034

  17. Quantification, Distribution, and Possible Source of Bacterial Biofilm in Mouse Automated Watering Systems

    PubMed Central

    Meier, Thomas R; Maute, Carrie J; Cadillac, Joan M; Lee, Ji Young; Righter, Daniel J; Hugunin, Kelly MS; Deininger, Rolf A; Dysko, Robert C

    2008-01-01

    The use of automated watering systems for providing drinking water to rodents has become commonplace in the research setting. Little is known regarding bacterial biofilm growth within the water piping attached to the racks (manifolds). The purposes of this project were to determine whether the mouse oral flora contributed to the aerobic bacterial component of the rack biofilm, quantify bacterial growth in rack manifolds over 6 mo, assess our rack sanitation practices, and quantify bacterial biofilm development within sections of the manifold. By using standard methods of bacterial identification, the aerobic oral flora of 8 strains and stocks of mice were determined on their arrival at our animal facility. Ten rack manifolds were sampled before, during, and after sanitation and monthly for 6 mo. Manifolds were evaluated for aerobic bacterial growth by culture on R2A and trypticase soy agar, in addition to bacterial ATP quantification by bioluminescence. In addition, 6 racks were sampled at 32 accessible sites for evaluation of biofilm distribution within the watering manifold. The identified aerobic bacteria in the oral flora were inconsistent with the bacteria from the manifold, suggesting that the mice do not contribute to the biofilm bacteria. Bacterial growth in manifolds increased while they were in service, with exponential growth of the biofilm from months 3 to 6 and a significant decrease after sanitization. Bacterial biofilm distribution was not significantly different across location quartiles of the rack manifold, but bacterial levels differed between the shelf pipe and connecting elbow pipes. PMID:18351724

  18. Glial cells in the mouse enteric nervous system can undergo neurogenesis in response to injury

    PubMed Central

    Laranjeira, Catia; Sandgren, Katarina; Kessaris, Nicoletta; Richardson, William; Potocnik, Alexandre; Vanden Berghe, Pieter; Pachnis, Vassilis

    2011-01-01

    The enteric nervous system (ENS) in mammals forms from neural crest cells during embryogenesis and early postnatal life. Nevertheless, multipotent progenitors of the ENS can be identified in the adult intestine using clonal cultures and in vivo transplantation assays. The identity of these neurogenic precursors in the adult gut and their relationship to the embryonic progenitors of the ENS are currently unknown. Using genetic fate mapping, we here demonstrate that mouse neural crest cells marked by SRY box–containing gene 10 (Sox10) generate the neuronal and glial lineages of enteric ganglia. Most neurons originated from progenitors residing in the gut during mid-gestation. Afterward, enteric neurogenesis was reduced, and it ceased between 1 and 3 months of postnatal life. Sox10-expressing cells present in the myenteric plexus of adult mice expressed glial markers, and we found no evidence that these cells participated in neurogenesis under steady-state conditions. However, they retained neurogenic potential, as they were capable of generating neurons with characteristics of enteric neurons in culture. Furthermore, enteric glia gave rise to neurons in vivo in response to chemical injury to the enteric ganglia. Our results indicate that despite the absence of constitutive neurogenesis in the adult gut, enteric glia maintain limited neurogenic potential, which can be activated by tissue dissociation or injury. PMID:21865647

  19. Systemic overexpression of matricellular protein CCN1 exacerbates obliterative bronchiolitis in mouse tracheal allografts.

    PubMed

    Raissadati, Alireza; Nykänen, Antti I; Tuuminen, Raimo; Syrjälä, Simo O; Krebs, Rainer; Arnaudova, Ralica; Rouvinen, Eeva; Wang, Xiaomin; Poller, Wolfgang; Lemström, Karl B

    2015-12-01

    Obliterative bronchiolitis (OB) involves airway epithelial detachment, fibroproliferation, and inflammation, resulting in chronic rejection and transplant failure. Cysteine-rich 61 (CCN1) is an integrin receptor antagonist with a context-dependent role in inflammatory and fibroproliferative processes. We used a mouse tracheal OB model to investigate the role of CCN1 in the development of lung allograft OB. C57Bl/6 mice received a systemic injection of CCN1-expressing adenoviral vectors 2 days prior to subcutaneous implantation of tracheal allografts from major MHC-mismatched BALB/c mice. We treated another group of tracheal allograft recipients with cyclic arginine-glycine-aspartic acid peptide to dissect the role of αvβ3-integrin signaling in mediating CCN1 effects in tracheal allografts. Allografts were removed 4 weeks after transplantation and analyzed for luminal occlusion, inflammation, and vasculogenesis. CCN1 overexpression induced luminal occlusion (P < 0.05), fibroproliferation, and smooth muscle cell proliferation (P < 0.05). Selective activation of αvβ3-integrin receptor failed to mimic the actions of CCN1, and blocking failed to inhibit the effects of CCN1 in tracheal allografts. In conclusion, CCN1 exacerbates tracheal OB by enhancing fibroproliferation via an αvβ3-integrin-independent pathway. Further experiments are required to uncover its potentially harmful role in the development of OB after lung transplantation. PMID:26174800

  20. Deletion of mouse FXR gene disturbs multiple neurotransmitter systems and alters neurobehavior

    PubMed Central

    Huang, Fei; Wang, Tingting; Lan, Yunyi; Yang, Li; Pan, Weihong; Zhu, Yonghui; Lv, Boyang; Wei, Yuting; Shi, Hailian; Wu, Hui; Zhang, Beibei; Wang, Jie; Duan, Xiaofeng; Hu, Zhibi; Wu, Xiaojun

    2015-01-01

    Farnesoid X receptor (FXR) is a nuclear hormone receptor involved in bile acid synthesis and homeostasis. Dysfunction of FXR is involved in cholestasis and atherosclerosis. FXR is prevalent in liver, gallbladder, and intestine, but it is not yet clear whether it modulates neurobehavior. In the current study, we tested the hypothesis that mouse FXR deficiency affects a specific subset of neurotransmitters and results in an unique behavioral phenotype. The FXR knockout mice showed less depressive-like and anxiety-related behavior, but increased motor activity. They had impaired memory and reduced motor coordination. There were changes of glutamatergic, GABAergic, serotoninergic, and norepinephrinergic neurotransmission in either hippocampus or cerebellum. FXR deletion decreased the amount of the GABA synthesis enzyme GAD65 in hippocampus but increased GABA transporter GAT1 in cerebral cortex. FXR deletion increased serum concentrations of many bile acids, including taurodehydrocholic acid, taurocholic acid, deoxycholic acid (DCA), glycocholic acid (GCA), tauro-α-muricholic acid, tauro-ω-muricholic acid, and hyodeoxycholic acid (HDCA). There were also changes in brain concentrations of taurocholic acid, taurodehydrocholic acid, tauro-ω-muricholic acid, tauro-β-muricholic acid, deoxycholic acid, and lithocholic acid (LCA). Taken together, the results from studies with FXR knockout mice suggest that FXR contributes to the homeostasis of multiple neurotransmitter systems in different brain regions and modulates neurobehavior. The effect appears to be at least partially mediated by bile acids that are known to cross the blood-brain barrier (BBB) inducing potential neurotoxicity. PMID:25870546

  1. Expression of the mouse PR domain protein Prdm8 in the developing central nervous system.

    PubMed

    Komai, Tae; Iwanari, Hiroko; Mochizuki, Yasuhiro; Hamakubo, Takao; Shinkai, Yoichi

    2009-10-01

    It was first shown in the PR (PRDI-BF1 and RIZ homology) domain family proteins that the PR domain has homology to the SET (Su(var)3-9, Enhancer-of-zeste and Trithorax) domain, a catalytic domain of the histone lysine methyltransferases. Recently, there are many reports that the PR domain proteins have important roles in development and/or cell differentiation. In this report, we show the expression patterns of one of the mouse PR domain proteins, Prdm8, in the developing central nervous system. In the developing retina, Prdm8 expression was detected in postmitotic neurons in the inner nuclear layer and the ganglion cell layer, and its expression became restricted predominantly to the rod bipolar cells when retinogenesis was completed. In the developing spinal cord, Prdm8 was expressed first in the progenitor populations of ventral interneurons and motor neurons, and later in a subpopulation of interneurons. In the developing brain, Prdm8 expression was observed in postmitotic neurons in the intermediate zone and the cortical plate. In the postnatal brain, Prdm8 was expressed mainly in layer 4 neurons of the cerebral cortex. These results show that Prdm8 expression is tightly regulated in a spatio-temporal manner during neural development and mainly restricted to postmitotic neurons, except in the spinal cord. PMID:19616129

  2. A Self-regulatory System of Interlinked Signaling Feedback Loops Controls Mouse Limb Patterning

    NASA Astrophysics Data System (ADS)

    Benazet, Jean-Denis; Bischofberger, Mirko; Tiecke, Eva; Gonalves, Alexandre; Martin, James F.; Zuniga, Aime; Naef, Felix; Zeller, Rolf

    Developmental pathways need to be robust against environmental and genetic variation to enable reliable morphogenesis. Here, we take a systems biology approach to explain how robustness is achieved in the developing mouse limb, a classical model of organogenesis. By combining quantitative genetics with computational modeling we established a computational model of multiple interlocked feedback modules, involving sonic hedgehog (SHH) morphogen, fibroblast growth factor (FGFs) signaling, bone morphogenetic protein (BMP) and its antagonist GREM1. Earlier modeling work had emphasized the versatile kinetic characteristics of interlocked feedback loops operating at different time scales. Here we develop and then validate a similar computational model to show how BMP4 first initiates and SHH then propagates feedback in the network through differential transcriptional regulation of Grem1 to control digit specification. This switch occurs by linking a fast BMP4/GREM1 module to a slower SHH/GREM1/FGF feedback loop. Simulated gene expression profiles modeled normal limb development as well those of single-gene knockouts. Sensitivity analysis showed how the model was robust and insensitive to variability in parameters. A surprising prediction of the model was that an early Bmp4 signal is essential to kick-start Grem1 expression and the digit specification system. We experimentally validated the prediction using inducible alleles and showed that early, but not late, removal of Bmp4 dramatically disrupted limb development. Sensitivity analysis showed how robustness emerges from this circuitry. This study shows how modeling and computation can help us understand how self-regulatory signaling networks achieve robust regulation of limb development, by exploiting interconnectivity among the three signaling pathways. We expect that similar computational analyses will shed light on the origins of robustness in other developmental systems, and I will discuss some recent examples from

  3. Management of the baseline shift using a new and simple method for respiratory-gated radiation therapy: Detectability and effectiveness of a flexible monitoring system

    SciTech Connect

    Tachibana, Hidenobu; Kitamura, Nozomi; Ito, Yasushi; Kawai, Daisuke; Nakajima, Masaru; Tsuda, Akihisa; Shiizuka, Hisao

    2011-07-15

    Purpose: In respiratory-gated radiation therapy, a baseline shift decreases the accuracy of target coverage and organs at risk (OAR) sparing. The effectiveness of audio-feedback and audio-visual feedback in correcting the baseline shift in the breathing pattern of the patient has been demonstrated previously. However, the baseline shift derived from the intrafraction motion of the patient's body cannot be corrected by these methods. In the present study, the authors designed and developed a simple and flexible system. Methods: The system consisted of a web camera and a computer running our in-house software. The in-house software was adapted to template matching and also to no preimage processing. The system was capable of monitoring the baseline shift in the intrafraction motion of the patient's body. Another marker box was used to monitor the baseline shift due to the flexible setups required of a marker box for gated signals. The system accuracy was evaluated by employing a respiratory motion phantom and was found to be within AAPM Task Group 142 tolerance (positional accuracy <2 mm and temporal accuracy <100 ms) for respiratory-gated radiation therapy. Additionally, the effectiveness of this flexible and independent system in gated treatment was investigated in healthy volunteers, in terms of the results from the differences in the baseline shift detectable between the marker positions, which the authors evaluated statistically. Results: The movement of the marker on the sternum [1.599 {+-} 0.622 mm (1 SD)] was substantially decreased as compared with the abdomen [6.547 {+-} 0.962 mm (1 SD)]. Additionally, in all of the volunteers, the baseline shifts for the sternum [-0.136 {+-} 0.868 (2 SD)] were in better agreement with the nominal baseline shifts than was the case for the abdomen [-0.722 {+-} 1.56 mm (2 SD)]. The baseline shifts could be accurately measured and detected using the monitoring system, which could acquire the movement of the marker on the

  4. 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

    PubMed Central

    2011-01-01

    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 this work we

  5. Human monoclonal antibodies specific to hepatitis B virus generated in a human/mouse radiation chimera: the Trimera system.

    PubMed

    Eren, R; Lubin, I; Terkieltaub, D; Ben-Moshe, O; Zauberman, A; Uhlmann, R; Tzahor, T; Moss, S; Ilan, E; Shouval, D; Galun, E; Daudi, N; Marcus, H; Reisner, Y; Dagan, S

    1998-02-01

    An approach to develop fully human monoclonal antibodies in a human/mouse radiation chimera, the Trimera system, is described. In this system, functional human lymphocytes are engrafted in normal strains of mice which are rendered immuno-incompetent by lethal total body irradiation followed by radioprotection with severe combined immunodeficient (SCID) mouse bone marrow. Following transplantation, human lymphocytes colonize murine lymphatic organs and secrete human immunoglobulins. We have established this system as a tool to develop fully human monoclonal antibodies, and applied it for the generation of monoclonal antibodies specific for hepatitis B virus surface antigen. A strong memory response to hepatitis B surface antigen was elicited in Trimera engrafted with lymphocytes from human donors positive for antibodies to hepatitis B surface antigen. The human specific antibody fraction in the Trimera was 10(2)-10(3)-fold higher as compared with that found in the donors. Spleens were harvested from Trimera mice showing high specific-antibody titres and cells were fused to a human-mouse heteromyeloma fusion partner. Several stable hybridoma clones were isolated and characterized. These hybridomas produce high-affinity, IgG, anti-hepatitis B surface antigen antibodies demonstrating the potential of the Trimera system for generating fully human monoclonal antibodies. The biological function and the neutralizing activity of these antibodies are currently being tested. PMID:9616363

  6. Effect of Systemic Iron Overload and a Chelation Therapy in a Mouse Model of the Neurodegenerative Disease Hereditary Ferritinopathy

    PubMed Central

    Li, Wei; Goodwin, Charles B.; Richine, Briana; Acton, Anthony; Chan, Rebecca J.; Peacock, Munro; Muhoberac, Barry B.; Ghetti, Bernardino; Vidal, Ruben

    2016-01-01

    Mutations in the ferritin light chain (FTL) gene cause the neurodegenerative disease neuroferritinopathy or hereditary ferritinopathy (HF). HF is characterized by a severe movement disorder and by the presence of nuclear and cytoplasmic iron-containing ferritin inclusion bodies (IBs) in glia and neurons throughout the central nervous system (CNS) and in tissues of multiple organ systems. Herein, using primary mouse embryonic fibroblasts from a mouse model of HF, we show significant intracellular accumulation of ferritin and an increase in susceptibility to oxidative damage when cells are exposed to iron. Treatment of the cells with the iron chelator deferiprone (DFP) led to a significant improvement in cell viability and a decrease in iron content. In vivo, iron overload and DFP treatment of the mouse model had remarkable effects on systemic iron homeostasis and ferritin deposition, without significantly affecting CNS pathology. Our study highlights the role of iron in modulating ferritin aggregation in vivo in the disease HF. It also puts emphasis on the potential usefulness of a therapy based on chelators that can target the CNS to remove and redistribute iron and to resolubilize or prevent ferritin aggregation while maintaining normal systemic iron stores. PMID:27574973

  7. Effect of Systemic Iron Overload and a Chelation Therapy in a Mouse Model of the Neurodegenerative Disease Hereditary Ferritinopathy.

    PubMed

    Garringer, Holly J; Irimia, Jose M; Li, Wei; Goodwin, Charles B; Richine, Briana; Acton, Anthony; Chan, Rebecca J; Peacock, Munro; Muhoberac, Barry B; Ghetti, Bernardino; Vidal, Ruben

    2016-01-01

    Mutations in the ferritin light chain (FTL) gene cause the neurodegenerative disease neuroferritinopathy or hereditary ferritinopathy (HF). HF is characterized by a severe movement disorder and by the presence of nuclear and cytoplasmic iron-containing ferritin inclusion bodies (IBs) in glia and neurons throughout the central nervous system (CNS) and in tissues of multiple organ systems. Herein, using primary mouse embryonic fibroblasts from a mouse model of HF, we show significant intracellular accumulation of ferritin and an increase in susceptibility to oxidative damage when cells are exposed to iron. Treatment of the cells with the iron chelator deferiprone (DFP) led to a significant improvement in cell viability and a decrease in iron content. In vivo, iron overload and DFP treatment of the mouse model had remarkable effects on systemic iron homeostasis and ferritin deposition, without significantly affecting CNS pathology. Our study highlights the role of iron in modulating ferritin aggregation in vivo in the disease HF. It also puts emphasis on the potential usefulness of a therapy based on chelators that can target the CNS to remove and redistribute iron and to resolubilize or prevent ferritin aggregation while maintaining normal systemic iron stores. PMID:27574973

  8. Are treatment guides and rational drug use policies adequately exploited in combating respiratory system diseases?

    PubMed

    Dogan, Mustafa; Mutlu, Levent C; Yilmaz, İbrahim; Bilir, Bulent; Varol Saracoglu, Gamze; Yildirim Guzelant, Aliye

    2016-01-01

    The aim of the present study was to increase awareness regarding the rational use of medicines. The data were obtained via the Material Resources Management System Module of the Ministry of Health. For the appropriateness of treatments, the Global Initiative for Asthma, the Global Initiative for Chronic Obstructive Lung Disease, and the guidelines for the rational use of medicines were used. We also investigated whether any de-escalation method or physical exercise was performed. Statistical analyses were performed using descriptive statistics to determine the mean, standard deviation, and frequency. The results showed that healthcare providers ignored potential drug reactions or adverse interactions, and reflecting the lack of adherence to the current treatment guides, 35.8% irrational use of medicines was recorded. Thus, de-escalation methods should be used to decrease costs or narrow the antibiotic spectrum, antibiotic selection should consider the resistance patterns, culturing methods should be analyzed, and monotherapy should be preferred over combination treatments. PMID:26166817

  9. Nanotechnology in respiratory medicine.

    PubMed

    Omlor, Albert Joachim; Nguyen, Juliane; Bals, Robert; Dinh, Quoc Thai

    2015-01-01

    Like two sides of the same coin, nanotechnology can be both boon and bane for respiratory medicine. Nanomaterials open new ways in diagnostics and treatment of lung diseases. Nanoparticle based drug delivery systems can help against diseases such as lung cancer, tuberculosis, and pulmonary fibrosis. Moreover, nanoparticles can be loaded with DNA and act as vectors for gene therapy in diseases like cystic fibrosis. Even lung diagnostics with computer tomography (CT) or magnetic resonance imaging (MRI) profits from new nanoparticle based contrast agents. However, the risks of nanotechnology also have to be taken into consideration as engineered nanomaterials resemble natural fine dusts and fibers, which are known to be harmful for the respiratory system in many cases. Recent studies have shown that nanoparticles in the respiratory tract can influence the immune system, can create oxidative stress and even cause genotoxicity. Another important aspect to assess the safety of nanotechnology based products is the absorption of nanoparticles. It was demonstrated that the amount of pulmonary nanoparticle uptake not only depends on physical and chemical nanoparticle characteristics but also on the health status of the organism. The huge diversity in nanotechnology could revolutionize medicine but makes safety assessment a challenging task. PMID:26021823

  10. Use of a feline respiratory epithelial cell culture system grown at the air-liquid interface to characterize the innate immune response following feline herpesvirus 1 infection.

    PubMed

    Nelli, Rahul K; Maes, Roger; Kiupel, Matti; Hussey, Gisela Soboll

    2016-03-01

    Infection with feline herpesvirus-1 (FHV-1) accounts for 50% of viral upper respiratory diseases in domestic cats and is a significant cause of ocular diseases. Despite the clinical significance and high prevalence of FHV-1 infection, currently available vaccines cannot completely protect cats from infection and lifelong latency. FHV-1 infects via the mucous membranes and replicates in respiratory epithelial cells, but very little is known about the early innate immunity at this site. To address questions about immunity to FHV-1, feline respiratory epithelial cells cultured at air-liquid interface (ALI-FRECs) were established by collecting respiratory tracts from 6 healthy cats after euthanasia. Cells were isolated, cultured and characterized histologically and immunologically before infection with FHV-1. The expression of Toll-like receptors (TLRs), cytokine and chemokine responses were measured by real time PCR. ALI-FRECs morphologically resembled the natural airways of cats with multilayered columnar epithelial cells and cilia. Immunological properties of the natural airways were maintained in ALI-FRECs, as evidenced by the expression of TLRs, cytokines, chemokines, interferons, beta-defensins, and other regulatory genes. Furthermore, ALI-FRECs were able to support infection and replication of FHV-1, as well as modulate transcriptional regulation of various immune genes in response to infection. IL-1β and TNFα were increased in ALI-FRECs by 24hpi, whereas expression levels of IFN-α and TLR9 were not increased until 36hpi. In contrast, TLR3, GM-CSF and TGF-1β expression was down-regulated at 36hpi. The data presented show the development of a system ideal for investigating the molecular pathogenesis and immunity of FHV-1 or other respiratory pathogens. PMID:26795546

  11. Early development of electrical excitability in the mouse enteric nervous system.

    PubMed

    Hao, Marlene M; Lomax, Alan E; McKeown, Sonja J; Reid, Christopher A; Young, Heather M; Bornstein, Joel C

    2012-08-01

    Neural activity is integral to the development of the enteric nervous system (ENS). A subpopulation of neural crest-derived cells expresses pan-neuronal markers at early stages of ENS development (at E10.5 in the mouse). However, the electrical activity of these cells has not been previously characterized, and it is not known whether all cells expressing neuronal markers are capable of firing action potentials (APs). In this study, we examined the activity of "neuron"-like cells (expressing pan-neuronal markers or with neuronal morphology) in the gut of E11.5 and E12.5 mice using whole-cell patch-clamp electrophysiology and compared them to the activity of neonatal and adult enteric neurons. Around 30-40% of neuron-like cells at E11.5 and E12.5 fired APs, some of which were very similar to those of adult enteric neurons. All APs were sensitive to tetrodotoxin (TTX), indicating that they were driven by voltage-gated Na+ currents. Expression of mRNA encoding several voltage-gated Na+ channels by the E11.5 gut was detected using RT-PCR. The density of voltage-gated Na+ currents increased from E11.5 to neonates. Immature active responses, mediated in part by TTX- and lidocaine-insensitive channels, were observed in most cells at E11.5 and E12.5, but not in P0/P1 or adult neurons. However, some cells expressing neuronal markers at E11.5 or E12.5 did not exhibit an active response to depolarization. Spontaneous depolarizations resembling excitatory postsynaptic potentials were observed at E12.5. The ENS is one of the earliest parts of the developing nervous system to exhibit mature forms of electrical activity. PMID:22875929

  12. Therapeutic impact of systemic AAV-mediated RNA interference in a mouse model of myotonic dystrophy.

    PubMed

    Bisset, Darren R; Stepniak-Konieczna, Ewa A; Zavaljevski, Maja; Wei, Jessica; Carter, Gregory T; Weiss, Michael D; Chamberlain, Joel R

    2015-09-01

    RNA interference (RNAi) offers a promising therapeutic approach for dominant genetic disorders that involve gain-of-function mechanisms. One candidate disease for RNAi therapy application is myotonic dystrophy type 1 (DM1), which results from toxicity of a mutant mRNA. DM1 is caused by expansion of a CTG repeat in the 3' UTR of the DMPK gene. The expression of DMPK mRNA containing an expanded CUG repeat (CUG(exp)) leads to defects in RNA biogenesis and turnover. We designed miRNA-based RNAi hairpins to target the CUG(exp) mRNA in the human α-skeletal muscle actin long-repeat (HSA(LR)) mouse model of DM1. RNAi expression cassettes were delivered to HSA(LR) mice using recombinant adeno-associated viral (rAAV) vectors injected intravenously as a route to systemic gene therapy. Vector delivery significantly reduced disease pathology in muscles of the HSA(LR) mice, including a reduction in the CUG(exp) mRNA, a reduction in myotonic discharges, a shift toward adult pre-mRNA splicing patterns, reduced myofiber hypertrophy and a decrease in myonuclear foci containing the CUG(exp) mRNA. Significant reversal of hallmarks of DM1 in the rAAV RNAi-treated HSA(LR) mice indicate that defects characteristic of DM1 can be mitigated with a systemic RNAi approach targeting the nuclei of terminally differentiated myofibers. Efficient rAAV-mediated delivery of RNAi has the potential to provide a long-term therapy for DM1 and other dominant muscular dystrophies. PMID:26082468

  13. Long-term effects of mustard gas on respiratory system of Iranian veterans after Iraq-Iran war: a review.

    PubMed

    Razavi, Seyed-Mansour; Ghanei, Mostafa; Salamati, Payman; Safiabadi, Mehdi

    2013-01-01

    To review long-term respiratory effects of mustard gas on Iranian veterans having undergone Iraq-Iran war. Electronic databases of Scopus, Medline, ISI, IranMedex, and Irandoc sites were searched. We accepted articles published in scientific journals as a quality criterion.The main pathogenic factors are free radical mediators. Prevalence of pulmonary involvement is approximately 42.5%. The most common complaints are cough and dyspnea. Major respiratory complications are chronic obstructive pulmonary disease, bronchiectasis, and asthma. Spirometry results can reveal restrictive and obstructive pulmonary disease. Plain chest X-ray does not help in about 50% of lung diseases. High-resolution CT of the lung is the best modality for diagnostic assessment of parenchymal lung and bronchi. There is no definite curative treatment for mustard lung. The effective treatment regimens consist of oxygen administration, use of vaporized moist air, respiratory physiotherapy, administration of mucolytic agents, bronchodilators, corticosteroids, and long-acting beta-2 agonists, antioxidants, surfactant, magnesium ions, therapeutic bronchoscopy, laser therapy, placement of respiratory stents, early tracheostomy in laryngospasm, and ultimately lung transplantation. High-resolution CT of the lung is the most accurate modality for the evaluation of the lung parenchyma and bronchi. The treatment efficacy of patients exposed to mustard gas depends on patient conditions (acute or chronic, upper or lower respiratory tract involvement). There are various treatment protocols, but unfortunately none of them is definitely curable. PMID:23735551

  14. Respiratory Paradoxical Adverse Drug Reactions Associated with Acetylcysteine and Carbocysteine Systemic Use in Paediatric Patients: A National Survey

    PubMed Central

    Dubus, Jean-Christophe; Bavoux, Françoise; Boyer-Gervoise, Marie-José; Jean-Pastor, Marie-Josèphe; Chalumeau, Martin

    2011-01-01

    Objective To report pediatric cases of paradoxical respiratory adverse drug reactions (ADRs) after exposure to oral mucolytic drugs (carbocysteine, acetylcysteine) that led to the withdrawal of licenses for these drugs for infants in France and then Italy. Design The study followed the recommendations of the European guidelines of pharmacovigilance for medicines used in the paediatric population. Setting Cases voluntarily reported by physicians from 1989 to 2008 were identified in the national French pharmacovigilance public database and in drug company databases. Patients The definition of paradoxical respiratory ADRs was based on the literature. Exposure to mucolytic drugs was arbitrarily defined as having received mucolytic drugs for at least 2 days (>200 mg) and at least until the day before the first signs of the suspected ADR. Results The non-exclusive paradoxical respiratory ADRs reported in 59 paediatric patients (median age 5 months, range 3 weeks to 34 months, 98% younger than 2 years old) were increased bronchorrhea or mucus vomiting (n = 27), worsening of respiratory distress during respiratory tract infection (n = 35), dyspnoea (n = 18), cough aggravation or prolongation (n = 11), and bronchospasm (n = 1). Fifty-one (86%) children required hospitalization or extended hospitalization because of the ADR; one patient died of pulmonary oedema after mucus vomiting. Conclusion Parents, physicians, pharmacists, and drug regulatory agencies should know that the benefit risk ratio of mucolytic drugs is at least null and most probably negative in infants according to available evidence. PMID:21818391

  15. Effects of High Altitude on Sleep and Respiratory System and Theirs Adaptations

    PubMed Central

    San, Turhan; Polat, Senol; Cingi, Cemal; Eskiizmir, Gorkem; Oghan, Fatih; Cakir, Burak

    2013-01-01

    High-altitude (HA) environments have adverse effects on the normal functioning body of people accustomed to living at low altitudes because of the change in barometric pressure which causes decrease in the amount of oxygen leading to hypobaric hypoxia. Sustained exposure to hypoxia has adverse effects on body weight, muscle structure and exercise capacity, mental functioning, and sleep quality. The most important step of acclimatization is the hyperventilation which is achieved by hypoxic ventilatory response of the peripheral chemoreceptors. Hyperventilation results in increase in arterial carbondioxide concentration. Altitude also affects sleep and cardiac output, which is the other determinant of oxygen delivery. Upon initial exposure to HA, the resting pulse rate increases rapidly, but with acclimatization, heart rate and cardiac output tend to fall. Another important component that leads to decrease in cardiac output is the reduction in the stroke volume with acclimatization. During sleep at HA, the levels of CO2 in the blood can drop very low and this can switch off the drive to breathe. Only after the body senses a further drop in O2 levels breathing is started again. Periodic breathing is thought to result from instability in the control system through the hypoxic drive or the response to CO2. PMID:23690739

  16. Effects of high altitude on sleep and respiratory system and theirs adaptations.

    PubMed

    San, Turhan; Polat, Senol; Cingi, Cemal; Eskiizmir, Gorkem; Oghan, Fatih; Cakir, Burak

    2013-01-01

    High-altitude (HA) environments have adverse effects on the normal functioning body of people accustomed to living at low altitudes because of the change in barometric pressure which causes decrease in the amount of oxygen leading to hypobaric hypoxia. Sustained exposure to hypoxia has adverse effects on body weight, muscle structure and exercise capacity, mental functioning, and sleep quality. The most important step of acclimatization is the hyperventilation which is achieved by hypoxic ventilatory response of the peripheral chemoreceptors. Hyperventilation results in increase in arterial carbon-dioxide concentration. Altitude also affects sleep and cardiac output, which is the other determinant of oxygen delivery. Upon initial exposure to HA, the resting pulse rate increases rapidly, but with acclimatization, heart rate and cardiac output tend to fall. Another important component that leads to decrease in cardiac output is the reduction in the stroke volume with acclimatization. During sleep at HA, the levels of CO2 in the blood can drop very low and this can switch off the drive to breathe. Only after the body senses a further drop in O2 levels breathing is started again. Periodic breathing is thought to result from instability in the control system through the hypoxic drive or the response to CO2. PMID:23690739

  17. The thermal tolerance of crayfish could be estimated from respiratory electron transport system activity.

    PubMed

    Simčič, Tatjana; Pajk, Franja; Jaklič, Martina; Brancelj, Anton; Vrezec, Al

    2014-04-01

    Whether electron transport system (ETS) activity could be used as an estimator of crayfish thermal tolerance has been investigated experimentally. Food consumption rate, respiration rates in the air and water, the difference between energy consumption and respiration costs at a given temperature ('potential growth scope', PGS), and ETS activity of Orconectes limosus and Pacifastacus leniusculus were determined over a temperature range of 5-30°C. All concerned parameters were found to be temperature dependent. The significant correlation between ETS activity and PGS indicates that they respond similarly to temperature change. The regression analysis of ETS activity as an estimator of thermal tolerance at the mitochondrial level and PGS as an indicator of thermal tolerance at the organismic level showed the shift of optimum temperature ranges of ETS activity to the right for 2° in O. limosus and for 3° in P. leniusculus. Thus, lower estimated temperature optima and temperatures of optimum ranges of PGS compared to ETS activity could indicate higher thermal sensitivity at the organismic level than at a lower level of complexity (i.e. at the mitochondrial level). The response of ETS activity to temperature change, especially at lower and higher temperatures, indicates differences in the characteristics of the ETSs in O. limosus and P. leniusculus. O. limosus is less sensitive to high temperature. The significant correlation between PGS and ETS activity supports our assumption that ETS activity could be used for the rapid estimation of thermal tolerance in crayfish species. PMID:24679968

  18. Former migrant mineworkers with respiratory disease: the South African compensation system, and implications for neighbouring countries.

    PubMed

    Steen, T W; Mabongo, N; Moeti, T; Monare, B; Trapido, A S

    2000-01-01

    In the region of Southern Africa, substantial numbers of people, primarily males, have been employed in the South African mining industry. Migrant workers from neighbouring countries have constituted a large part of the work force. Until recently, there has been little or no attention directed toward the state of health of these individuals, despite the fact that their work involves a high health risk, especially in regard to mine-related lung diseases. In addition, the South African workers' compensation programme has seldom been utilised by the migrant worker who is a victim of occupational disease. However, recent experiences from Botswana show that compensation claims can be successfully made from the neighbouring countries where the migrant workers originate. Efforts are being made to address the problem systematically, and the government of Botswana is actively involved. The major occupational lung disorders are described briefly, and differential diagnostic problems with pulmonary TB are discussed. Furthermore, a survey of the compensation system in South Africa is presented, and practical steps for medical examinations involving compensation claims are described. PMID:14674203

  19. [Determination of the contents of trace elements in chinese herbal medicines for treating respiratory system diseases].

    PubMed

    Han, Li-Qin; Dong, Shun-Fu; Liu, Jian-Hua

    2008-02-01

    There is an intimate connection between trace elements and body healthiness, trace elements and organism depend on each other, and each trace element exists with certain proportion, which preserve physio-function. If the balance is of maladjustment, diseases may occur or develop. The trace elements were determined in 16 kinds of Chinese herbal medicines by atomic absorption spectrometry. The medicines include lilium brownii, herba houttuyniae, licorice root, radices isatidis seu baphicacanthi, Sehizandra sinensis Bail, Scutellaria baicalensis Georgi, Beimu, Polygonum multiflorum Thunb, Lithospermum officinalel, Rhizoma acori gramjnoi, Pinellia ternate Breit, Salisburia adiantifolia, Lonicera japonica, Radices puerarire, Bupleurum falcatum and Ligusticum wallichii, all of which could be bought on the market. Sixteen kinds of Chinese herbal medicines commonly used to treat respiratroy system diseases in clinic were selected, dried and powdered, completely mixed, 1.000 0 g was weighed accurately with analytical balance, and 3 portions were used for each kind of sample. The atomic absorption spectrometry was used to determine the contents of trace elements (Cu, Zn, Fe, Cr, Ni and Mn), and the content discrepancy of the trace elements in different medicines was observed the results shows that the contents of the trace elements were rich in the 16 kinds of Chinese herbal medicines, there were more contents of Fe, Zn and Mn, but they were different in different medicines. And there were more trace elements in Salisburia adiantifolia, Polygonum multiflorum Thunb, Bupleurum falcatum, Sehizandra sinensis Bail, Pinellia ternate Breit and Lithospermum officinalel, and lower trace elements in Radices puerarire, Rhizoma acori gramjnoi and Radices isatidis seu baphicacanthi. The analytic results provided useful data for using Chinese herbal medicines and provided theoretical basis for studying Chinese herbal medicines theory. PMID:18479045

  20. Jellyfish blooms result in a major microbial respiratory sink of carbon in marine systems.

    PubMed

    Condon, Robert H; Steinberg, Deborah K; del Giorgio, Paul A; Bouvier, Thierry C; Bronk, Deborah A; Graham, William M; Ducklow, Hugh W

    2011-06-21

    Jellyfish blooms occur in many estuarine and coastal regions and may be increasing in their magnitude and extent worldwide. Voracious jellyfish predation impacts food webs by converting large quantities of carbon (C), fixed by primary producers and consumed by secondary producers, into gelatinous biomass, which restricts C transfer to higher trophic levels because jellyfish are not readily consumed by other predators. In addition, jellyfish release colloidal and dissolved organic matter (jelly-DOM), and could further influence the functioning of coastal systems by altering microbial nutrient and DOM pathways, yet the links between jellyfish and bacterioplankton metabolism and community structure are unknown. Here we report that jellyfish released substantial quantities of extremely labile C-rich DOM, relative to nitrogen (25.6 ± 31.6 C:1N), which was quickly metabolized by bacterioplankton at uptake rates two to six times that of bulk DOM pools. When jelly-DOM was consumed it was shunted toward bacterial respiration rather than production, significantly reducing bacterial growth efficiencies by 10% to 15%. Jelly-DOM also favored the rapid growth and dominance of specific bacterial phylogenetic groups (primarily γ-proteobacteria) that were rare in ambient waters, implying that jelly-DOM was channeled through a small component of the in situ microbial assemblage and thus induced large changes in community composition. Our findings suggest major shifts in microbial structure and function associated with jellyfish blooms, and a large detour of C toward bacterial CO(2) production and away from higher trophic levels. These results further suggest fundamental transformations in the biogeochemical functioning and biological structure of food webs associated with jellyfish blooms. PMID:21646531

  1. Molecular cloning of mouse amino acid transport system B0, a neutral amino acid transporter related to Hartnup disorder.

    PubMed

    Bröer, Angelika; Klingel, Karin; Kowalczuk, Sonja; Rasko, John E J; Cavanaugh, Juleen; Bröer, Stefan

    2004-06-01

    Resorption of amino acids in kidney and intestine is mediated by transporters, which prefer groups of amino acids with similar physico-chemical properties. It is generally assumed that most neutral amino acids are transported across the apical membrane of epithelial cells by system B(0). Here we have characterized a novel member of the Na(+)-dependent neurotransmitter transporter family (B(0)AT1) isolated from mouse kidney, which shows all properties of system B(0). Flux experiments showed that the transporter is Na(+)-dependent, electrogenic, and actively transports most neutral amino acids but not anionic or cationic amino acids. Superfusion of mB(0)AT1-expressing oocytes with neutral amino acids generated inward currents, which were proportional to the fluxes observed with labeled amino acids. In situ hybridization showed strong expression in intestinal microvilli and in the proximal tubule of the kidney. Expression of mouse B(0)AT1 was restricted to kidney, intestine, and skin. It is generally assumed that mutations of the system B(0) transporter underlie autosomal recessive Hartnup disorder. In support of this notion mB(0)AT1 is located on mouse chromosome 13 in a region syntenic to human chromosome 5p15, the locus of Hartnup disorder. Thus, the human homologue of this transporter is an excellent functional and positional candidate for Hartnup disorder. PMID:15044460

  2. Evaluation of respiratory impedance in patients with chronic obstructive pulmonary disease by an impulse oscillation system.

    PubMed

    Gong, Su-Gang; Yang, Wen-Lan; Zheng, Wei; Liu, Jin-Ming

    2014-11-01

    An impulse oscillometry system (IOS) assesses pulmonary resistance and reactance. The present study investigated which IOS measurement is correlated with airflow obstruction, airway conductance and lung volume in chronic obstructive pulmonary disease (COPD). A total of 180 patients with COPD were selected and 95 agreed to follow‑up 1 year after the initial tests. IOS measurements [R5, R20, X5 and resonant frequency (Fres)], body plethysmography [forced end‑expiratory flow (FEF)75, total lung capacity, residual volume (RV) and total inspiratory resistance (Rtot)] and spirometry [forced expiratory volume in 1 sec (FEV1)] were performed. Pearson's or Spearman's correlation tests were used to determine the correlation between the IOS and other measurements. R5, X5 and Fres were all significantly associated (P<0.05) with FEV1, FEF75, RV and Rtot. However, R20 was not correlated with these measurements except from FEF75 and Rtot (r values were all<0.25). The strongest associations were observed with FEV1 and the reactance measurements X5 (r=0.635), Fres (r=‑0.721) and R5 (r=‑0.496); FEF75 with X5 (r=0.505), Fres (r=‑0.629) and R5 (r=‑0.468); RV with X5 (r=‑0.485), Fres (r=0.570) and R5 (r=0.326); and Rtot with X5 (r=‑0.691), Fres (r=0.632) and R5 (r=0.570). There was a significant increase in FEV1 and X5 after one year as compared with the RV. The other measurements did not change over the year. The changes in X5, Fres and R5 were significantly correlated with the changes in FEV1 and the correlation coefficients were 0.355, ‑0.364 and ‑0.381, respectively. Similarly, the changes in X5, Fres and R5 were significantly correlated with the changes in RV and the correlation coefficients were ‑0.264, 0.287 and 0.318, respectively. In the COPD patients, the IOS reactance measurements were more closely correlated with other pulmonary function measurements rather than with resistance measurements. The IOS reactance measurements, particularly X5, appear to

  3. 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.

    PubMed

    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. PMID:24295373

  4. Correlation and prediction uncertainties in the CyberKnife Synchrony respiratory tracking system

    SciTech Connect

    Pepin, Eric W.; Wu, Huanmei; Zhang, Yuenian; Lord, Bryce

    2011-07-15

    Purpose: The CyberKnife uses an online prediction model to improve radiation delivery when treating lung tumors. This study evaluates the prediction model used by the CyberKnife radiation therapy system in terms of treatment margins about the gross tumor volume (GTV). Methods: From the data log files produced by the CyberKnife synchrony model, the uncertainty in radiation delivery can be calculated. Modeler points indicate the tracked position of the tumor and Predictor points predict the position about 115 ms in the future. The discrepancy between Predictor points and their corresponding Modeler points was analyzed for 100 treatment model data sets from 23 de-identified lung patients. The treatment margins were determined in each anatomic direction to cover an arbitrary volume of the GTV, derived from the Modeler points, when the radiation is targeted at the Predictor points. Each treatment model had about 30 min of motion data, of which about 10 min constituted treatment time; only these 10 min were used in the analysis. The frequencies of margin sizes were analyzed and truncated Gaussian normal functions were fit to each direction's distribution. The standard deviation of each Gaussian distribution was then used to describe the necessary margin expansions in each signed dimension in order to achieve the desired coverage. In this study, 95% modeler point coverage was compared to 99% modeler coverage. Two other error sources were investigated: the correlation error and the targeting error. These were added to the prediction error to give an aggregate error for the CyberKnife during treatment of lung tumors. Results: Considering the magnitude of 2{sigma} from the mean of the Gaussian in each signed dimension, the margin expansions needed for 95% modeler point coverage were 1.2 mm in the lateral (LAT) direction and 1.7 mm in the anterior-posterior (AP) direction. For the superior-inferior (SI) direction, the fit was poor; but empirically, the expansions were 3.5 mm

  5. Respiratory fluid mechanics

    NASA Astrophysics Data System (ADS)

    Grotberg, James B.

    2011-02-01

    This article covers several aspects of respiratory fluid mechanics that have been actively investigated by our group over the years. For the most part, the topics involve two-phase flows in the respiratory system with applications to normal and diseased lungs, as well as therapeutic interventions. Specifically, the topics include liquid plug flow in airways and at airway bifurcations as it relates to surfactant, drug, gene, or stem cell delivery into the lung; liquid plug rupture and its damaging effects on underlying airway epithelial cells as well as a source of crackling sounds in the lung; airway closure from "capillary-elastic instabilities," as well as nonlinear stabilization from oscillatory core flow which we call the "oscillating butter knife;" liquid film, and surfactant dynamics in an oscillating alveolus and the steady streaming, and surfactant spreading on thin viscous films including our discovery of the Grotberg-Borgas-Gaver shock.

  6. Broad respiratory virus detection in infants hospitalized for bronchiolitis by use of a multiplex RT-PCR DNA microarray system.

    PubMed

    Huguenin, Antoine; Moutte, Lauryane; Renois, Fanny; Leveque, Nicolas; Talmud, Deborah; Abely, Michel; Nguyen, Yohan; Carrat, Fabrice; Andreoletti, Laurent

    2012-06-01

    Newly available molecular tools allow a sensitive detection of a broad panel of viruses in respiratory tract specimens. In the present study, the application of a multiplex RT-PCR DNA microarray in diagnosis and epidemiological survey of viral infections in infants hospitalized for bronchiolitis was assessed. One hundred and thirty-eight nasopharyngeal aspirates collected from October 2007 to September 2008 were tested by direct immunofluorescence and viral culture, a combination of referenced RT-PCRs and the DNA microarray. One or more viruses were detected in 96, 126 and 126 of the specimens by direct immunofluorescence and viral culture, RT-PCRs and DNA microarray, respectively (70 vs. 91 vs. 91%, P < 10(-3)). The RT-PCRs and the DNA microarray yielded concordant results for 99% of specimens and identified mixed viral infections in 85 (62%). The most common associations were: human bocavirus and respiratory syncytial virus (32%), adenovirus and respiratory syncytial virus (30%), and parainfluenza virus type 3 and respiratory syncytial virus (23%). None of the bronchiolitis severity parameters including intensive care unit admission, O(2) supply, O(2) saturation percentage, O(2) length and length of stay at the hospital appeared to be significantly increased in multiple viral infections compared to single viral infections (P > 0.1). In conclusion, the use of this DNA microarray in clinical virology practice allows rapid and accurate identification of common and uncommon viral respiratory pathogens in infants hospitalized for bronchiolitis. It should improve the clinical management, the epidemiological survey, and the prevention of the nosocomial transmission of respiratory viruses in pediatric wards. PMID:22499022

  7. 3D mouse shape reconstruction based on phase-shifting algorithm for fluorescence molecular tomography imaging system.

    PubMed

    Zhao, Yue; Zhu, Dianwen; Baikejiang, Reheman; Li, Changqing

    2015-11-10

    This work introduces a fast, low-cost, robust method based on fringe pattern and phase shifting to obtain three-dimensional (3D) mouse surface geometry for fluorescence molecular tomography (FMT) imaging. We used two pico projector/webcam pairs to project and capture fringe patterns from different views. We first calibrated the pico projectors and the webcams to obtain their system parameters. Each pico projector/webcam pair had its own coordinate system. We used a cylindrical calibration bar to calculate the transformation matrix between these two coordinate systems. After that, the pico projectors projected nine fringe patterns with a phase-shifting step of 2π/9 onto the surface of a mouse-shaped phantom. The deformed fringe patterns were captured by the corresponding webcam respectively, and then were used to construct two phase maps, which were further converted to two 3D surfaces composed of scattered points. The two 3D point clouds were further merged into one with the transformation matrix. The surface extraction process took less than 30 seconds. Finally, we applied the Digiwarp method to warp a standard Digimouse into the measured surface. The proposed method can reconstruct the surface of a mouse-sized object with an accuracy of 0.5 mm, which we believe is sufficient to obtain a finite element mesh for FMT imaging. We performed an FMT experiment using a mouse-shaped phantom with one embedded fluorescence capillary target. With the warped finite element mesh, we successfully reconstructed the target, which validated our surface extraction approach. PMID:26560789

  8. The static pressure-volume relationship of the respiratory system determined with a computer-controlled ventilator.

    PubMed

    Svantesson, C; Drefeldt, B; Jonson, B

    1997-07-01

    The pressure-volume relationship of the respiratory system offers a guideline for setting of ventilators. The occlusion method for determination of the static elastic pressure-volume (Pel(st)/V) relationship is used as a reference and the aim of the study was to improve it with respect to time consumption and precision of recording and analysis. The inspiratory Pel(st)/V curve was determined with a computer-controlled ventilator using its pressure and flow sensors. During an automated procedure, an operator-defined volume history preceded each of a number of study breaths. These were interrupted at different volumes evenly distributed over a predefined volume interval. Total positive end-expiratory pressure (PEEP) was measured and could be separated into its components, external PEEP and auto-PEEP. The volume relationship between the curve and the current tidal volume was defined. An analytical method for definition of a linear segment of the Pel(st)/V curve and determination of its compliance is presented. In eight healthy human anaesthetized subjects duplicate Pel(st)/V curves were studied with respect to compliance and the position along the volume axis of the linear segment. The difference in compliance between measurements was 1.6 +/- 1.3 ml cmH2O(-1) or 1.2 +/- 0.9%. The position of the curve differed between measurements by 15 +/- 10 ml or by 1.1 +/- 0.9%. In a patient with acute lung injury the feasibility of applying a numerical method for a more detailed description of the Pel(st)/V curve was illustrated. PMID:19361153

  9. The relationship between respiratory exchange ratio, plasma lactate and muscle lactate concentrations in exercising horses using a valved gas collection system.

    PubMed Central

    Gauvreau, G M; Young, S S; Staempfli, H; McCutcheon, L J; Wilson, B A; McDonell, W N

    1996-01-01

    A valved gas collection system for horses was validated, then used to examine the relationship between the respiratory exchange ratio (RER), and plasma and muscle lactate in exercising horses. Four healthy Standardbred horses were trained to breathe through the apparatus while exercising on a treadmill. Comparisons of arterial blood gas tensions were made at 3 work levels for each horse, without (control), and with the gas collection system present. At the highest work level, the arterial oxygen tension (PaO2) was significantly lower (P < 0.05), and the arterial carbon dioxide tension (PaCO2) was significantly higher (P < 0.05), than control levels when the apparatus was present; however arterial oxygen content remained unchanged. The horses completed a standardized incremental treadmill test on 4 occasions to determine the repeatability of measurements of oxygen consumption (VO2), carbon dioxide production (VCO2), inspired minute ventilation (VI), respiratory exchange ratio (RER), ventilatory equivalent for oxygen (VI/VO2), tidal volume (VT), and ventilatory frequency (VF). All gas exchange and respiratory measurements showed good reproducibility with the mean coefficient of variation of the 4 horses ranging from 3.8 to 12%. We examined the relationship between 3 indices of energy metabolism in horses performing treadmill exercise: respiratory exchange ratio (RER), central venous plasma and muscle lactate concentrations. A relationship between RER and plasma lactate concentration was established. To compare muscle and plasma lactate concentrations, the horses completed a discontinuous exercise test without the gas collection apparatus present. Significant relationships (P < 0.05), between plasma lactate concentration and RER, and between plasma and muscle lactate concentration, were described for each horse. The valved gas collection system produced a measurable but tolerable degree of interference to respiration, and provided reproducible measurements of gas

  10. Expression of receptor protein tyrosine phosphatase δ, PTPδ, in mouse central nervous system.

    PubMed

    Shishikura, Maria; Nakamura, Fumio; Yamashita, Naoya; Uetani, Noriko; Iwakura, Yoichiro; Goshima, Yoshio

    2016-07-01

    Protein tyrosine phosphate δ (PTPδ), one of the receptor type IIa protein tyrosine phosphates, is known for its roles in axon guidance, synapse formation, cell adhesion, and tumor suppression. Alternative splicing of this gene generates at least four (A-D) isoforms; however, the major isoform in vivo is yet to be determined. The protein localization has neither been revealed. We have generated anti-mouse PTPδ-specific monoclonal antibody and analyzed the protein expression in wild-type and Ptpδ knockout mice. Immunoblot analysis of various organs revealed that neuronal tissues express both C-and D-isoforms of PTPδ, whereas non-neuronal tissues express only C-isoform. Immunohistochemistry of wild-type or Ptpδ heterozygous sections showed that olfactory bulb, cerebral cortex, hippocampus, cerebellum, and several nuclei in brain stem exhibit moderate to strong positive signals. These signals were absent in Ptpδ knockout specimens. Higher magnification revealed differences between expression patterns of PTPδ mRNA and its protein product. In hippocampus, weak mRNA expression in CA1 stratum pyramidale but strong immunostaining in the stratum lacunosum moleculare was observed, suggesting the axonal expression of PTPδ in the entorhinal cortical afferents. Olfactory mitral cells exhibited mRNA expression in cell bodies and protein localization in their dendritic fields, glomerular and external plexiform layers. Nissl staining showed that the external plexiform layer was reduced in Ptpδ knockout mice. Golgi-impregnation confirmed the poor dendritic growth of homozygous mitral cells. These results suggest that PTPδ may localize in axons as well as in dendrites to regulate their elaboration in the central nervous system. PMID:27026654

  11. Central nervous system dysfunction in a mouse model of FA2H deficiency.

    PubMed

    Potter, Kathleen A; Kern, Michael J; Fullbright, George; Bielawski, Jacek; Scherer, Steven S; Yum, Sabrina W; Li, Jian J; Cheng, Hua; Han, Xianlin; Venkata, Jagadish Kummetha; Khan, P Akbar Ali; Rohrer, Bärbel; Hama, Hiroko

    2011-07-01

    Fatty acid 2-hydroxylase (FA2H) is responsible for the synthesis of myelin galactolipids containing hydroxy fatty acid (hFA) as the N-acyl chain. Mutations in the FA2H gene cause leukodystrophy, spastic paraplegia, and neurodegeneration with brain iron accumulation. Using the Cre-lox system, we developed two types of mouse mutants, Fa2h(-/-) mice (Fa2h deleted in all cells by germline deletion) and Fa2h(flox/flox) Cnp1-Cre mice (Fa2h deleted only in oligodendrocytes and Schwann cells). We found significant demyelination, profound axonal loss, and abnormally enlarged axons in the CNS of Fa2h(-/-) mice at 12 months of age, while structure and function of peripheral nerves were largely unaffected. Fa2h(-/-) mice also exhibited histological and functional disruption in the cerebellum at 12 months of age. In a time course study, significant deterioration of cerebellar function was first detected at 7 months of age. Further behavioral assessments in water T-maze and Morris water maze tasks revealed significant deficits in spatial learning and memory at 4 months of age. These data suggest that various regions of the CNS are functionally compromised in young adult Fa2h(-/-) mice. The cerebellar deficits in 12-month-old Fa2h(flox/flox) Cnp1-Cre mice were indistinguishable from Fa2h(-/-) mice, indicating that these phenotypes likely stem from the lack of myelin hFA-galactolipids. In contrast, Fa2h(flox/flox) Cnp1-Cre mice did not show reduced performance in water maze tasks, indicating that oligodendrocytes are not involved in the learning and memory deficits found in Fa2h(-/-) mice. These findings provide the first evidence that FA2H has an important function outside of oligodendrocytes in the CNS. PMID:21491498

  12. Mild systemic inflammation and moderate hypoxia transiently alter neuronal excitability in mouse somatosensory cortex.

    PubMed

    Mordel, Jérôme; Sheikh, Aminah; Tsohataridis, Simeon; Kanold, Patrick O; Zehendner, Christoph M; Luhmann, Heiko J

    2016-04-01

    During the perinatal period, the brain is highly vulnerable to hypoxia and inflammation, which often cause white matter injury and long-term neuronal dysfunction such as motor and cognitive deficits or epileptic seizures. We studied the effects of moderate hypoxia (HYPO), mild systemic inflammation (INFL), or the combination of both (HYPO+INFL) in mouse somatosensory cortex induced during the first postnatal week on network activity and compared it to activity in SHAM control animals. By performing in vitro electrophysiological recordings with multi-electrode arrays from slices prepared directly after injury (P8-10), one week after injury (P13-16), or in young adults (P28-30), we investigated how the neocortical network developed following these insults. No significant difference was observed between the four groups in an extracellular solution close to physiological conditions. In extracellular 8mM potassium solution, slices from the HYPO, INFL, and HYPO+INFL group were more excitable than SHAM at P8-10 and P13-16. In these two age groups, the number and frequency of spontaneous epileptiform events were significantly increased compared to SHAM. The frequency of epileptiform events was significantly reduced by the NMDA antagonist D-APV in HYPO, INFL, and HYPO+INFL, but not in SHAM, indicating a contribution of NMDA receptors to this pathophysiological activity. In addition, the AMPA/kainate receptor antagonist CNQX suppressed the remaining epileptiform activity. Electrical stimulation evoked prominent epileptiform activity in slices from HYPO, INFL and HYPO+INFL animals. Stimulation threshold to elicit epileptiform events was lower in these groups than in SHAM. Evoked events spread over larger areas and lasted longer in treated animals than in SHAM. In addition, the evoked epileptiform activity was reduced in the older (P28-30) group indicating that cortical dysfunction induced by hypoxia and inflammation was transient and compensated during early development. PMID

  13. Translation and processing of mouse hepatitis virus virion RNA in a cell-free system

    SciTech Connect

    Denison, M.R.; Perlman, S.

    1986-10-01

    The first event after infection with mouse hepatitis virus strain A59 (MHV-A59) is presumed to be the synthesis of an RNA-dependent RNA polymerase from the input genomic RNA. The synthesis and processing of this putative ploymerase protein was studied in a cell-free translation system utilizing 60S RNA from MHV-A59 virions. The polypeptide products of this reaction included two major species of 220 and 28 kilodaltons. Kinetics experiments indicated that both p220 and p28 appeared after 60 min of incubation and that protein p28 was synthesized initially as the N-terminal portion of a larger precursor protein. When the cell-free translation products were labeled with N-formyl(/sup 35/S)methionyl-tRNA/sub i/, p28 was the predominant radioactive product, confirming its N-terminal location within a precursor protein. Translation in the presence of the protease inhibitors leupeptin and ZnCl/sub 2/ resulted in the disappearance of p28 and p220 and the appearance of a new protein, p250. This product, which approached the maximal size predicted for a protein synthesized from genomic RNA, was not routinely detected in the absence of inhibitors even under conditions which optimized the translation reaction for elongation of proteins. Subsequent chelation of ZnCl/sub 2/ resulted in the partial cleavage of the precursor protein and the reappearance of p28. One-dimensional peptide mapping with Staphylococcus aureus V-8 protease confirmed the precursor-product relationship of p250 and p28. The results show that MHV virion RNA, like many other viral RNAs, is translated into a large polyprotein, which is cleaved soon after synthesis into smaller, presumably functional proteins. This is in marked contrast to the synthesis of other MHV proteins, in which minimal proteolytic processing occurs.

  14. Nonlinear optical techniques for imaging and manipulating the mouse central nervous system

    NASA Astrophysics Data System (ADS)

    Farrar, Matthew John

    The spinal cord of vertebrates serves as the conduit for somatosensory information and motor control, as well as being the locus of neural circuits that govern fast reflexes and patterned behaviors, such as walking in mammals or swimming in fish. Consequently, pathologies of the spinal cord -such as spinal cord injury (SCI)- lead to loss of motor control and sensory perception, with accompanying decline in life expectancy and quality of life. Despite the devastating effects of these diseases, few therapies exist to substantially ameliorate patient outcome. In part, studies of spinal cord pathology have been limited by the inability to perform in vivo imaging at the level of cellular processes. The focus of this thesis is to present the underlying theory for and demonstration of novel multi-photon microscopy (MPM) and optical manipulation techniques as they apply to studies the mouse central nervous system (CNS), with an emphasis on the spinal cord. The scientific findings which have resulted from the implementation of these techniques are also presented. In particular, we have demonstrated that third harmonic generation is a dye-free method of imaging CNS myelin, a fundamental constituent of the spinal cord that is difficult to label using exogenous dyes and/or transgenic constructs. Since gaining optical access to the spinal cord is a prerequisite for spinal cord imaging, we review our development of a novel spinal cord imaging chamber and surgical procedure which allowed us to image for multiple weeks following implantation without the need for repeated surgeries. We also have used MPM to characterize spinal venous blood flow before and after point occlusions. We review a novel nonlinear microscopy technique that may serve to show optical interfaces in three dimensions inside scattering tissue. Finally, we discuss a model and show results of optoporation, a means of transfecting cells with genetic constructs. Brief reviews of MPM and SCI are also presented.

  15. The transcobalamin receptor knockout mouse: a model for vitamin B12 deficiency in the central nervous system.

    PubMed

    Lai, Shao-Chiang; Nakayama, Yasumi; Sequeira, Jeffrey M; Wlodarczyk, Bogdan J; Cabrera, Robert M; Finnell, Richard H; Bottiglieri, Teodoro; Quadros, Edward V

    2013-06-01

    The membrane receptor (TCblR/CD320) for transcobalamin (TC)-bound cobalamin (Cbl) facilitates the cellular uptake of Cbl. A genetically modified mouse model involving ablation of the CD320 gene was generated to study the effects on cobalamin homeostasis. The nonlethal nature of this knockout and the lack of systemic cobalamin deficiency point to other mechanisms for cellular Cbl uptake in the mouse. However, severe cobalamin depletion in the central nervous system (CNS) after birth (P<0.01) indicates that TCblR is the only receptor responsible for Cbl uptake in the CNS. Metabolic Cbl deficiency in the brain was evident from the increased methylmalonic acid (P<0.01-0.04), homocysteine (P<0.01), cystathionine (P<0.01), and the decreased S-adenosylmethionine/S-adenosyl homocysteine ratio (P<0.01). The CNS pathology of Cbl deficiency seen in humans may not manifest in this mouse model; however, it does provide a model with which to evaluate metabolic pathways and genes affected. PMID:23430977

  16. Real-time tumor tracking using sequential kV imaging combined with respiratory monitoring: a general framework applicable to commonly used IGRT systems

    PubMed Central

    Cho, Byungchul; Poulsen, Per Rugaard; Keall, Paul J

    2010-01-01

    Clinical image guided radiotherapy (IGRT) systems have kV imagers and respiratory monitors, the combination of which provides an ‘internal–external’ correlation for respiratory-induced tumor motion tracking. We developed a general framework of correlation-based position estimation that is applicable to various imaging configurations, particularly alternate stereoscopic (ExacTrac) or rotational monoscopic (linacs) imaging, where instant 3D target positions cannot be measured. By reformulating the least-squares estimation equation for the correlation model, the necessity to measure 3D target positions from synchronous stereoscopic images can be avoided. The performance of this sequential image-based estimation was evaluated in comparison with a synchronous image-based estimation. Both methods were tested in simulation studies using 160 abdominal/thoracic tumor trajectories and an external respiratory signal dataset. The sequential image-based estimation method (1) had mean 3D errors less than 1 mm at all the imaging intervals studied (0.2, 1, 2, 5 and 10 s), (2) showed minimal dependencies of the accuracy on the geometry and (3) was equal in accuracy to the synchronous image-based estimation method when using the same image input. In conclusion, the sequential image-based estimation method can achieve sub-mm accuracy for commonly used IGRT systems, and is equally accurate and more broadly applicable than the synchronous image-based estimation method. PMID:20484777

  17. Boussignac CPAP system for brain death confirmation with apneic test in case of acute lung injury/adult respiratory distress syndrome – series of cases

    PubMed Central

    Wieczorek, Andrzej; Gaszynski, Tomasz

    2015-01-01

    Introduction There are some patients with severe respiratory disturbances like adult respiratory distress syndrome (ARDS) and suspicion of brain death, for whom typical performance of the apneic test is difficult to complete because of quick desaturation and rapid deterioration without effective ventilation. To avoid failure of brain death confirmation and possible loss of organ donation another approach to apneic test is needed. We present two cases of patients with clinical symptoms of brain death, with lung pathology (acute lung injury, ARDS, lung embolism and lung infection), in whom apneic tests for recognizing brain death were difficult to perform. During typical performance of apneic test involving the use of oxygen catheter for apneic oxygenation we observed severe desaturation with growing hypotension and hemodynamic destabilization. But with the use of Boussignac CPAP system all necessary tests were successfully completed, confirming the patient’s brain death, which gave us the opportunity to perform procedures for organ donation. The main reason of apneic test difficulties was severe gas exchange disturbances secondary to ARDS. Thus lack of positive end expiratory pressure during classical performance of apneic test leads to quick desaturation and rapid hemodynamic deterioration, limiting the observation period below dedicated at least 10-minute interval. Conclusion The Boussignac CPAP system may be an effective tool for performing transparent apneic test in case of serious respiratory disturbances, especially in the form of acute lung injury or ARDS. PMID:26124664

  18. Lungs and Respiratory System

    MedlinePlus

    ... growth. Without oxygen, the body's cells would die. Carbon dioxide is the waste gas that is produced when ... also enabling the body to get rid of carbon dioxide in the air breathed out. Respiration is the ...

  19. Lungs and Respiratory System

    MedlinePlus

    ... called alveoli, where the exchange of oxygen and carbon dioxide actually takes place. Each lung houses about 300- ... growth. Without oxygen, the body's cells would die. Carbon dioxide is the waste gas produced when carbon is ...

  20. Social Stress, Smoking Behavior and Mortality from Cancer of the Respiratory System: A Macro-Social Analysis.

    ERIC Educational Resources Information Center

    Linsky, Arnold S.; And Others

    This study investigated the relationship between the stressfulness of each state's social environment, smoking, and mortality rates for respiratory cancer. It was based on a health behavior model which assumed that under conditions of high stress some people fail to exercise normal prudence in either protecting their health or engage in practices…

  1. Radial-femoral concordance in time and frequency domain-based estimates of systemic arterial respiratory variation.

    PubMed

    Thiele, Robert H; Colquhoun, Douglas A; Tucker-Schwartz, Jason M; Gillies, George T; Durieux, Marcel E

    2012-10-01

    Commonly used arterial respiratory variation metrics are based on mathematical analysis of arterial waveforms in the time domain. Because the shape of the arterial waveform is dependent on the site at which it is measured, we hypothesized that analysis of the arterial waveform in the frequency domain might provide a relatively site-independent means of measuring arterial respiratory variation. Radial and femoral arterial blood pressures were measured in nineteen patients undergoing liver transplantation. Systolic pressure variation (SPV), pulse pressure variation (PPV), area under the curve variation (AUCV), and mean arterial pressure variation (MAPV) at radial and femoral sites were calculated off-line. Two metrics, "Spectral Peak Ratio" (SPeR) and "Spectral Power Ratio" (SPoR) based on ratios of the spectral peak and spectral area (power) at the respiratory and cardiac frequencies, were calculated at both radial and femoral sites. Variance among radial-femoral differences was compared and correlation coefficients describing the relationship between respiratory variation at the radial and femoral sites were developed. The variance in radial-femoral differences were significantly different (p < 0.001). The correlation between radial and femoral estimates of respiratory variation were 0.746, 0.658, 0.858, 0.882, 0.941, and 0.925 for SPV, PPV, AUCV, MAPV, SPeR, and SPoR, respectively. Assuming a PPV treatment threshold of 12 % (or equivalent), differences in treatment decisions based on radial or femoral estimates would arise in 12, 14, 5.4, 5.7, 4.8, and 5.5 % of minutes for SPV, PPV, AUCV, MAPV, spectral peak ratio, and spectral power ratio, respectively. As compared to frequency domain-based estimates of respiratory variation, SPV and PPV are relatively dependent on the anatomic site at which they are measured. Spectral peak and power ratios are relatively site-independent means of measuring respiratory variation, and may offer a useful alternative to time

  2. CYTOGENETIC ANALYSIS OF THE L5178Y/TK+/- YIELDS TK-/- MOUSE LYMPHOMA MUTAGENESIS ASSAY SYSTEM

    EPA Science Inventory

    The L5178Y/TK t/- TK-/- mouse lymphoma mutagen assay, which allows selection of forward mutations at the autosomal thymidine kinase (TK) locus, uses a TK t/- heterozygous cell line, TK t/- 3.7.2C Quantitation of colonies of mutant TK-/- cells in the assay forms the basis for calc...

  3. The IRP/IRE system in vivo: insights from mouse models

    PubMed Central

    Wilkinson, Nicole; Pantopoulos, Kostas

    2014-01-01

    Iron regulatory proteins 1 and 2 (IRP1 and IRP2) post-transcriptionally control the expression of several mRNAs encoding proteins of iron, oxygen and energy metabolism. The mechanism involves their binding to iron responsive elements (IREs) in the untranslated regions of target mRNAs, thereby controlling mRNA translation or stability. Whereas IRP2 functions solely as an RNA-binding protein, IRP1 operates as either an RNA-binding protein or a cytosolic aconitase. Early experiments in cultured cells established a crucial role of IRPs in regulation of cellular iron metabolism. More recently, studies in mouse models with global or localized Irp1 and/or Irp2 deficiencies uncovered new physiological functions of IRPs in the context of systemic iron homeostasis. Thus, IRP1 emerged as a key regulator of erythropoiesis and iron absorption by controlling hypoxia inducible factor 2α (HIF2α) mRNA translation, while IRP2 appears to dominate the control of iron uptake and heme biosynthesis in erythroid progenitor cells by regulating the expression of transferrin receptor 1 (TfR1) and 5-aminolevulinic acid synthase 2 (ALAS2) mRNAs, respectively. Targeted disruption of either Irp1 or Irp2 in mice is associated with distinct phenotypic abnormalities. Thus, Irp1−/− mice develop polycythemia and pulmonary hypertension, while Irp2−/− mice present with microcytic anemia, iron overload in the intestine and the liver, and neurologic defects. Combined disruption of both Irp1 and Irp2 is incombatible with life and leads to early embryonic lethality. Mice with intestinal- or liver-specific disruption of both Irps are viable at birth but die later on due to malabsorption or liver failure, respectively. Adult mice lacking both Irps in the intestine exhibit a profound defect in dietary iron absorption due to a “mucosal block” that is caused by the de-repression of ferritin mRNA translation. Herein, we discuss the physiological function of the IRE/IRP regulatory system. PMID

  4. What do Children Aged Four to Seven Know about the Digestive System and the Respiratory System of the Human Being and of Other Animals?

    NASA Astrophysics Data System (ADS)

    Garcia-Barros, Susana; Martínez-Losada, Cristina; Garrido, María

    2011-10-01

    The object of this paper is to learn what little children know about the inside of their bodies before they have studied these particular aspects at school. The data for our project were collected by means of drawings made by 342 Spanish children aged four to seven. They were required to depict where the food, drink, and air which enter their bodies go. In addition to this, we intend to study how the ideas of children evolve during three consecutive years. For this purpose, a group of 32 subjects was monitored. Our findings show that the children recognise specific organs in their own bodies which they associate with the intake of food and air. Furthermore, they usually extrapolate those organs to other animals they are familiar with. Their ideas about the digestive system are more adequate than the ones about the respiratory system, though their ideas improve as they become older, above all those concerning the digestive system. Taking these findings as a basis, this paper suggests some points to be taken into consideration for teaching purposes.

  5. Light microscopic autoradiographic localization of mu and delta opioid binding sites in the mouse central nervous system

    SciTech Connect

    Moskowitz, A.S.; Goodman, R.R.

    1984-05-01

    Much work has been done on opioid systems in the rat CNS. Although the mouse is widely used in pharmacological studies of opioid action, little has been done to characterize opioid systems in this species. In the present study the distribution of mu and delta opioid binding sites in the mouse CNS was examined using a quantitative in vitro autoradiography procedure. Tritiated dihydromorphine was used to visualize mu sites and (3H-d-Ala2-d-Leu5)enkephalin with a low concentration of morphine was used to visualize delta sites. Mu and delta site localizations in the mouse are very similar to those previously described in the rat (Goodman, R.R., S.H. Snyder, M.J. Kuhar, and W.S. Young, 3d (1980) Proc. Natl. Acad. Sci. U.S.A. 77:6239-6243), with certain exceptions and additions. Mu and delta sites were observed in sensory processing areas, limbic system, extrapyramidal motor system, and cranial parasympathetic system. Differential distributions of mu and delta sites were noted in many areas. Mu sites were prominent in laminae I, IV, and VI of the neocortex, in patches in the striatum, and in the ventral pallidum, nucleus accumbens, medial and midline thalamic nuclei, medial habenular nucleus, interpeduncular nucleus, and laminae I and II of the spinal cord. In contrast, delta sites were prominent in all laminae of the neocortex, olfactory tubercle, diffusely throughout the striatum, and in the basal, lateral, and cortical nuclei of the amygdala. The determination of the differential distributions of opioid binding sites should prove useful in suggesting anatomical substrates for the actions of opiates and opioids.

  6. Toxin-induced respiratory distress.

    PubMed

    McKay, Charles A

    2014-02-01

    This article describes the impact of various toxic substances on the airway and pulmonary system. Pulmonary anatomy and physiology provide the basis for understanding the response to toxin-induced injury. Simple asphyxiants displace oxygen from the inspired air. Respiratory irritants include water-soluble and water-insoluble compounds. Several inhaled agents produce direct airway injury, which may be mediated by caustic, thermal, and hydrocarbon exposures. Unique pulmonary toxins and toxicants are discussed, as well as inhaled toxin mixtures. Several inhaled toxins may also impair oxygen transport. The pulmonary system may also provide a mechanism for systemic toxin delivery on respiratory exposure. PMID:24275172

  7. Developmental and maintenance defects in Rett syndrome neurons identified by a new mouse staging system in vitro

    PubMed Central

    Baj, Gabriele; Patrizio, Angela; Montalbano, Alberto; Sciancalepore, Marina; Tongiorgi, Enrico

    2013-01-01

    Rett Syndrome (RTT) is a neurodevelopmental disorder associated with intellectual disability, mainly caused by loss-of-function mutations in the MECP2 gene. RTT brains display decreased neuronal size and dendritic arborization possibly caused by either a developmental failure or a deficit in the maintenance of dendritic arbor structure. To distinguish between these two hypotheses, the development of Mecp2-knockout mouse hippocampal neurons was analyzed in vitro. Since a staging system for the in vitro development of mouse neurons was lacking, mouse and rat hippocampal neurons development was compared between 1–15 days in vitro (DIV) leading to a 6-stage model for both species. Mecp2-knockout hippocampal neurons displayed reduced growth of dendritic branches from stage 4 (DIV4) onwards. At stages 5–6 (DIV9-15), synapse number was lowered in Mecp2-knockout neurons, suggesting increased synapse elimination. These results point to both a developmental and a maintenance setback affecting the final shape and function of neurons in RTT. PMID:24550777

  8. Distinct Human and Mouse Membrane Trafficking Systems for Sweet Taste Receptors T1r2 and T1r3

    PubMed Central

    Shimizu, Madoka; Goto, Masao; Kawai, Takayuki; Yamashita, Atsuko; Kusakabe, Yuko

    2014-01-01

    The sweet taste receptors T1r2 and T1r3 are included in the T1r taste receptor family that belongs to class C of the G protein-coupled receptors. Heterodimerization of T1r2 and T1r3 is required for the perception of sweet substances, but little is known about the mechanisms underlying this heterodimerization, including membrane trafficking. We developed tagged mouse T1r2 and T1r3, and human T1R2 and T1R3 and evaluated membrane trafficking in human embryonic kidney 293 (HEK293) cells. We found that human T1R3 surface expression was only observed when human T1R3 was coexpressed with human T1R2, whereas mouse T1r3 was expressed without mouse T1r2 expression. A domain-swapped chimera and truncated human T1R3 mutant showed that the Venus flytrap module and cysteine-rich domain (CRD) of human T1R3 contain a region related to the inhibition of human T1R3 membrane trafficking and coordinated regulation of human T1R3 membrane trafficking. We also found that the Venus flytrap module of both human T1R2 and T1R3 are needed for membrane trafficking, suggesting that the coexpression of human T1R2 and T1R3 is required for this event. These results suggest that the Venus flytrap module and CRD receive taste substances and play roles in membrane trafficking of human T1R2 and T1R3. These features are different from those of mouse receptors, indicating that human T1R2 and T1R3 are likely to have a novel membrane trafficking system. PMID:25029362

  9. Ibuprofen slows migration and inhibits bowel colonization by enteric nervous system precursors in zebrafish, chick and mouse.

    PubMed

    Schill, Ellen Merrick; Lake, Jonathan I; Tusheva, Olga A; Nagy, Nandor; Bery, Saya K; Foster, Lynne; Avetisyan, Marina; Johnson, Stephen L; Stenson, William F; Goldstein, Allan M; Heuckeroth, Robert O

    2016-01-15

    Hirschsprung Disease (HSCR) is a potentially deadly birth defect characterized by the absence of the enteric nervous system (ENS) in distal bowel. Although HSCR has clear genetic causes, no HSCR-associated mutation is 100% penetrant, suggesting gene-gene and gene-environment interactions determine HSCR occurrence. To test the hypothesis that certain medicines might alter HSCR risk we treated zebrafish with medications commonly used during early human pregnancy and discovered that ibuprofen caused HSCR-like absence of enteric neurons in distal bowel. Using fetal CF-1 mouse gut slice cultures, we found that ibuprofen treated enteric neural crest-derived cells (ENCDC) had reduced migration, fewer lamellipodia and lower levels of active RAC1/CDC42. Additionally, inhibiting ROCK, a RHOA effector and known RAC1 antagonist, reversed ibuprofen effects on migrating mouse ENCDC in culture. Ibuprofen also inhibited colonization of Ret+/- mouse bowel by ENCDC in vivo and dramatically reduced bowel colonization by chick ENCDC in culture. Interestingly, ibuprofen did not affect ENCDC migration until after at least three hours of exposure. Furthermore, mice deficient in Ptgs1 (COX 1) and Ptgs2 (COX 2) had normal bowel colonization by ENCDC and normal ENCDC migration in vitro suggesting COX-independent effects. Consistent with selective and strain specific effects on ENCDC, ibuprofen did not affect migration of gut mesenchymal cells, NIH3T3, or WT C57BL/6 ENCDC, and did not affect dorsal root ganglion cell precursor migration in zebrafish. Thus, ibuprofen inhibits ENCDC migration in vitro and bowel colonization by ENCDC in vivo in zebrafish, mouse and chick, but there are cell type and strain specific responses. These data raise concern that ibuprofen may increase Hirschsprung disease risk in some genetically susceptible children. PMID:26586201

  10. Development of system using beam's eye view images to measure respiratory motion tracking errors in image-guided robotic radiosurgery system.

    PubMed

    Inoue, Mitsuhiro; Shiomi, Hiroya; Iwata, Hiromitsu; Taguchi, Junichi; Okawa, Kohei; Kikuchi, Chie; Inada, Kosaku; Iwabuchi, Michio; Murai, Taro; Koike, Izumi; Tatewaki, Koshi; Ohta, Seiji; Inoue, Tomio

    2015-01-01

    The accuracy of the CyberKnife Synchrony Respiratory Tracking System (SRTS) is considered to be patient-dependent because the SRTS relies on an individual correlation between the internal tumor position (ITP) and the external marker position (EMP), as well as a prediction method to compensate for the delay incurred to adjust the position of the linear accelerator (linac). We aimed to develop a system for obtaining pretreatment statistical measurements of the SRTS tracking error by using beam's eye view (BEV) images, to enable the prediction of the patient-specific accuracy. The respiratory motion data for the ITP and the EMP were derived from cine MR images obtained from 23 patients. The dynamic motion phantom was used to reproduce both the ITP and EMP motions. The CyberKnife was subsequently operated with the SRTS, with a CCD camera mounted on the head of the linac. BEV images from the CCD camera were recorded during the tracking of a ball target by the linac. The tracking error was measured at 15 Hz using in-house software. To assess the precision of the position detection using an MR image, the positions of test tubes (determined from MR images) were compared with their actual positions. To assess the precision of the position detection of the ball, ball positions measured from BEV images were compared with values measured using a Vernier caliper. The SRTS accuracy was evaluated by determining the tracking error that could be identified with a probability of more than 95% (Ep95). The detection precision of the tumor position (determined from cine MR images) was < 0.2 mm. The detection precision of the tracking error when using the BEV images was < 0.2mm. These two detection precisions were derived from our measurement system and were not obtained from the SRTS. The median of Ep95 was found to be 1.5 (range, 1.0-3.5) mm. The difference between the minimum and maximum Ep95 was 2.5mm, indicating that this provides a better means of evaluating patient-specific SRTS

  11. Pathophysiology and Classification of Respiratory Failure.

    PubMed

    Lamba, Tejpreet Singh; Sharara, Rihab Saeed; Singh, Anil C; Balaan, Marvin

    2016-01-01

    Respiratory failure is a condition in which the respiratory system fails in one or both of its gas exchange functions. It is a major cause of morbidity and mortality in patients admitted to intensive care units. It is a result of either lung failure, resulting in hypoxemia, or pump failure, resulting in alveolar hypoventilation and hypercapnia. This article covers the basic lung anatomy, pathophysiology, and classification of respiratory failure. PMID:26919670

  12. Development of a novel clinical scoring system for on-farm diagnosis of bovine respiratory disease in pre-weaned dairy calves

    PubMed Central

    Love, William J.; Lehenbauer, Terry W.; Kass, Philip H.; Van Eenennaam, Alison L.

    2014-01-01

    Several clinical scoring systems for diagnosis of bovine respiratory disease (BRD) in calves have been proposed. However, such systems were based on subjective judgment, rather than statistical methods, to weight scores. Data from a pair-matched case-control study on a California calf raising facility was used to develop three novel scoring systems to diagnose BRD in preweaned dairy calves. Disease status was assigned using both clinical signs and diagnostic test results for BRD-associated pathogens. Regression coefficients were used to weight score values. The systems presented use nasal and ocular discharge, rectal temperature, ear and head carriage, coughing, and respiratory quality as predictors. The systems developed in this research utilize fewer severity categories of clinical signs, require less calf handling, and had excellent agreement (Kappa > 0.8) when compared to an earlier scoring system. The first scoring system dichotomized all clinical predictors but required inducing a cough. The second scoring system removed induced cough as a clinical abnormality but required distinguishing between three levels of nasal discharge severity. The third system removed induced cough and forced a dichotomized variable for nasal discharge. The first system presented in this study used the following predictors and assigned values: coughing (induced or spontaneous coughing, 2 points), nasal discharge (any discharge, 3 points), ocular discharge (any discharge, 2 points), ear and head carriage (ear droop or head tilt, 5 points), fever (≥39.2°C or 102.5°F, 2 points), and respiratory quality (abnormal respiration, 2 points). Calves were categorized “BRD positive” if their total score was ≥4. This system correctly classified 95.4% cases and 88.6% controls. The second presented system categorized the predictors and assigned weights as follows: coughing (spontaneous only, 2 points), mild nasal discharge (unilateral, serous, or watery discharge, 3 points), moderate to

  13. Effects of pressure-controlled and volume-controlled ventilation on respiratory mechanics and systemic stress response during laparoscopic cholecystectomy.

    PubMed

    Sen, Oznur; Umutoglu, Tarik; Aydın, Nurdan; Toptas, Mehmet; Tutuncu, Ayse Cigdem; Bakan, Mefkur

    2016-01-01

    Pressure-controlled ventilation (PCV) is less frequently employed in general anesthesia. With its high and decelerating inspiratory flow, PCV has faster tidal volume delivery and different gas distribution. The same tidal volume setting, delivered by PCV versus volume-controlled ventilation (VCV), will result in a lower peak airway pressure and reduced risk of barotrauma. We hypothesized that PCV instead of VCV during laparoscopic surgery could achieve lower airway pressures and reduce the systemic stress response. Forty ASA I-II patients were randomly selected to receive either the PCV (Group PC, n = 20) or VCV (Group VC, n = 20) during laparoscopic cholecystectomy. Blood sampling was made for baseline arterial blood gases (ABG), cortisol, insulin, and glucose levels. General anesthesia with sevoflurane and fentanyl was employed to all patients. After anesthesia induction and endotracheal intubation, patients in Group PC were given pressure support to form 8 mL/kg tidal volume and patients in Group VC was maintained at 8 mL/kg tidal volume calculated using predicted body weight. All patients were maintained with 5 cmH2O positive-end expiratory pressure (PEEP). Respiratory parameters were recorded before and 30 min after pneumoperitonium. Assessment of ABG and sampling for cortisol, insulin and glucose levels were repeated 30 min after pneumoperitonium and 60 min after extubation. The P-peak levels observed before (18.9 ± 3.8 versus 15 ± 2.2 cmH2O) and during (23.3 ± 3.8 versus 20.1 ± 2.9 cmH2O) pneumoperitoneum in Group VC were significantly higher. Postoperative partial arterial oxygen pressure (PaO2) values are higher (98 ± 12 versus 86 ± 11 mmHg) in Group PC. Arterial carbon dioxide pressure (PaCO2) values (41.8 ± 5.4 versus 36.7 ± 3.5 mmHg) during pneumoperitonium and post-operative mean cortisol and insulin levels were higher in Group VC. When compared to VCV mode, PCV mode may improve compliance during pneumoperitoneum

  14. Intrarenal mouse renin-angiotensin system during ANG II-induced hypertension and ACE inhibition.

    PubMed

    Gonzalez-Villalobos, Romer A; Satou, Ryousuke; Ohashi, Naro; Semprun-Prieto, Laura C; Katsurada, Akemi; Kim, Catherine; Upchurch, G M; Prieto, Minolfa C; Kobori, Hiroyuki; Navar, L Gabriel

    2010-01-01

    Angiotensin-converting enzyme (ACE) inhibition (ACEi) ameliorates the development of hypertension and the intrarenal ANG II augmentation in ANG II-infused mice. To determine if these effects are associated with changes in the mouse intrarenal renin-angiotensin system, the expression of angiotensinogen (AGT), renin, ACE, angiotensin type 1 receptor (AT(1)R) mRNA (by quanitative RT-PCR) and protein [by Western blot (WB) and/or immunohistochemistry (IHC)] were analyzed. C57BL/6J male mice (9-12 wk old) were distributed as controls (n = 10), ANG II infused (ANG II = 8, 400 ng x kg(-1) x min(-1) for 12 days), ACEi only (ACEi = 10, lisinopril, 100 mg/l), and ANG II infused + ACEi (ANG II + ACEi = 11). When compared with controls (1.00), AGT protein (by WB) was increased by ANG II (1.29 +/- 0.13, P < 0.05), and this was not prevented by ACEi (ACEi + ANG II, 1.31 +/- 0.14, P < 0.05). ACE protein (by WB) was increased by ANG II (1.21 +/- 0.08, P < 0.05), and it was reduced by ACEi alone (0.88 +/- 0.07, P < 0.05) or in combination with ANG II (0.80 +/- 0.07, P < 0.05). AT(1)R protein (by WB) was increased by ANG II (1.27 +/- 0.06, P < 0.05) and ACEi (1.17 +/- 0.06, P < 0.05) but not ANG II + ACEi [1.15 +/- 0.06, not significant (NS)]. Tubular renin protein (semiquantified by IHC) was increased by ANG II (1.49 +/- 0.23, P < 0.05) and ACEi (1.57 +/- 0.15, P < 0.05), but not ANG II + ACEi (1.10 +/- 0.15, NS). No significant changes were observed in AGT, ACE, or AT(1)R mRNA. In summary, reduced responses of intrarenal tubular renin, ACE, and the AT(1)R protein to the stimulatory effects of chronic ANG II infusions, in the presence of ACEi, are associated with the effects of this treatment to ameliorate augmentations in blood pressure and intrarenal ANG II content during ANG II-induced hypertension. PMID:19846570

  15. Intrarenal mouse renin-angiotensin system during ANG II-induced hypertension and ACE inhibition

    PubMed Central

    Satou, Ryousuke; Ohashi, Naro; Semprun-Prieto, Laura C.; Katsurada, Akemi; Kim, Catherine; Upchurch, G. M.; Prieto, Minolfa C.; Kobori, Hiroyuki; Navar, L. Gabriel

    2010-01-01

    Angiotensin-converting enzyme (ACE) inhibition (ACEi) ameliorates the development of hypertension and the intrarenal ANG II augmentation in ANG II-infused mice. To determine if these effects are associated with changes in the mouse intrarenal renin-angiotensin system, the expression of angiotensinogen (AGT), renin, ACE, angiotensin type 1 receptor (AT1R) mRNA (by quanitative RT-PCR) and protein [by Western blot (WB) and/or immunohistochemistry (IHC)] were analyzed. C57BL/6J male mice (9–12 wk old) were distributed as controls (n = 10), ANG II infused (ANG II = 8, 400 ng·kg−1·min−1 for 12 days), ACEi only (ACEi = 10, lisinopril, 100 mg/l), and ANG II infused + ACEi (ANG II + ACEi = 11). When compared with controls (1.00), AGT protein (by WB) was increased by ANG II (1.29 ± 0.13, P < 0.05), and this was not prevented by ACEi (ACEi + ANG II, 1.31 ± 0.14, P < 0.05). ACE protein (by WB) was increased by ANG II (1.21 ± 0.08, P < 0.05), and it was reduced by ACEi alone (0.88 ± 0.07, P < 0.05) or in combination with ANG II (0.80 ± 0.07, P < 0.05). AT1R protein (by WB) was increased by ANG II (1.27 ± 0.06, P < 0.05) and ACEi (1.17 ± 0.06, P < 0.05) but not ANG II + ACEi [1.15 ± 0.06, not significant (NS)]. Tubular renin protein (semiquantified by IHC) was increased by ANG II (1.49 ± 0.23, P < 0.05) and ACEi (1.57 ± 0.15, P < 0.05), but not ANG II + ACEi (1.10 ± 0.15, NS). No significant changes were observed in AGT, ACE, or AT1R mRNA. In summary, reduced responses of intrarenal tubular renin, ACE, and the AT1R protein to the stimulatory effects of chronic ANG II infusions, in the presence of ACEi, are associated with the effects of this treatment to ameliorate augmentations in blood pressure and intrarenal ANG II content during ANG II-induced hypertension. PMID:19846570

  16. Evaluation and reduction of respiratory motion artifacts in small animal SPECT with GATE

    NASA Astrophysics Data System (ADS)

    Lee, C.-L.; Park, S.-J.; Kim, H.-J.

    2015-09-01

    The degradation of image quality caused by respiration is a major impediment to accurate lesion detection in single photon emission computed tomography (SPECT) imaging. This study was performed to evaluate the effects of lung motion on image quantification. A small animal SPECT system with NaI(Tl) was modeled in the Geant4 application for tomographic emission (GATE) simulation for a lung lesion using a 4D mouse whole-body phantom. SPECT images were obtained using 120 projection views acquired from 0o to 360o with a 3o step. Slices were reconstructed using ordered subsets expectation maximization (OS-EM) without attenuation correction with five iterations and four subsets. Image quality was compared between the static mode without respiratory motion, and dynamic mode with respiratory motion in terms of spatial resolution was measured by the full width at half maximum (FWHM), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR). The FWHM of the non-gated image and the respiratory gated image were also compared. Spatial resolution improved as activity increased and lesion diameter decreased in the static and dynamic modes. The SNR and CNR increased significantly as lesion activity increased and lesion diameter decreased. Our results show that respiratory motion leads to reduced contrast and quantitative accuracy and that image quantification depends on both the amplitude and the pattern of the respiratory motion. We verified that respiratory motion can have a major effect on the accuracy of measurement of lung lesions and that respiratory gating can reduce activity smearing on SPECT images.

  17. Immediate and long-term effects in the hematopoietic system and the morphology of the respiratory system in experimental animals under chronic combined action of external gamma exposure and inhalation exposure.

    NASA Astrophysics Data System (ADS)

    Tatarkin, Sergey; Moukhamedieva, Lana; Aleksandr, Shafirkin; Barantseva, Maria; Ivanova, Svetlana

    The need to solve hygiene problems valuation of environmental factors in the implementation of the projected manned interplanetary missions, determined the relevance of studying the effect of external gamma-irradiation with inhalation of mixtures of chemicals on the parameters of major critical body systems: hematopoiesis and respiratory (morphological and morphometric parameters) in the short and long periods. The study conducted on 504 male mice F1 (CBA × C57BL6) under chronic fractional gamma-irradiation (within 10 weeks at a total dose 350sGr) and then under inhalation by mixtures of chemicals in low concentrations. Duration of the experiment (124 days) and 90 -day recovery period. Displaying adaptive reorganization in hematopoietic system, which was characterized by a tension of regulatory systems of animals and by a proliferation of bone marrow cells and by dynamic changes in amount of lymphoid cells in peripheral blood, elevated levels of the antioxidant activity of red blood cells, and morphological manifestations of "incomplete recovery " of the spleen, which are retained in the recovery period. Morphological changes in the respiratory organs of animals testified about immunogenesis activation and development of structural changes as a chronic inflammatory process. Increase of fibrous connective tissue in the walls of the trachea, bronchus and lung, against reduction of loose fibrous connective tissue (more pronounced in respiratory parts of the respiratory system) in experimental animals, which may indicate a reduction of the functional reserves of the body and increase the risk of adverse long-term effects.

  18. Mouse genome database 2016

    PubMed Central

    Bult, Carol J.; Eppig, Janan T.; Blake, Judith A.; Kadin, James A.; Richardson, Joel E.

    2016-01-01

    The Mouse Genome Database (MGD; http://www.informatics.jax.org) is the primary community model organism database for the laboratory mouse and serves as the source for key biological reference data related to mouse genes, gene functions, phenotypes and disease models with a strong emphasis on the relationship of these data to human biology and disease. As the cost of genome-scale sequencing continues to decrease and new technologies for genome editing become widely adopted, the laboratory mouse is more important than ever as a model system for understanding the biological significance of human genetic variation and for advancing the basic research needed to support the emergence of genome-guided precision medicine. Recent enhancements to MGD include new graphical summaries of biological annotations for mouse genes, support for mobile access to the database, tools to support the annotation and analysis of sets of genes, and expanded support for comparative biology through the expansion of homology data. PMID:26578600

  19. Mouse genome database 2016.

    PubMed

    Bult, Carol J; Eppig, Janan T; Blake, Judith A; Kadin, James A; Richardson, Joel E

    2016-01-01

    The Mouse Genome Database (MGD; http://www.informatics.jax.org) is the primary community model organism database for the laboratory mouse and serves as the source for key biological reference data related to mouse genes, gene functions, phenotypes and disease models with a strong emphasis on the relationship of these data to human biology and disease. As the cost of genome-scale sequencing continues to decrease and new technologies for genome editing become widely adopted, the laboratory mouse is more important than ever as a model system for understanding the biological significance of human genetic variation and for advancing the basic research needed to support the emergence of genome-guided precision medicine. Recent enhancements to MGD include new graphical summaries of biological annotations for mouse genes, support for mobile access to the database, tools to support the annotation and analysis of sets of genes, and expanded support for comparative biology through the expansion of homology data. PMID:26578600

  20. The effect of open and closed endotracheal tube suctioning