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Sample records for primary human nasal

  1. Nasal trauma: Primary reconstruction with open rhinoplasty.

    PubMed

    Konstantinidis, I; Malliari, H; Metaxas, S

    2011-01-01

    Due to the prominent location of the nose, the most common facial traumas are nasal injuries. Although nasal traumas usually require staged intervention at a later period of time, in selected cases, primary reconstruction can be effective. A 20-year-old man who was referred from the emergency department with nasal trauma is presented. He reported a fall after feeling unsteady, which caused a direct nasal injury. Clinical examination revealed septal fracture with obstruction of the left nasal cavity and deformity of the nasal pyramid (inverted V deformity). The patient also had a complete dissection of the columella skin. Epistaxis was self-limited, and an open rhinoplasty procedure was decided because the trauma occurred 1 h before admission and there was no significant edema. Surgical intervention included septal reconstruction combined with restoration of the nasal pyramid and columella. One month later, the patient had patent nasal airways, and he was satisfied with the aesthetic result. PMID:22942663

  2. Nasal trauma: Primary reconstruction with open rhinoplasty

    PubMed Central

    Konstantinidis, I; Malliari, H; Metaxas, S

    2011-01-01

    Due to the prominent location of the nose, the most common facial traumas are nasal injuries. Although nasal traumas usually require staged intervention at a later period of time, in selected cases, primary reconstruction can be effective. A 20-year-old man who was referred from the emergency department with nasal trauma is presented. He reported a fall after feeling unsteady, which caused a direct nasal injury. Clinical examination revealed septal fracture with obstruction of the left nasal cavity and deformity of the nasal pyramid (inverted V deformity). The patient also had a complete dissection of the columella skin. Epistaxis was self-limited, and an open rhinoplasty procedure was decided because the trauma occurred 1 h before admission and there was no significant edema. Surgical intervention included septal reconstruction combined with restoration of the nasal pyramid and columella. One month later, the patient had patent nasal airways, and he was satisfied with the aesthetic result. PMID:22942663

  3. Primary Nasal Reconstruction in Self-Inflicted Nasal Injury.

    PubMed

    Kapadia, Abizer; John, Jerry R; Gaba, Sunil; Sharma, Ramesh Kumar

    2015-10-01

    Self-inflicted injury of the nose is extremely rare. It may be associated with severe psychopathology and suicidal ideation. The authors report a case of a 24-year-old man, who presented with soft-tissue loss over both the alae of his nose. He had cut off the alar rims with an ordinary razor blade. He was overtly concerned about his nose being excessively broad and fat. A diagnosis of body dysmorphic disorder with nonsuicidal self-injury was made. Patient was observed during 72 hours in hospital with psychiatric support and local dressings. The authors undertook primary nasal reconstruction with nasolabial flaps on both sides for coverage. In conclusion, self-inflicted nasal injury mandates a judicious balancing of psychiatric support and surgical reconstruction. This can prevent untoward sequelae including further self-harm and suicide.

  4. In vivo Cigarette Smoke Exposure Decreases CCL20, SLPI, and BD-1 Secretion by Human Primary Nasal Epithelial Cells

    PubMed Central

    Jukosky, James; Gosselin, Benoit J.; Foley, Leah; Dechen, Tenzin; Fiering, Steven; Crane-Godreau, Mardi A.

    2016-01-01

    Smokers and individuals exposed to second-hand cigarette smoke have a higher risk of developing chronic sinus and bronchial infections. This suggests that cigarette smoke (CS) has adverse effects on immune defenses against pathogens. Epithelial cells are important in airway innate immunity and are the first line of defense against infection. Airway epithelial cells not only form a physical barrier but also respond to the presence of microbes by secreting antimicrobials, cytokines, and chemokines. These molecules can lyse infectious microorganisms and/or provide signals critical to the initiation of adaptive immune responses. We examined the effects of CS on antimicrobial secretions of primary human nasal epithelial cells (PHNECs). Compared to non-CS-exposed individuals, PHNEC from in vivo CS-exposed individuals secreted less chemokine ligand (C-C motif) 20 (CCL20), Beta-defensin 1 (BD-1), and SLPI apically, less BD-1 and SLPI basolaterally, and more CCL20 basolaterally. Cigarette smoke extract (CSE) exposure in vitro decreased the apical secretion of CCL20 and beta-defensin 1 by PHNEC from non-CS-exposed individuals. Exposing PHNEC from non-CS exposed to CSE also significantly decreased the levels of many mRNA transcripts that are involved in immune signaling. Our results show that in vivo or in vitro exposure to CS alters the secretion of key antimicrobial peptides from PHNEC, but that in vivo CS exposure is a much more important modifier of antimicrobial peptide secretion. Based on the gene expression data, it appears that CSE disrupts multiple immune signaling pathways in PHNEC. Our results provide mechanistic insight into how CS exposure alters the innate immune response and increases an individual’s susceptibility to pathogen infection. PMID:26793127

  5. In vivo Cigarette Smoke Exposure Decreases CCL20, SLPI, and BD-1 Secretion by Human Primary Nasal Epithelial Cells.

    PubMed

    Jukosky, James; Gosselin, Benoit J; Foley, Leah; Dechen, Tenzin; Fiering, Steven; Crane-Godreau, Mardi A

    2015-01-01

    Smokers and individuals exposed to second-hand cigarette smoke have a higher risk of developing chronic sinus and bronchial infections. This suggests that cigarette smoke (CS) has adverse effects on immune defenses against pathogens. Epithelial cells are important in airway innate immunity and are the first line of defense against infection. Airway epithelial cells not only form a physical barrier but also respond to the presence of microbes by secreting antimicrobials, cytokines, and chemokines. These molecules can lyse infectious microorganisms and/or provide signals critical to the initiation of adaptive immune responses. We examined the effects of CS on antimicrobial secretions of primary human nasal epithelial cells (PHNECs). Compared to non-CS-exposed individuals, PHNEC from in vivo CS-exposed individuals secreted less chemokine ligand (C-C motif) 20 (CCL20), Beta-defensin 1 (BD-1), and SLPI apically, less BD-1 and SLPI basolaterally, and more CCL20 basolaterally. Cigarette smoke extract (CSE) exposure in vitro decreased the apical secretion of CCL20 and beta-defensin 1 by PHNEC from non-CS-exposed individuals. Exposing PHNEC from non-CS exposed to CSE also significantly decreased the levels of many mRNA transcripts that are involved in immune signaling. Our results show that in vivo or in vitro exposure to CS alters the secretion of key antimicrobial peptides from PHNEC, but that in vivo CS exposure is a much more important modifier of antimicrobial peptide secretion. Based on the gene expression data, it appears that CSE disrupts multiple immune signaling pathways in PHNEC. Our results provide mechanistic insight into how CS exposure alters the innate immune response and increases an individual's susceptibility to pathogen infection. PMID:26793127

  6. Primary Nasal Tuberculosis in a 10-Year-Old Girl

    PubMed Central

    Özer, Murat; Özsurekçi, Yasemin; Cengiz, Ali Bülent; Özçelik, Uğur; Yalçın, Ebru; Gököz, Özay

    2016-01-01

    Nasal tuberculosis is a rare clinical entity which mainly presents in elderly people. Nasal tuberculosis has always been considered to be secondary to tuberculosis of the lungs, and in rare instances it is a primary infection, usually when mycobacteria are inhaled. We describe the case of a 10-year-old girl who was successfully treated for primary nasal tuberculosis. This patient is one of the very few children who have been reported to have primary nasal tuberculosis. PMID:27366187

  7. Primary Nasal Tuberculosis in a 10-Year-Old Girl.

    PubMed

    Özer, Murat; Özsurekçi, Yasemin; Cengiz, Ali Bülent; Özçelik, Uğur; Yalçın, Ebru; Gököz, Özay

    2016-01-01

    Nasal tuberculosis is a rare clinical entity which mainly presents in elderly people. Nasal tuberculosis has always been considered to be secondary to tuberculosis of the lungs, and in rare instances it is a primary infection, usually when mycobacteria are inhaled. We describe the case of a 10-year-old girl who was successfully treated for primary nasal tuberculosis. This patient is one of the very few children who have been reported to have primary nasal tuberculosis.

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

    SciTech Connect

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

    2015-10-15

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

  9. Airflow patterns in a human nasal model

    SciTech Connect

    Hornung, D.E.; Leopold, D.A.; Youngentob, S.L.; Sheehe, P.R.; Gagne, G.M.; Thomas, F.D.; Mozell, M.M.

    1987-02-01

    Nasal airflow patterns were studied by using xenon 133 gas to image the course taken by air as it flowed through a plastic model of the human nasal cavity. The model was produced from the head of a human cadaver, and was anatomically correct. A needle catheter was used to infuse the radioactive xenon into a continuous flow of room air maintained through the model by a variable vacuum source connected to the nasopharynx. The radioactive gas was infused at one of five release sites in the nostril, and the distribution of the radioactivity was imaged in the sagittal plane with a scintillation camera. The data were organized to show the activity in six contiguous regions of the midnose. For each catheter, release site activity patterns were determined for three flow rates. The results of this experiment showed that both catheter position and flow rate had significant and reproducible effects on the distribution of radioactivity within the model.

  10. A strain of pathogenic Naegleria isolated from a human nasal swab.

    PubMed

    Chang, S L; Healy, G R; McCabe, L; Shumaker, J B; Schultz, M G

    1975-01-01

    The 161A strain of Naegleria isolated from a human nasal swab and reported earlier was further studied for its growth pattern, cyst-wall appearance, cytopathic effect on primary monkey kidney cells, and pathogenicity in mice. Results obtained in the study establish the pathogenic status of this strain. This constitutes the first isolation of a pathogenic Naegleria from a human nasal cavity. PMID:829906

  11. Cultivate Primary Nasal Epithelial Cells from Children and Reprogram into Induced Pluripotent Stem Cells.

    PubMed

    Ulm, Ashley; Mayhew, Christopher N; Debley, Jason; Khurana Hershey, Gurjit K; Ji, Hong

    2016-01-01

    Nasal epithelial cells (NECs) are the part of the airways that respond to air pollutants and are the first cells infected with respiratory viruses. They are also involved in many airway diseases through their innate immune response and interaction with immune and airway stromal cells. NECs are of particular interest for studies in children due to their accessibility during clinical visits. Human induced pluripotent stem cells (iPSCs) have been generated from multiple cell types and are a powerful tool for modeling human development and disease, as well as for their potential applications in regenerative medicine. This is the first protocol to lay out methods for successful generation of iPSCs from NECs derived from pediatric participants for research purposes. It describes how to obtain nasal epithelial cells from children, how to generate primary NEC cultures from these samples, and how to reprogram primary NECs into well-characterized iPSCs. Nasal mucosa samples are useful in epidemiological studies related to the effects of air pollution in children, and provide an important tool for studying airway disease. Primary nasal cells and iPSCs derived from them can be a tool for providing unlimited material for patient-specific research in diverse areas of airway epithelial biology, including asthma and COPD research. PMID:27022951

  12. Resident aerobic microbiota of the adult human nasal cavity.

    PubMed

    Rasmussen, T T; Kirkeby, L P; Poulsen, K; Reinholdt, J; Kilian, M

    2000-10-01

    Recent evidence strongly suggests that the microbiota of the nasal cavity plays a crucial role in determining the reaction patterns of the mucosal and systemic immune system. However, little is known about the normal microbiota of the nasal cavity. The purpose of this study was to determine the microbiota in different parts of the nasal cavity and to develop and evaluate methods for this purpose. Samples were collected from 10 healthy adults by nasal washes and by swabbing of the mucosa through a sterile introduction device. Both methods gave results that were quantitatively and qualitatively reproducible, and revealed significant differences in the density of the nasal microbiota between individuals. The study revealed absence of gram-negative bacteria that are regular members of the commensal microbiota of the pharynx. Likewise, viridans type streptococci were sparsely represented. The nasal microbiota was dominated by species of the genera Corynebacterium, Aureobacterium, Rhodococcus, and Staphylococcus, including S. epidermis, S. capitis, S. hominis, S. haemolyticus, S. lugdunensis and S. warneri. These studies show that the microbiota of the nasal cavity of adults is strikingly different from that of the pharynx, and that the nasal cavity is a primary habitat for several species of diphtheroids recognized as opportunistic pathogens. Under special circumstances, single species, including IgA1 protease-producing bacteria, may become predominant in a restricted area of the nasal mucosa. PMID:11200821

  13. Nasal cytochrome P4502A: Identification in rats and humans

    SciTech Connect

    Thornton-Manning, J.R.; Hotchkiss, J.A.; Ding, Xinxin

    1995-12-01

    The nasal mucosa, the first tissue of contact for inhaled xenobiotics, possesses substantial enobiotic-metabolizing capacti. Enzymes of the nasal cavity may metabolize xenobiotics to innocuous, more water-soluble compounds that are eliminated from the body, or they may bioactivate them to toxic metabolites. These toxic metabolites may find to cellular macromolecules in the nasal cavity or be transported to other parts of the body where they may react. Nasal carcinogenesis in rodents often results from bioactivation of xenobiotics. The increased incidences of nasal tumors associated with certain occupations suggest that xenobiotic bioactivation may be important in human nasal cancer etiology, as well. The increasing popularity of the nose as a route of drug administration makes information concerning nasal drug metabolism and disposition vital to accomplish therapeutic goals. For these reasons, the study of xenobiotic-met abolizing capacity of the nasal cavity is an important area of health-related research. In the present study, we have confirmed the presence of CYP2A6 mRNA in human respiratory mucosa.

  14. Air-conditioning in the human nasal cavity.

    PubMed

    Elad, David; Wolf, Michael; Keck, Tilman

    2008-11-30

    Healthy humans normally breathe through their nose even though its complex geometry imposes a significantly higher resistance in comparison with mouth breathing. The major functional roles of nasal breathing are defense against infiltrating particles and conditioning of the inspired air to nearly alveolar conditions in order to maintain the internal milieu of the lung. The state-of-the-art of the existing knowledge on nasal air-conditioning will be discussed in this review, including in vivo measurements in humans and computational studies on nasal air-conditioning capacity. Areas where further studies will improve our understanding and may help medical diagnosis and intervention in pathological states will be introduced. PMID:18565805

  15. Responses to nasal irritation obtained from the human nasal mucosa.

    PubMed

    Hummel, T; Kraetsch, H G; Pauli, E; Kobal, G

    1998-12-01

    Responses to chemical irritation can be obtained from the human respiratory mucosa in response to stimulation with gaseous CO2; these negative mucosal potentials (NMPs) are thought to be summated receptor potentials from chemosensitive nociceptors. The present study aimed to investigate the relation of this response to both stimulus concentration and perceived intensity. A total of 29 healthy volunteers participated. Maximum negative amplitudes occurred 1.1 s after stimulus onset. The negativity exhibited a higher coefficient of correlation to intensity estimates of the painful sensations (r = .65) than to the stimulus concentration (r = .46); it appeared at the same time when the subjects' tracking of the painful sensations reached its maximum amplitude. These findings suggest that the NMP is suited for the investigation of peripheral nociceptive events in man.

  16. Measuring and Characterizing the Human Nasal Cycle

    PubMed Central

    Kahana-Zweig, Roni; Geva-Sagiv, Maya; Weissbrod, Aharon; Secundo, Lavi; Soroker, Nachum; Sobel, Noam

    2016-01-01

    Nasal airflow is greater in one nostril than in the other because of transient asymmetric nasal passage obstruction by erectile tissue. The extent of obstruction alternates across nostrils with periodicity referred to as the nasal cycle. The nasal cycle is related to autonomic arousal and is indicative of asymmetry in brain function. Moreover, alterations in nasal cycle periodicity have been linked to various diseases. There is therefore need for a tool allowing continuous accurate measurement and recording of airflow in each nostril separately. Here we provide detailed instructions for constructing such a tool at minimal cost and effort. We demonstrate application of the tool in 33 right-handed healthy subjects, and derive several statistical measures for nasal cycle characterization. Using these measures applied to 24-hour recordings we observed that: 1: subjects spent slightly longer in left over right nostril dominance (left = 2.63 ± 0.89 hours, right = 2.17 ± 0.89 hours, t(32) = 2.07, p < 0.05), 2: cycle duration was shorter in wake than in sleep (wake = 2.02 ± 1.7 hours, sleep = 4.5 ± 1.7 hours, (t(30) = 5.73, p < 0.0001). 3: slower breathing was associated with a more powerful cycle (the extent of difference across nostrils) (r = 0.4, p < 0.0001), and 4: the cycle was influenced by body posture such that lying on one side was associated with greater flow in the contralateral nostril (p < 0.002). Finally, we provide evidence for an airflow cycle in each nostril alone. These results provide characterization of an easily obtained measure that may have diagnostic implications for neurological disease and cognitive state. PMID:27711189

  17. Culturing of Human Nasal Epithelial Cells at the Air Liquid Interface

    PubMed Central

    Müller, Loretta; Brighton, Luisa E.; Carson, Johnny L.; Fischer, William A.; Jaspers, Ilona

    2013-01-01

    In vitro models using human primary epithelial cells are essential in understanding key functions of the respiratory epithelium in the context of microbial infections or inhaled agents. Direct comparisons of cells obtained from diseased populations allow us to characterize different phenotypes and dissect the underlying mechanisms mediating changes in epithelial cell function. Culturing epithelial cells from the human tracheobronchial region has been well documented, but is limited by the availability of human lung tissue or invasiveness associated with obtaining the bronchial brushes biopsies. Nasal epithelial cells are obtained through much less invasive superficial nasal scrape biopsies and subjects can be biopsied multiple times with no significant side effects. Additionally, the nose is the entry point to the respiratory system and therefore one of the first sites to be exposed to any kind of air-borne stressor, such as microbial agents, pollutants, or allergens. Briefly, nasal epithelial cells obtained from human volunteers are expanded on coated tissue culture plates, and then transferred onto cell culture inserts. Upon reaching confluency, cells continue to be cultured at the air-liquid interface (ALI), for several weeks, which creates more physiologically relevant conditions. The ALI culture condition uses defined media leading to a differentiated epithelium that exhibits morphological and functional characteristics similar to the human nasal epithelium, with both ciliated and mucus producing cells. Tissue culture inserts with differentiated nasal epithelial cells can be manipulated in a variety of ways depending on the research questions (treatment with pharmacological agents, transduction with lentiviral vectors, exposure to gases, or infection with microbial agents) and analyzed for numerous different endpoints ranging from cellular and molecular pathways, functional changes, morphology, etc. In vitro models of differentiated human nasal epithelial

  18. Culturing of human nasal epithelial cells at the air liquid interface.

    PubMed

    Müller, Loretta; Brighton, Luisa E; Carson, Johnny L; Fischer, William A; Jaspers, Ilona

    2013-10-08

    In vitro models using human primary epithelial cells are essential in understanding key functions of the respiratory epithelium in the context of microbial infections or inhaled agents. Direct comparisons of cells obtained from diseased populations allow us to characterize different phenotypes and dissect the underlying mechanisms mediating changes in epithelial cell function. Culturing epithelial cells from the human tracheobronchial region has been well documented, but is limited by the availability of human lung tissue or invasiveness associated with obtaining the bronchial brushes biopsies. Nasal epithelial cells are obtained through much less invasive superficial nasal scrape biopsies and subjects can be biopsied multiple times with no significant side effects. Additionally, the nose is the entry point to the respiratory system and therefore one of the first sites to be exposed to any kind of air-borne stressor, such as microbial agents, pollutants, or allergens. Briefly, nasal epithelial cells obtained from human volunteers are expanded on coated tissue culture plates, and then transferred onto cell culture inserts. Upon reaching confluency, cells continue to be cultured at the air-liquid interface (ALI), for several weeks, which creates more physiologically relevant conditions. The ALI culture condition uses defined media leading to a differentiated epithelium that exhibits morphological and functional characteristics similar to the human nasal epithelium, with both ciliated and mucus producing cells. Tissue culture inserts with differentiated nasal epithelial cells can be manipulated in a variety of ways depending on the research questions (treatment with pharmacological agents, transduction with lentiviral vectors, exposure to gases, or infection with microbial agents) and analyzed for numerous different endpoints ranging from cellular and molecular pathways, functional changes, morphology, etc. In vitro models of differentiated human nasal epithelial

  19. Mechanics of airflow in the human nasal airways.

    PubMed

    Doorly, D J; Taylor, D J; Schroter, R C

    2008-11-30

    The mechanics of airflow in the human nasal airways is reviewed, drawing on the findings of experimental and computational model studies. Modelling inevitably requires simplifications and assumptions, particularly given the complexity of the nasal airways. The processes entailed in modelling the nasal airways (from defining the model, to its production and, finally, validating the results) is critically examined, both for physical models and for computational simulations. Uncertainty still surrounds the appropriateness of the various assumptions made in modelling, particularly with regard to the nature of flow. New results are presented in which high-speed particle image velocimetry (PIV) and direct numerical simulation are applied to investigate the development of flow instability in the nasal cavity. These illustrate some of the improved capabilities afforded by technological developments for future model studies. The need for further improvements in characterising airway geometry and flow together with promising new methods are briefly discussed.

  20. Shape of the human nasal cavity promotes retronasal smell

    NASA Astrophysics Data System (ADS)

    Trastour, Sophie; Melchionna, Simone; Mishra, Shruti; Zwicker, David; Lieberman, Daniel E.; Kaxiras, Efthimios; Brenner, Michael P.

    2015-11-01

    Humans are exceptionally good at perceiving the flavor of food. Flavor includes sensory input from taste receptors but is dominated by olfactory (smell) receptors. To smell food while eating, odors must be transported to the nasal cavity during exhalation. Olfactory performance of this retronasal route depends, among other factors, on the position of the olfactory receptors and the shape of the nasal cavity. One biological hypothesis is that the derived configuration of the human nasal cavity has resulted in a greater capacity for retronasal smell, hence enhanced flavor perception. We here study the air flow and resulting odor deposition as a function of the nasal geometry and the parameters of exhalation. We perform computational fluid dynamics simulations in realistic geometries obtained from CT scans of humans. Using the resulting flow fields, we then study the deposition of tracer particles in the nasal cavity. Additionally, we derive scaling laws for the odor deposition rate as a function of flow parameters and geometry using boundary layer theory. These results allow us to assess which changes in the evolution of the human nose led to significant improvements of retronasal smell.

  1. Human nasal mucosal changes after exposure to urban pollution.

    PubMed Central

    Calderon-Garcidueñas, L; Rodriguez-Alcaraz, A; Garcia, R; Sanchez, G; Barragan, G; Camacho, R; Ramirez, L

    1994-01-01

    Millions of people worldwide are living in areas where ozone (O3) concentrations exceed health standards (an hourly average of 235 micrograms/m3/0.12 ppm, not to be exceeded more than once per year). Ozone induces acute nasal inflammatory responses and significant epithelial lesions in experimental animals and humans. To determine the nasal effects of a 15-day exposure to an urban polluted atmosphere with O3 as the main pollutant, we studied a population of healthy, young males newly arrived to southwest metropolitan Mexico City (SWMMC). The study included 49 non-smoking residents in an unpolluted port, Veracruz City; 14 subjects stayed in the port and served as controls, while 35 subjects traveled to SWMMC and had serial nasal lavages at different times after arriving in SWMMC. Subjects had exposures to ambient O3 an average of 10.2 hr/day, with a total cumulative O3 exposure of 10.644 ppm.hr. Nasal inflammatory responses, polymorphonuclear leukocyte PMN-CD11b surface expression, rhinoscopic changes, and respiratory symptoms were evaluated. Exposed subjects had massive nasal epithelial shedding and significant responses in PMN nasal influx (p < 0.00001) and in PMN-CD11b expression (p < 0.05). Cumulative O3 exposure correlated with respiratory symptoms, PMNs (rs = 0.2374, p < 0.01), and CD11b (rs = 0.3094, p < 0.01); 94% of exposed subjects experienced respiratory symptoms, and 97% left the city with an abnormal nasal mucosa by rhinoscopy. Nasal epithelial changes persisted 2 weeks after the exposed subjects returned to their nonpolluted environment. Exposure to an urban polluted atmosphere induces significant and persistent nasal epithelial alterations in healthy subjects.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 1. Figure 2. A Figure 2. B Figure 2. C Figure 2. D Figure 2. E Figure 2. F Figure 3. A Figure 3. B Figure 4. A Figure 4. B Figure 5. A Figure 5. B PMID:7713020

  2. Effects of nasal drug delivery device and its orientation on sprayed particle deposition in a realistic human nasal cavity.

    PubMed

    Tong, Xuwen; Dong, Jingliang; Shang, Yidan; Inthavong, Kiao; Tu, Jiyuan

    2016-10-01

    In this study, the effects of nasal drug delivery device and the spray nozzle orientation on sprayed droplets deposition in a realistic human nasal cavity were numerically studied. Prior to performing the numerical investigation, an in-house designed automated actuation system representing mean adults actuation force was developed to produce realistic spray plume. Then, the spray plume development was filmed by high speed photography system, and spray characteristics such as spray cone angle, break-up length, and average droplet velocity were obtained through off-line image analysis. Continuing studies utilizing those experimental data as boundary conditions were applied in the following numerical spray simulations using a commercially available nasal spray device, which was inserted into a realistic adult nasal passage with external facial features. Through varying the particle releasing direction, the deposition fractions of selected particle sizes on the main nasal passage for targeted drug delivery were compared. The results demonstrated that the middle spray direction showed superior spray efficiency compared with upper or lower directions, and the 10µm agents were the most suitable particle size as the majority of sprayed agents can be delivered to the targeted area, the main passage. This study elaborates a comprehensive approach to better understand nasal spray mechanism and evaluate its performance for existing nasal delivery practices. Results of this study can assist the pharmaceutical industry to improve the current design of nasal drug delivery device and ultimately benefit more patients through optimized medications delivery. PMID:27509293

  3. Effects of nasal drug delivery device and its orientation on sprayed particle deposition in a realistic human nasal cavity.

    PubMed

    Tong, Xuwen; Dong, Jingliang; Shang, Yidan; Inthavong, Kiao; Tu, Jiyuan

    2016-10-01

    In this study, the effects of nasal drug delivery device and the spray nozzle orientation on sprayed droplets deposition in a realistic human nasal cavity were numerically studied. Prior to performing the numerical investigation, an in-house designed automated actuation system representing mean adults actuation force was developed to produce realistic spray plume. Then, the spray plume development was filmed by high speed photography system, and spray characteristics such as spray cone angle, break-up length, and average droplet velocity were obtained through off-line image analysis. Continuing studies utilizing those experimental data as boundary conditions were applied in the following numerical spray simulations using a commercially available nasal spray device, which was inserted into a realistic adult nasal passage with external facial features. Through varying the particle releasing direction, the deposition fractions of selected particle sizes on the main nasal passage for targeted drug delivery were compared. The results demonstrated that the middle spray direction showed superior spray efficiency compared with upper or lower directions, and the 10µm agents were the most suitable particle size as the majority of sprayed agents can be delivered to the targeted area, the main passage. This study elaborates a comprehensive approach to better understand nasal spray mechanism and evaluate its performance for existing nasal delivery practices. Results of this study can assist the pharmaceutical industry to improve the current design of nasal drug delivery device and ultimately benefit more patients through optimized medications delivery.

  4. Transfer of human nasal papilloma into nude mice.

    PubMed

    Riglar, C; Mackay, I R; Burns, G F; Dowling, J P; Millar, H S

    1984-08-01

    We transferred tumor tissue from two inverted schneiderian nasal papillomas to hypothymic nude mice. Tissue from one tumor, which later underwent malignant change, was transferred three times. Forty days lapsed before growth was evident, with a subsequent period of rapid growth. Histologic appearances of the primary tumor and xenografts were similar. Although the data are derived from only two cases, our findings suggest that the capacity of these tumors to grow in nude mice may be an index of their malignant potential.

  5. Effects of endogenous formaldehyde in nasal tissues on inhaled formaldehyde dosimetry predictions in the rat, monkey, and human nasal passages.

    PubMed

    Schroeter, Jeffry D; Campbell, Jerry; Kimbell, Julia S; Conolly, Rory B; Clewell, Harvey J; Andersen, Melvin E

    2014-04-01

    Formaldehyde is a nasal carcinogen in rodents at high doses and is an endogenous compound that is present in all living cells. Due to its high solubility and reactivity, quantitative risk estimates for inhaled formaldehyde have relied on internal dose estimates in the upper respiratory tract. Dosimetry calculations are complicated by the presence of endogenous formaldehyde concentrations in the respiratory mucosa. Anatomically accurate computational fluid dynamics (CFD) models of the rat, monkey, and human nasal passages were used to simulate uptake of inhaled formaldehyde. An epithelial structure was implemented in the nasal CFD models to estimate formaldehyde absorption from air:tissue partitioning, species-specific metabolism, first-order clearance, DNA binding, and endogenous formaldehyde production. At an exposure concentration of 1 ppm, predicted formaldehyde nasal uptake was 99.4, 86.5, and 85.3% in the rat, monkey, and human, respectively. Endogenous formaldehyde in nasal tissues did not significantly affect wall mass flux or nasal uptake predictions at exposure concentrations > 500 ppb; however, reduced nasal uptake was predicted at lower exposure concentrations. At an exposure concentration of 1 ppb, predicted nasal uptake was 17.5 and 42.8% in the rat and monkey; net desorption of formaldehyde was predicted in the human model. The nonlinear behavior of formaldehyde nasal absorption will affect the dose-response analysis and subsequent risk estimates at low exposure concentrations. Updated surface area partitioning of nonsquamous epithelium and average flux values in regions where DNA-protein cross-links and cell proliferation rates were measured in rats and monkeys are reported for use in formaldehyde risk models of carcinogenesis.

  6. Multifocal primary cutaneous extranodal NK/T lymphoma nasal type*

    PubMed Central

    de Vasconcelos, Pedro; Ferreira, Cristina; Soares-Almeida, Luís; Filipe, Paulo

    2016-01-01

    Nasal type extranodal NK/T-cell lymphoma is a distinct entity according to the World Health Organization classification. Although 60% to 90% of patients with this disease present with a destructive mass in the midline facial tissues, it may also primarily or secondarily involve extranasal sites, like the skin. We report the case of a 77-year-old patient that came to our department with erythematous plaques of the right leg and eczematous lesions of the trunk. These lesions were biopsied and the patient was diagnosed with extranodal NK/T-cell lymphoma, nasal type. He was treated with multi-agent systemic chemotherapy but died 5 months after diagnosis. This case highlights the rarity and variability of cutaneous features of this disease and its aggressive course and poor prognosis. PMID:27192524

  7. Immediate effect of benzalkonium chloride in decongestant nasal spray on the human nasal mucosal temperature.

    PubMed

    Lindemann, J; Leiacker, R; Wiesmiller, K; Rettinger, G; Keck, T

    2004-08-01

    Benzalkonium chloride is a preservative commonly used in nasal decongestant sprays. It has been suggested that benzalkonium chloride may be harmful to the nasal mucosa. Decongestion with the vasoconstrictor xylometazoline containing benzalkonium chloride has been shown to cause a significant reduction of the nasal mucosal temperature. The purpose of the present study was to determine the short-term influence of xylometazoline nasal spray with and without benzalkonium chloride on the nasal mucosal temperature. Healthy volunteers (30) were included in the study. Fifteen volunteers received xylometazoline nasal spray (1.0 mg/mL) containing benzalkonium chloride (0.1 mg/mL) and 15 age-matched subjects, received xylometazoline nasal spray without benzalkonium chloride. Using a miniaturized thermocouple the septal mucosal temperature was continuously measured at defined intranasal detection sites before and after application of the nasal spray. The mucosal temperature values did not significantly differ between the group receiving xylometazoline containing benzalkonium chloride and the group receiving xylometazoline spray without benzalkonium chloride before and after decongestion (P > 0.05). In both study groups septal mucosal temperatures significantly decreased after decongestion (P < 0.05) because of a reduction of the nasal mucosal blood flow following vasoconstriction. This study indicates that benzalkonium chloride itself does not seem to influence nasal blood flow and nasal mucosal temperature in topical nasal decongestants. PMID:15270822

  8. Bioactivation of the Nasal Toxicant 2,6-Dichlorobenzonitrile: An Assessment of Metabolic Activity in Human Nasal Mucosa and Identification of Indicators of Exposure and Potential Toxicity

    PubMed Central

    Xie, Fang; D’Agostino, Jaime; Zhou, Xin; Ding, Xinxin

    2013-01-01

    The herbicide 2,6-dichlorobenzonitrile (DCBN) is a potent nasal toxicant in rodents; however it is not known whether DCBN causes similar nasal toxicity in humans. The tissue-selective toxicity of DCBN in mouse nasal mucosa is largely dependent on target tissue bioactivation by CYP2A5. The human orthologs of CYP2A5, CYP2A6 and CYP2A13, are both expressed in nasal mucosa, and are capable of activating DCBN. In this study, we directly determined the ability of human nasal mucosa to bioactivate DCBN. We also tested the suitability of a glutathione conjugate of DCBN (GS-DCBN) or its derivatives as biomarkers of DCBN exposure and nasal toxicity in mouse models. We found that human fetal nasal-mucosa microsomes catalyze the formation of GS-DCBN, with a Km value comparable to that of adult mouse nasal-mucosa microsomes. The activity of the human nasal-mucosa microsomes was inhibited by 8-methoxypsoralen, a known CYP2A inhibitor. GS-DCBN and its metabolites were detected in the nasal mucosa and nasal-wash fluid obtained from DCBN-treated mice, in amounts that increased with escalations in DCBN dose, and they were all still detectable at 24 h after a DCBN treatment (at 10 mg/kg). Further studies in Cyp2a5-null mice indicated that GS-DCBN and its metabolites in nasal-wash fluid were generated in the nasal mucosa, rather than in other organs. Thus, our data indicate for the first time that the human nasal mucosa is capable of bioactivating DCBN, and that GS-DCBN and its metabolites in nasal-wash fluid may collectively serve as indicators of DCBN exposure and potential nasal toxicity in humans. PMID:23360412

  9. Toxic rhinitis-induced changes of human nasal mucosa innervation.

    PubMed

    Groneberg, David A; Heppt, Werner; Cryer, Annette; Wussow, Anke; Peiser, Christian; Zweng, Martina; Dinh, Q Thai; Witt, Christian; Fischer, Axel

    2003-01-01

    Irritative toxic rhinitis is a nasal disorder induced by chemical compounds like ozone, formaldehyde, nickel, chrome, solvents and tobacco smoke. These noxious stimuli may have effects on the nasal innervation leading to a cascade of neuro-immune interactions and an augmentation of the symptoms. Here we examined changes in the neuropeptide content of mucosal parasympathetic, sympathetic and sensory nerves of patients with toxic rhinitis caused by chronic cigarette smoke exposure. Semiquantitative immunohistochemistry using antibodies against calcitonin gene-related peptide (CGRP), substance P (SP), neuropeptide tyrosine (NPY), and vasoactive intestinal peptide (VIP) was carried out on cryostat sections of human nasal mucosa obtained from normal subjects and patients with toxic rhinitis and revealed significant differences between both groups. Toxic rhinitis patients had significantly elevated expression scores for VIP (2.83 +/- 0.31 vs 1.27 +/- 0.47 control group) and NPY (3.17 +/- 0.31 vs 0.91 +/- 0.37 control group) revealing an increase of mediators in distinct subpopulations of airway nerves. In summary, the present studies indicate a differential participation of subclasses of mucosal nerves in the pathophysiology of toxic rhinitis. Airway innervation may have a major role in the pathophysiology of toxic rhinitis associated with chronic cigarette smoke exposure.

  10. Synchronous double primary cancer of the lung and nasal vestibule: A case report and literature review

    PubMed Central

    JI, HUAI JUN; ZANG, QI; WANG, WEI; SUN, NING BO; CAO, MING; ZHU, QIANG; JIANG, ZHONG MIN

    2016-01-01

    Squamous cell carcinoma (SCC) of the nasal vestibule is a rare tumor entity, and its occurrence combined with lung cancer is even rarer. Thus, several patients are often initially misdiagnosed or remain undiagnosed. This is the case report of a 55-year-old male patient who presented to our hospital with a neoplasm in the left lung. The patient was treated with left upper pulmonary lobectomy and the subsequent histopathological examination of the surgical specimen revealed a poorly differentiated SCC. On postoperative week 4, the patient presented with purulent and bloody discharge from the left nostril and was misdiagnosed with an upper jaw cyst. After another 3 weeks, the patient was re-admitted to the hospital with a mass of left nostril and nasal congestion. Tru-Cut biopsies from the nasal area and histopathological examination revealed a moderately differentiated SCC. According to the clinical presentation and the histopathological findings, the patient was diagnosed with double primary cancer of the lung and the nasal vestibule. The mass of the left nostril was significantly reduced in size with radiotherapy. To the best of our knowledge, there is no similar case previously reported in the literature. Due to the rarity of scc of the nasal vestibule concomittant with lung cancer, we herein present this case report with a review of the relevant literature and investigation of the clinical characteristics. PMID:27123284

  11. Exhaled nasal nitric oxide output is reduced in humans at night during the sleep period.

    PubMed

    O'Hearn, Daniel J; Giraud, George D; Sippel, Jeffrey M; Edwards, Chad; Chan, Benjamin; Holden, William E

    2007-04-16

    The physiologic function of nasal nitric oxide (NO) release is unknown. In prior experiments, topical NG-nitro-L-arginine methyl ester (L-NAME) on nasal mucosa reduced exhaled nasal NO output and caused daytime sleepiness. We hypothesized that nasal NO output is reduced at night during the sleep period. We measured exhaled nasal NO concentration and minute ventilation and calculated nasal NO output in humans over 24 h. Daytime awake NO output was greater than NO output at night during sleep or transient wakefulness. Exhaled NO concentration decreased during sleep along with minute ventilation. A daytime voluntary reduction in minute ventilation also decreased nasal NO output but exhaled NO concentration increased. Nasal NO output was not changed by body position. We conclude that exhaled nasal NO output is decreased at night due to decreased mass flow of NO into nasal air in addition to decreased minute ventilation. Our findings suggest a role of nasal NO in sleep or in the physiologic processes accompanying sleep.

  12. Transport and Deposition of Welding Fume Agglomerates in a Realistic Human Nasal Airway.

    PubMed

    Tian, Lin; Inthavong, Kiao; Lidén, Göran; Shang, Yidan; Tu, Jiyuan

    2016-07-01

    Welding fume is a complex mixture containing ultra-fine particles in the nanometer range. Rather than being in the form of a singular sphere, due to the high particle concentration, welding fume particles agglomerate into long straight chains, branches, or other forms of compact shapes. Understanding the transport and deposition of these nano-agglomerates in human respiratory systems is of great interest as welding fumes are a known health hazard. The neurotoxin manganese (Mn) is a common element in welding fumes. Particulate Mn, either as soluble salts or oxides, that has deposited on the olfactory mucosa in human nasal airway is transported along the olfactory nerve to the olfactory bulb within the brain. If this Mn is further transported to the basal ganglia of the brain, it could accumulate at the part of the brain that is the focal point of its neurotoxicity. Accounting for various dynamic shape factors due to particle agglomeration, the current computational study is focused on the exposure route, the deposition pattern, and the deposition efficiency of the inhaled welding fume particles in a realistic human nasal cavity. Particular attention is given to the deposition pattern and deposition efficiency of inhaled welding fume agglomerates in the nasal olfactory region. For particles in the nanoscale, molecular diffusion is the dominant transport mechanism. Therefore, Brownian diffusion, hydrodynamic drag, Saffman lift force, and gravitational force are included in the model study. The deposition efficiencies for single spherical particles, two kinds of agglomerates of primary particles, two-dimensional planar and straight chains, are investigated for a range of primary particle sizes and a range of number of primary particles per agglomerate. A small fraction of the inhaled welding fume agglomerates is deposited on the olfactory mucosa, approximately in the range 0.1-1%, and depends on particle size and morphology. The strong size dependence of the deposition

  13. Early depictions of the human anterior nasal septum.

    PubMed

    Pirsig, Wolfgang; Sokiranski, Roman

    2006-06-01

    In the literature, remarks on the depiction of the anterior nasal septum in prehistoric times cannot be found. Studying works of art from some archaeological sites of Asia, Asia Minor, Near East, Egypt, and Southeastern Europe the anatomical depiction of the columella and the nostrils in human figures are shown. These figures or heads, partly appearing as masks, were made of ivory, stone, marble, terracotta, steatite, reeds and clay, or of burned limestone. Faces and figures sculpted in the time between the Upper Palaeolithic (30,000 - 25,000 BC) and the Early Bronze Age (3,300 - 2,400 BC) are presented as examples of our ancestors' outstanding skill to create works of art with an astonishing ability to observe anatomical details. The tendency to create a human nose in a natural manner can already be recognized in the figurines of the Upper Palaeolithic.

  14. Nociceptive and reflexive responses recorded from the human nasal mucosa.

    PubMed

    Thürauf, N; Hummel, T; Kettenmann, B; Kobal, G

    1993-12-01

    Slow electrical responses after painful stimulation with carbon dioxide, which is known to specifically activate nociceptors, were recorded from the nasal respiratory epithelium in human volunteers. The negative component of these potentials (negative mucosal potential NMP) has been hypothesized to be a summated receptor potential. The aim of the present study was to characterize the stimulus-response relationship and to demonstrate that the NMP is restricted to the site of stimulation, i.e., to the area of activated nociceptors. Eight healthy volunteers participated in the experiments. The NMP was recorded from the nasal septum and intensity ratings were obtained for each of the applied stimuli. To control for autonomic reflexes, blood flow changes were additionally recorded using a laser Doppler flow meter. Both increasing stimulus duration and increasing concentration produced a significant increase in the subjects' intensity estimates, in the NMP's amplitudes and areas under the curve, but did not change the local blood flow in a dose-related manner. The odorant hydrogen sulphide, which was used as a non-painful control stimulus, did not elicit mucosal potentials or produce blood flow changes. By recording both ipsi- and contralaterally it was also demonstrated that the NMP could only be obtained at the stimulated site, thus supporting the hypothesis that the NMP is a specific peripheral nociceptive correlate.

  15. A Recently Established Murine Model of Nasal Polyps Demonstrates Activation of B Cells, as Occurs in Human Nasal Polyps.

    PubMed

    Kim, Dong-Young; Lee, Sun Hye; Carter, Roderick G; Kato, Atsushi; Schleimer, Robert P; Cho, Seong H

    2016-08-01

    Animal model systems are invaluable for examining human diseases. Our laboratory recently established a mouse model of nasal polyps (NPs) and investigated similarities and differences between this mouse model and human NPs. We especially focus on the hypothesis that B cell activation occurs during NP generation in the murine model. After induction of ovalbumin-induced allergic rhinosinusitis, 6% ovalbumin and Staphylococcus aureus enterotoxin B (10 ng) were instilled into the nasal cavity of mice three times per week for 8 weeks. The development of structures that somewhat resemble NPs (which we will refer to as NPs) was confirmed by hematoxylin and eosin staining. The mRNA and protein levels of various inflammatory cell markers and mediators were measured by real-time PCR in nasal tissue and by ELISA in nasal lavage fluid (NLF), respectively. Total Ig isotype levels in NLF were also quantitated using the Mouse Ig Isotyping Multiplex kit (EMD Millipore, Billerica, MA) on a Luminex 200 instrument (Life Technologies, Grand Island, NY). Similar to human NPs, there were significant increases in gene expression of inflammatory cell markers, such as CD19, CD138, CD11c, and mast cell protease-6 in nasal tissue samples of the NP group compared with those of the control group. In further investigations of B cell activation, mRNA expressions of B cell activating factor and a proliferation-inducing ligand were found to be significantly increased in mouse NP tissue. B cell-activating factor protein concentration and IgA and IgG1 levels in NLF were significantly higher in the NP group compared with the control group. In this study, the NP mouse model demonstrated enhanced B cell responses, which are reminiscent of B cell responses in human NPs. PMID:27163839

  16. Nasal High-Flow Therapy for Primary Respiratory Support in Preterm Infants.

    PubMed

    Roberts, Calum T; Owen, Louise S; Manley, Brett J; Frøisland, Dag H; Donath, Susan M; Dalziel, Kim M; Pritchard, Margo A; Cartwright, David W; Collins, Clare L; Malhotra, Atul; Davis, Peter G

    2016-09-22

    Background Treatment with nasal high-flow therapy has efficacy similar to that of nasal continuous positive airway pressure (CPAP) when used as postextubation support in neonates. The efficacy of high-flow therapy as the primary means of respiratory support for preterm infants with respiratory distress has not been proved. Methods In this international, multicenter, randomized, noninferiority trial, we assigned 564 preterm infants (gestational age, ≥28 weeks 0 days) with early respiratory distress who had not received surfactant replacement to treatment with either nasal high-flow therapy or nasal CPAP. The primary outcome was treatment failure within 72 hours after randomization. Noninferiority was determined by calculating the absolute difference in the risk of the primary outcome; the chosen margin of noninferiority was 10 percentage points. Infants in whom high-flow therapy failed could receive rescue CPAP; infants in whom CPAP failed were intubated and mechanically ventilated. Results Trial recruitment stopped early at the recommendation of the independent data and safety monitoring committee because of a significant difference in the primary outcome between treatment groups. Treatment failure occurred in 71 of 278 infants (25.5%) in the high-flow group and in 38 of 286 infants (13.3%) in the CPAP group (risk difference, 12.3 percentage points; 95% confidence interval [CI], 5.8 to 18.7; P<0.001). The rate of intubation within 72 hours did not differ significantly between the high-flow and CPAP groups (15.5% and 11.5%, respectively; risk difference, 3.9 percentage points; 95% CI, -1.7 to 9.6; P=0.17), nor did the rate of adverse events. Conclusions When used as primary support for preterm infants with respiratory distress, high-flow therapy resulted in a significantly higher rate of treatment failure than did CPAP. (Funded by the National Health and Medical Research Council and others; Australian New Zealand Clinical Trials Registry number, ACTRN

  17. Nasal High-Flow Therapy for Primary Respiratory Support in Preterm Infants.

    PubMed

    Roberts, Calum T; Owen, Louise S; Manley, Brett J; Frøisland, Dag H; Donath, Susan M; Dalziel, Kim M; Pritchard, Margo A; Cartwright, David W; Collins, Clare L; Malhotra, Atul; Davis, Peter G

    2016-09-22

    Background Treatment with nasal high-flow therapy has efficacy similar to that of nasal continuous positive airway pressure (CPAP) when used as postextubation support in neonates. The efficacy of high-flow therapy as the primary means of respiratory support for preterm infants with respiratory distress has not been proved. Methods In this international, multicenter, randomized, noninferiority trial, we assigned 564 preterm infants (gestational age, ≥28 weeks 0 days) with early respiratory distress who had not received surfactant replacement to treatment with either nasal high-flow therapy or nasal CPAP. The primary outcome was treatment failure within 72 hours after randomization. Noninferiority was determined by calculating the absolute difference in the risk of the primary outcome; the chosen margin of noninferiority was 10 percentage points. Infants in whom high-flow therapy failed could receive rescue CPAP; infants in whom CPAP failed were intubated and mechanically ventilated. Results Trial recruitment stopped early at the recommendation of the independent data and safety monitoring committee because of a significant difference in the primary outcome between treatment groups. Treatment failure occurred in 71 of 278 infants (25.5%) in the high-flow group and in 38 of 286 infants (13.3%) in the CPAP group (risk difference, 12.3 percentage points; 95% confidence interval [CI], 5.8 to 18.7; P<0.001). The rate of intubation within 72 hours did not differ significantly between the high-flow and CPAP groups (15.5% and 11.5%, respectively; risk difference, 3.9 percentage points; 95% CI, -1.7 to 9.6; P=0.17), nor did the rate of adverse events. Conclusions When used as primary support for preterm infants with respiratory distress, high-flow therapy resulted in a significantly higher rate of treatment failure than did CPAP. (Funded by the National Health and Medical Research Council and others; Australian New Zealand Clinical Trials Registry number, ACTRN

  18. Phagocytosis of Aspergillus fumigatus conidia by primary nasal epithelial cells in vitro

    PubMed Central

    Botterel, Françoise; Gross, Karine; Ibrahim-Granet, Oumaïma; Khoufache, Khaled; Escabasse, Virginie; Coste, André; Cordonnier, Catherine; Escudier, Estelle; Bretagne, Stéphane

    2008-01-01

    Background Invasive aspergillosis, which is mainly caused by the fungus Aspergillus fumigatus, is an increasing problem in immunocompromised patients. Infection occurs by inhalation of airborne conidia, which are first encountered by airway epithelial cells. Internalization of these conidia into the epithelial cells could serve as a portal of entry for this pathogenic fungus. Results We used an in vitro model of primary cultures of human nasal epithelial cells (HNEC) at an air-liquid interface. A. fumigatus conidia were compared to Penicillium chrysogenum conidia, a mould that is rarely responsible for invasive disease. Confocal microscopy, transmission electron microscopy, and anti-LAMP1 antibody labeling studies showed that conidia of both species were phagocytosed and trafficked into a late endosomal-lysosomal compartment as early as 4 h post-infection. In double immunolabeling experiments, the mean percentage of A. fumigatus conidia undergoing phagocytosis 4 h post-infection was 21.8 ± 4.5%. Using combined staining with a fluorescence brightener and propidium iodide, the mean rate of phagocytosis was 18.7 ± 9.3% and the killing rate 16.7 ± 7.5% for A. fumigatus after 8 h. The phagocytosis rate did not differ between the two fungal species for a given primary culture. No germination of the conidia was observed until 20 h of observation. Conclusion HNEC can phagocytose fungal conidia but killing of phagocytosed conidia is low, although the spores do not germinate. This phagocytosis does not seem to be specific to A. fumigatus. Other immune cells or mechanisms are required to kill A. fumigatus conidia and to avoid further invasion. PMID:18564423

  19. In vivo deposition of ultrafine aerosols in human nasal and oral airways

    SciTech Connect

    Yeh, Hsu-Chi; Swift, D.L.; Simpson, S.Q.

    1995-12-01

    The extrathoracic airways, including the nasal passage, oral passage, pharynx, and larynx, are the first targets for inhaled particles and provide an important defense for the lung. Understanding the deposition efficiency of the nasal and oral passages is therefore crucial for assessing doses of inhaled particles to the extrathoracic airways and the lung. Significant inter-subject variability in nasal deposition has been shown in recent studies by Rasmussen, T.R. et al, using 2.6 {mu}m particles in 10 human subjects and in our preliminary studies using 0.004-0.15 {mu}m particles in four adult volunteers. No oral deposition was reported in either of these studies. Reasons for the intersubject variations have been frequently attributed to the geometry of the nasal passages. The aims of the present study were to measure in vivo the nasal airway dimensions and the deposition of ultrafine aerosols in both the nasal and oral passages, and to determine the relationship between nasal airway dimensions and aerosol deposition. A statistical procedure incorporated with the diffusion theory was used to model the dimensional features of the nasal airways which may be responsible for the biological variability in particle deposition. In summary, we have correlated deposition of particles in the size range of 0.004 to 0.15 {mu}m with the nasal dimensions of each subject.

  20. 132 Characterization of 2 Epithelial Cell Air-Liquid Interface (ALI) Culture Models for Human Healthy Nasal Mucosa and Nasal Polyps

    PubMed Central

    de Borja Callejas, Fco; Martínez-Antón, Asunción; Roca-Ferrer, Jordi; Cortijo, Julio; Picado, César; Mullol, Joaquim

    2012-01-01

    Background Primary human airway epithelial cells, when submerged in culture, undergo a dedifferentiation with loss of many features of the in vivo airway epithelium. However, when cultured in an air-liquid interface (ALI), cells develop a well-differentiated, polarized, and pseudostratified epithelium. The aim of the current study was to characterize the mucociliary differentiation of human nasal mucosa and polyp epithelial cells cultured using an ALI system. Methods Nasal mucosa (NM, n = 3) and nasal polyps (NP, n = 3) were obtained from patients undergoing nasal corrective surgery and endoscopic sinus surgery, respectively. Epithelial cells were obtained from the explant method, and differentiated in ALI culture during 28 days. Cultures were studied at different time points (0, 7, 14, 21, and 28 days): tissue ultrastructure by scanning electron microscopy (SEM) and transmission electron microscopy (TEM); mucous (MUC5AC, MUC5B) and serous (lactoferrin) cell secretion by ELISA; and cytokeratin 18 (epithelial marker), β-tubulin IV (cilia marker), MUC5AC (goblet cell marker), and p63 (basal cell marker) expression by immunocytochemistry. Results In both NM and NP ALI cultures and at days 14 and 28, a pseudostratified epithelium with ciliated, mucus-secreting and basal cells was observed, and expression of cytokeratin 18, b-tubulin IV, MUC5AC and p63 was detected. In NP cultures, both MUC5AC (day 14: 2.2 ± 0.1-folds; day 28: 3.6-fold ± 0.7-fold) and MUC5B (day 14: 3.2-fold ± 0.6-fold; day 28: 3.1-fold ± 1-fold) increased over time compared to day 0 (P < 0.05). In NM cultures, only MUC5B (day 14: 3.9-fold ± 0.9-fold; day 28: 3.4-fold ± 0.4-fold; P < 0.05) but not MUC5AC increased over time compared to day 0 (P < 0.05). Secretion of lactoferrin was present but showed no changes over time in either NM or NP ALI cultures. Conclusions Epithelial cell ALI cultures provide a well-differentiated human nasal mucosa and polyp tissues that may be used as an in vitro model

  1. Differential induction of innate defense antimicrobial peptides in primary nasal epithelial cells upon stimulation with inflammatory cytokines, Th17 cytokines or bacterial conditioned medium from Staphylococcus aureus isolates.

    PubMed

    Burgey, Christine; Kern, Winfried V; Römer, Winfried; Rieg, Siegbert

    2016-01-01

    To date it is incompletely understood why half of the human population is intrinsically resistant to Staphylococcus aureus colonization whereas the other half is intermittently or permanently colonized. Nasal colonization represents the primary niche for S. aureus. We therefore investigated whether primary nasal epithelial cells (HNEC) express antimicrobial peptides (AMPs) upon stimulation by inflammatory cytokines or bacterial conditioned medium (BCM) of different colonizing and invasive staphylococci. Stimulation with classical cytokines (IL-1β, TNF-α, IFN-γ) potently induced hBD-3 and RNase7 in HNEC. Th17 cytokines (IL-17A, IL-17F, IL-22) yielded comparably weak hBD-3 and RNase7 induction and no synergistic effects with classical cytokines. BCM of S. aureus and Staphylococcus epidermidis isolates moderately induced hBD3 and RNase7 mRNA expression without significant differences when comparing colonizing vs. invasive isolates. Our results indicate that HNEC contribute to the innate defense by secretion of an AMP-containing chemical defense shield along the nasal mucosa i.e. within the primary colonization niche of S. aureus. Further studies are needed to investigate whether a deficient AMP expression in the nasal mucosa may be related to different S. aureus carrier states. AMPs or AMP-inducing agents may be promising candidates for future topical decolonization regimens that aim to prevent invasive S. aureus infections.

  2. Deformities of the nasal septum in human foetuses.

    PubMed

    Ruano-Gil, D; Montserrat-Viladiu, J M; Vilanova-Trías, J; Burgés-Vila, J

    1980-06-01

    In a seris of 50 embryos and foetuses ranging from 20 mm to 190 mm in length two foetuses of 34 and 37 mm (48 to 50 days old) were found, that presented deformities of the septum of the cartilaginous nasal capsule, representing 4% of our material. The deformities consisted of curves of the nasal septum, located to both vomeronasal nerves. We therefore think that this study is interesting because it adds a new factor, the congenital one, to the etiology of deformities of the nasal septum.

  3. Bone-forming capacity of adult human nasal chondrocytes

    PubMed Central

    Pippenger, Benjamin E; Ventura, Manuela; Pelttari, Karoliina; Feliciano, Sandra; Jaquiery, Claude; Scherberich, Arnaud; Walboomers, X Frank; Barbero, Andrea; Martin, Ivan

    2015-01-01

    Nasal chondrocytes (NC) derive from the same multipotent embryological segment that gives rise to the majority of the maxillofacial bone and have been reported to differentiate into osteoblast-like cells in vitro. In this study, we assessed the capacity of adult human NC, appropriately primed towards hypertrophic or osteoblastic differentiation, to form bone tissue in vivo. Hypertrophic induction of NC-based micromass pellets formed mineralized cartilaginous tissues rich in type X collagen, but upon implantation into subcutaneous pockets of nude mice remained avascular and reverted to stable hyaline-cartilage. In the same ectopic environment, NC embedded into ceramic scaffolds and primed with osteogenic medium only sporadically formed intramembranous bone tissue. A clonal study could not demonstrate that the low bone formation efficiency was related to a possibly small proportion of cells competent to become fully functional osteoblasts. We next tested whether the cues present in an orthotopic environment could induce a more efficient direct osteoblastic transformation of NC. Using a nude rat calvarial defect model, we demonstrated that (i) NC directly participated in frank bone formation and (ii) the efficiency of survival and bone formation by NC was significantly higher than that of reference osteogenic cells, namely bone marrow-derived mesenchymal stromal cells. This study provides a proof-of-principle that NC have the plasticity to convert into bone cells and thereby represent an easily available cell source to be further investigated for craniofacial bone regeneration. PMID:25689393

  4. Transport and Deposition of Welding Fume Agglomerates in a Realistic Human Nasal Airway.

    PubMed

    Tian, Lin; Inthavong, Kiao; Lidén, Göran; Shang, Yidan; Tu, Jiyuan

    2016-07-01

    Welding fume is a complex mixture containing ultra-fine particles in the nanometer range. Rather than being in the form of a singular sphere, due to the high particle concentration, welding fume particles agglomerate into long straight chains, branches, or other forms of compact shapes. Understanding the transport and deposition of these nano-agglomerates in human respiratory systems is of great interest as welding fumes are a known health hazard. The neurotoxin manganese (Mn) is a common element in welding fumes. Particulate Mn, either as soluble salts or oxides, that has deposited on the olfactory mucosa in human nasal airway is transported along the olfactory nerve to the olfactory bulb within the brain. If this Mn is further transported to the basal ganglia of the brain, it could accumulate at the part of the brain that is the focal point of its neurotoxicity. Accounting for various dynamic shape factors due to particle agglomeration, the current computational study is focused on the exposure route, the deposition pattern, and the deposition efficiency of the inhaled welding fume particles in a realistic human nasal cavity. Particular attention is given to the deposition pattern and deposition efficiency of inhaled welding fume agglomerates in the nasal olfactory region. For particles in the nanoscale, molecular diffusion is the dominant transport mechanism. Therefore, Brownian diffusion, hydrodynamic drag, Saffman lift force, and gravitational force are included in the model study. The deposition efficiencies for single spherical particles, two kinds of agglomerates of primary particles, two-dimensional planar and straight chains, are investigated for a range of primary particle sizes and a range of number of primary particles per agglomerate. A small fraction of the inhaled welding fume agglomerates is deposited on the olfactory mucosa, approximately in the range 0.1-1%, and depends on particle size and morphology. The strong size dependence of the deposition

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

    SciTech Connect

    Rodgers, D.A.; Nikula, K.J.; Avila, K.

    1995-12-01

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

  6. Cephalometric Pattern and Nasal Patency in Children with Primary Snoring: The Evidence of a Direct Correlation

    PubMed Central

    Zicari, Anna Maria; Duse, Marzia; Occasi, Francesca; Luzzi, Valeria; Ortolani, Emanuela; Bardanzellu, Flaminia; Bertin, Serena; Polimeni, Antonella

    2014-01-01

    Introduction Sleep disordered breathing (SDB) might affect craniofacial growth and children with obstructive sleep apnea syndrome present an increase in total and lower anterior heights of the face and a more anterior and inferior position of the hyoid bone when compared to nasal breathers. Objective To investigate the correlation between rhinomanometric and cephalometric parameters in children with primary snoring (PS), without apnea or gas exchange abnormalities. Materials and Methods Thirty children with habitual snoring (16 females and 14 males) aged 4–8 years (mean age 6.85±1.51 years) were selected by a SDB validate questionnaire. All subjects underwent lateral cephalometric, panoramic radiographies. Results In our sample 10 children (33%) had snoring 3 nights/week, 11 (37%) 4–6 nights/week and 9 (30%) every night/week. Overall 7 patients (23.3%) were affected by adenoid hypertrophy (AH), 4 (13.3%) by tonsillar hypertrophy (TH) and 13 (43.3%) by AH and TH. We found a more vertical position of the hyoid bone to the mandibular plane (H⊥VT) in patients with a higher frequency (7.3±2.7 vs 7.6±3.7 vs 10.9±2.5 in children snoring 3 nights/week, 4–6 nights/week and every night/week respectively; p = 0.032). Concerning nasal patency significant correlations were found with ANB (maxillary and jaw position with respect to the cranial base), NS∧Ar (growth predictor), sumangle, FMA (total divergence), SnaSnp∧GoMe (inferior divergence), BaN∧PtGn (facial growth pattern), Phw1_PsP (posterosuperior airway space), AHC3H (the horizontal distance between the most anterosuperior point of the hyoid bone and the third cervical vertebra). Conclusion The present study supports the relationship between nasal obstruction and specific craniofacial characteristics in children with primary snoring and lead us to hypothesize that nasal obstruction might explain the indirect link between snoring and cephalometric alterations. PMID:25360610

  7. Human Papillomavirus (HPV) Prevalence in Nasal and Antrochoanal Polyps and Association with Clinical Data

    PubMed Central

    Knör, Mareike; Tziridis, Konstantin; Agaimy, Abbas; Zenk, Johannes; Wendler, Olaf

    2015-01-01

    Objectives The pathogenesis of sinonasal polyposis remains unclear, in spite of several investigative approaches. Antrochoanal polyps, a subgroup of sinonasal polyposis along with allergic- and chronic-inflammatory nasal polyps, mostly originate from the maxillary sinus and develop as a unilateral, pedunculated mass towards the nasopharynx. The human papillomavirus (HPV) is discussed as a possible causative and influencing factor in development and progression of sinonasal polyposis. This study aims to elucidate HPV frequency in nasal polyps and antrochoanal polyps. Materials and Methods Genomic DNA from 257 tissue specimens (166 nasal polyps, 39 antrochoanal polyps and 52 nasal turbinates) was subjected to three different established HPV- polymerase chain reaction assays, testing for 37 low- and high-risk HPV. In addition, immunohistochemical analyses for HPV16 were carried out, as well as immunohistochemistry and western blots of p16, a biomarker for HPV induced cancer. Results HPV-DNA was detected in 53.8% of antrochoanal polyps, 15.1% of nasal polyps, and 5.8% of nasal turbinates. HPV16 was the predominant type with a detection rate of 76% in nasal polyps and 62% in antrochoanal polyps. Immunohistochemically, HPV positive tissues stained positive for HPV16 antigens and p16 in epithelial cell layers. No significant p16 overexpression was traceable in antrochoanal polyps, nasal polyps and nasal turbinates by western blot. There was no correlation of HPV-status with sex, age, smoking, alcohol consumption or allergic background. Conclusion The present study shows a significant frequency of high-risk type HPV16 in antrochoanal polyps. Absence of oncogenic transformation or correlation of the HPV-status with clinical data suggests a latent superinfection, possibly because of anatomical proximity to the oropharynx. PMID:26509801

  8. Reconstituted Human Upper Airway Epithelium as 3-D In Vitro Model for Nasal Polyposis

    PubMed Central

    de Borja Callejas, Francisco; Martínez-Antón, Asunción; Alobid, Isam; Fuentes, Mireya; Cortijo, Julio; Picado, César

    2014-01-01

    Background Primary human airway epithelial cells cultured in an air-liquid interface (ALI) develop a well-differentiated epithelium. However, neither characterization of mucociliar differentiation overtime nor the inflammatory function of reconstituted nasal polyp (NP) epithelia have been described. Objectives 1st) To develop and characterize the mucociliar differentiation overtime of human epithelial cells of chronic rhinosinusitis with nasal polyps (CRSwNP) in ALI culture system; 2nd) To corroborate that 3D in vitro model of NP reconstituted epithelium maintains, compared to control nasal mucosa (NM), an inflammatory function. Methods Epithelial cells were obtained from 9 NP and 7 control NM, and differentiated in ALI culture for 28 days. Mucociliary differentiation was characterized at different times (0, 7, 14, 21, and 28 days) using ultrastructure analysis by electron microscopy; ΔNp63 (basal stem/progenitor cell), β-tubulin IV (cilia), and MUC5AC (goblet cell) expression by immunocytochemistry; and mucous (MUC5AC, MUC5B) and serous (Lactoferrin) secretion by ELISA. Inflammatory function of ALI cultures (at days 0, 14, and 28) through cytokine (IL-8, IL-1β, IL-6, IL-10, TNF-α, and IL-12p70) and chemokine (RANTES, MIG, MCP-1, IP-10, eotaxin-1, and GM-CSF) production was analysed by CBA (Cytometric Bead Array). Results In both NP and control NM ALI cultures, pseudostratified epithelium with ciliated, mucus-secreting, and basal cells were observed by electron microscopy at days 14 and 28. Displaying epithelial cell re-differentation, β-tubulin IV and MUC5AC positive cells increased, while ΔNp63 positive cells decreased overtime. No significant differences were found overtime in MUC5AC, MUC5B, and lactoferrin secretions between both ALI cultures. IL-8 and GM-CSF were significantly increased in NP compared to control NM regenerated epithelia. Conclusion Reconstituted epithelia from human NP epithelial cells cultured in ALI system provides a 3D in vitro model

  9. Prevalence of human papilloma virus and human herpes virus types 1-7 in human nasal polyposis.

    PubMed

    Zaravinos, Apostolos; Bizakis, John; Spandidos, Demetrios A

    2009-09-01

    This study aimed to investigate the prevalence of human papilloma virus (HPV), herpes simplex virus-1/-2 (HSV-1/-2), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpes virus-6/-7 (HHV-6/-7) in 23 human nasal polyps by applying PCR. Two types of control tissues were used: adjacent inferior/middle turbinates from the patients and inferior/middle turbinates from 13 patients undergoing nasal corrective surgery. EBV was the virus most frequently detected (35%), followed by HPV (13%), HSV-1 (9%), and CMV (4%). The CMV-positive polyp was simultaneously positive for HSV-1. HPV was also detected in the adjacent turbinates (4%) and the adjacent middle turbinate (4%) of one of the HPV-positive patients. EBV, HSV, and CMV were not detected in the adjacent turbinates of the EBV-, HSV- or CMV-positive patients. All mucosae were negative for the VZV, HHV-6, and HHV-7. This is the first study to deal with the involvement of a comparable group of viruses in human nasal polyposis. The findings support the theory that the presence of viral EBV markedly influences the pathogenesis of these benign nasal tumors. The low incidence of HPV detected confirms the hypothesis that HPV is correlated with infectious mucosal lesions to a lesser extent than it is with proliferative lesions, such as inverted papilloma. The low incidence of HSV-1 and CMV confirms that these two herpes viruses may play a minor role in the development of nasal polyposis. Double infection with HSV-1 and CMV may also play a minor, though causative, role in nasal polyp development. VZV and HHV-6/-7 do not appear to be involved in the pathogenesis of these mucosal lesions.

  10. Nasal Anatomy

    MedlinePlus

    ... Nasal Anatomy Sinus Anatomy Nasal Physiology Nasal Endoscopy Skull Base Anatomy Virtual Anatomy Disclosure Statement CONDITIONS Adult ... Nasal Anatomy Sinus Anatomy Nasal Physiology Nasal Endoscopy Skull Base Anatomy Virtual Anatomy Disclosure Statement Printer Friendly ...

  11. Airborne Fine Particulate Matter Induces Oxidative Stress and Inflammation in Human Nasal Epithelial Cells.

    PubMed

    Hong, Zhicong; Guo, Zhiqiang; Zhang, Ruxin; Xu, Jian; Dong, Weiyang; Zhuang, Guoshun; Deng, Congrui

    2016-01-01

    Airborne fine particulate matter with an aerodynamic diameter equal to or smaller than 2.5 μm is abbreviated as PM2.5, which is one of the main components in air pollution. Exposure to PM2.5 is associated with increased risk of many human diseases, including chronic and allergic rhinitis, but the underlying molecular mechanism for its toxicity has not been fully elucidated. We have hypothesized that PM2.5 may cause oxidative stress and enhance inflammatory responses in nasal epithelial cells. Accordingly, we used human RPMI 2650 cells, derived from squamous cell carcinoma of the nasal septum, as a model of nasal epithelial cells, and exposed them to PM2.5 that was collected at Fudan University (31.3°N, 121.5°E) in Shanghai, China. PM2.5 exposure decreased the viability of RPMI 2650 cells, suggesting that PM2.5 may impair the barrier function of nasal epithelial cells. Moreover, PM2.5 increased the levels of intracellular reactive oxygen species (ROS) and the nuclear translocation of NF-E2-related factor-2 (Nrf2). Importantly, PM2.5 also decreased the activities of superoxide dismutase, catalase and glutathione peroxidase. Pretreatment with N-Acetyl-L-cysteine (an anti-oxidant) reduced the degree of the PM2.5-induced oxidative stress in RPMI 2650 cells. In addition, PM2.5 increased the production of granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-α, interleukin-13 and eotaxin (C-C motif chemokine ligand 11), each of which initiates and/or augments local inflammation. These results suggest that PM2.5 may induce oxidative stress and inflammatory responses in human nasal epithelial cells, thereby leading to nasal inflammatory diseases. The present study provides insights into cellular injury induced by PM2.5. PMID:27246665

  12. Airborne Fine Particulate Matter Induces Oxidative Stress and Inflammation in Human Nasal Epithelial Cells.

    PubMed

    Hong, Zhicong; Guo, Zhiqiang; Zhang, Ruxin; Xu, Jian; Dong, Weiyang; Zhuang, Guoshun; Deng, Congrui

    2016-01-01

    Airborne fine particulate matter with an aerodynamic diameter equal to or smaller than 2.5 μm is abbreviated as PM2.5, which is one of the main components in air pollution. Exposure to PM2.5 is associated with increased risk of many human diseases, including chronic and allergic rhinitis, but the underlying molecular mechanism for its toxicity has not been fully elucidated. We have hypothesized that PM2.5 may cause oxidative stress and enhance inflammatory responses in nasal epithelial cells. Accordingly, we used human RPMI 2650 cells, derived from squamous cell carcinoma of the nasal septum, as a model of nasal epithelial cells, and exposed them to PM2.5 that was collected at Fudan University (31.3°N, 121.5°E) in Shanghai, China. PM2.5 exposure decreased the viability of RPMI 2650 cells, suggesting that PM2.5 may impair the barrier function of nasal epithelial cells. Moreover, PM2.5 increased the levels of intracellular reactive oxygen species (ROS) and the nuclear translocation of NF-E2-related factor-2 (Nrf2). Importantly, PM2.5 also decreased the activities of superoxide dismutase, catalase and glutathione peroxidase. Pretreatment with N-Acetyl-L-cysteine (an anti-oxidant) reduced the degree of the PM2.5-induced oxidative stress in RPMI 2650 cells. In addition, PM2.5 increased the production of granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-α, interleukin-13 and eotaxin (C-C motif chemokine ligand 11), each of which initiates and/or augments local inflammation. These results suggest that PM2.5 may induce oxidative stress and inflammatory responses in human nasal epithelial cells, thereby leading to nasal inflammatory diseases. The present study provides insights into cellular injury induced by PM2.5.

  13. Biomarkers of inflammation in ozone-exposed humans: Comparison of the nasal and bronchoalveolar lavage

    SciTech Connect

    Graham, D.E.; Koren, H.S.

    1989-06-01

    An influx of neutrophils (PMNs), a primary feature of acute inflammation, has been associated with the development of lower lung disorders, such as emphysema and idiopathic fibrosis, as well as airway hyperreactivity and increased mucus secretion. It was previously established that an acute inflammatory response in the upper respiratory tract of humans could be studied by analysis of nasal lavages (NL), which is inexpensive, non-invasive, and atraumatic. However, the relationship of the cellular changes in the upper respiratory tract to changes in the lower airways has not been thoroughly investigated in humans. Here the cellular changes detected in the NL with those detected in the bronchoalveolar lavage (BAL) taken from the same individual have been compared. Ten subjects were exposed to either filtered air or 0.4 ppm ozone (O3), with exercise, for 2 hrs. The NL was done prior to, immediately following an 18 hr post exposure, while the BAL was done only at 18 hr post exposure. A significant increase in PMNs was detected in the NL immediately post exposure to 03, (7.7-fold increase; p=.003), and remained elevated in the 18 hr post-03 NL (6.1-fold increase; p<.001).

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

    PubMed

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

    2011-12-01

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

  15. The response of human nasal and bronchial organotypic tissue cultures to repeated whole cigarette smoke exposure.

    PubMed

    Talikka, Marja; Kostadinova, Radina; Xiang, Yang; Mathis, Carole; Sewer, Alain; Majeed, Shoaib; Kuehn, Diana; Frentzel, Stefan; Merg, Celine; Geertz, Marcel; Martin, Florian; Ivanov, Nikolai V; Peitsch, Manuel C; Hoeng, Julia

    2014-01-01

    Exposure to cigarette smoke (CS) is linked to the development of respiratory diseases, and there is a need to understand the mechanisms whereby CS causes damage. Although animal models have provided valuable insights into smoking-related respiratory tract damage, modern toxicity testing calls for reliable in vitro models as alternatives for animal experimentation. We report on a repeated whole mainstream CS exposure of nasal and bronchial organotypic tissue cultures that mimic the morphological, physiological, and molecular attributes of the human respiratory tract. Despite the similar cellular staining and cytokine secretion in both tissue types, the transcriptomic analyses in the context of biological network models identified similar and diverse biological processes that were impacted by CS-exposed nasal and bronchial cultures. Our results demonstrate that nasal and bronchial tissue cultures are appropriate in vitro models for the assessment of CS-induced adverse effects in the respiratory system and promising alternative to animal experimentation. PMID:25297719

  16. Exposure of human nasal epithelial cells to formaldehyde does not lead to DNA damage in lymphocytes after co-cultivation.

    PubMed

    Neuss, Simone; Moepps, Barbara; Speit, Günter

    2010-07-01

    We performed in vitro co-cultivation experiments with primary human nasal epithelial cells (HNEC) and isolated lymphocytes to investigate whether reactive formaldehyde (FA) can be passed on from nasal epithelial cells (site of first contact) to lymphocytes located in close proximity and induce DNA damage in these cells. A modified comet assay was used as a sensitive method for the detection of FA-induced DNA-protein cross links (DPX) because DPX are the most relevant type of FA-induced DNA damage. Our results clearly indicate that co-cultivation of lymphocytes with HNEC exposed to FA for 1 h causes a concentration-related induction of DPX in lymphocytes when co-cultivation takes place in the exposure medium. However, when the exposure medium is changed after FA treatment of HNEC and before lymphocytes are added, no induction of DPX is measured in lymphocytes even after exposure of HNEC to high FA concentrations (300 microM) and extended co-cultivation (4 h). Direct measurement of FA in the cell culture medium by a sensitive fluorescent detection kit indicated that FA is actually not released even from highly exposed cells into the cell culture medium. These results suggest that FA that has entered nasal epithelial cells is not released and does not damage other cells in close proximity to the epithelial cells. If these results also apply to the in vivo situation, FA would only be genotoxic towards directly exposed cells (site of first contact) and there should be no significant delivery of inhaled FA to other cells and distant sites. Our results do not support a recently proposed hypothetic mechanism for FA-induced leukaemia by damaging circulating haematopoietic stem cells or haematopoietic progenitor cells in nasal passages, which then travel to the bone marrow and become initiated leukaemic stem cells.

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

    SciTech Connect

    Calderon-Garciduenas, L.; Osnaya-Brizuela, N.; Ramirez-Martinez, L.

    1996-02-01

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

  18. Polyvinylidene fluoride film based nasal sensor to monitor human respiration pattern: an initial clinical study.

    PubMed

    Roopa Manjunatha, G; Rajanna, K; Mahapatra, D Roy; Nayak, M M; Krishnaswamy, Uma Maheswari; Srinivasa, R

    2013-12-01

    Design and development of a piezoelectric polyvinylidene fluoride (PVDF) thin film based nasal sensor to monitor human respiration pattern (RP) from each nostril simultaneously is presented in this paper. Thin film based PVDF nasal sensor is designed in a cantilever beam configuration. Two cantilevers are mounted on a spectacle frame in such a way that the air flow from each nostril impinges on this sensor causing bending of the cantilever beams. Voltage signal produced due to air flow induced dynamic piezoelectric effect produce a respective RP. A group of 23 healthy awake human subjects are studied. The RP in terms of respiratory rate (RR) and Respiratory air-flow changes/alterations obtained from the developed PVDF nasal sensor are compared with RP obtained from respiratory inductance plethysmograph (RIP) device. The mean RR of the developed nasal sensor (19.65 ± 4.1) and the RIP (19.57 ± 4.1) are found to be almost same (difference not significant, p > 0.05) with the correlation coefficient 0.96, p < 0.0001. It was observed that any change/alterations in the pattern of RIP is followed by same amount of change/alterations in the pattern of PVDF nasal sensor with k = 0.815 indicating strong agreement between the PVDF nasal sensor and RIP respiratory air-flow pattern. The developed sensor is simple in design, non-invasive, patient friendly and hence shows promising routine clinical usage. The preliminary result shows that this new method can have various applications in respiratory monitoring and diagnosis. PMID:23771706

  19. Validation of Human Physiologically Based Pharmacokinetic Model for Vinyl Acetate Against Human Nasal Dosimetry Data

    SciTech Connect

    Hinderliter, Paul M.; Thrall, Karla D.; Corley, Rick A.; Bloemen, Louis J.; Bogdanffy, M S.

    2005-05-01

    Vinyl acetate has been shown to induce nasal lesions in rodents in inhalation bioassays. A physiologically based pharmacokinetic (PBPK) model for vinyl acetate has been used in human risk assessment, but previous in vivo validation was conducted only in rats. Controlled human exposures to vinyl acetate were conducted to provide validation data for the application of the model in humans. Five volunteers were exposed to 1, 5, and 10 ppm 13 C1 , 13 C2 vinyl acetate via inhalation. A probe inserted into thenasopharyngeal region sampled both 13 C1 , 13 C2 vinyl acetate and the major metabolite 13 C1 , 13 C2 acetaldehyde during rest and light exercise. Nasopharyngeal air concentrations were analyzed in real time by ion trap mass spectrometry (MS/MS). Experimental concentrations of both vinyl acetate and acetaldehyde were then compared to predicted concentrations calculated from the previously published human model. Model predictions of vinyl acetate nasal extraction compared favorably with measured values of vinyl acetate, as did predictions of nasopharyngeal acetaldehyde when compared to measured acetaldehyde. The results showed that the current PBPK model structure and parameterization are appropriate for vinyl acetate. These analyses were conducted from 1 to 10 ppm vinyl acetate, a range relevant to workplace exposure standards but which would not be expected to saturate vinyl acetate metabolism. Risk assessment based on this model further concluded that 24 h per day exposures up to 1 ppm do not present concern regarding cancer or non-cancer toxicity. Validation of the vinyl acetate human PBPK model provides support for these conclusions.

  20. Temperature effect on the ciliary beat frequency of human nasal and tracheal ciliated cells.

    PubMed

    Clary-Meinesz, C F; Cosson, J; Huitorel, P; Blaive, B

    1992-01-01

    Even though all human respiratory cilia are similar in structure, they experience a wide range of temperatures between the initial part of the nasal fossae which behave as heat exchangers and the inferior part of the trachea, particularly when we inhale exceedingly cold or hot air. The ciliary beat frequency of ciliated cells from human nasal mucosa and from bronchial mucosa averages 8 Hz when measured at room temperature. In the present study we compared the ciliary beat frequency of human cells from nasal and tracheal mucosa brushings at different temperatures from 5 degrees C to 50 degrees C using two different techniques, ex vivo and in vitro: ex vivo in culture medium less than 24 h after sampling and in vitro after demembranation and reactivation according to a standard procedure developed in our laboratory. Measuring the ATP-reactivated ciliary beat frequency allowed us to check the thermal parameters of the dynein ATPase and all the axonemal machinery. No significant difference in frequency was observed between nasal fossae cilia and tracheal cilia when comparing extreme temperatures in both experimental procedures. PMID:1305479

  1. [Role of radiotherapy in the treatment of NK/T-cell nasal type and primary cerebral lymphomas].

    PubMed

    Boros, A; Michot, J-M; Hoang-Xuan, K; Mazeron, R

    2016-10-01

    The head and neck are common sites for extranodal non-Hodgkin lymphomas. Radiotherapy plays an important role in the treatment of low-grade lymphomas, with curative or palliative intent. In the case of high-grade lymphomas, its combination with chemotherapy is debated. Its role is however undeniable in two specific entities: NK/T-cell lymphoma NK/T nasal type, and primary central nervous system lymphomas, which are the subject of this review. PMID:27614517

  2. Biomechanical characterisation of the human nasal cartilages; implications for tissue engineering.

    PubMed

    Griffin, M F; Premakumar, Y; Seifalian, A M; Szarko, M; Butler, P E M

    2016-01-01

    Nasal reconstruction is currently performed using autologous grafts provides but is limited by donor site morbidity, tissue availability and potentially graft failure. Additionally, current alternative alloplastic materials are limited by their high extrusion and infection rates. Matching mechanical properties of synthetic materials to the native tissue they are replacing has shown to be important in the biocompatibility of implants. To date the mechanical properties of the human nasal cartilages has not been studied in depth to be able to create tissue-engineered replacements with similar mechanical properties to native tissue. The young's modulus was characterized in compression on fresh-frozen human cadaveric septal, alar, and lateral cartilage. Due to the functional differences experienced by the various aspects of the septal cartilage, 16 regions were evaluated with an average elastic modulus of 2.72 ± 0.63 MPa. Furthermore, the posterior septum was found to be significantly stiffer than the anterior septum (p < 0.01). The medial and lateral alar cartilages were tested at four points with an elastic modulus ranging from 2.09 ± 0.81 MPa, with no significant difference between the cartilages (p < 0.78). The lateral cartilage was tested once in all cadavers with an average elastic modulus of 0.98 ± 0.29 MPa. In conclusion, this study provides new information on the compressive mechanical properties of the human nasal cartilage, allowing surgeons to have a better understanding of the difference between the mechanical properties of the individual nasal cartilages. This study has provided a reference, by which tissue-engineered should be developed for effective cartilage replacements for nasal reconstruction.

  3. Biomechanical characterisation of the human nasal cartilages; implications for tissue engineering.

    PubMed

    Griffin, M F; Premakumar, Y; Seifalian, A M; Szarko, M; Butler, P E M

    2016-01-01

    Nasal reconstruction is currently performed using autologous grafts provides but is limited by donor site morbidity, tissue availability and potentially graft failure. Additionally, current alternative alloplastic materials are limited by their high extrusion and infection rates. Matching mechanical properties of synthetic materials to the native tissue they are replacing has shown to be important in the biocompatibility of implants. To date the mechanical properties of the human nasal cartilages has not been studied in depth to be able to create tissue-engineered replacements with similar mechanical properties to native tissue. The young's modulus was characterized in compression on fresh-frozen human cadaveric septal, alar, and lateral cartilage. Due to the functional differences experienced by the various aspects of the septal cartilage, 16 regions were evaluated with an average elastic modulus of 2.72 ± 0.63 MPa. Furthermore, the posterior septum was found to be significantly stiffer than the anterior septum (p < 0.01). The medial and lateral alar cartilages were tested at four points with an elastic modulus ranging from 2.09 ± 0.81 MPa, with no significant difference between the cartilages (p < 0.78). The lateral cartilage was tested once in all cadavers with an average elastic modulus of 0.98 ± 0.29 MPa. In conclusion, this study provides new information on the compressive mechanical properties of the human nasal cartilage, allowing surgeons to have a better understanding of the difference between the mechanical properties of the individual nasal cartilages. This study has provided a reference, by which tissue-engineered should be developed for effective cartilage replacements for nasal reconstruction. PMID:26676857

  4. Cytotoxicity of Different Excipients on RPMI 2650 Human Nasal Epithelial Cells.

    PubMed

    Horváth, Tamás; Bartos, Csilla; Bocsik, Alexandra; Kiss, Lóránd; Veszelka, Szilvia; Deli, Mária A; Újhelyi, Gabriella; Szabó-Révész, Piroska; Ambrus, Rita

    2016-01-01

    The nasal route receives a great deal of attention as a non-invasive method for the systemic administration of drugs. For nasal delivery, specific formulations containing excipients are used. Because of the sensitive respiratory mucosa, not only the active ingredients, but also additives need to be tested in appropriate models for toxicity. The aim of the study was to measure the cytotoxicity of six pharmaceutical excipients, which could help to reach larger residence time, better permeability, and increased solubility dissolution rate. The following excipients were investigated on RPMI 2650 human nasal septum tumor epithelial cells: β-d-mannitol, sodium hyaluronate, α and β-cyclodextrin, polyvinyl alcohol and methylcellulose. 3-(4,5-dimethyltiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) dye conversion assay and real-time impedance analysis were used to investigate cytotoxicity. No excipient showed toxicity at 0.3% (w/v) concentration or below while 1% concentration a significantly reduced metabolic activity was measured by MTT assay for methylcellulose and cyclodextrins. Using impedance measurements, only β-cyclodextrin (1%) was toxic to cells. Mannitol at 1% concentration had a barrier opening effect on epithelial cells, but caused no cellular damage. Based on the results, all additives at 0.3%, sodium hyaluronate and polyvinyl alcohol at 1% concentrations can be safely used for nasal formulations. PMID:27213303

  5. Topographical differences in distribution and responsiveness of trigeminal sensitivity within the human nasal mucosa.

    PubMed

    Meusel, Thomas; Negoias, Simona; Scheibe, Mandy; Hummel, Thomas

    2010-11-01

    The study was designed to provide a topographical map of the sensitivity of the human nasal respiratory epithelium towards trigeminal chemosensory stimuli. As an electrophysiological measure of intranasal trigeminal activation at the level of the epithelium, we used the so-called negative mucosa potential (NMP), a measure that represents the sum of generator potentials of trigeminal receptor neurons after chemical stimulation. Sixty subjects participated (30 men and 30 women; mean age 23.5 years). Measurements were made in response to stimulation with menthol, CO(2), ethanol, and cinnamaldehyde, which are known to activate trigeminal receptors to various degrees. Recordings of the NMP were made from five intranasal sites: the anterior septum, the posterior septum, the tip of the middle turbinate, the tip of the lower turbinate, and the lateral side wall of the posterior nasal cavity. The recording electrode was positioned under endoscopic control. The largest NMP amplitudes were recorded at the anterior septum in response to stimulation with CO(2). Comparing all recording sites, significant differences were observed between responses at the posterior septum and the lateral side wall of the posterior nasal cavity in response to stimulation by ethanol, menthol, and CO(2). These findings suggest that the presence of topographical and chemosensory differences in the responsiveness of the nasal mucosa to irritants.

  6. Surface mapping for visualization of wall stresses during inhalation in a human nasal cavity.

    PubMed

    Inthavong, Kiao; Shang, Yidan; Tu, Jiyuan

    2014-01-01

    Airflow analysis can assist in better understanding the physiology however the human nasal cavity is an extremely complicated geometry that is difficult to visualize in 3D space, let alone in 2D space. In this paper, an anatomically accurate 3D surface of the nasal passages derived from CT data was unwrapped and transformed into a 2D space, into a UV-domain (where u and v are the coordinates) to allow a complete view of the entire wrapped surface. This visualization technique allows surface flow parameters to be analyzed with greater precision. A UV-unwrapping tool is developed and a strategy is presented to allow deeper analysis to be performed. This includes (i) the ability to present instant comparisons of geometry and flow variables between any number of different nasal cavity models through normalization of the 2D unwrapped surface; (ii) visualization of an entire surface in one view and; (iii) a planar surface that allows direct 1D and 2D analytical solutions of diffusion of inhaled vapors and particles through the nasal walls. This work lays a foundation for future investigations that correlates adverse and therapeutic health responses to local inhalation of gases and particles.

  7. Toxicology of the nasal passages

    SciTech Connect

    Barrow, C.S.

    1986-01-01

    Contents of this work include: Comparative Anatomy and Function of the Nasal Passages; Light Microscopic Examination of the Rat Nasal Passages: Preparation and Morphologic Features; Histopathology of Acute and Subacute Nasal Toxicity; Pathology of Chronic Nasal Toxic Responses Including Cancer; Responses of the Nasal Mucociliary Apparatus to Airborne Irritants; Effects of Chemical Exposure on Olfaction in Humans, Possible Consequences of Cytochrome P-450-Dependent Monooxygenases in Nasal Tissues.

  8. Micro and nanoparticle deposition in human nasal passage pre and post virtual maxillary sinus endoscopic surgery.

    PubMed

    Abouali, Omid; Keshavarzian, Erfan; Farhadi Ghalati, Pejman; Faramarzi, Abolhasan; Ahmadi, Goodarz; Bagheri, Mohammad Hadi

    2012-05-31

    Realistic 3-D models of the human nasal passages were developed pre and post virtual uncinectomy and Middle Meatal Antrostomy. A 3-D computational domain was constructed by a series of coronal CT scan images from a healthy subject. Then a virtual uncinectomy intervention and maxillary antrostomy were performed on the left nasal passage by removing the uncinate process and exposing the maxillary sinus antrum. For several breathing rates corresponding to low or moderate activities, the airflows in the nasal passages were simulated numerically pre and post virtual routine maxillary sinus endoscopic surgery. The airflow distribution in the nasal airway, maxillary and frontal sinuses were analyzed and compared between pre and post surgery cases. A Lagrangian trajectory analysis approach was used for evaluating the path and deposition of microparticles in the nasal passages and maxillary sinuses. A diffusion model was used for nanoparticle transport and deposition analysis. The deposition rate of the inhaled micro and nanoparticles in the sinuses were evaluated and compared for pre and post operation conditions. The results showed that after maxillary sinus endoscopic surgery, the inhaled nano and microparticles can easily enter this sinus due to penetration of the airflow into the sinus cavity. This was in contrast to the preoperative condition in which almost no particles entered the sinuses. These results could be of importance for a better understanding of the effect of sinus endoscopic surgery on patient exposure to particulate pollution and inhalation drug delivery. The significantly higher airflow rate and particle deposition in the sinus could be a reason for the discomfort reported by some patient after maxillary sinus endoscopic surgery. PMID:22465001

  9. Human parvovirus 4 in nasal and fecal specimens from children, Ghana.

    PubMed

    Drexler, Jan Felix; Reber, Ulrike; Muth, Doreen; Herzog, Petra; Annan, Augustina; Ebach, Fabian; Sarpong, Nimarko; Acquah, Samuel; Adlkofer, Julia; Adu-Sarkodie, Yaw; Panning, Marcus; Tannich, Egbert; May, Jürgen; Drosten, Christian; Eis-Hübinger, Anna Maria

    2012-10-01

    Nonparenteral transmission might contribute to human parvovirus 4 (PARV4) infections in sub-Saharan Africa. PARV4 DNA was detected in 8 (0.83%) of 961 nasal samples and 5 (0.53%) of 943 fecal samples from 1,904 children in Ghana. Virus concentrations ≤ 6-7 log(10) copies/mL suggest respiratory or fecal-oral modes of PARV4 transmission.

  10. Persistent Nasal Carriage of Staphylococcus aureus Is Associated with Deficient Induction of Human β-Defensin 3 after Sterile Wounding of Healthy Skin In Vivo ▿

    PubMed Central

    Zanger, Philipp; Nurjadi, Dennis; Vath, Bernadette; Kremsner, Peter G.

    2011-01-01

    Persistent nasal carriage of Staphylococcus aureus is the primary reservoir for this pathogen and a risk factor for infection. The nares of 12 to 30% of healthy individuals are persistently colonized with staphylococci. Elucidating the yet enigmatic determinants of this phenomenon is of major public health interest. We hypothesized that differences in the levels of antimicrobial peptides (AMPs) that are found in human skin and have pronounced antistaphylococcal activity may contribute to this phenomenon. We compared constitutive and induced mRNA levels of RNase 7 and human β-defensin 3 (HBD-3) in healthy and experimentally wounded gluteal skin of 60 volunteers after ascertaining their carrier status through repeated nasal cultures. We found that levels of HBD-3 expression in skin of persistent nasal carriers of S. aureus were lower: induced levels in carriers were 63% (95% confidence interval, 43 to 94%; P = 0.02) and constitutive levels were 76% (95% confidence interval, 52 to 110%; P = 0.14) of those found in noncarriers. No such associations were present for RNase 7. In conjunction with existing knowledge, these findings suggest that healthy individuals with deficient HBD-3 expression in keratinocytes are more prone to persistent nasal colonization with S. aureus. PMID:21464083

  11. Giant Primary Schwannoma of the Left Nasal Cavity and Ethmoid Sinus

    PubMed Central

    Kong, Justin; Oh, Lawrence; Cox, Daniel; Forer, Martin

    2016-01-01

    A unilateral tumour in the nasal cavity or paranasal sinuses is commonly caused by polyps, cysts, and mucoceles, as well as invasive tumours such as papillomas and squamous cell carcinomas. Schwannomas, in contrast, are rare lesions in this area (Minhas et al., 2013). We present a case of a 52-year-old female who presented with a 4-year progressive history of mucous hypersecretion, nasal obstruction, pain, and fullness. Imaging of the paranasal sinuses showed complete opacification of the entire left nasal cavity and sinuses by a tumour causing subsequent obstruction of the frontal and maxillary sinuses. The tumour was completely excised endoscopically. Histopathology was consistent with that of a schwannoma. PMID:27379190

  12. Giant Primary Schwannoma of the Left Nasal Cavity and Ethmoid Sinus.

    PubMed

    Wong, Eugene; Kong, Justin; Oh, Lawrence; Cox, Daniel; Forer, Martin

    2016-01-01

    A unilateral tumour in the nasal cavity or paranasal sinuses is commonly caused by polyps, cysts, and mucoceles, as well as invasive tumours such as papillomas and squamous cell carcinomas. Schwannomas, in contrast, are rare lesions in this area (Minhas et al., 2013). We present a case of a 52-year-old female who presented with a 4-year progressive history of mucous hypersecretion, nasal obstruction, pain, and fullness. Imaging of the paranasal sinuses showed complete opacification of the entire left nasal cavity and sinuses by a tumour causing subsequent obstruction of the frontal and maxillary sinuses. The tumour was completely excised endoscopically. Histopathology was consistent with that of a schwannoma. PMID:27379190

  13. Host innate inflammatory factors and staphylococcal protein A influence the duration of human Staphylococcus aureus nasal carriage

    PubMed Central

    Cole, Amy L.; Muthukrishnan, Gowrishankar; Chong, Christine; Beavis, Ashley; Eade, Colleen R.; Wood, Matthew P.; Deichen, Michael G.; Cole, Alexander M.

    2016-01-01

    Human Staphylococcus aureus (SA) nasal carriage provides a reservoir for the dissemination of infectious strains; however, factors regulating the establishment and persistence of nasal colonization are mostly unknown. We measured carriage duration and nasal fluid inflammatory markers after nasally inoculating healthy participants with their previously isolated SA strains. Ten out of 15 studies resulted in rapid clearance (9±6 days) that corresponded with upregulated chemokines, growth factors, and predominantly Th1-type cytokines, but not IL-17. Nasal SA persistence corresponded with elevated baseline levels of MIP-1β, IL-1β, and IL-6, no induction of inflammatory factors post-inoculation, and decreased IL-1RA:IL-1β ratio. SA-expressed staphylococcal protein A (SpA) levels correlated positively with carriage duration. Competitive inoculation studies revealed that isogenic SpA knockout (ΔSpA) strains were cleared faster than wild-type only in participants with upregulated inflammatory markers post-inoculation. The remaining participants did not mount an inflammatory response and did not clear either strain. ΔSpA strains demonstrated lower growth rates in carrier nasal fluids and lower survival rates when incubated with neutrophils. Collectively, the presented studies identify innate immune effectors that cooperatively modulate nasal carriage duration, and confirm SpA as a bacterial co-determinant of SA nasal carriage. PMID:26838052

  14. Effects of Endogenous Formaldehyde in Nasal Tissues on Inhaled Formmaldehyde Dosimetry Predictions in the Rat, Monkey, and Human Nasal Passages

    EPA Science Inventory

    ABSTRACT Formaldehyde, a nasal carcinogen, is also an endogenous compound that is present in all living cells. Due to its high solubility and reactivity, quantitative risk estimates for inhaled formaldehyde rely on internal dose calculations in the upper respiratory tract which ...

  15. Standardizing Nasal Nitric Oxide Measurement as a Test for Primary Ciliary Dyskinesia

    PubMed Central

    Hazucha, Milan J.; Chawla, Kunal K.; Baker, Brock R.; Shapiro, Adam J.; Brown, David E.; LaVange, Lisa M.; Horton, Bethany J.; Qaqish, Bahjat; Carson, Johnny L.; Davis, Stephanie D.; Dell, Sharon D.; Ferkol, Thomas W.; Atkinson, Jeffrey J.; Olivier, Kenneth N.; Sagel, Scott D.; Rosenfeld, Margaret; Milla, Carlos; Lee, Hye-Seung; Krischer, Jeffrey; Zariwala, Maimoona A.; Knowles, Michael R.

    2013-01-01

    Rationale: Several studies suggest that nasal nitric oxide (nNO) measurement could be a test for primary ciliary dyskinesia (PCD), but the procedure and interpretation have not been standardized. Objectives: To use a standard protocol for measuring nNO to establish a disease-specific cutoff value at one site, and then validate at six other sites. Methods: At the lead site, nNO was prospectively measured in individuals later confirmed to have PCD by ciliary ultrastructural defects (n = 143) or DNAH11 mutations (n = 6); and in 78 healthy and 146 disease control subjects, including individuals with asthma (n = 37), cystic fibrosis (n = 77), and chronic obstructive pulmonary disease (n = 32). A disease-specific cutoff value was determined, using generalized estimating equations (GEEs). Six other sites prospectively measured nNO in 155 consecutive individuals enrolled for evaluation for possible PCD. Measurements and Main Results: At the lead site, nNO values in PCD (mean ± standard deviation, 20.7 ± 24.1 nl/min; range, 1.5–207.3 nl/min) only rarely overlapped with the nNO values of healthy control subjects (304.6 ± 118.8; 125.5–867.0 nl/min), asthma (267.8 ± 103.2; 125.0–589.7 nl/min), or chronic obstructive pulmonary disease (223.7 ± 87.1; 109.7–449.1 nl/min); however, there was overlap with cystic fibrosis (134.0 ± 73.5; 15.6–386.1 nl/min). The disease-specific nNO cutoff value was defined at 77 nl/minute (sensitivity, 0.98; specificity, >0.999). At six other sites, this cutoff identified 70 of the 71 (98.6%) participants with confirmed PCD. Conclusions: Using a standardized protocol in multicenter studies, nNO measurement accurately identifies individuals with PCD, and supports its usefulness as a test to support the clinical diagnosis of PCD. PMID:24024753

  16. Human Nasal Challenge with Streptococcus pneumoniae Is Immunising in the Absence of Carriage

    PubMed Central

    Gritzfeld, Jenna F.; Wright, Angela D.; Armitage, Kathryn; Jambo, Kondwani C.; Bate, Emily; El Batrawy, Sherouk; Collins, Andrea; Gordon, Stephen B.

    2012-01-01

    Infectious challenge of the human nasal mucosa elicits immune responses that determine the fate of the host-bacterial interaction; leading either to clearance, colonisation and/or disease. Persistent antigenic exposure from pneumococcal colonisation can induce both humoral and cellular defences that are protective against carriage and disease. We challenged healthy adults intra-nasally with live 23F or 6B Streptococcus pneumoniae in two sequential cohorts and collected nasal wash, bronchoalveolar lavage (BAL) and blood before and 6 weeks after challenge. We hypothesised that both cohorts would successfully become colonised but this did not occur except for one volunteer. The effect of bacterial challenge without colonisation in healthy adults has not been previously assessed. We measured the antigen-specific humoral and cellular immune responses in challenged but not colonised volunteers by ELISA and Flow Cytometry. Antigen-specific responses were seen in each compartment both before and after bacterial challenge for both cohorts. Antigen-specific IgG and IgA levels were significantly elevated in nasal wash 6 weeks after challenge compared to baseline. Immunoglobulin responses to pneumococci were directed towards various protein targets but not capsular polysaccharide. 23F but not 6B challenge elevated IgG anti-PspA in BAL. Serum immunoglobulins did not increase in response to challenge. In neither challenge cohort was there any alteration in the frequencies of TNF, IL-17 or IFNγ producing CD4 T cells before or after challenge in BAL or blood. We show that simple, low dose mucosal exposure with pneumococci may immunise mucosal surfaces by augmenting anti-protein immunoglobulin responses; but not capsular or cellular responses. We hypothesise that mucosal exposure alone may not replicate the systemic immunising effect of experimental or natural carriage in humans. PMID:22496648

  17. Morphometric Study of Nasal Bone and Piriform Aperture in Human Dry Skull of Indian Origin

    PubMed Central

    Dixit, Aparna; Rani, Mamta

    2016-01-01

    Introduction Nasal bone and piriform aperture shows racial and geographical differences because of variable climate. The aim of this study was to evaluate the dimensions (maximal width and length), the size and the shape of the piriform aperture (PA) and their sexual dimorphism in North Indian adult. Materials and Methods In this observational study, dimension of piriform aperture and nasal bone were measured using digital vernier caliper after assessing landmarks around the piriform aperture on the norma frontalis in Frankfurt plane in 40 skull of Indian orgin. Results The mean width of the piriform aperture was 24.9±1.59 mm in males and 22.77±1.57 mm in females, the mean length was 29.57±3.28mm in females and 31.16±3.58mm in males. The difference between males and females was significant, and our data correlates well with the previously data acquired from humans skulls. Most of North Indian skulls have platyrhine type of piriform aperture (triangular to oval shape with pyriform aperture index of 0.79). Mean length and width of nasal bone were 17.58±2.47mm and 12.1±0.97mm respectively without sexual. Conclusion Shape and size analysis of the piriform aperture and nasal bone showed the existence of a significant sexual dimorphism. These results encourage us to go further with functional and imaging correlations. This study will also be helpful in forensic research and anthropology. PMID:26894050

  18. Live Attenuated Influenza Vaccine Strains Elicit a Greater Innate Immune Response than Antigenically-Matched Seasonal Influenza Viruses during Infection of Human Nasal Epithelial Cell Cultures

    PubMed Central

    Fischer, William A.; Brighton, Missy; Jaspers, Ilona

    2014-01-01

    Influenza viruses are global pathogens that infect approximately 10–20% of the world’s population each year. Vaccines, including the live attenuated influenza vaccine (LAIV), are the best defense against influenza infections. The LAIV is a novel vaccine that actively replicates in the human nasal epithelium and elicits both mucosal and systemic protective immune responses. The differences in replication and innate immune responses following infection of human nasal epithelium with influenza seasonal wild type (WT) and LAIV viruses remain unknown. Using a model of primary differentiated human nasal epithelial cell (hNECs) cultures, we compared influenza WT and antigenically-matched cold adapted (CA) LAIV virus replication and the subsequent innate immune response including host cellular pattern recognition protein expression, host innate immune gene expression, secreted pro-inflammatory cytokine production, and intracellular viral RNA levels. Growth curves comparing virus replication between WT and LAIV strains revealed significantly less infectious virus production during LAIV compared with WT infection. Despite this disparity in infectious virus production the LAIV strains elicited a more robust innate immune response with increased expression of RIG-I, TLR-3, IFNβ, STAT-1, IRF-7, MxA, and IP-10. There were no differences in cytotoxicity between hNEC cultures infected with WT and LAIV strains as measured by basolateral levels of LDH. Elevated levels of intracellular viral RNA during LAIV as compared with WT virus infection of hNEC cultures at 33°C may explain the augmented innate immune response via the up-regulation of pattern recognition receptors and down-stream type I IFN expression. Taken together our results suggest that the decreased replication of LAIV strains in human nasal epithelial cells is associated with a robust innate immune response that differs from infection with seasonal influenza viruses, limits LAIV shedding and plays a role in the

  19. Live attenuated influenza vaccine strains elicit a greater innate immune response than antigenically-matched seasonal influenza viruses during infection of human nasal epithelial cell cultures.

    PubMed

    Fischer, William A; Chason, Kelly D; Brighton, Missy; Jaspers, Ilona

    2014-03-26

    Influenza viruses are global pathogens that infect approximately 10-20% of the world's population each year. Vaccines, including the live attenuated influenza vaccine (LAIV), are the best defense against influenza infections. The LAIV is a novel vaccine that actively replicates in the human nasal epithelium and elicits both mucosal and systemic protective immune responses. The differences in replication and innate immune responses following infection of human nasal epithelium with influenza seasonal wild type (WT) and LAIV viruses remain unknown. Using a model of primary differentiated human nasal epithelial cell (hNECs) cultures, we compared influenza WT and antigenically-matched cold adapted (CA) LAIV virus replication and the subsequent innate immune response including host cellular pattern recognition protein expression, host innate immune gene expression, secreted pro-inflammatory cytokine production, and intracellular viral RNA levels. Growth curves comparing virus replication between WT and LAIV strains revealed significantly less infectious virus production during LAIV compared with WT infection. Despite this disparity in infectious virus production the LAIV strains elicited a more robust innate immune response with increased expression of RIG-I, TLR-3, IFNβ, STAT-1, IRF-7, MxA, and IP-10. There were no differences in cytotoxicity between hNEC cultures infected with WT and LAIV strains as measured by basolateral levels of LDH. Elevated levels of intracellular viral RNA during LAIV as compared with WT virus infection of hNEC cultures at 33°C may explain the augmented innate immune response via the up-regulation of pattern recognition receptors and down-stream type I IFN expression. Taken together our results suggest that the decreased replication of LAIV strains in human nasal epithelial cells is associated with a robust innate immune response that differs from infection with seasonal influenza viruses, limits LAIV shedding and plays a role in the silent

  20. Topical vasoconstrictor (oxymetazoline) does not affect histamine-induced mucosal exudation of plasma in human nasal airways.

    PubMed

    Svensson, C; Pipkorn, U; Alkner, U; Baumgarten, C R; Persson, C G

    1992-03-01

    Mucosal exudation of almost unfiltered plasma proteins, plasma-derived mediators and fluid has recently been advanced as a major respiratory defence mechanism. Oxymetazoline chloride is a commonly used decongestant agent. By reducing blood flow it may reduce mucosal exudation and thus compromise the mucosal defence capacity. This study examines the effect of topically applied oxymetazoline on histamine-induced plasma exudation into human nasal airways. Twelve normal volunteers participated in a double-blind, randomized, cross-over and placebo-controlled study with pretreatment with a single dose oxymetazoline chloride (5 micrograms or 50 micrograms; a dose previously known to reduce nasal mucosal blood flow by almost 50%) prior to the histamine challenge sequence. Nasal lavages were performed every 10 min for 140 min, and three histamine challenges were performed at 30-min intervals during this period. The concentrations of two exudative indices, N-alpha-tosyl-L-arginine methyl ester (TAME)-esterase activity and albumin, were measured in the nasal lavage fluids. Nasal symptoms (sneezing, nasal secretion and blockage) were assessed by a scoring technique. Histamine induced all three symptoms with correlatively raised levels of the biochemical markers for plasma exudation. Oxymetazoline chloride caused a significant decrease in nasal stuffiness, but did not influence the other nasal symptoms or the histamine-induced plasma exudation. It is concluded that histamine-induced plasma exudation is not influenced by topical oxymetazoline. Thus, an important airway defence reaction such as plasma exudation may be little affected by topical alpha-adrenoreceptor-mediated vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. The influence of vegetative stimuli on the human nasal mucous membrane.

    PubMed

    Simon, H; Schmidt-Kloiber, H

    1985-03-01

    Measuring probes were inserted into the inferior nasal meatus in humans to record the effects of certain defined vegetative stimuli on the cavernous state and the temperature of the mucous membrane. An unilateral carotis compression induces a bilateral reactivity of the mucous membrane in the sense of a sympathicus stimulus. An unilateral bulbus pressure causes a bilateral reaction of the mucous membrane opposite to that of carotis compression. Blocking of the stellate ganglion produces a tonus reduction of the nervus sympathicus as was also found in animal experiments by other authors. Trigeminus stimulation induces a swelling of the nasal mucous membrane, whereas a voluntary breathing stop causes decongestion. Facial blushing, the only undefined and involuntary stimulus, is followed by an unswelling and a decrease of mucous membrane temperature. The results of our investigations are in agreement with analogous animal experiments. This is not surprising as man has a vegetative nervous system which is essentially unchanged from the beginning of evolutionary development. Only blushing is an expression of a reaction behaviour characteristic of human beings only. PMID:4001756

  2. A model of human nasal epithelial cells adapted for direct and repeated exposure to airborne pollutants.

    PubMed

    Bardet, Gaëlle; Achard, Sophie; Loret, Thomas; Desauziers, Valérie; Momas, Isabelle; Seta, Nathalie

    2014-08-17

    Airway epithelium lining the nasal cavity plays a pivotal role in respiratory tract defense and protection mechanisms. Air pollution induces alterations linked to airway diseases such as asthma. Only very few in vitro studies to date have succeeded in reproducing physiological conditions relevant to cellular type and chronic atmospheric pollution exposure. We therefore, set up an in vitro model of human Airway Epithelial Cells of Nasal origin (hAECN) close to real human cell functionality, specifically adapted to study the biological effects of exposure to indoor gaseous pollution at the environmental level. hAECN were exposed under air-liquid interface, one, two, or three-times at 24 h intervals for 1 h, to air or formaldehyde (200 μg/m(3)), an indoor air gaseous pollutant. All experiments were ended at day 4, when both cellular viability and cytokine production were assessed. Optimal adherence and confluence of cells were obtained 96 h after cell seeding onto collagen IV-precoated insert. Direct and repeated exposure to formaldehyde did not produce any cellular damage or IL-6 production change, although weak lower IL-8 production was observed only after the third exposure. Our model is significantly better than previous ones due to cell type and the repeated exposure protocol.

  3. Adult Human Nasal Mesenchymal-Like Stem Cells Restore Cochlear Spiral Ganglion Neurons After Experimental Lesion

    PubMed Central

    Bas, Esperanza; Van De Water, Thomas R.; Lumbreras, Vicente; Rajguru, Suhrud; Goss, Garrett; Hare, Joshua M.

    2014-01-01

    A loss of sensory hair cells or spiral ganglion neurons from the inner ear causes deafness, affecting millions of people. Currently, there is no effective therapy to repair the inner ear sensory structures in humans. Cochlear implantation can restore input, but only if auditory neurons remain intact. Efforts to develop stem cell-based treatments for deafness have demonstrated progress, most notably utilizing embryonic-derived cells. In an effort to bypass limitations of embryonic or induced pluripotent stem cells that may impede the translation to clinical applications, we sought to utilize an alternative cell source. Here, we show that adult human mesenchymal-like stem cells (MSCs) obtained from nasal tissue can repair spiral ganglion loss in experimentally lesioned cochlear cultures from neonatal rats. Stem cells engraft into gentamicin-lesioned organotypic cultures and orchestrate the restoration of the spiral ganglion neuronal population, involving both direct neuronal differentiation and secondary effects on endogenous cells. As a physiologic assay, nasal MSC-derived cells engrafted into lesioned spiral ganglia demonstrate responses to infrared laser stimulus that are consistent with those typical of excitable cells. The addition of a pharmacologic activator of the canonical Wnt/β-catenin pathway concurrent with stem cell treatment promoted robust neuronal differentiation. The availability of an effective adult autologous cell source for inner ear tissue repair should contribute to efforts to translate cell-based strategies to the clinic. PMID:24172073

  4. Nicotine causes genotoxic damage but is not metabolized during long-term exposure of human nasal miniorgan cultures.

    PubMed

    Ginzkey, Christian; Steussloff, Gudrun; Koehler, Christian; Hackenberg, Stephan; Richter, Elmar; Hagen, Rudolf; Kleinsasser, Norbert H

    2014-08-17

    Human nasal miniorgan cultures (MOC) are a useful tool in ecogenotoxicology. Repetitive exposure to nicotine showed reversible DNA damage, and stable CYP2A6 expression was demonstrated in nasal MOC in previous investigations. The aim of the present study was to evaluate the genotoxic effect of nicotine in nasal MOC after chronic nicotine exposure, and to monitor possible metabolism capacities. MOC were dissected from human nasal mucosa and cultured under standard cell culture conditions. MOC were exposed to nicotine for 3 weeks at concentrations of 1 μM and 1 mM. The concentrations were chosen based on nicotine plasma levels in heavy smokers, and possible concentrations used in topical application of nicotine nasal spray. DNA damage was assessed by the comet assay at days 7, 14 and 21. Concentrations of nicotine and cotinine were analyzed in cell culture medium by gas chromatography/mass spectrometry to determine a possible metabolism of nicotine by MOC. Distinct DNA damage in MOC could be demonstrated after 1 week of exposure to 1 μM and 1 mM nicotine. This effect decreased after 2 and 3 weeks with no statistically relevant DNA migration. No nicotine metabolism could be detected by changes in nicotine and cotinine concentrations in the supernatants. This is the first time genotoxic effects have been evaluated in nasal MOC after chronic nicotine exposure for up to 3 weeks. Genotoxic effects were present after 1 week of culture with a decrease over time. Down-regulation of nicotinic acetylcholine receptors, which are expressed in nasal mucosa, may be a possible explanation. The lack of nicotine metabolism in this model could be explained by the functional loss of CYP2A6 during chronic nicotine exposure. Further investigations are necessary to provide a more detailed description of the underlying mechanisms involved in DNA damage by nicotine. PMID:24983901

  5. Comparison of exhaled nitric oxide and cardiorespiratory indices between nasal and oral breathing during submaximal exercise in humans.

    PubMed

    Yasuda, Y; Itoh, T; Miyamura, M; Nishino, H

    1997-10-01

    In order to examine the origin and role of nitric oxide (NO) in exhaled air during exercise, exhaled NO outputs of 8 healthy human subjects were compared using different breathing methods, through the mouth or nose, at two intensities of bicycle exercise. The concentration of NO in the exhaled air and ventilatory gas exchange variables were measured by a chemiluminescence analyzer and a mixing chamber method, respectively. The concentration and total output of NO in the expired air was significantly higher under nasal breathing than under oral breathing for both exercise intensities, whereas no significant difference was observed in cardiorespiratory variables between them. NO output increased significantly when exercise intensity was increased from unloaded (0 W) to 60 W under nasal breathing, but not under oral breathing. A negative correlation among subjects was found between NO output and minute ventilation in both breathing methods only for unloaded exercise. Data indicate that nasal airways have a large contribution, at least 50% of total NO output in the exhaled air during nasal breathing, but this nasal NO may have no further modulation on respiratory function during submaximal exercise by healthy humans.

  6. Numerical simulation of airflow and micro-particle deposition in human nasal airway pre- and post-virtual sphenoidotomy surgery.

    PubMed

    Bahmanzadeh, Hojat; Abouali, Omid; Faramarzi, Mohammad; Ahmadi, Goodarz

    2015-06-01

    In the present study, the effects of endoscopic sphenoidotomy surgery on the flow patterns and deposition of micro-particles in the human nasal airway and sphenoid sinus were investigated. A realistic model of a human nasal passage including nasal cavity and paranasal sinuses was constructed using a series of CT scan images of a healthy subject. Then, a virtual sphenoidotomy by endoscopic sinus surgery was performed in the left nasal passage and sphenoid sinus. Transient airflow patterns pre- and post-surgery during a full breathing cycle (inhalation and exhalation) were simulated numerically under cyclic flow condition. The Lagrangian approach was used for evaluating the transport and deposition of inhaled micro-particles. An unsteady particle tracking was performed for the inhalation phase of the breathing cycle for the case that particles were continuously entering into the nasal airway. The total deposition pattern and sphenoid deposition fraction of micro-particles were evaluated and compared for pre- and post-surgery cases. The presented results show that sphenoidotomy increased the airflow into the sphenoid sinus, which led to increased deposition of micro-particles in this region. Particles up to 25 μm were able to penetrate into the sphenoid in the post-operation case, and the highest deposition in the sphenoid for the resting breathing rate occurred for 10 μm particles at about 1.5%.

  7. Human upper respiratory tract responses to inhaled pollutants with emphasis on nasal lavage

    SciTech Connect

    Koren, H.S.; Devlin, R.B.

    1992-01-01

    A set of symptoms has been described during the past two decades which has been called the sick building syndrome. These symptoms include eye, nose, and throat irritation; headache; mental fatigue; and respiratory distress. It is likely that volatile organic compounds (VOC) present in synthetic materials used in homes and office buildings contribute to these symptoms. However, there have been few studies in which humans have been exposed to known amounts of VOC under carefully controlled conditions. In the study 14 subjects have been exposed to a mixture of VOC (25 mg/cu m total hydrocarbon) representative of what is found in new homes and office buildings. Since irritation of the nose and throat are symptoms often associated with the upper respiratory tract and may result from an inflammatory response in the upper airways, the authors have used nasal lavage to monitor neutrophil (PMN) influx into the nasal passages following exposure to VOC. The authors report statistically significant increases in PMNs both immediately after a four hour exposure to VOC, as well as 18 hours later.

  8. Detection of novel Chlamydiae and Legionellales from human nasal samples of healthy volunteers.

    PubMed

    Corsaro, Daniele; Venditti, Danielle

    2015-07-01

    Chlamydiae are intracellular bacterial parasites of eukaryotes, ranging from amoebae to humans. They comprise many novel members and are investigated as emerging pathogens. Environmental studies highlighted similarities between the ecologies of chlamydiae and legionellae, both groups being important agents of respiratory infections. Herein, we analyzed nasal samples from healthy persons, searching for the presence of amoebae, chlamydiae and legionellae. From a total of 25 samples, we recovered by PCR eight samples positive to chlamydiae and six samples positive to legionellae. Among these samples, four were positive to both organisms. The sequencing of 16S rDNAs allowed to identify (i) among Chlamydiae: Parachlamydia acanthamoebae, Chlamydophila psittaci, Chlamydophila felis, and members of Rhabdochlamydiaceae, Simkaniaceae and E6 lineage and (ii) among Legionellaceae: Legionella longbeachae, Legionella bozemanii and Legionella impletisoli. Unexpectedly, we also recovered Diplorickettsia sp. Amoebae collected from nasal mucosae, Acanthamoeba and Vermamoeba, were endosymbiont-free, and chlamydiae revealed refractory to amoeba coculture. This study shows common exposure to chlamydiae and legionellae and suggests open air activities like gardening as a probable additional source of infection.

  9. Detection of novel Chlamydiae and Legionellales from human nasal samples of healthy volunteers.

    PubMed

    Corsaro, Daniele; Venditti, Danielle

    2015-07-01

    Chlamydiae are intracellular bacterial parasites of eukaryotes, ranging from amoebae to humans. They comprise many novel members and are investigated as emerging pathogens. Environmental studies highlighted similarities between the ecologies of chlamydiae and legionellae, both groups being important agents of respiratory infections. Herein, we analyzed nasal samples from healthy persons, searching for the presence of amoebae, chlamydiae and legionellae. From a total of 25 samples, we recovered by PCR eight samples positive to chlamydiae and six samples positive to legionellae. Among these samples, four were positive to both organisms. The sequencing of 16S rDNAs allowed to identify (i) among Chlamydiae: Parachlamydia acanthamoebae, Chlamydophila psittaci, Chlamydophila felis, and members of Rhabdochlamydiaceae, Simkaniaceae and E6 lineage and (ii) among Legionellaceae: Legionella longbeachae, Legionella bozemanii and Legionella impletisoli. Unexpectedly, we also recovered Diplorickettsia sp. Amoebae collected from nasal mucosae, Acanthamoeba and Vermamoeba, were endosymbiont-free, and chlamydiae revealed refractory to amoeba coculture. This study shows common exposure to chlamydiae and legionellae and suggests open air activities like gardening as a probable additional source of infection. PMID:25697709

  10. Comparison of Staphylococcus aureus isolates associated with food intoxication with isolates from human nasal carriers and human infections.

    PubMed

    Wattinger, L; Stephan, R; Layer, F; Johler, S

    2012-04-01

    Staphylococcus aureus represents an organism of striking versatility. While asymptomatic nasal colonization is widespread, it can also cause serious infections, toxinoses and life-threatening illnesses in humans and animals. Staphylococcal food poisoning (SFP), one of the most prevalent causes of foodborne intoxication worldwide, results from oral intake of staphylococcal enterotoxins leading to violent vomiting, diarrhea and cramps shortly upon ingestion. The aim of the present study was to compare isolates associated with SFP to isolates collected from cases of human nasal colonization and clinical infections in order to investigate the role of S. aureus colonizing and infecting humans as a possible source of SFP. Spa typing and DNA microarray profiling were used to characterize a total of 120 isolates, comprising 50 isolates collected from the anterior nares of healthy donors, 50 isolates obtained from cases of clinical infections in humans and 20 isolates related to outbreaks of staphylococcal food poisoning. Several common spa types were found among isolates of all three sources (t015, t018, t056, t084). DNA microarray results showed highly similar virulence gene profiles for isolates from all tested sources. These results suggest contamination of foodstuff with S. aureus colonizing and infecting food handlers to represent a source of SFP.

  11. Effectiveness of steam inhalation and nasal irrigation for chronic or recurrent sinus symptoms in primary care: a pragmatic randomized controlled trial

    PubMed Central

    Little, Paul; Stuart, Beth; Mullee, Mark; Thomas, Tammy; Johnson, Sophie; Leydon, Gerry; Rabago, David; Richards-Hall, Samantha; Williamson, Ian; Yao, Guiqing; Raftery, James; Zhu, Shihua; Moore, Michael

    2016-01-01

    Background: Systematic reviews support nasal saline irrigation for chronic or recurrent sinus symptoms, but trials have been small and few in primary care settings. Steam inhalation has also been proposed, but supporting evidence is lacking. We investigated whether brief pragmatic interventions to encourage use of nasal irrigation or steam inhalation would be effective in relieving sinus symptoms. Methods: We conducted a pragmatic randomized controlled trial involving adults (age 18–65 yr) from 72 primary care practices in the United Kingdom who had a history of chronic or recurrent sinusitis and reported a “moderate to severe” impact of sinus symptoms on their quality of life. Participants were recruited between Feb. 11, 2009, and June 30, 2014, and randomly assigned to 1 of 4 advice strategies: usual care, daily nasal saline irrigation supported by a demonstration video, daily steam inhalation, or combined treatment with both interventions. The primary outcome measure was the Rhinosinusitis Disability Index (RSDI). Patients were followed up at 3 and 6 months. We imputed missing data using multiple imputation methods. Results: Of the 961 patients who consented, 871 returned baseline questionnaires (210 usual care, 219 nasal irrigation, 232 steam inhalation and 210 combined treatment). A total of 671 (77.0%) of the 871 participants reported RSDI scores at 3 months. Patients’ RSDI scores improved more with nasal irrigation than without nasal irrigation by 3 months (crude change −7.42 v. −5.23; estimated adjusted mean difference between groups −2.51, 95% confidence interval −4.65 to −0.37). By 6 months, significantly more patients maintained a 10-point clinically important improvement in the RSDI score with nasal irrigation (44.1% v. 36.6%); fewer used over-the-counter medications (59.4% v. 68.0%) or intended to consult a doctor in future episodes. Steam inhalation reduced headache but had no significant effect on other outcomes. The proportion of

  12. Verruculogen associated with Aspergillus fumigatus hyphae and conidia modifies the electrophysiological properties of human nasal epithelial cells

    PubMed Central

    Khoufache, Khaled; Puel, Olivier; Loiseau, Nicolas; Delaforge, Marcel; Rivollet, Danièle; Coste, André; Cordonnier, Catherine; Escudier, Estelle; Botterel, Françoise; Bretagne, Stéphane

    2007-01-01

    Background The role of Aspergillus fumigatus mycotoxins in the colonization of the respiratory tract by conidia has not been studied extensively, even though patients at risk from invasive aspergillosis frequently exhibit respiratory epithelium damage. In a previous study, we found that filtrates of A. fumigatus cultures can specifically alter the electrophysiological properties of human nasal epithelial cells (HNEC) compared to those of non pathogenic moulds. Results We fractionated the organic phase of filtrate from 3-day old A. fumigatus cultures using high-performance liquid chromatography. The different fractions were tested for their ability to modify the electrophysiological properties of HNEC in an in vitro primary culture model. The fraction collected between 20 and 30 min mimicked the effects of the whole filtrate, i.e. decrease of transepithelial resistance and increase of potential differences, and contained secondary metabolites such as helvolic acid, fumagillin, and verruculogen. Only verruculogen (10-8 M) had effects similar to the whole filtrate. We verified that verruculogen was produced by a collection of 67 human, animal, plant and environmental A. fumigatus isolates. Using MS-MS analysis, we found that verruculogen was associated with both mycelium and conidia extracts. Conclusion Verruculogen is a secondary metabolite that modifies the electrophysiological properties of HNEC. The role of these modifications in the colonization and invasion of the respiratory epithelium by A. fumigatus on first contact with the epithelium remains to be determined. PMID:17244350

  13. Effect of budesonide and nedocromil sodium on IL-6 and IL-8 release from human nasal mucosa and polyp epithelial cells.

    PubMed

    Xaubet, A; Mullol, J; Roca-Ferrer, J; Pujols, L; Fuentes, M; Pérez, M; Fabra, J M; Picado, C

    2001-05-01

    We investigated the effect of budesonide and nedocromil sodium on the secretion of IL-6 and IL-8 by cultured epithelial cells from healthy nasal mucosa and nasal polyps. Human epithelial cell conditioned media was generated with fetal calf serum (FCS) in the presence or absence of budesonide and/or nedocromil sodium. Budesonide inhibited FCS-induced IL-6 and IL-8 release in a dose-dependent manner. The IC25 (25% inhibitory concentration) of budesonide on IL-6 release was higher in nasal polyp than in nasal mucosa epithelial cells (34 nM vs. 200 pM). The IC25 of budesonide on IL-8 release was higher in nasal mucosa than in nasal polyps (145 pM vs. 4 pM). Nedocromil sodium caused a dose-related inhibitory effect on IL-8 release from nasal mucosa (IC25, 207 nM), while it only had a significant effect in nasal polyps at 10(-5) M. Nedocromil sodium had no effect on IL-6 release. The inhibitory effect of budesonide was higher than that of nedocromil sodium on both nasal polyps and nasal mucosa. Budesonide and nedocromil sodium may exert their anti-inflammatory action in the respiratory mucosa by modulating the secretion of IL-6 and IL-8. The different effect of budesonide and nedocromil sodium on IL-6 and IL-8 release may be explained by differences in the mechanisms which regulate the upregulation of these cytokines in inflammatory responses.

  14. Dosimetry of nasal uptake of soluble and reactive gases: A first study of inter-human variability (Journal Article)

    EPA Science Inventory

    Anatomically accurate human child and adult nasal tract models will be used in concert with computationally simulated air flow information to investigate the influence of age-related differences in anatomy on inhalation dosimetry in the upper and lower airways. The findings of t...

  15. Effects of pH and dose on nasal absorption of scopolamine hydrobromide in human subjects

    NASA Technical Reports Server (NTRS)

    Ahmed, S.; Sileno, A. P.; deMeireles, J. C.; Dua, R.; Pimplaskar, H. K.; Xia, W. J.; Marinaro, J.; Langenback, E.; Matos, F. J.; Putcha, L.; Romeo, V. D.; Behl, C. R.

    2000-01-01

    PURPOSE: The present study was conducted to evaluate the effects of formulation pH and dose on nasal absorption of scopolamine hydrobromide, the single most effective drug available for the prevention of nausea and vomiting induced by motion sickness. METHODS: Human subjects received scopolamine nasally at a dose of 0.2 mg/0.05 mL or 0.4 mg/0.10 mL, blood samples were collected at different time points, and plasma scopolamine concentrations were determined by LC-MS/MS. RESULTS: Following administration of a 0.2 mg dose, the average Cmax values were found to be 262+/-118, 419+/-161, and 488+/-331 pg/ mL for pH 4.0, 7.0, and 9.0 formulations, respectively. At the 0.4 mg dose the average Cmax values were found to be 503+/-199, 933+/-449, and 1,308+/-473 pg/mL for pH 4.0, 7.0, and 9.0 formulations, respectively. At a 0.2 mg dose, the AUC values were found to be 23,208+/-6,824, 29,145+/-9,225, and 25,721+/-5,294 pg x min/mL for formulation pH 4.0, 7.0, and 9.0, respectively. At a 0.4 mg dose, the average AUC value was found to be high for pH 9.0 formulation (70,740+/-29,381 pg x min/mL) as compared to those of pH 4.0 (59,573+/-13,700 pg x min/mL) and pH 7.0 (55,298+/-17,305 pg x min/mL) formulations. Both the Cmax and AUC values were almost doubled with doubling the dose. On the other hand, the average Tmax, values decreased linearly with a decrease in formulation pH at both doses. For example, at a 0.4 mg dose, the average Tmax values were 26.7+/-5.8, 15.0+/-10.0, and 8.8+/-2.5 minutes at formulation pH 4.0, 7.0, and 9.0, respectively. CONCLUSIONS: Nasal absorption of scopolamine hydrobromide in human subjects increased substantially with increases in formulation pH and dose.

  16. Intrinsic chemosensory signal recorded from the human nasal mucosa in patients with smell loss.

    PubMed

    Ishimaru, Tadashi; Krone, Franziska; Scheibe, Mandy; Gudziol, Volker; Negoias, Simona; Hummel, Thomas

    2013-03-01

    Physiological investigation of olfactory receptor function in hyposmic or anosmic patients is rare. Pioneers examined the electro-olfactogram in patients with olfactory disturbance. Although the electro-olfactogram is an established method to record olfactory responses from human olfactory epithelium, the response is only measured at specific sites of the olfactory mucosa. In contrast to that the response of the olfactory epithelium to chemosensory stimuli can be studied in a specific nasal area by means of intrinsic optical signal recording. Five functionally anosmic patients were included in the present study. In all patients, responses could be obtained following trigeminal stimulation with CO2. In some patients, responses could be obtained after olfactory stimulation with H2S and PEA. The present data show that in the studied patients trigeminal function seems to be preserved, while it appears that in some patients olfactory function is preserved to a certain degree.

  17. Retinoic acid and hydrocortisone strengthen the barrier function of human RPMI 2650 cells, a model for nasal epithelial permeability.

    PubMed

    Kürti, Levente; Veszelka, Szilvia; Bocsik, Alexandra; Ozsvári, Béla; Puskás, László G; Kittel, Agnes; Szabó-Révész, Piroska; Deli, Mária A

    2013-05-01

    The nasal pathway represents an alternative route for non-invasive systemic administration of drugs. The main advantages of nasal drug delivery are the rapid onset of action, the avoidance of the first-pass metabolism in the liver and the easy applicability. In vitro cell culture systems offer an opportunity to model biological barriers. Our aim was to develop and characterize an in vitro model based on confluent layers of the human RPMI 2650 cell line. Retinoic acid, hydrocortisone and cyclic adenosine monophosphate, which influence cell attachment, growth and differentiation have been investigated on the barrier formation and function of the nasal epithelial cell layers. Real-time cell microelectronic sensing, a novel label-free technique was used for dynamic monitoring of cell growth and barrier properties of RPMI 2650 cells. Treatments enhanced the formation of adherens and tight intercellular junctions visualized by electron microscopy, the presence and localization of junctional proteins ZO-1 and β-catenin demonstrated by fluorescent immunohistochemistry, and the barrier function of nasal epithelial cell layers. The transepithelial resistance of the RPMI 2650 cell model reached 50 to 200 Ω × cm(2), the permeability coefficient for 4.4 kDa FITC-dextran was 9.3 to 17 × 10(-6) cm/s, in agreement with values measured on nasal mucosa from in vivo and ex vivo experiments. Based on these results human RPMI 2650 cells seem to be a suitable nasal epithelial model to test different pharmaceutical excipients and various novel formulations, such as nanoparticles for toxicity and permeability.

  18. Primary bone natural killer/T cell lymphoma, nasal type without EBV infection: a case report

    PubMed Central

    Tian, Chen; Wang, Yafei; Zhu, Lei; Yu, Yong; Zhang, Yizhuo

    2015-01-01

    Primary bone NK/T cell lymphoma is very rare. We report a case of 52-year-old man of primary bone NK/T cell lymphoma and then progressed to NK leukemia. The patient had low-grade fever for 4-month, and Ultrasonic B revealed a diffuse hepatosplenomegaly without lymphadenopathy. PET scanning showed increased FDG uptake in many bones of the whole body. The diagnosis was established by bone specimen. These neoplastic cells demonstrated a typical immunophenotype of CD56, CD3, CD2 and MPO positive, and CD5, CD20, CD30, PAX-5, CD4 and CD8 negative. Primary bone ENKTL is very rare; it should be made with the combination of clinical feature, PET-CT image, and pathological characteristics, and should be distinguished from other lymphomas or leukemia involved in bone. PMID:26823813

  19. The effects of oxymetazoline on lysozyme secretion from the human nasal mucosa.

    PubMed

    Browning, S; Housley, D; Richards, R; Eccles, R

    1997-11-01

    Lysozyme is a protein secreted by nasal submucosal glands. Its secretion is under cholinergic control. It is considered important in nasal defence as it enzymatically hydrolyses peptidoglycan bonds in bacterial cell walls and has specific activity against Gram-positive bacteria in vitro. Oxymetazoline is freely available as a non-prescription nasal decongestant. Some recent work has shown that it has no effect on histamine-induced plasma exudation but little is known about its effects on glandular secretion. The current study is a randomized controlled study that investigates the effect of topical oxymetazoline on the total protein and lysozyme content of nasal fluid. Thirty healthy volunteers were randomized to receive either a normal saline nasal spray (placebo) or an active spray of oxymetazoline, 0.05% (w/v) in saline. NAR was assessed in all subjects using posterior rhinomanometry and nasal lavage before the application of the spray and again 10 min later. The results were analysed using non-parametric statistics. There was a significant decrease in both the lysozyme and total protein content of nasal lavage after application of oxymetazoline when compared with placebo (p < 0.05). A possible mechanism for the observed decease in total protein and lysozyme would be that the vasoconstrictor effects of oxymetazoline also apply to the vessels supplying nasal submucosal glands and that this decrease in blood supply is reflected by a decrease in secretion.

  20. EFFECT OF DIESEL EXHAUST PARTICLES ON HUMAN NASAL LAVAGE CELLS AND DNA ADDUCTS

    EPA Science Inventory

    The overall aim of this study is to determine (using a nasal challenge model) the effect of diesel exhaust particles (DEP) on nasal responses including induction of inflammation, immune changes and DNA damage. We are also examining how treatment of DEP with ozone (oz-DEP)modify ...

  1. Endogenous antioxidants and nasal human epithelium response to air pollutants: genotoxic and inmmuno-cytochemical evaluation.

    PubMed

    Fortoul, T I; Rojas-Lemus, M; Avila-Casado, M C; Rodriguez-Lara, V; Montaño, L F; Muñoz-Comonfort, A; Lopez-Zepeda, L S

    2010-10-01

    Nasal epithelium is a source for identifying atmospheric pollution impact. Antioxidants play a relevant role in the protection of the cells from environmental injury, but scarce information is available about the interaction of endogenous antioxidants and genotoxic damage in nasal epithelium from urban populations highly exposed to traffic-generated air pollutants. An immunocytochemical and genotoxic evaluation was implemented in nasal cell epithelium in a population chronically exposed to atmospheric pollution from autumn 2004 to autumn 2005. Superoxide dismutase (SOD) and Catalase (CAT) were evaluated in nasal scrapings by morphometry and genotoxicity by comet assay. An increase in DNA damage correlates with a decrease in SOD and CAT in nasal cells during autumn and the inverse result was observed during summer (R = 0.88). Not only should exogenous antioxidant supplements be encouraged, but also a healthy diet to strengthen intracellular defenses against oxidative stress induced by exposure to air pollutants. PMID:20981858

  2. Nasal Cancer

    MedlinePlus

    ... the way to your throat as you breathe. Cancer of the nasal cavity and paranasal sinuses is ... be like those of infections. Doctors diagnose nasal cancer with imaging tests, lighted tube-like instruments that ...

  3. Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type, with Primary Manifestation as an Upper Eyelid Swelling.

    PubMed

    Kanzaki, Akiko; Funasaka, Yoko; Nakamizo, Munenaga; Shima, Ayaka; Ryotokuji, Takeshi; Dan, Kazuo; Terasaki, Mika; Sugisaki, Yuichi; Fukuda, Yu; Kawana, Seiji; Saeki, Hidehisa

    2016-01-01

    Extranodal natural killer/T-cell lymphoma (ENK/TCL) is most often in the nose or the nasopharynx but can present elsewhere. We report a rare case of ENK/TCL that presented as swelling of an upper eyelid without ocular involvement. A 76-year-old man visited our hospital with a swollen lesion of the left upper eyelid which had appeared 2 months earlier. A biopsy of the upper eyelid revealed slight perivascular and periadnexal infiltration of mononuclear cells with dermal edema. Treatment with oral prednisolone at a dosage of 20 mg/day decreased the eyelid swelling. However, 5 months later, exacerbation of the swelling and nasal congestion were observed. A second biopsy of the upper eyelid revealed a diffuse dermal infiltrate composed of mononuclear cells with an angiocentic growth pattern. Immunohistochemical studies and in situ hybridization showed natural killer-lineage antigens (CD56, granzyme B, and T-cell intracellular antigen 1) with expression of Epstein-Barr virus. These findings lead to the diagnosis of ENK/TCL. We treated the patient with radiation therapy (50 Gy) and 3 courses of a regimen including dexamethasone, carboplatin, etoposide, and ifosphamide. This case suggests that ENK/TCL can present with swelling of an upper eyelid as the primary sign of the skin lesion. Swelling of an upper eyelid should be considered in the differential diagnosis of ENK/TCL. PMID:27680487

  4. Aspects of nitrogen dioxide toxicity in environmental urban concentrations in human nasal epithelium

    SciTech Connect

    Koehler, C.; Ginzkey, C.; Friehs, G.; Hackenberg, S.; Froelich, K.; Scherzed, A.; Burghartz, M.; Kessler, M.; Kleinsasser, N.

    2010-06-01

    Cytotoxicity and genotoxicity of nitrogen dioxide (NO{sub 2}) as part of urban exhaust pollution are widely discussed as potential hazards to human health. This study focuses on toxic effects of NO{sub 2} in realistic environmental concentrations with respect to the current limit values in a human target tissue of volatile xenobiotics, the epithelium of the upper aerodigestive tract. Nasal epithelial cells of 10 patients were cultured as an air-liquid interface and exposed to 0.01 ppm NO{sub 2}, 0.1 ppm NO{sub 2}, 1 ppm NO{sub 2}, 10 ppm NO{sub 2} and synthetic air for half an hour. After exposure, genotoxicity was evaluated by the alkaline single-cell microgel electophoresis (Comet) assay and by induction of micronuclei in the micronucleus test. Depression of proliferation and cytotoxic effects were determined using the micronucleus assay and trypan blue exclusion assay, respectively. The experiments revealed genotoxic effects by DNA fragmentation starting at 0.01 ppm NO{sub 2} in the Comet assay, but no micronucleus inductions, no changes in proliferation, no signs of necrosis or apoptosis in the micronucleus assay, nor did the trypan blue exclusion assay show any changes in viability. The present data reveal a possible genotoxicity of NO{sub 2} in urban concentrations in a screening test. However, permanent DNA damage as indicated by the induction of micronuclei was not observed. Further research should elucidate the effects of prolonged exposure.

  5. 21 CFR 874.3900 - Nasal dilator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Prosthetic Devices § 874.3900 Nasal dilator. (a) Identification. A nasal... nasal airflow. The device decreases airway resistance and increases nasal airflow. The external...

  6. 21 CFR 874.3900 - Nasal dilator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Prosthetic Devices § 874.3900 Nasal dilator. (a) Identification. A nasal... nasal airflow. The device decreases airway resistance and increases nasal airflow. The external...

  7. Acute reinforcing effects of low-dose nicotine nasal spray in humans.

    PubMed

    Perkins, K A; Grobe, J E; Caggiula, A; Wilson, A S; Stiller, R L

    1997-02-01

    Tobacco smoking behavior is reinforced by nicotine intake, but there has been little human research examining self-administration of nicotine per se, isolated from tobacco. In this study, 10 smokers (5 men, 5 women) who wanted to quit smoking sampled 0 (placebo), 0.75, and 1.5 ug/kg/spray nicotine via nasal spray during separate lab sessions before engaging in a free choice session, involving ad lib access to all three spray doses. Subjects also ad lib smoked during another session. For the group as a whole, neither nicotine spray dose was self-administered significantly more than placebo during the free choice session, suggesting low abuse potential. However, 4 of 10 subjects self-administered 1.5 ug/kg/spray on more than 50% of all sprays (vs. 33% chance) and were designated nicotine "choosers," while the others were "nonchoosers." Choosers responded to initial nicotine spray exposure during sampling sessions with greater positive subjective effects (similar to their responses to tobacco smoking), smoked more during the ad lib smoking session (i.e., self-administered more nicotine via tobacco smoking), and tended to be more heavily dependent smokers. They did not report greater withdrawal relief or less aversive effects from nicotine, suggesting their greater nicotine choice reflected greater positive reinforcement rather than negative reinforcement. These results are consistent with the few existing studies demonstrating that acute nicotine intake per se, in the absence of tobacco, may be reinforcing in some smokers.

  8. Human upper respiratory tract responses to inhaled pollutants with emphasis on nasal lavage

    SciTech Connect

    Koren, H.S.; Devlin, R.B. )

    1992-04-30

    A set of symptoms has been described during the past two decades. These symptoms, which have been called the sick building syndrome, include eye, nose, and throat irritation; headache; mental fatigue; and respiratory distress. It is likely that VOCs present in synthetic materials used in homes and office buildings contribute to these symptoms. There have been few studies, however, in which humans have been exposed to known amounts of VOCs under carefully controlled conditions. In this study, 14 subjects have been exposed to a mixture of VOCs (25 mg/m3 total hydrocarbon) representative of what is found in new homes and office buildings. Because irritation of the nose and throat are symptoms often associated with the upper respiratory tract and may result from an inflammatory response in the upper airways, we have used NAL to monitor PMN influx into the nasal passages following exposure to VOCs. We report statistically significant increases in PMNs both immediately after a 4-hr exposure to VOCs, as well as 18 hr later.

  9. Effects of retinoic acid receptor-selective agonists on human nasal epithelial cell differentiation.

    PubMed

    Million, K; Tournier, F; Houcine, O; Ancian, P; Reichert, U; Marano, F

    2001-12-01

    Retinoids play a critical role in the maintenance of the mucociliary phenotype of epithelial cells in the upper respiratory tract. To determine the role of retinoic acid receptors (RARs) in the regulation of epithelial differentiation, we tested the effect of the synthetic retinoids CD336, CD2019, and CD666, selective agonists for RARalpha, RARbeta, and RARgamma, respectively, during differentiation of human nasal epithelial (HNE) cells in vitro. Using glutamylated tubulin and transglutaminase I (Tg I) as markers of ciliated cell and squamous cell differentiation, respectively, we showed that retinoic acid (RA) stimulated mucociliary differentiation and, in parallel, inhibited squamous cell differentiation. The agonists of the three RARs independently induced ciliogenesis and inhibited squamous cell differentiation by downregulating Tg I expression in a dose- and time-dependent manner. Antagonists specific for the three RARs abolished the effects of the corresponding agonists, demonstrating an RAR-specific mediated effect. Moreover, treatment of retinoid-deficient cultures with RAR agonists induced conversion of the squamous-like phenotype into a ciliated phenotype. In conclusion, all three RARs are potentially involved in the differentiating effects of RA in respiratory epithelial cells.

  10. Acute reinforcing effects of low-dose nicotine nasal spray in humans.

    PubMed

    Perkins, K A; Grobe, J E; Caggiula, A; Wilson, A S; Stiller, R L

    1997-02-01

    Tobacco smoking behavior is reinforced by nicotine intake, but there has been little human research examining self-administration of nicotine per se, isolated from tobacco. In this study, 10 smokers (5 men, 5 women) who wanted to quit smoking sampled 0 (placebo), 0.75, and 1.5 ug/kg/spray nicotine via nasal spray during separate lab sessions before engaging in a free choice session, involving ad lib access to all three spray doses. Subjects also ad lib smoked during another session. For the group as a whole, neither nicotine spray dose was self-administered significantly more than placebo during the free choice session, suggesting low abuse potential. However, 4 of 10 subjects self-administered 1.5 ug/kg/spray on more than 50% of all sprays (vs. 33% chance) and were designated nicotine "choosers," while the others were "nonchoosers." Choosers responded to initial nicotine spray exposure during sampling sessions with greater positive subjective effects (similar to their responses to tobacco smoking), smoked more during the ad lib smoking session (i.e., self-administered more nicotine via tobacco smoking), and tended to be more heavily dependent smokers. They did not report greater withdrawal relief or less aversive effects from nicotine, suggesting their greater nicotine choice reflected greater positive reinforcement rather than negative reinforcement. These results are consistent with the few existing studies demonstrating that acute nicotine intake per se, in the absence of tobacco, may be reinforcing in some smokers. PMID:9050080

  11. Enhancing Effect of Borneol and Muscone on Geniposide Transport across the Human Nasal Epithelial Cell Monolayer

    PubMed Central

    Chen, Zhenzhen; Gong, Xin; Lu, Yang; Du, Shouying; Yang, Zhihui; Bai, Jie; Li, Pengyue; Wu, Huichao

    2014-01-01

    Geniposide is widely used in the treatment of cerebral ischemic stroke and cerebrovascular diseases for its anti-thrombotic and anti-inflammatory effects. Recent studies demonstrated that geniposide could be absorbed promptly and thoroughly by intranasal administration in mice and basically transported into the brain. Here, we explored its transport mechanism and the effect of borneol and muscone on its transport by human nasal epithelial cell (HNEC) monolayer. The cytotoxicity of geniposide, borneol, muscone and their combinations on HNECs was evaluated by the MTT assay. Transcellular transport of geniposide and the influence of borneol and muscone were studied using the HNEC monolayer. Immunostaining and transepithelial electrical resistance were measured to assess the integrity of the monolayer. The membrane fluidity of HNEC was evaluated by fluorescence recovery after photobleaching. Geniposide showed relatively poor absorption in the HNEC monolayer and it was not a P-gp substrate. Geniposide transport in both directions significantly increased when co-administrated with increasing concentrations of borneol and muscone. The enhancing effect of borneol and muscone on geniposide transport across the HNEC may be attributed to the significant enhancement on cell membrane fluidity, disassembly effect on tight junction integrity and the process was reversible. These results indicated that intranasal administration has good potential to treat cerebrovascular diseases. PMID:24992195

  12. Human Immunodeficiency Virus (HIV) Primary Infection

    MedlinePlus

    ... rashes clinical tools newsletter | contact Share | Human Immunodeficiency Virus (HIV) Primary Infection Information for adults A A ... weeks following exposure to HIV (the human immunodeficiency virus). Chronic infection with this virus can cause AIDS ( ...

  13. Cartilage tissue engineering of nasal septal chondrocyte-macroaggregates in human demineralized bone matrix.

    PubMed

    Liese, Juliane; Marzahn, Ulrike; El Sayed, Karym; Pruss, Axel; Haisch, Andreas; Stoelzel, Katharina

    2013-06-01

    Tissue Engineering is an important method for generating cartilage tissue with isolated autologous cells and the support of biomaterials. In contrast to various gel-like biomaterials, human demineralized bone matrix (DBM) guarantees some biomechanical stability for an application in biomechanically loaded regions. The present study combined for the first time the method of seeding chondrocyte-macroaggregates in DBM for the purpose of cartilage tissue engineering. After isolating human nasal chondrocytes and creating a three-dimensional macroaggregate arrangement, the DBM was cultivated in vitro with the macroaggregates. The interaction of the cells within the DBM was analyzed with respect to cell differentiation and the inhibitory effects of chondrocyte proliferation. In contrast to chondrocyte-macroaggregates in the cell-DBM constructs, morphologically modified cells expressing type I collagen dominated. The redifferentiation of chondrocytes, characterized by the expression of type II collagen, was only found in low amounts in the cell-DBM constructs. Furthermore, caspase 3, a marker for apoptosis, was detected in the chondrocyte-DBM constructs. In another experimental setting, the vitality of chondrocytes as related to culture time and the amount of DBM was analyzed with the BrdU assay. Higher amounts of DBM tended to result in significantly higher proliferation rates of the cells within the first 48 h. After 96 h, the vitality decreased in a dose-dependent fashion. In conclusion, this study provides the proof of concept of chondrocyte-macroaggregates with DBM as an interesting method for the tissue engineering of cartilage. The as-yet insufficient redifferentiation of the chondrocytes and the sporadic initiation of apoptosis will require further investigations.

  14. Effect of oxygen tension on tissue-engineered human nasal septal chondrocytes

    PubMed Central

    Twu, Chih-Wen; Reuther, Marsha S.; Briggs, Kristen K.; Sah, Robert L.; Masuda, Koichi

    2014-01-01

    Tissue-engineered nasal septal cartilage may provide a source of autologous tissue for repair of craniofacial defects. Although advances have been made in manipulating the chondrocyte culture environment for production of neocartilage, consensus on the best oxygen tension for in vitro growth of tissue-engineered cartilage has not been reached. The objective of this study was to determine whether in vitro oxygen tension influences chondrocyte expansion and redifferentiation. Proliferation of chondrocytes from 12 patients expanded in monolayer under hypoxic (5% or 10%) or normoxic (21%) oxygen tension was compared over 14 days of culture. The highest performing oxygen level was used for further expansion of the monolayer cultures. At confluency, chondrocytes were redifferentiated by encapsulation in alginate beads and cultured for 14 days under hypoxic (5 or 10%) or normoxic (21%) oxygen tension. Biochemical and histological properties were evaluated. Chondrocyte proliferation in monolayer and redifferentiation in alginate beads were supported by all oxygen tensions tested. Chondrocytes in monolayer culture had increased proliferation at normoxic oxygen tension (p = 0.06), as well as greater accumulation of glycosaminoglycan (GAG) during chondrocyte redifferentiation (p < 0.05). Chondrocytes released from beads cultured under all three oxygen levels showed robust accumulation of GAG and type II collagen with a lower degree of type I collagen immunoreactivity. Finally, formation of chondrocyte clusters was associated with decreasing oxygen tension (p < 0.05). Expansion of human septal chondrocytes in monolayer culture was greatest at normoxic oxygen tension. Both normoxic and hypoxic culture of human septal chondrocytes embedded in alginate beads supported robust extracellular matrix deposition. However, GAG accumulation was significantly enhanced under normoxic culture conditions. Chondrocyte cluster formation was associated with hypoxic oxygen tension. PMID:25565047

  15. Nasal disease and asthma.

    PubMed

    Marseglia, G L; Merli, P; Caimmi, D; Licari, A; Labó, E; Marseglia, A; Ciprandi, G; La Rosa, M

    2011-10-01

    The nose plays a primary role within the airways, working as a filter and air-conditioner, together with other important functions. Thus, it is not surprising that nasal diseases are associated with several other comorbidities, including both upper and lower airways, such as bronchial hyperresponsiveness (BHR) and asthma. Several studies have investigated the relationship existing between the upper and the lower airways and new insights are rising. Nevertheless, some uncertainties still remain, mainly because nasal disorders are quite heterogeneous, overlapping (i.e. rhinitis-rhinosinusitis-sinusitis, acute or chronic, allergic or non-allergic) and difficult to diagnose, so that, frequently, many studies don’t differentiate between the various conditions. For this reason, the purpose of this review is to systematically analyze present epidemiological, pathophysiological and clinical data on the relationship between nasal diseases and asthma, splitting up three main conditions: allergic rhinitis, chronic rhinosinusitis and nasal polyposis. PMID:22032779

  16. Responsiveness of human nasal mucosa to trigeminal stimuli depends on the site of stimulation.

    PubMed

    Frasnelli, Johannes; Heilmann, Stefan; Hummel, Thomas

    2004-05-13

    There is evidence that functionally different areas can be distinguished within the nasal mucosa with regard to stimulation site and stimulus properties. The aim of the present study was the comparison of electrophysiological and psychophysical measures obtained in response to mechanical and chemosomatosensory stimulation of two different regions of the nasal mucosa. A total of 40 volunteers participated in this study (age range 21-36 years). Chemosomatosensory event-related potentials (ERPs) were recorded using gaseous CO2 as stimulant, while somatosensory ERPs were recorded in response to intranasal mechanical stimuli (air puffs). Stimuli were released to the anterior portion and to the posterior portion of the nasal cavity. A significant interaction between stimulus properties and site of stimulation could be detected after analysis of ERP parameters and intensity ratings. Thus, the chemosensory stimulus was perceived as stronger in the anterior portion of the nasal cavity whereas this was not the case for mechanosensory stimuli. In addition, mechanosensory stimuli were found to evoke ERPs with shorter latencies. These results underline the idea that the respiratory mucosa should not be seen as a homogeneous tissue. It exhibits varying sensitivities to trigeminal stimulation depending on stimulus quality and site of stimulation. Hence, perception of chemosensory stimuli seems to be most accurate in the anterior portion of the nasal cavity, while sensitivity to mechanical stimuli appears to be highest in the posterior portion. In addition, these differences within the respiratory mucosa may contribute to differences in the perception of orthonasal and retronasal odorous stimulation.

  17. N-acetylcysteine inhibits Na+ absorption across human nasal epithelial cells.

    PubMed

    Rochat, Thierry; Lacroix, Jean-Silvain; Jornot, Lan

    2004-10-01

    N-acetylcysteine (NAC) is a widely used mucolytic drug in patients with a variety of respiratory disorders. The mechanism of action is based on rupture of the disulfide bridges of the high molecular glycoproteins present in the mucus, resulting in smaller subunits of the glycoproteins and reduced viscosity of the mucus. Because Na(+) absorption regulates airway surface liquid volume and thus the efficiency of mucociliary clearance, we asked whether NAC affects the bioelectric properties of human nasal epithelial cells. A 24-h basolateral treatment with 10 mM of NAC decreased the transepithelial potential difference and short-circuit current (I(SC)) by 40%, and reduced the amiloride-sensitive current by 50%, without affecting the transepithelial resistance. After permeabilization of the basolateral membranes of cells with amphotericin B in the presence of a mucosal-to-serosal Na(+) gradient (135:25 mM), NAC inhibited 45% of the amiloride-sensitive current. The Na(+)-K(+)-ATPase pump activity and the basolateral K(+) conductance were not affected by NAC treatment. NAC did not alter total cell mRNA and protein levels of alpha-epithelial Na(+) channel (EnaC) subunit, but reduced abundance of alpha-ENaC subunits in the apical cell membrane as quantified by biotinylation. This effect can be ascribed to the sulphydryl (SH) group of NAC, since N-acetylserine and S-carboxymethyl-l-cysteine were ineffective. Given the importance of epithelial Na(+) channels in controlling the thin layer of fluid that covers the surface of the airways, the increase in the fluidity of the airway mucus following NAC treatment in vivo might be in part related to downregulation of Na(+) absorption and consequently water transport. PMID:15281093

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

    PubMed

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

    2013-12-01

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

  19. N-acetylcysteine inhibits Na+ absorption across human nasal epithelial cells.

    PubMed

    Rochat, Thierry; Lacroix, Jean-Silvain; Jornot, Lan

    2004-10-01

    N-acetylcysteine (NAC) is a widely used mucolytic drug in patients with a variety of respiratory disorders. The mechanism of action is based on rupture of the disulfide bridges of the high molecular glycoproteins present in the mucus, resulting in smaller subunits of the glycoproteins and reduced viscosity of the mucus. Because Na(+) absorption regulates airway surface liquid volume and thus the efficiency of mucociliary clearance, we asked whether NAC affects the bioelectric properties of human nasal epithelial cells. A 24-h basolateral treatment with 10 mM of NAC decreased the transepithelial potential difference and short-circuit current (I(SC)) by 40%, and reduced the amiloride-sensitive current by 50%, without affecting the transepithelial resistance. After permeabilization of the basolateral membranes of cells with amphotericin B in the presence of a mucosal-to-serosal Na(+) gradient (135:25 mM), NAC inhibited 45% of the amiloride-sensitive current. The Na(+)-K(+)-ATPase pump activity and the basolateral K(+) conductance were not affected by NAC treatment. NAC did not alter total cell mRNA and protein levels of alpha-epithelial Na(+) channel (EnaC) subunit, but reduced abundance of alpha-ENaC subunits in the apical cell membrane as quantified by biotinylation. This effect can be ascribed to the sulphydryl (SH) group of NAC, since N-acetylserine and S-carboxymethyl-l-cysteine were ineffective. Given the importance of epithelial Na(+) channels in controlling the thin layer of fluid that covers the surface of the airways, the increase in the fluidity of the airway mucus following NAC treatment in vivo might be in part related to downregulation of Na(+) absorption and consequently water transport.

  20. Differential response of human nasal and bronchial epithelial cells upon exposure to size-fractionated dairy dust.

    PubMed

    Hawley, Brie; Schaeffer, Joshua; Poole, Jill A; Dooley, Gregory P; Reynolds, Stephen; Volckens, John

    2015-01-01

    Exposure to organic dusts is associated with increased respiratory morbidity and mortality in agricultural workers. Organic dusts in dairy farm environments are complex, polydisperse mixtures of toxic and immunogenic compounds. Previous toxicological studies focused primarily on exposures to the respirable size fraction; however, organic dusts in dairy farm environments are known to contain larger particles. Given the size distribution of dusts from dairy farm environments, the nasal and bronchial epithelia represent targets of agricultural dust exposures. In this study, well-differentiated normal human bronchial epithelial cells and human nasal epithelial cells were exposed to two different size fractions (PM10 and PM>10) of dairy parlor dust using a novel aerosol-to-cell exposure system. Levels of proinflammatory transcripts (interleukin [IL]-8, IL-6, and tumor necrosis factor [TNF]-α) were measured 2 h after exposure. Lactate dehydrogenase (LDH) release was also measured as an indicator of cytotoxicity. Cell exposure to dust was measured in each size fraction as a function of mass, endotoxin, and muramic acid levels. To our knowledge, this is the first study to evaluate the effects of distinct size fractions of agricultural dust on human airway epithelial cells. Our results suggest that both PM10 and PM>10 size fractions elicit a proinflammatory response in airway epithelial cells and that the entire inhalable size fraction needs to be considered when assessing potential risks from exposure to agricultural dusts. Further, data suggest that human bronchial cells respond differently to these dusts than human nasal cells, and therefore that the two cell types need to be considered separately in airway cell models of agricultural dust toxicity. PMID:25965193

  1. Primary Intestinal Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type: A Comprehensive Clinicopathological Analysis of 55 Cases

    PubMed Central

    Yu, Bao-Hua; Shui, Ruo-Hong; Sheng, Wei-Qi; Wang, Chao-Fu; Lu, Hong-Fen; Zhou, Xiao-Yan; Zhu, Xiong-Zeng; Li, Xiao-Qiu

    2016-01-01

    Purpose To investigate the clinicopathological features, survival and prognostic factors of primary intestinal extranodal natural killer/T-cell lymphoma, nasal type (PI-ENKTCL). Methods Clinical and histological characteristics of PI-ENKTCL cases were retrospectively evaluated. Immunohistochemical phenotype and status of Epstein-Barr virus (EBV) and T-cell receptor (TCR) gene rearrangement were examined. The overall survival and prognostic parameters were also analyzed. Results Fifty-five (2.7%) cases with PI-ENKTCL were identified out of 2017 archived ENKTCL cases, with a median age of 39 years and a male to female ratio of 2.1:1. The most common symptom was abdominal pain (90.9%), accompanied frequently with fever and less commonly with intestinal perforation or B symptoms. Small intestine (50.9%) was the most common site to be involved. 47.3% and 36.4% cases presented with stage I and II diseases, respectively. Histologically, most cases displayed characteristic morphologic changes of ENKTCL. Cytoplasmic CD3, TIA-1 and CD56 expression was found in 100%, 94.5% and 89.1% of cases, respectively. In situ hybridization detection for EBV demonstrated positive results in all cases. Monoclonal TCR gene rearrangement was found in 52.9% of tested cases. Chemotherapy with a DICE or L-asparaginase/peg-asparginase-containing regimen was most often employed. Both advanced tumor stage and B symptoms were independent inferior prognostic factors (p = 0.001 and p = 0.010). Noticeably, 6 cases demonstrated a CD4-positive phenotype. These cases featured a relatively older median age (58 years), predominance of small/medium-sized neoplastic cells, a higher rate of TCR rearrangement and slightly favorable outcome. Conclusion We reported by far the largest series of PI-ENKTCL, and demonstrated its heterogeneity, aggressive clinical behavior and unsatisfying response to the current therapeutic strategies. Those CD4-positive cases might represent a unique subtype of PI-ENKTCL or

  2. Transcriptomic analysis across nasal, temporal, and macular regions of human neural retina and RPE/choroid by RNA-Seq.

    PubMed

    Whitmore, S Scott; Wagner, Alex H; DeLuca, Adam P; Drack, Arlene V; Stone, Edwin M; Tucker, Budd A; Zeng, Shemin; Braun, Terry A; Mullins, Robert F; Scheetz, Todd E

    2014-12-01

    Proper spatial differentiation of retinal cell types is necessary for normal human vision. Many retinal diseases, such as Best disease and male germ cell associated kinase (MAK)-associated retinitis pigmentosa, preferentially affect distinct topographic regions of the retina. While much is known about the distribution of cell types in the retina, the distribution of molecular components across the posterior pole of the eye has not been well-studied. To investigate regional difference in molecular composition of ocular tissues, we assessed differential gene expression across the temporal, macular, and nasal retina and retinal pigment epithelium (RPE)/choroid of human eyes using RNA-Seq. RNA from temporal, macular, and nasal retina and RPE/choroid from four human donor eyes was extracted, poly-A selected, fragmented, and sequenced as 100 bp read pairs. Digital read files were mapped to the human genome and analyzed for differential expression using the Tuxedo software suite. Retina and RPE/choroid samples were clearly distinguishable at the transcriptome level. Numerous transcription factors were differentially expressed between regions of the retina and RPE/choroid. Photoreceptor-specific genes were enriched in the peripheral samples, while ganglion cell and amacrine cell genes were enriched in the macula. Within the RPE/choroid, RPE-specific genes were upregulated at the periphery while endothelium associated genes were upregulated in the macula. Consistent with previous studies, BEST1 expression was lower in macular than extramacular regions. The MAK gene was expressed at lower levels in macula than in extramacular regions, but did not exhibit a significant difference between nasal and temporal retina. The regional molecular distinction is greatest between macula and periphery and decreases between different peripheral regions within a tissue. Datasets such as these can be used to prioritize candidate genes for possible involvement in retinal diseases with

  3. A Real-time Method to Evaluate the Nasal Deposition and Clearance of Acetone in the Human Volunteer

    SciTech Connect

    Thrall, Karla D. ); Schwartz, Ronald E.; Weitz, Karl K. ); Soelberg, Jolen J. ); Foureman, Gary L.; Prah, James D.; Timchalk, Charles

    2003-05-01

    Nasal dosimetry models have become increasingly quantitative as insights into tissue deposition/clearance and computational fluid dynamics have become available. Validation of these models requires sufficient experimental data. However, investigations into respiratory deposition, particularly in human volunteers, have been historically limited due to methodological limitations. To overcome this, a method for evaluating the nasal wash-in, wash-out phenomena of a highly water-soluble compound in human volunteers was developed and characterized. This methodology was assessed using controlled human inhalation exposures to uniformly labeled 13C-acetone at approximately 1 ppm concentration for 30 minutes under different breathing maneuvers (inhale nose/exhale nose; inhale nose/exhale mouth; inhale mouth/exhale nose). A small-diameter air-sampling probe inserted in the nasopharyngeal cavity of the volunteer was connected directly to an ion-trap mass spectrometer capable of sampling every 0.8 sec. A second ion-trap mass spectrometer simultaneously sampled from the volunteer?s exhaled breath stream via a breath-inlet device interface. Together, the two mass spectrometers provided real-time appraisal of the 13C-acetone concentrations in the nasopharyngeal region and in the exhaled breath stream before, during, and after the different breathing maneuvers. The breathing cycle (depth and frequency) and heart rate were concurrently monitored throughout the exposure using a heart rate monitor and a human plethysmograph to differentiate inhalation and exhalation. Graphical overlay of the plethysmography results with the mass spectrometer measurements show clear quantifiable differences in 13C-acetone levels at the nasal probe as a function of breathing maneuvers. Breath-by-breath analysis of 13C-acetone concentrations indicate that between 40-75% of the compound is absorbed upon inhalation and nearly all of that absorbed released back into the breath stream during exhalation.

  4. Transcriptomic analysis across nasal, temporal, and macular regions of human neural retina and RPE/choroid by RNA-Seq

    PubMed Central

    Whitmore, S. Scott; Wagner, Alex H.; DeLuca, Adam P.; Drack, Arlene V.; Stone, Edwin M.; Tucker, Budd A.; Zeng, Shemin; Braun, Terry A.; Mullins, Robert F.; Scheetz, Todd E.

    2014-01-01

    Proper spatial differentiation of retinal cell types is necessary for normal human vision. Many retinal diseases, such as Best disease and male germ cell associated kinase (MAK)-associated retinitis pigmentosa, preferentially affect distinct topographic regions of the retina. While much is known about the distribution of cell-types in the retina, the distribution of molecular components across the posterior pole of the eye has not been well-studied. To investigate regional difference in molecular composition of ocular tissues, we assessed differential gene expression across the temporal, macular, and nasal retina and retinal pigment epithelium (RPE)/choroid of human eyes using RNA-Seq. RNA from temporal, macular, and nasal retina and RPE/choroid from four human donor eyes was extracted, poly-A selected, fragmented, and sequenced as 100 bp read pairs. Digital read files were mapped to the human genome and analyzed for differential expression using the Tuxedo software suite. Retina and RPE/choroid samples were clearly distinguishable at the transcriptome level. Numerous transcription factors were differentially expressed between regions of the retina and RPE/choroid. Photoreceptor-specific genes were enriched in the peripheral samples, while ganglion cell and amacrine cell genes were enriched in the macula. Within the RPE/choroid, RPE-specific genes were upregulated at the periphery while endothelium associated genes were upregulated in the macula. Consistent with previous studies, BEST1 expression was lower in macular than extramacular regions. The MAK gene was expressed at lower levels in macula than in extramacular regions, but did not exhibit a significant difference between nasal and temporal retina. The regional molecular distinction is greatest between macula and periphery and decreases between different peripheral regions within a tissue. Datasets such as these can be used to prioritize candidate genes for possible involvement in retinal diseases with

  5. [Adult of Drosophila melanogaster parasitized in human nasal cavity: a case report].

    PubMed

    Zhan, Xiaodong; Tang, Xiaoniu; Wang, Shaosheng

    2015-05-01

    We reported a case of adult Drosophila melanogaster parasitized in nasal cavity of a 81-year-old woman who was living in Xuancheng City, Anhui Province now. She was admitted for treatment of cerebral infarction and water accumulation in the lungs in 2014 June. The patient was also suffering from secretory otitis media, a history of hypertension and heart stents were placed in 2007. A foreign body was found in the left nasal cavity during the preoperative examination process, and then the part of the inflammatory tissue was removed through the nasal endoscopy, and sent to our department for identification. There are three adults of Drosophila in paraffin-embedded biopsy specimens. The parasites length is approximately 3mm, with huge red compound eyes. The end of the body is tip, with 5 ring lines in back, has no dark spots. The abdomen of the parasites have seven sections. Tarsus of foot I have no sex comb on base, and they are male adult of Drosophila melanogaster after identification. After a thorough reviewing of medical history, we knew the patient began to sneeze violently and frequently six years ago. But there was no clear or purulent nasal discharge flowing, therefore did not attract attention. After removing the parasites the sneezing symptoms were relieved, and had no abnormal symptoms in the follow-up 6 months. PMID:26281068

  6. Airflow in the Human Nasal Passage and Sinuses of Chronic Rhinosinusitis Subjects

    PubMed Central

    Kumar, Haribalan; Jain, Ravi; Douglas, Richard G.; Tawhai, Merryn H.

    2016-01-01

    Endoscopic surgery is performed on patients with chronic inflammatory disease of the paranasal sinuses to improve sinus ventilation. Little is known about how sinus surgery affects sinonasal airflow. In this study nasal passage geometry was reconstructed from computed tomographic imaging from healthy normal, pre-operative, and post-operative subjects. Transient air flow through the nasal passage during calm breathing was simulated. Subject-specific differences in ventilation of the nasal passage were observed. Velocity magnitude at ostium was different between left and right airway. In FESS, airflow in post-surgical subjects, airflow at the maxillary sinus ostium was upto ten times higher during inspiration. In a Lothrop procedure, airflow at the frontal sinus ostium can be upto four times higher during inspiration. In both post-operative subjects, airflow at ostium was not quasi-steady. The subject-specific effect (of surgery) on sinonasal interaction evaluated through airflow simulations may have important consequences for pre- and post-surgical assessment and surgical planning, and design for improvement of the delivery efficiency of nasal therapeutics. PMID:27249219

  7. Different reactions of human nasal and Eustachian tube mucosa after hyperbaric oxygen exposure: a pilot study.

    PubMed

    Mutzbauer, Till S; Neubauer, Birger; Tetzlaff, Kay

    2013-03-01

    Impairment of Eustachian tube function has been observed after hyperbaric oxygen treatment as well as after diving on oxygen used as breathing gas. The aim of the present study was to evaluate the influence of hyperbaric oxygen exposure on Eustachian tube ventilatory function and airflow characteristics of the nose. Six police task force divers performing two consecutive dives within a regular training schedule on oxygen were examined. Middle ear impedance, and nasal airflow velocities before and after diving as well as on the morning after the dive day were measured. Middle ear impedance decreased overnight in comparison to pre-dive values (P = 0.027) as well as compared to the value after the first dive (P = 0.032). Rhinoflowmetry did not reveal any changes of nasal airflow velocities related to the dives. Furthermore, no association between middle ear impedance and nasal airflow velocities was found. An impairment of Eustachian tube ventilatory function was obtained after hyperbaric oxygen exposure during dives employing oxygen as breathing gas. This impairment, however, was not associated with altered airflow characteristics of divers' noses. Thus, it seems unlikely that hyperbaric oxygen exerts an effect on the nasal mucosa similar to that on the Eustachian tube mucosa.

  8. A Review of the Comparative Anatomy, Histology, Physiology and Pathology of the Nasal Cavity of Rats, Mice, Dogs and Non-human Primates. Relevance to Inhalation Toxicology and Human Health Risk Assessment.

    PubMed

    Chamanza, R; Wright, J A

    2015-11-01

    There are many significant differences in the structural and functional anatomy of the nasal cavity of man and laboratory animals. Some of the differences may be responsible for the species-specific nasal lesions that are often observed in response to inhaled toxicants. This paper reviews the comparative anatomy, physiology and pathology of the nasal cavity of the rat, mouse, dog, monkey and man, highlighting factors that may influence the distribution of nasal lesions. Gross anatomical variations such as turbinate structure, folds or grooves on nasal walls, or presence or absence of accessory structures, may influence nasal airflow and species-specific uptake and deposition of inhaled material. In addition, interspecies variations in the morphological and biochemical composition and distribution of the nasal epithelium may affect the local tissue susceptibility and play a role in the development of species-specific nasal lesions. It is concluded that, while the nasal cavity of the monkey might be more similar to that of man, each laboratory animal species provides a model that responds in a characteristic and species-specific manner. Therefore for human risk assessment, careful consideration must be given to the anatomical differences between a given animal model and man.

  9. A multicentre, randomised controlled, non-inferiority trial, comparing high flow therapy with nasal continuous positive airway pressure as primary support for preterm infants with respiratory distress (the HIPSTER trial): study protocol

    PubMed Central

    Roberts, Calum T; Owen, Louise S; Manley, Brett J; Donath, Susan M; Davis, Peter G

    2015-01-01

    Introduction High flow (HF) therapy is an increasingly popular mode of non-invasive respiratory support for preterm infants. While there is now evidence to support the use of HF to reduce extubation failure, there have been no appropriately designed and powered studies to assess the use of HF as primary respiratory support soon after birth. Our hypothesis is that HF is non-inferior to the standard treatment—nasal continuous positive airway pressure (NCPAP)— as primary respiratory support for preterm infants. Methods and analysis The HIPSTER trial is an unblinded, international, multicentre, randomised, non-inferiority trial. Eligible infants are preterm infants of 28–36+6 weeks’ gestational age (GA) who require primary non-invasive respiratory support for respiratory distress in the first 24 h of life. Infants are randomised to treatment with either HF or NCPAP. The primary outcome is treatment failure within 72 h after randomisation, as determined by objective oxygenation, blood gas, and apnoea criteria, or the need for urgent intubation and mechanical ventilation. Secondary outcomes include the incidence of intubation, pneumothorax, bronchopulmonary dysplasia, nasal trauma, costs associated with hospital care and parental stress. With a specified non-inferiority margin of 10%, using a two-sided 95% CI and 90% power, the study requires 375 infants per group (total 750 infants). Ethics and dissemination Ethical approval has been granted by the relevant human research ethics committees at The Royal Women's Hospital (13/12), The Royal Children's Hospital (33144A), The Mercy Hospital for Women (R13/34), and the South-Eastern Norway Regional Health Authority (2013/1657). The trial is currently recruiting at 9 centres in Australia and Norway. The trial results will be published in peer-reviewed international journals, and presented at national and international conferences. Trial registration number Australian New Zealand Clinical Trials Registry ID: ACTRN

  10. Hydrogen sulphide in human nasal air quantified using thermal desorption and selected ion flow tube mass spectrometry.

    PubMed

    Wondimu, Taddese; Wang, Rui; Ross, Brian

    2014-09-01

    The discovery that hydrogen sulphide (H2S) acts as a gasotransmitter when present at very low concentrations (sub-parts per billion (ppbv)) has resulted in the need to quickly quantify trace amounts of the gas in complex biological samples. Selected ion flow tube mass spectrometry (SIFT-MS) is capable of real-time quantification of H2S but many SIFT-MS instruments lack sufficient sensitivity for this application. In this study we investigate the utility of combining thermal desorption with SIFT-MS for quantifying H2S in the 0.1-1 ppbv concentration range. Human orally or nasally derived breath, and background ambient air, were collected in sampling bags and dried by passing through CaCl2 and H2S pre-concentrated using a sorbent trap optimised for the capture of this gas. The absorbed H2S was then thermally desorbed and quantified by SIFT-MS. H2S concentrations in ambient air, nasal breath and oral breath collected from 10 healthy volunteers were 0.12  ±  0.02 (mean ± SD), 0.40  ±  0.11 and 3.1  ±  2.5 ppbv respectively, and in the oral cavity H2S, quantified by SIFT-MS without pre-concentration, was present at 13.5  ±  8.6 ppbv. The oral cavity H2S correlates well with oral breath H2S but not with nasal breath H2S, suggesting that oral breath H2S derives mainly from the oral cavity but nasal breath is likely pulmonary in origin. The successful quantification of such low concentrations of H2S in nasal air using a rapid analytical procedure paves the way for the straightforward analysis of H2S in breath and may assist in elucidating the role that H2S plays in biological systems.

  11. Nasal polyps

    MedlinePlus

    ... BS, Burks AW, et al, eds. Middleton's Allergy: Principles and Practice . 8th ed. Philadelphia, PA: Elsevier Saunders; 2014:chap 43. Becker SS. Surgical management of polyps in the treatment of nasal airway ...

  12. Nasal Physiology

    MedlinePlus

    ... nose is constantly exposed to inhaled debris and microbes (viruses, bacteria, and fungus). The respiratory system has ... Mucus is designed to trap inhaled particles (including microbes) that are subsequently cleared from the airways. Nasal ...

  13. Neandertal nasal structures and upper respiratory tract “specialization”

    PubMed Central

    Franciscus, Robert G.

    1999-01-01

    Schwartz and Tattersall [Schwartz, J. H. & Tattersall, I. (1996) Proc. Natl. Acad. Sci. USA 93, 10852–10854] have argued for a previously unrecognized suite of autapomorphies in the internal nasal region of Neandertals that make them unique, not only among hominids, but possibly among all other terrestrial mammals. These purported autapomorphies include (i) the development of an internal nasal margin bearing a well developed and vertically oriented medial projection; (ii) a pronounced medial swelling of the lateral nasal wall into the posterior nasal cavity; and (iii) the lack of an ossified roof over the lacrimal groove. In addition, Laitman et al. [Laitman, J. T., Reidenberg, J. S., Marquez, S. & Gannon, P. J. (1996) Proc. Natl. Acad. Sci. USA 93, 10543–10545] pointed to these features as evidence for upper respiratory tract specializations among the Neandertals, indicating potential differences in behavior compared with modern humans. Critically reviewing the anatomical basis for Schwartz and Tattersall’s contentions reveals several serious problems with their analysis, including (i) reliance on specimens with damaged, incomplete, or, in some cases, entirely absent relevant anatomy; (ii) failure to consider primary vs. secondary spatial consequences in nasal trait conceptualization; and (iii) failure to consider actual ranges of variation in these traits in both fossil and recent humans. Accordingly, the unique phylogenetic and adaptive “specializations” attributed to Neandertal internal nasal structures are unwarranted. PMID:9990106

  14. [Primary human demodicosis. A disease sui generis].

    PubMed

    Hsu, C-K; Zink, A; Wei, K-J; Dzika, E; Plewig, G; Chen, W

    2015-03-01

    Human Demodex mites (Demodex folliculorum and Demodex brevis) are unique in that they are an obligate human ectoparasite that can inhabit the pilosebaceous unit lifelong without causing obvious host immune response in most cases. The mode of symbiosis between humans and human Demodex mites is unclear, while the pathogenicity of human Demodex mites in many inflammatory skin diseases is now better understood. Primary human demodicosis is a skin disease sui generis not associated with local or systemic immunosuppression. Diagnosis is often underestimated and differentiation from folliculitis, papulopustular rosacea and perioral dermatitis is not always straightforward. Dependent on the morphology and degree of inflammation, the clinical manifestations can be classified into spinulate, papulopustular, nodulocystic, crustic and fulminant demodicosis. Therapy success can be achieved only with acaricides/arachidicides. The effective doses, optimal regimen and antimicrobial resistance remain to be determined. PMID:25744530

  15. Neuropeptides and nasal secretion.

    PubMed

    Baraniuk, J N; Kaliner, M

    1991-10-01

    The nasal mucosa is innervated by the sensory, parasympathetic, and sympathetic nervous systems. Nociceptive sensory nerves are stimulated by mucosal injury, inhalation of irritants, or mast cell degranulation and release of the calcitonin gene-related peptide, the tachykinins substance P and neurokinin A, and other peptides by the axon response mechanism. Sensory nerve stimulation initiates systemic reflexes, such as the sneeze, and central parasympathetic reflexes which release acetylcholine, vasoactive intestinal peptide, and other peptides and lead to glandular secretion. In concert, these proinflammatory neural responses lead to vasodilation, vascular permeability, and glandular secretion. Sympathetic nerves release neuropeptide Y and norepinephrine, potent vasoconstrictors which act to decompress the nasal mucosa and produce nasal patency. The balance between the effects of parasympathetic and sympathetic neurotransmitters may regulate nasal homeostasis, whereas the nociceptive sensory system may be held in reserve as a defense mechanism. Dysfunction of these systems may lead to pathological nasal syndromes. In the future, specific neuropeptide agonists and antagonists may be useful for the treatment of human rhinitic diseases. PMID:1928355

  16. Pathogenesis of nasal polyps: an update.

    PubMed

    Pawliczak, Rafal; Lewandowska-Polak, Anna; Kowalski, Marek L

    2005-11-01

    The cause of nasal polyp formation is still unknown. Genetic predisposition has been suggested, but there are scanty data to support such theories. Activated epithelial cells may be the major source of mediators inducing influx of inflammatory cells (mostly eosinophils) and proliferation and activation of fibroblasts leading to nasal polyp formation. Infectious agents (including viruses, bacteria, or fungi) may be potential primary factors activating nasal epithelial cells. Proinflammatory cytokines and growth factors play important roles in the persistence of mucosal inflammation associated with nasal polyps. Arachidonic acid metabolites seem to be particularly important in the pathogenesis of nasal polyps in patients with aspirin hypersensitivity rhinosinusitis/asthma syndrome. PMID:16216171

  17. Isolation and characterization of a variant of human papillomavirus type 11 from a nasal inverting (Schneiderian) papilloma.

    PubMed

    Pater, A; Gardner, H; Respler, D S; Jahn, A; Pater, M M

    1988-06-01

    We have previously reported the presence of a variant of human papillomavirus (HPV) type 11 in a nasal inverting papilloma [Respler et al., 1987]. In the present study, we have cloned molecularly the DNA of this variant at its unique restriction enzyme Bam HI site into lambda BF101 phage. Restriction enzyme mapping and DNA sequencing revealed that the genome of this virus contained an extra 531 base pair (bp) which was the repeat of most of the noncoding region (ncr) of HPV 11. Insertion of transcriptional control elements, including the repeated sequence, in front of the chloramphenicol acetyltransferase (CAT) gene resulted in a 5- to 30-fold increase in expression in transfected cells, as compared to the constructs containing a single ncr of HPV 11. This increased expression was due to enhanced levels of CAT RNA the synthesis of which is initiated by the viral promoter element. PMID:2839608

  18. Right-hemisphere preponderance of responses to painful CO2 stimulation of the human nasal mucosa.

    PubMed

    Hari, R; Portin, K; Kettenmann, B; Jousmäki, V; Kobal, G

    1997-08-01

    We recorded whole-scalp cerebral magnetic fields from healthy adults to painful CO2 pulses (duration 200 ms, concentration 65-90%), led to the left or right nostril once every 20 or 30 s. The stimuli were embedded in a continuous airflow (140 ml/s, 36.5 degrees C, relative humidity 80%) to prevent alterations in the mechanical and thermal conditions of the nasal mucosa. The recording passband was 0.03-90 Hz and 16 single responses were averaged per run. Five out of the 9 subjects showed replicable and artifact-free responses 280-400 ms after stimulus onset. The main responses originated close to the second somatosensory cortex (SII), most frequently in the right hemisphere, and also in the rolandic areas, mostly on the left. The signals were considerably stronger over the right than the left frontotemporal region, with a right-to-left ratio of 2.3 for areal mean signal amplitudes calculated across 16 channels, for both left and right nostril stimuli. Air puffs delivered to the nasal mucosa resulted in a trend for right-hemisphere dominant responses, but responses to air puff stimulation of the lip and the forehead were symmetric. The right-hemisphere dominance of the SII responses may be associated with the painful, and thus unpleasant, nature of the CO2 stimulus, thereby suggesting involvement of the right hemisphere in emotional/motivational aspects of trigeminal pain, in agreement with the role of the trigeminal pathways as a general warning system.

  19. Proton-coupled oligopeptide transporter (POT) family expression in human nasal epithelium and their drug transport potential.

    PubMed

    Agu, Remigius; Cowley, Elizabeth; Shao, Di; Macdonald, Christopher; Kirkpatrick, David; Renton, Ken; Massoud, Emad

    2011-06-01

    The molecular and functional expression of peptide transporters (PEPT1 and PEPT2, PHT1, PHT2) in human nasal epithelium was investigated. Quantitative/reverse transcriptase polymerase chain reaction (qPCR/RT-PCR), Western blotting and indirect immuno-histochemistry were used to investigate the functional gene and protein expression for the transporters. Uptake and transport studies were performed using metabolically stable peptides [β-alanyl-L-lysyl-Nε-7-amino-4-methyl-coumarin-3-acetic acid (β-Ala-Lys-AMCA) and β-alanyl-L-histidine (carnosine)]. The effects of concentration, temperature, polarity, competing peptides, and inhibitors on peptide uptake and transport were investigated. PCR products corresponding to PEPT1 (150 bp), PEPT2 (127 bp), PHT1 (110 bp) and PHT2 (198 bp) were detected. Immunohistochemistry and Western blotting confirmed the functional expression of PEPT1 and PEPT2 genes. The uptake of β-Ala-Lys-AMCA was concentration-dependent and saturable (Vmax =4.1 ( 0.07 μmol/min/mg protein, Km = 0.6 ( 0.07 μM). The optimal pH for intracellular accumulation of β-Ala-Lys-AMCA was 6.5. Whereas dipeptides and carbonyl cyanide m-chlorophenylhydrazone (CCCP) significantly inhibited peptide uptake and transport, L-Phe had no effect on peptide transport. The permeation of β-alanyl-L-histidine was concentration-, direction-, and temperature-dependent. The uptake, permeation, qPCR/RT-PCR and protein expression data showed that the human nasal epithelium functionally expresses proton-coupled oligopeptide transporters.

  20. Non-pharmacological management of nasal polyp: a case report.

    PubMed

    Rastogi, Rajiv; Murthy, B T C; Vinudha

    2009-01-01

    Nasal polyp causes difficulty in breathing due to blockage of nasal passage. The pathogenesis of nasal polyposis is not known. The primary medical therapy available for nasal polyposis is steroid administration. Antihistamines, decongestants and cromolyn sodium provide little benefit. With this background of nasal polyp pathophysiology and the existing management, a case of nasal polyp was treated with the cleansing process of yoga i.e. neti kriya and naturopathy with good result. This isolated case report warrants a need for controlled clinical trial of neti kriya to establish its role in the management of nasal polyposis.

  1. Visual exploration of nasal airflow.

    PubMed

    Zachow, Stefan; Muigg, Philipp; Hildebrandt, Thomas; Doleisch, Helmut; Hege, Hans-Christian

    2009-01-01

    Rhinologists are often faced with the challenge of assessing nasal breathing from a functional point of view to derive effective therapeutic interventions. While the complex nasal anatomy can be revealed by visual inspection and medical imaging, only vague information is available regarding the nasal airflow itself: Rhinomanometry delivers rather unspecific integral information on the pressure gradient as well as on total flow and nasal flow resistance. In this article we demonstrate how the understanding of physiological nasal breathing can be improved by simulating and visually analyzing nasal airflow, based on an anatomically correct model of the upper human respiratory tract. In particular we demonstrate how various Information Visualization (InfoVis) techniques, such as a highly scalable implementation of parallel coordinates, time series visualizations, as well as unstructured grid multi-volume rendering, all integrated within a multiple linked views framework, can be utilized to gain a deeper understanding of nasal breathing. Evaluation is accomplished by visual exploration of spatio-temporal airflow characteristics that include not only information on flow features but also on accompanying quantities such as temperature and humidity. To our knowledge, this is the first in-depth visual exploration of the physiological function of the nose over several simulated breathing cycles under consideration of a complete model of the nasal airways, realistic boundary conditions, and all physically relevant time-varying quantities. PMID:19834215

  2. Phenotypic and functional characteristics of IL-21-expressing CD8+ T cells in human nasal polyps

    PubMed Central

    Xiao, Li; Jia, Lei; Bai, Lu; He, Long; Yang, Binyan; Wu, Changyou; Li, Huabin

    2016-01-01

    Although CD4+ T cells are recognized to play an important role in the inflammatory response of nasal polyps (NPs), the biological functions of CD8+ T cells in polypogenesis remain unclear. In this study, we analyzed cell markers, cytokine expression and transcription factors in IL-21-expressing CD8+ T cells in polyp tissues of NP patients. The results showed that the majority of IL-21-producing CD8+ T cells were effector memory cells and they co-expressed IFN-γ. IL-21-expressing CD8+ T cells in polyp tissues expressed higher CXCR5, PD-1, and ICOS levels than cells in control tissues and showed significantly higher T-bet and Bcl-6 expression levels compared with IL-21−CD8+ T cells. Purified polyp CD8+ T cells promoted IgG production from isolated polyp B cells in vitro, and recombinant IL-12 modulated the expression of IL-21, IFN-γ and CD40L in purified polyp CD8+ T cells. Moreover, the percentage of IL-21+CD8+ T cells in polyp tissues was positively correlated with endoscopic and CT scan scores in NP patients. These findings indicated that polyp CD8+ T cells, by co-expressing IL-21 and IFN-γ and other markers, display a Tfh cell functionality, which is associated with the clinical severity of NP patients. PMID:27468819

  3. Staphylococcus aureus nasal carriage among outpatients attending primary health care centers: a comparative study of two cities in Saudi Arabia and Egypt.

    PubMed

    Abou Shady, Hala M; Bakr, Alaa Eldin A; Hashad, Mahmoud E; Alzohairy, Mohammad A

    2015-01-01

    Epidemiological and molecular data on community acquired methicillin resistant Staphylococcus aureus (CA-MRSA) are still scarce in both Egypt and Saudi Arabia. There is almost no data regarding methicillin resistant Staphylococcus aureus (MRSA) prevalence in both countries. This study was conducted to investigate the prevalence and molecular epidemiology of S. aureus and MRSA nasal carriage among outpatients attending primary health care centers in two big cities in both countries. A total of 206 nasal swabs were obtained, 103 swabs from each country. S. aureus isolates were characterized by antibiotic susceptibility, presence of mecA and PVL genes, SCCmec-typing and spa typing, the corresponding Multi locus sequence typing clonal complex was assigned for each spa type based on Ridom StaphType database. MRSA was detected in 32% of the Egyptian outpatients while it was found in 25% of the Saudi Arabian outpatients. All MRSA isolates belonged to SCCmec type V and IVa, where some isolates in Saudi Arabia remained nontypeable. Surprisingly PVL(+) isolates were low in frequency: 15% of MRSA Egyptian isolates and 12% of MRSA isolates in Saudi Arabia. Two novel spa types were detected t11839 in Egypt, and t11841 in Saudi Arabia. We found 8 spa types among 20 isolates from Egypt, and 12 spa types out of 15 isolates from Saudi Arabia. Only two spa types t008 and t223 coexisted in both countries. Four clonal complexes (CC5, CC8, CC22, and CC80) were identified in both Egypt and Saudi Arabia. However, the data collected lacked a representation of isolates from different parts of each country as only one health center from each country was included, it still partially illustrates the CA-MRSA situation in both countries. In conclusion a set of control measures is required to prevent further increase in MRSA prevalence.

  4. COMPARISON OF PM-INDUCED GENE EXPRESSION PROFILES BETWEEN BRONCHIAL EPITHELIAL CELLS AND NASAL EPITHELIAL CELLS IN HUMAN

    EPA Science Inventory

    Epidemiologic studies have linked exposures to particulate matter (PM) and increased pulmonary mortality and morbidity. Bronchial epithelial cells (BEC) are the primary target of PM. PM exposure induces a wide array of biological responses in BEC. Primary human BEC, however, need...

  5. In Vitro Modeling of RSV Infection and Cytopathogenesis in Well-Differentiated Human Primary Airway Epithelial Cells (WD-PAECs).

    PubMed

    Broadbent, Lindsay; Villenave, Remi; Guo-Parke, Hong; Douglas, Isobel; Shields, Michael D; Power, Ultan F

    2016-01-01

    The choice of model used to study human respiratory syncytial virus (RSV) infection is extremely important. RSV is a human pathogen that is exquisitely adapted to infection of human hosts. Rodent models, such as mice and cotton rats, are semi-permissive to RSV infection and do not faithfully reproduce hallmarks of RSV disease in humans. Furthermore, immortalized airway-derived cell lines, such as HEp-2, BEAS-2B, and A549 cells, are poorly representative of the complexity of the respiratory epithelium. The development of a well-differentiated primary pediatric airway epithelial cell models (WD-PAECs) allows us to simulate several hallmarks of RSV infection of infant airways. They therefore represent important additions to RSV pathogenesis modeling in human-relevant tissues. The following protocols describe how to culture and differentiate both bronchial and nasal primary pediatric airway epithelial cells and how to use these cultures to study RSV cytopathogenesis. PMID:27464691

  6. Human nasal cartilage responds to oncostatin M in combination with interleukin 1 or tumour necrosis factor α by the release of collagen fragments via collagenases

    PubMed Central

    Morgan, T G; Rowan, A D; Dickinson, S C; Jones, D; Hollander, A P; Deehan, D; Cawston, T E

    2006-01-01

    Background The synergistic degradation of cartilage by oncostatin M (OSM) in combination with either interleukin 1 (IL1) or tumour necrosis factor α (TNFα) has been previously demonstrated using bovine nasal cartilage (BNC). Objectives (a) To investigate if human nasal cartilage (HNC) responds in the same way as BNC to these cytokine combinations, particularly in collagen degradation. (b) To compare the response of human nasal and articular cartilages. Methods Collagen release was assessed by measuring the hydroxyproline content of culture supernatants and proteoglycan release by the dimethylmethylene blue assay. Matrix metalloproteinase (MMP)‐1, MMP‐13, and tissue inhibitor of metalloproteinase 1 release were measured by specific enzyme linked immunosorbent assays (ELISAs), and collagenolytic activity was measured by a bioassay using radiolabelled collagen. Results OSM in combination with either IL1 or TNFα acted synergistically to induce collagenolysis from HNC, with a maximum of 79% collagen release. This degradation strongly correlated with MMP‐1 and MMP‐13 levels and collagenolytic activity. Conclusion Collagen release from human cartilage is marked and implicates both MMP‐1 and MMP‐13 in the synergistic degradation of human cartilage by OSM in combination with either IL1 or TNFα. HNC responds in the same way as BNC, thus validating the bovine cartilage degradation assay as a model relevant to human disease. PMID:15975972

  7. Mometasone Nasal Spray

    MedlinePlus

    ... allergies. It is also used to treat nasal polyps (swelling of the lining of the nose). Mometasone ... are using mometasone nasal spray to treat nasal polyps, it is usually sprayed in each nostril once ...

  8. The Effect of Menstrual Cycle on Nasal Resonance Characteristics in Females

    ERIC Educational Resources Information Center

    Kumar, Suman; Basu, Shriya; Sinha, Anisha; Chatterjee, Indranil

    2012-01-01

    The purpose of this study was to analyze resonance characteristics (nasality and nasalance values) during the menstrual cycle. Previous studies indicate changes in voice quality and nasal mucosa due to temporary falling estrogen levels in human females during their menstrual cycle. The present study compared the nasality and "nasalance scores"…

  9. A comparison of natural and passive methods to measure nasal deposition of utrafline aerosols using replicate human upper airway casts

    SciTech Connect

    Cheng, Kuo-Hsi; Swift, D.L.; Cheng, Yung-Sung; Yeh, Hsu-Chi

    1994-11-01

    The risk of lung cancer associated with exposure to radon progeny in underground miners has been investigated extensively by epidemiological studies. Results indicate that exposure to relatively high concentrations of radon progeny in mines is closely linked to an increased occurrence of lung cancer. Current risk estimates for the general population exposed to indoor radon are primarily based on extrapolations from studies of underground miners. To extend these data to radon exposures of the general population in homes, dosimetric modeling is being used to assess the differences in exposure-dose relationships between the mining and home environments. The human upper airways are the first filter against inhaled particles that would otherwise penetrate into the more distal respiratory tract. Understanding of nasal and oral filtration efficiency is the first step in evaluating dose to the lung from exposure to radon progeny. Of the many factors considered in assessing health effects from exposure to radon progeny, particle size and breathing rate are two important parameters that influence deposition patterns in the respiratory tract.

  10. The transmission of masticatory forces and nasal septum: structural comparison of the human skull and Gothic cathedral.

    PubMed

    Hilloowala, Rumy; Kanth, Hrishi

    2007-07-01

    This study extrapolates the transmission of masticatory forces to the cranium based on the architectural principles of Gothic cathedrals. The most significant finding of the study, obtained by analysis of coronal CT scans, is the role of the hard palate, and especially the vomer and the perpendicular plate of the ethmoid in masticatory force transmission. The study also confirms, experimentally, the paths of masticatory forces, cited in literature but based purely on morphological observations. Human skulls and Gothic cathedrals have similar morphological and functional characteristics. The load exerted by the roof of the cathedral is transmitted to the ground by piers and buttresses. These structures also resist the shearing forces exerted by high winds. Similarly, the mid-facial bones of the skull transmit the vertical as well as the lateral masticatory forces from the maxillary dentition to the skull base. The nonload bearing walls and stained glass windows of the cathedral correspond to the translucent wall of the maxilla. The passageway between the aisle and the nave of the cathedral is equivalent to the meatal openings in the lateral wall of the nasal cavity.

  11. Notes from the field: primary amebic meningoencephalitis associated with ritual nasal rinsing--St. Thomas, U.S. Virgin islands, 2012.

    PubMed

    2013-11-15

    On November 21, 2012, the U.S. Virgin Islands (USVI) Department of Health documented the first case and death from primary amebic meningoencephalitis (PAM) in the territory. PAM, a rare and almost universally fatal condition, results when Naegleria fowleri, a free-living thermophilic ameba found in warm freshwater, enters the nose and migrates to the brain. The patient was a man aged 47 years whose only reported freshwater exposures were the use of tap water for daily household activities and for ablution, a ritual cleansing that he practiced several times a day in preparation for Islamic prayer. Ablution can include nasal rinsing. On November 16, 2012, the patient had visited the emergency department with a headache; he was treated symptomatically and released. The following day, the patient returned to the emergency department by ambulance with fever, confusion, agitation, and a severe headache, for which he was admitted. Cerebrospinal fluid (CSF) studies were consistent with bacterial meningitis, and antibiotics were started. On November 18, neurologic findings included fixed nonresponsive pupils, no response in the upper or lower extremities, muted plantar responses, and no response to verbal commands. Microscopic examination of the CSF obtained from a second lumbar puncture revealed motile amebic trophozoites. CSF specimens sent to CDC for confirmatory testing were positive for N. fowleri by real-time polymerase chain reaction testing. On the morning of November 21, the patient was pronounced brain dead based on neurologic criteria. PMID:24226628

  12. [The influence of nasal flow aerodynamics on the nasal physiology].

    PubMed

    Betlejewski, Stanisław; Betlejewski, Andrzej

    2008-01-01

    The ability of the human nose to warm and humidify the respiratory air is important to maintaining the internal environment of the lungs, since ambient air is conditioned to nearly alveolar conditions (body temperature and fully saturated with water vapour) upon reaching the nasopharynx. Because of very short time of the inspiratory phase duration, as well as expiratory phase, only the rich vascularization of the nasal mucosa and specific organization of the submucosal vessels are not able to assure such effective physiological activity. Therefore the type of airflow during the respiration is essential to understanding the functional possibilities of the nasal mucosa. Most studies have investigated the airflow only in steady-flow conditions, where the laminar flow was observed. Anatomically accurate physical models of real nasal cavities and particle image velocimetry allow evaluation of the entire flow field in the nasal cavity. In these investigations a partially turbulent flow was observed even at low air velocities in most part of the nasal cavity. From a physiological perspective, a turbulent flow would seem sensible, since it enhances contact between air and the mucosal layer. By doing so, the nasal physiological functions - humidification, cleaning and warming are optimized.

  13. Immortalization of primary human smooth muscle cells.

    PubMed Central

    Perez-Reyes, N; Halbert, C L; Smith, P P; Benditt, E P; McDougall, J K

    1992-01-01

    Primary human aortic and myometrial smooth muscle cells (SMCs) were immortalized using an amphotropic recombinant retroviral construct containing the E6 and E7 open reading frames (ORFs) of human papillomavirus type 16. The SMCs expressing the E6/E7 ORFs have considerably elevated growth rates when compared with nonimmortalized control cells and show no signs of senescence with long-term passage. The first SMC line derived in this study has been maintained in continuous tissue culture for greater than 1 year (greater than 180 population doublings). The immortalized SMCs have decreased cell size and decreased content of muscle-specific alpha-actin filaments as determined by indirect immunofluorescence. Southern blot analysis has demonstrated the stable integration of the E6/E7 ORFs in the retrovirally infected cells, and radioimmunoprecipitation has confirmed the continued expression of the E6 and E7 genes. Cytogenetic studies of the SMC lines have revealed essentially diploid populations except for the myometrial clonal line, which became aneuploid at late passage (greater than 125 doublings). These cell lines were not tumorigenic in nude mice. Images PMID:1311088

  14. Topographical differences in the trigeminal sensitivity of the human nasal mucosa.

    PubMed

    Scheibe, Mandy; Zahnert, Thomas; Hummel, Thomas

    2006-09-18

    The aim of the study was to investigate differences in the distribution of intranasal trigeminal receptors in humans using an electrophysiological measure of trigeminally induced activation, the negative mucosa potential. A total of 29 young, healthy volunteers participated, results were on the basis of data from 18 participants. The trigeminal irritant CO2 was presented using a computer-controlled olfactometer. Negative mucosa potential recording sites included the anterior olfactory cleft, the anterior septum, and the lower turbinate. Lowest amplitudes of the negative mucosa potential were found in the olfactory cleft, maximum amplitudes at the septum. Intranasal measurements of CO2 concentrations suggested that these differences were not due to the intranasal distribution of CO2. These results are compatible with the idea that the trigeminal system acts as a sentinel of the human airways.

  15. Determination of thiocyanate (biomarkers of ETS) and other inorganic ions in human nasal discharge samples using ion chromatography.

    PubMed

    Narkowicz, Sylwia; Polkowska, Żaneta; Marć, Mariusz; Simeonov, Vasil; Namieśnik, Jacek

    2013-10-01

    Environmental tobacco smoke (ETS) is a mixture of air and tobacco smoke containing more than 4000 chemical substances. In view of the health risks of many of these substances, studies are needed to determine biomarkers of exposure to ETS constituents in people who actively or passively are exposed to the toxic compounds. The methodologies for determining most biomarkers from saliva, urine and blood samples are known, but methods for analyzing these compounds in nasal discharges are not available. The objective of this work was to develop an analytical procedure for the determination of thiocyanate and other biomarker compounds in samples of nasal discharge using ion chromatography.

  16. 21 CFR 874.3900 - Nasal dilator.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Nasal dilator. 874.3900 Section 874.3900 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Prosthetic Devices § 874.3900 Nasal dilator. (a) Identification. A...

  17. 21 CFR 874.3900 - Nasal dilator.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Nasal dilator. 874.3900 Section 874.3900 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Prosthetic Devices § 874.3900 Nasal dilator. (a) Identification. A...

  18. 21 CFR 874.3900 - Nasal dilator.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Nasal dilator. 874.3900 Section 874.3900 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Prosthetic Devices § 874.3900 Nasal dilator. (a) Identification. A...

  19. Global patterns in human consumption of net primary production

    NASA Astrophysics Data System (ADS)

    Imhoff, Marc L.; Bounoua, Lahouari; Ricketts, Taylor; Loucks, Colby; Harriss, Robert; Lawrence, William T.

    2004-06-01

    The human population and its consumption profoundly affect the Earth's ecosystems. A particularly compelling measure of humanity's cumulative impact is the fraction of the planet's net primary production that we appropriate for our own use. Net primary production-the net amount of solar energy converted to plant organic matter through photosynthesis-can be measured in units of elemental carbon and represents the primary food energy source for the world's ecosystems. Human appropriation of net primary production, apart from leaving less for other species to use, alters the composition of the atmosphere, levels of biodiversity, energy flows within food webs and the provision of important ecosystem services. Here we present a global map showing the amount of net primary production required by humans and compare it to the total amount generated on the landscape. We then derive a spatial balance sheet of net primary production `supply' and `demand' for the world. We show that human appropriation of net primary production varies spatially from almost zero to many times the local primary production. These analyses reveal the uneven footprint of human consumption and related environmental impacts, indicate the degree to which human populations depend on net primary production `imports' and suggest policy options for slowing future growth of human appropriation of net primary production.

  20. Global patterns in human consumption of net primary production.

    PubMed

    Imhoff, Marc L; Bounoua, Lahouari; Ricketts, Taylor; Loucks, Colby; Harriss, Robert; Lawrence, William T

    2004-06-24

    The human population and its consumption profoundly affect the Earth's ecosystems. A particularly compelling measure of humanity's cumulative impact is the fraction of the planet's net primary production that we appropriate for our own use. Net primary production--the net amount of solar energy converted to plant organic matter through photosynthesis--can be measured in units of elemental carbon and represents the primary food energy source for the world's ecosystems. Human appropriation of net primary production, apart from leaving less for other species to use, alters the composition of the atmosphere, levels of biodiversity, energy flows within food webs and the provision of important ecosystem services. Here we present a global map showing the amount of net primary production required by humans and compare it to the total amount generated on the landscape. We then derive a spatial balance sheet of net primary production 'supply' and 'demand' for the world. We show that human appropriation of net primary production varies spatially from almost zero to many times the local primary production. These analyses reveal the uneven footprint of human consumption and related environmental impacts, indicate the degree to which human populations depend on net primary production 'imports' and suggest policy options for slowing future growth of human appropriation of net primary production.

  1. Global Patterns in Human Consumption of Net Primary Production

    NASA Technical Reports Server (NTRS)

    Imhoff, Marc L.; Bounoua, Lahouari; Ricketts, Taylor; Loucks, Colby; Harriss, Robert; Lawrence William T.

    2004-01-01

    The human population and its consumption profoundly affect the Earth's ecosystems. A particularly compelling measure of humanity's cumulative impact is the fraction of the planet's net primary production that we appropriate for our Net primary production-the net amount of solar energy converted to plant organic matter through photosynthesis-can be measured in units of elemental carbon and represents the primary food energy source for the world's ecosystems. Human appropriation of net primary production, apart from leaving less for other species to use, alters the composition of the atmosphere, levels of biodiversity, flows within food webs and the provision of important primary production required by humans and compare it to the total amount generated on the landscape. We then derive a spatial ba!mce sheet of net primary production supply and demand for the world. We show that human appropriation of net primary production varies spatially from almost zero to many times the local primary production. These analyses reveal the uneven footprint of human consumption and related environmental impacts, indicate the degree to which human populations depend on net primary production "imports" and suggest policy options for slowing future growth of human appropriation of net primary production.

  2. A hybrid CFD-PBPK model for naphthalene in rat and human with IVIVE for nasal tissue metabolism and cross-species dosimetry.

    PubMed

    Campbell, Jerry L; Andersen, Melvin E; Clewell, Harvey J

    2014-05-01

    A PBPK model for naphthalene in the rat and human that incorporates a hybrid CFD-PBPK description of the upper respiratory tract was developed to support cross-species dosimetry comparisons of naphthalene concentrations and tissue normalized rate of metabolism in the nasal respiratory and olfactory epithelium, lung and liver. In vitro measurements of metabolic rates from microsomal incubations published for rat and monkey (surrogate for human) were scaled to the specific tissue based on the tissue microsomal content and volume of tissue. The model reproduces time courses for naphthalene blood concentrations from intravenous and inhalation exposures in rats and upper respiratory tract extraction data in both naïve rats and rats pre-treated to inhibit nasal metabolism. This naphthalene model was applied to estimate human equivalent inhalation concentrations (HECs) corresponding to several NOAELs or LOAELs for the non-cancer effects of naphthalene in rats. Two approaches for cross-species extrapolation were compared: (1) equivalence based on tissue naphthalene concentration and (2) equivalence based on amount metabolized per minute (normalized to tissue volume). At the NOAEL of 0.1 ppm, the regional gas dosimetry ratio (RGDR) based on naphthalene concentration was 0.18 for the dorsal olfactory region; however, the RGDR rises to 5.4 when based on the normalized amount metabolized due to the lower of expression of CYP isozymes in the nasal epithelium of primates and humans. The resulting HEC is 0.12 ppm (0.63 mg/m(3)) continuous exposure at the rat NOAEL of 0.1 ppm (6 h/day, 5 days/week).

  3. Primary Bioassay of Human Myeloma Stem Cells

    PubMed Central

    Hamburger, Anne; Salmon, Sydney E.

    1977-01-01

    The ability to clone primary tumors in soft agar has proven useful in the study of the kinetics and biological properties of tumor stem cells. We report the development of an in vitro assay which permits formation of colonies of human monoclonal plasma cells in soft agar. Colony growth has been observed from bone marrow aspirates from 75% of the 70 patients with multiple myeloma or related monoclonal disorders studied. Growth was induced with either 0.02 ml of human type O erythrocytes or 0.25 ml of medium conditioned by the adherent spleen cells of mineral oil-primed BALB/c mice. 5-500 colonies appeared after 2-3 wk in culture yielding a plating efficiency of 0.001-0.1%. The number of myeloma colonies was proportional to the number of cells plated between concentrations of 105-106 and back-extrapolated through zero, suggesting that colonies were clones derived from single myeloma stem cells. Morphological, histochemical, and functional criteria showed the colonies to consist of immature plasmablasts and mature plasma cells. 60-80% of cells picked from colonies contained intracytoplasmic monoclonal immunoglobulin. Colony growth was most easily achieved from the bone marrow cells of untreated patients or those in relapse. Only 50% of bone marrow samples from patients in remission were successfully cultured. Tritiated thymidine suicide studies provided evidence that for most myeloma patients, a very high proportion of myeloma colony-forming cells was actively in transit through the cell cycle. Velocity sedimentation at 1 g showed myeloma stem cells sedimented in a broad band with a peak at 13 mm/h. Antibody to granulocyte colony-stimulating factor did not reduce the number or size of the colonies. Increased numbers of myeloma colonies were seen when the marrow was depleted of colony-stimulating factor elaborating adherent cells before plating. This bioassay should prove useful in studying the in vitro biological behavior of certain bone marrow-derived (B

  4. TGF-beta 1 downregulates CFTR expression and function in nasal polyps of non-CF patients.

    PubMed

    Prulière-Escabasse, Virginie; Fanen, Pascale; Dazy, Anne Catherine; Lechapt-Zalcman, Emmanuèle; Rideau, Dominique; Edelman, Aleksander; Escudier, Estelle; Coste, André

    2005-01-01

    Nasal polyposis is a chronic inflammatory disease of the upper airways. It has been suggested that ion transports and CFTR expression could be modified in epithelial cells from nasal polyps of non-cystic fibrosis patients. We compared human nasal epithelial cells from nasal polyps (NP) with control nasal mucosa (CM). The level of CFTR mRNA was studied by Northern blot analysis and protein expression was studied by immunoprecipitation both ex vivo and in vitro in primary cultures of human nasal epithelial cells at the air-liquid interface. Ion transports were evaluated by short-circuit measurements in vitro. CFTR gene and protein expressions were significantly decreased in NP native tissues and in culture on day 4, when a global defect of ion transports was observed in NP cultures, but not in CM. We evaluated the effect of transforming growth factor (TGF)-beta 1 on CFTR expression and function in NP cultures on day 14 and showed, for the first time, that TGF-beta 1 was able to significantly downregulate the level of CFTR mRNA and cAMP-dependent current in NP cultures. Finally, we showed that the effects of TGF-beta 1 on ion transports could be reversed after 48-h removal of TGF-beta1 in NP cultures. In conclusion, our data strongly suggest that chronic inflammation in nasal polyposis downregulates CFTR gene and protein expression.

  5. Evaluating the Effectiveness of the Lateral Intercrural Suture to Decrease the Interdomal Distance to Improve the Definition of the Nasal Tip in Primary Rhinoplasty

    PubMed Central

    Soares, Caio Márcio Correia; Mocelin, Marcos; Pasinato, Rogerio; Berger, Cezar Augusto Sarraf; Grocoske, Francisco Luiz Busato; Issa, Maria Julia Abrão

    2014-01-01

    Introduction Several surgical techniques emphasizing sutures on the lower lateral cartilage have been studied by surgeons as instruments to improve nasal tip remodeling. It is already known that the domal divergence angle and its definition angle can be modified by lateral intercrural suture (LIS). Techniques for measuring these structures are not yet standardized. Objectives Assess the efficacy of LIS using polydioxanone 4–0 absorbable thread by interdomal distance and systematize the LIS technique to improve nasal tip definition. Materials and Methods This prospective study measured and analyzed interdomal distances measured preoperatively and perioperatively compared with 3- and 6-month postoperative measurements. Results LIS was efficient on reducing interdomal distances. Conclusion LIS is statistically safe and efficient and has low morbidity when utilized in patients with mild to moderate deformities, because it reduces the domal divergence angle, effectively sustaining the nasal tip. PMID:25992073

  6. Beclomethasone Nasal Spray

    MedlinePlus

    ... the lining of the nose) after nasal polyp removal surgery. Beclomethasone nasal spray should not be used ... room temperature and away from excess heat and moisture (not in the bathroom).Unneeded medications should be ...

  7. Nasal Wash Treatment

    MedlinePlus

    ... Make the nasal wash solution. Do not use tap water for the nasal wash (unless boiled or filtered ... water. You may use: Distilled water Sterilized water Tap water that has been boiled for 1 minute (at ...

  8. Post-Nasal Drip

    MedlinePlus

    ... guaifenesin (Humibid®, Robitussin®) may also thin secretions. Nasal irrigations may alleviate thickened secretions. These can be performed ... device or a Water Pik® with a nasal irrigation nozzle. Warm water with baking soda or salt ( ...

  9. Nasal corticosteroid sprays

    MedlinePlus

    ... Allergic rhinitis symptoms , such as congestion, runny nose, sneezing, itching, or swelling of the nasal passageway Nasal ... Repeat these steps for the other nostril. Avoid sneezing or blowing your nose right after spraying.

  10. Nasal mucosal biopsy

    MedlinePlus

    Biopsy - nasal mucosa; Nose biopsy ... to fast for a few hours before the biopsy. ... Nasal mucosal biopsy is usually done when abnormal tissue is seen during examination of the nose. It may also be done ...

  11. Poly(I:C) reduces expression of JAM-A and induces secretion of IL-8 and TNF-{alpha} via distinct NF-{kappa}B pathways in human nasal epithelial cells

    SciTech Connect

    Ohkuni, Tsuyoshi; Kojima, Takashi; Ogasawara, Noriko; Masaki, Tomoyuki; Fuchimoto, Jun; Kamekura, Ryuta; Koizumi, Jun-ichi; Ichimiya, Shingo; Murata, Masaki; Tanaka, Satoshi; Himi, Tetsuo; Sawada, Norimasa

    2011-01-01

    Human nasal epithelium is an important physical barrier and innate immune defense protecting against inhaled substances and pathogens. Toll-like receptor (TLR) signaling, which plays a key role in the innate immune response, has not been well characterized in human nasal epithelial cells (HNECs), including the epithelial tight junctional barrier. In the present study, mRNAs of TLR1-10 were detected in hTERT-transfected HNECs, which can be used as an indispensable and stable model of normal HNECs, similar to primary cultured HNECs. To investigate the changes of tight junction proteins and the signal transduction pathways via TLRs in HNECs in vitro, hTERT-transfected HNECs were treated with TLR2 ligand P{sub 3}CSK{sub 4}, TLR3 ligand poly(I:C), TLR4 ligand LPS, TLR7/8 ligand CL097, TLR8 ligand ssRNA40/LyoVec, and TLR9 ligand ODN2006. In hTERT-transfected HNECs, treatment with poly(I:C) significantly reduced expression of the tight junction protein JAM-A and induced secretion of proinflammatory cytokines IL-8 and TNF-{alpha}. Both the reduction of JAM-A expression and the induction of secretion of IL-8 and TNF-{alpha} after treatment with poly(I:C) were modulated by distinct signal transduction pathways via EGFR, PI3K, and p38 MAPK and finally regulated by a TLR3-mediated NF-{kappa}B pathway. The control of TLR3-mediated signaling pathways in HNECs may be important not only in infection by viral dsRNA but also in autoimmune diseases caused by endogenous dsRNA released from necrotic cells.

  12. Persistence of nasal colonization with human pathogenic bacteria and associated antimicrobial resistance in the German general population

    PubMed Central

    Köck, R.; Werner, P.; Friedrich, A.W.; Fegeler, C.; Becker, K.; Bindewald, O.; Bui, T.T.; Eckhoff, C.; Epping, R.; Kähmann, L.; Meurer, M.; Steger, J.; von Auenmüller, L.

    2015-01-01

    The nares represent an important bacterial reservoir for endogenous infections. This study aimed to assess the prevalence of nasal colonization by different important pathogens, the associated antimicrobial susceptibility and risk factors. We performed a prospective cohort study among 1878 nonhospitalized volunteers recruited from the general population in Germany. Participants provided nasal swabs at three time points (each separated by 4–6 months). Staphylococcus aureus, Enterobacteriaceae and important nonfermenters were cultured and subjected to susceptibility testing. Factors potentially influencing bacterial colonization patterns were assessed. The overall prevalence of S. aureus, Enterobacteriaceae and nonfermenters was 41.0, 33.4 and 3.7%, respectively. Thirteen participants (0.7%) were colonized with methicillin-resistant S. aureus. Enterobacteriaceae were mostly (>99%) susceptible against ciprofloxacin and carbapenems (100%). Extended-spectrum β-lactamase–producing isolates were not detected among Klebsiella oxytoca, Klebsiella pneumoniae and Escherichia coli. Several lifestyle- and health-related factors (e.g. household size, travel, livestock density of the residential area or occupational livestock contact, atopic dermatitis, antidepressant or anti-infective drugs) were associated with colonization by different microorganisms. This study unexpectedly demonstrated high nasal colonization rates with Enterobacteriaceae in the German general population, but rates of antibiotic resistance were low. Methicillin-resistant S. aureus carriage was rare but highly associated with occupational livestock contact. PMID:26862431

  13. Persistence of nasal colonization with human pathogenic bacteria and associated antimicrobial resistance in the German general population.

    PubMed

    Köck, R; Werner, P; Friedrich, A W; Fegeler, C; Becker, K

    2016-01-01

    The nares represent an important bacterial reservoir for endogenous infections. This study aimed to assess the prevalence of nasal colonization by different important pathogens, the associated antimicrobial susceptibility and risk factors. We performed a prospective cohort study among 1878 nonhospitalized volunteers recruited from the general population in Germany. Participants provided nasal swabs at three time points (each separated by 4-6 months). Staphylococcus aureus, Enterobacteriaceae and important nonfermenters were cultured and subjected to susceptibility testing. Factors potentially influencing bacterial colonization patterns were assessed. The overall prevalence of S. aureus, Enterobacteriaceae and nonfermenters was 41.0, 33.4 and 3.7%, respectively. Thirteen participants (0.7%) were colonized with methicillin-resistant S. aureus. Enterobacteriaceae were mostly (>99%) susceptible against ciprofloxacin and carbapenems (100%). Extended-spectrum β-lactamase-producing isolates were not detected among Klebsiella oxytoca, Klebsiella pneumoniae and Escherichia coli. Several lifestyle- and health-related factors (e.g. household size, travel, livestock density of the residential area or occupational livestock contact, atopic dermatitis, antidepressant or anti-infective drugs) were associated with colonization by different microorganisms. This study unexpectedly demonstrated high nasal colonization rates with Enterobacteriaceae in the German general population, but rates of antibiotic resistance were low. Methicillin-resistant S. aureus carriage was rare but highly associated with occupational livestock contact. PMID:26862431

  14. Nasal Lobular Capillary Hemangioma

    PubMed Central

    Patil, Prashant; Singla, Saurabh; Mane, Ranoji; Jagdeesh, K. S.

    2013-01-01

    Nasal lobular capillary hemangioma is a rare benign tumor of the paranasal sinuses. This lesion is believed to grow rapidly in size over time. The exact etiopathogenesis is still a dilemma. We discuss a case of nasal lobular capillary hemangioma presenting with a history of epistaxis. Contrast enhanced computed tomography of paranasal sinuses revealed an intensely enhancing soft-tissue mass in the left nasal cavity and left middle and inferior meati with no obvious bony remodeling or destruction. We present imaging and pathologic features of nasal lobular capillary hemangioma and differentiate it from other entities like nasal angiofibroma. PMID:24228209

  15. The nasal cavity microbiota of healthy adults

    PubMed Central

    2014-01-01

    Background The microbiota of the nares has been widely studied. However, relatively few studies have investigated the microbiota of the nasal cavity posterior to the nares. This distinct environment has the potential to contain a distinct microbiota and play an important role in health. Results We obtained 35,142 high-quality bacterial 16S rRNA-encoding gene sequence reads from the nasal cavity and oral cavity (the dorsum of the tongue and the buccal mucosa) of 12 healthy adult humans and deposited these data in the Sequence Read Archive (SRA) of the National Center for Biotechnology Information (NCBI) (Bioproject: PRJNA248297). In our initial analysis, we compared the bacterial communities of the nasal cavity and the oral cavity from ten of these subjects. The nasal cavity bacterial communities were dominated by Actinobacteria, Firmicutes, and Proteobacteria and were statistically distinct from those on the tongue and buccal mucosa. For example, the same Staphylococcaceae operational taxonomic unit (OTU) was present in all of the nasal cavity samples, comprising up to 55% of the community, but Staphylococcaceae was comparatively uncommon in the oral cavity. Conclusions There are clear differences between nasal cavity microbiota and oral cavity microbiota in healthy adults. This study expands our knowledge of the nasal cavity microbiota and the relationship between the microbiota of the nasal and oral cavities. PMID:25143824

  16. Integrated Modular Teaching of Human Biology for Primary Care Practitioners

    ERIC Educational Resources Information Center

    Glasgow, Michael S.

    1977-01-01

    Describes the use of integrated modular teaching of the human biology component of the Health Associate Program at Johns Hopkins University, where the goal is to develop an understanding of the sciences as applied to primary care. Discussion covers the module sequence, the human biology faculty, goals of the human biology faculty, laboratory…

  17. Powered nasal polypectomy in the office setting.

    PubMed

    Krouse, J H; Christmas, D A

    1996-09-01

    The use of powered instrumentation has revolutionized the practice of functional endoscopic sinus surgery. We have expanded the role of the instrument to the treatment of polypoid disease of the nose within the office setting. We have found the technique to be both safe and effective, and to allow thorough exenteration of nasal polyps with minimal bleeding and discomfort. We recommend the use of the powered device as the primary tool in the surgical treatment of nasal polyps in the office.

  18. Computational study of human head response to primary blast waves of five levels from three directions.

    PubMed

    Wang, Chenzhi; Pahk, Jae Bum; Balaban, Carey D; Miller, Mark C; Wood, Adam R; Vipperman, Jeffrey S

    2014-01-01

    Human exposure to blast waves without any fragment impacts can still result in primary blast-induced traumatic brain injury (bTBI). To investigate the mechanical response of human brain to primary blast waves and to identify the injury mechanisms of bTBI, a three-dimensional finite element head model consisting of the scalp, skull, cerebrospinal fluid, nasal cavity, and brain was developed from the imaging data set of a human female. The finite element head model was partially validated and was subjected to the blast waves of five blast intensities from the anterior, right lateral, and posterior directions at a stand-off distance of one meter from the detonation center. Simulation results show that the blast wave directly transmits into the head and causes a pressure wave propagating through the brain tissue. Intracranial pressure (ICP) is predicted to have the highest magnitude from a posterior blast wave in comparison with a blast wave from any of the other two directions with same blast intensity. The brain model predicts higher positive pressure at the site proximal to blast wave than that at the distal site. The intracranial pressure wave invariably travels into the posterior fossa and vertebral column, causing high pressures in these regions. The severities of cerebral contusions at different cerebral locations are estimated using an ICP based injury criterion. Von Mises stress prevails in the cortex with a much higher magnitude than in the internal parenchyma. According to an axonal injury criterion based on von Mises stress, axonal injury is not predicted to be a cause of primary brain injury from blasts. PMID:25409326

  19. Computational study of human head response to primary blast waves of five levels from three directions.

    PubMed

    Wang, Chenzhi; Pahk, Jae Bum; Balaban, Carey D; Miller, Mark C; Wood, Adam R; Vipperman, Jeffrey S

    2014-01-01

    Human exposure to blast waves without any fragment impacts can still result in primary blast-induced traumatic brain injury (bTBI). To investigate the mechanical response of human brain to primary blast waves and to identify the injury mechanisms of bTBI, a three-dimensional finite element head model consisting of the scalp, skull, cerebrospinal fluid, nasal cavity, and brain was developed from the imaging data set of a human female. The finite element head model was partially validated and was subjected to the blast waves of five blast intensities from the anterior, right lateral, and posterior directions at a stand-off distance of one meter from the detonation center. Simulation results show that the blast wave directly transmits into the head and causes a pressure wave propagating through the brain tissue. Intracranial pressure (ICP) is predicted to have the highest magnitude from a posterior blast wave in comparison with a blast wave from any of the other two directions with same blast intensity. The brain model predicts higher positive pressure at the site proximal to blast wave than that at the distal site. The intracranial pressure wave invariably travels into the posterior fossa and vertebral column, causing high pressures in these regions. The severities of cerebral contusions at different cerebral locations are estimated using an ICP based injury criterion. Von Mises stress prevails in the cortex with a much higher magnitude than in the internal parenchyma. According to an axonal injury criterion based on von Mises stress, axonal injury is not predicted to be a cause of primary brain injury from blasts.

  20. Computational Study of Human Head Response to Primary Blast Waves of Five Levels from Three Directions

    PubMed Central

    Wang, Chenzhi; Pahk, Jae Bum; Balaban, Carey D.; Miller, Mark C.; Wood, Adam R.; Vipperman, Jeffrey S.

    2014-01-01

    Human exposure to blast waves without any fragment impacts can still result in primary blast-induced traumatic brain injury (bTBI). To investigate the mechanical response of human brain to primary blast waves and to identify the injury mechanisms of bTBI, a three-dimensional finite element head model consisting of the scalp, skull, cerebrospinal fluid, nasal cavity, and brain was developed from the imaging data set of a human female. The finite element head model was partially validated and was subjected to the blast waves of five blast intensities from the anterior, right lateral, and posterior directions at a stand-off distance of one meter from the detonation center. Simulation results show that the blast wave directly transmits into the head and causes a pressure wave propagating through the brain tissue. Intracranial pressure (ICP) is predicted to have the highest magnitude from a posterior blast wave in comparison with a blast wave from any of the other two directions with same blast intensity. The brain model predicts higher positive pressure at the site proximal to blast wave than that at the distal site. The intracranial pressure wave invariably travels into the posterior fossa and vertebral column, causing high pressures in these regions. The severities of cerebral contusions at different cerebral locations are estimated using an ICP based injury criterion. Von Mises stress prevails in the cortex with a much higher magnitude than in the internal parenchyma. According to an axonal injury criterion based on von Mises stress, axonal injury is not predicted to be a cause of primary brain injury from blasts. PMID:25409326

  1. Free Auricular Composite Graft for Acquired Nasal Stenosis

    PubMed Central

    Riley, Charles A.; Lawlor, Claire M.; Gray, Mingyang Liu; Graham, H. Devon

    2016-01-01

    Background: Acquired nasal stenosis poses a reconstructive challenge for the facial plastic surgeon. Many surgical options are available, ranging from primary closure to skin grafts to free flap reconstruction for complex defects. The free auricular composite graft is a single-stage procedure that can be used to repair nasal vestibular stenosis causing nasal obstruction. Case Report: We present the case of a patient with acquired nasal stenosis as a result of prolonged nasal tampon placement secondary to severe epistaxis and subsequent nasal vestibular infection. Repair via auricular composite graft was successful, and we provide a thorough explanation of graft design and operative technique. Conclusion: Free auricular composite grafts can produce desirable functional and aesthetic outcomes and should be considered in patients presenting with acquired nasal stenosis. PMID:27303225

  2. Effect of environmental contaminants on nasal lysozyme secretions.

    PubMed

    Noble, Rudolf E

    2002-02-01

    Human nasal secretions are comprised of lysozyme and albumin as their main protein components. Lysozyme, an anti-microbial substance, is produced by nasal serous cells while albumin is obtained, primarily, from increased nasal vasculature permeability. We measured lysozyme levels in nasal secretions following challenge by a variety of non-infectious environmental contaminants. The methodology given presents a simple and rapid method of collecting nasal secretions and determining their lysozyme content, a technique which can be used for a host of environmental irritants.

  3. Deposition of {open_quotes}unattached{close_quotes} radon daughters in models of human nasal and oral airways

    SciTech Connect

    Strong, J.C.; Swift, D.L.

    1992-12-31

    In order to estimate accurately an effective dose equivalent for exposures to radon daughters, knowledge of their deposition in the lung is required. However, the nose and mouth are effective filters for removing aerosol particles, especially in the range of sizes of {open_quotes}unattached{close_quotes} radon daughters. Therefore, it is equally important to have reliable data on deposition in this region of the respiratory tract. We will describe our work in studying nasal and oral deposition of {open_quotes}unattached{close_quotes} radon daughters in casts of these airways. Several hollow casts of adult and child nasal and oral airways were fabricated at The John Hopkins University from layers of Perspect{trademark} (an acrylic plastic). The shapes of the airway passages were obtained from nuclear magnetic resonance sectional images of healthy subjects. The casts were exposed to radon gas and daughters produced by flushing filtered air through a commercially available {sup 226}Ra source. The gas stream was drawn through a 1.4-L cylindrical tube to allow measurable growth of {sup 218}Po activity before it was passed through casts of both nasal passages or the oral cavity. The deposition of {open_quotes}unattached{close_quotes} {sup 218}Po was measured by comparing the activity collected on filters mounted in series and in parallel with a cast. Measurements were made at various flow rates (Q; 4 to 20 L min{sup -1}). The diffusion coefficient (D) of {sup 218}Po was measured each time the flow rate was changed, by replacing the cast with a stainless steel gauze screen and measuring the activity penetrating the screen. The measured diffusion coefficient ranged from 0.02 to 0.05 cm{sup 2} s{sup -1} and was found to vary with the residence time of {sup 218}Po in the growth tube. The deposition efficiency ({eta}) of {sup 218}Po measured in these casts ranged from 50 to 70%, and was similar to values we found previously, using casts of nasal and oral airways from cadavers.

  4. Correlation between nasal membrane permeability and nasal absorption rate.

    PubMed

    Zhang, Hefei; Lin, Chih-Wei; Donovan, Maureen D

    2013-03-01

    The objective of this study was to investigate the relationship between in vitro permeability (Papp) values obtained from isolated nasal tissues and the absorption rates (ka) of the same compounds following nasal administration in animals and humans. The Papp of a set of 11 drug compounds was measured using animal nasal explants and plasma time-concentration profiles for each of the same compounds following intravenous (IV) and intranasal (IN) administration were experimentally determined or obtained from literature reports. The plasma clearance was estimated from the IV plasma time-concentration profiles, and ka was determined from the IN plasma time-concentration profiles using a deconvolution approach. The level of correlation between Papp and ka was established using Pearson correlation analysis. A good correlation (r=0.77) representing a point-to-point relationship for each of the compounds was observed. This result indicates that the nasal absorption for many drug candidates can be estimated from a readily measured in vitro Papp value. PMID:23225081

  5. Isolation and molecular characterization of methicillin-resistant coagulase-negative staphylococci from nasal flora of healthy humans at three community institutions in Rio de Janeiro City.

    PubMed

    Silva, F R; Mattos, E M; Coimbra, M V; Ferreira-Carvalho, B T; Figueiredo, A M

    2001-08-01

    We describe the isolation and molecular characterization of methicillin-resistant coagulase-negative staphylococci (MRCNS) from the nasal flora of healthy humans from three institutions located in Rio de Janeiro City. Swabs were obtained from the nares of students attending a non-residential public school and adults from two military quarters. Isolates of staphylococci were tested for the presence of the mecA gene by hybridization with a specific probe. S. epidermidis was the most frequent MRCNS (38 of the total 45 CNS isolated). Twenty-five percent of nasal staphylococcal carriers studied were colonized with MRCNS. Pulsed-field gel electrophoresis (PFGE) of SmaI-digested genomic DNA was carried out to study the clonality of the methicillin-resistant S. epidermidis (MRSE) isolates. In addition to cross-colonization among individuals belonging to the same institution, familial cross-colonization appeared to contribute to the spread of the methicillin-resistant isolates among two inter-communicable institutions. Indeed, the wide genomic diversity among the MRSE flora suggests that the spread of the mecA gene among these isolates might also have occurred via horizontal transmission. Despite the limited number of institutions analysed, it is reasonable to conclude that our data do not represent a situation unique to the three organizations but may reflect other communities in Rio with respect to transmission of MRCNS. PMID:11561975

  6. Proteomic analysis of nasal epithelial cells from cystic fibrosis patients.

    PubMed

    Jeanson, Ludovic; Guerrera, Ida Chiara; Papon, Jean-François; Chhuon, Cerina; Zadigue, Patricia; Prulière-Escabasse, Virginie; Amselem, Serge; Escudier, Estelle; Coste, André; Edelman, Aleksander

    2014-01-01

    The pathophysiology of cystic fibrosis (CF) lung disease remains incompletely understood. New explanations for the pathogenesis of CF lung disease may be discovered by studying the patterns of protein expression in cultured human nasal epithelial cells (HNEC). To that aim, we compared the level of protein expressions in primary cultures of HNEC from nasal polyps secondary to CF (CFNP, n = 4), primary nasal polyps (NP, n = 8) and control mucosa (CTRL, n = 4) using isobaric tag for relative and absolute quantification (iTRAQ) labeling coupled with liquid chromatography (LC)-MS-MS. The analysis of the data revealed 42 deregulated protein expressions in CFNP compared to NP and CTRL, suggesting that these alterations are related to CF. Overall, AmiGo analysis highlighted six major pathways important for cell functions that seem to be impaired: metabolism, G protein process, inflammation and oxidative stress response, protein folding, proteolysis and structural proteins. Among them, glucose and fatty acid metabolic pathways could be impaired in CF with nine deregulated proteins. Our proteomic study provides a reproducible set of differentially expressed proteins in airway epithelial cells from CF patients and reveals many novel deregulated proteins that could lead to further studies aiming to clarify the involvement of such proteins in CF pathophysiology.

  7. Management of the cleft lip nasal deformity.

    PubMed

    Dutton, J M; Bumsted, R M

    2001-02-01

    Management of the cleft lip nasal deformity offers a unique and ongoing challenge in facial plastic surgery. Although there has been no consensus regarding the optimal timing and technique for surgical repair of this deformity, the authors have found a three-tiered approach to be satisfactory. This approach involves a primary rhinoplasty performed at the time of the initial cleft lip repair to address reconstruction of the nasal floor and sill, columellar lengthening, repositioning of the alar base, and repositioning of the skin and mucosa of the lower lateral cartilage. Following alveolar bone grafting, an intermediate rhinoplasty is often performed at 6 to 10 years of age through an open approach to correct the cartilaginous lower nasal deformity. A delayed rhinoplasty is then performed in the later teenage years to correct the bony dorsal deformity and the various causes of nasal obstruction.

  8. Measuring Nasal Obstruction.

    PubMed

    Keeler, Jarrod; Most, Sam P

    2016-08-01

    The nose and the nasal airway is highly complex with intricate 3-dimensional anatomy, with multiple functions in respiration and filtration of the respired air. Nasal airway obstruction (NAO) is a complex problem with no clearly defined "gold-standard" in measurement. There are 3 tools for the measurement of NAO: patient-derived measurements, physician-observed measurements, and objective measurements. We continue to work towards finding a link between subjective and objective nasal obstruction. The field of evaluation and surgical treatment for NAO has grown tremendously in the past 4-5 decades and will continue to grow as we learn more about the pathophysiology and treatment of nasal obstruction.

  9. The multisensory function of the human primary visual cortex.

    PubMed

    Murray, Micah M; Thelen, Antonia; Thut, Gregor; Romei, Vincenzo; Martuzzi, Roberto; Matusz, Pawel J

    2016-03-01

    It has been nearly 10 years since Ghazanfar and Schroeder (2006) proposed that the neocortex is essentially multisensory in nature. However, it is only recently that sufficient and hard evidence that supports this proposal has accrued. We review evidence that activity within the human primary visual cortex plays an active role in multisensory processes and directly impacts behavioural outcome. This evidence emerges from a full pallet of human brain imaging and brain mapping methods with which multisensory processes are quantitatively assessed by taking advantage of particular strengths of each technique as well as advances in signal analyses. Several general conclusions about multisensory processes in primary visual cortex of humans are supported relatively solidly. First, haemodynamic methods (fMRI/PET) show that there is both convergence and integration occurring within primary visual cortex. Second, primary visual cortex is involved in multisensory processes during early post-stimulus stages (as revealed by EEG/ERP/ERFs as well as TMS). Third, multisensory effects in primary visual cortex directly impact behaviour and perception, as revealed by correlational (EEG/ERPs/ERFs) as well as more causal measures (TMS/tACS). While the provocative claim of Ghazanfar and Schroeder (2006) that the whole of neocortex is multisensory in function has yet to be demonstrated, this can now be considered established in the case of the human primary visual cortex. PMID:26275965

  10. Human Appropriation of Net Primary Production - Can Earth Keep Up?

    NASA Technical Reports Server (NTRS)

    Imhoff, Marc L.

    2006-01-01

    The amount of Earth's vegetation or net primary production required to support human activities is powerful measure of aggregate human impacts on the biosphere. Biophysical models applied to consumption statistics were used to estimate the annual amount of net primary production in the form of elemental carbon required for food, fibre, and fuel-wood by the global population. The calculations were then compared to satellite-based estimates of Earth's average net primary production to produce a geographically explicit balance sheet of net primary production "supply" and "demand". Humans consume 20% of Earth's net primary production (11.5 petagrams carbon) annually and this percentage varies regionally from 6% (South America) to over 70% (Europe and Asia), and locally from near 0% (central Australia) to over 30,000% (New York City, USA). The uneven footprint of human consumption and related environmental impacts, indicate the degree to which human populations are vulnerable to climate change and suggest policy options for slowing future growth of NPP demand.

  11. 21 CFR 341.20 - Nasal decongestant active ingredients.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Nasal decongestant active ingredients. 341.20 Section 341.20 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... OVER-THE-COUNTER HUMAN USE Active Ingredients § 341.20 Nasal decongestant active ingredients....

  12. 21 CFR 341.20 - Nasal decongestant active ingredients.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Nasal decongestant active ingredients. 341.20 Section 341.20 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... OVER-THE-COUNTER HUMAN USE Active Ingredients § 341.20 Nasal decongestant active ingredients....

  13. 21 CFR 341.20 - Nasal decongestant active ingredients.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Nasal decongestant active ingredients. 341.20 Section 341.20 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... OVER-THE-COUNTER HUMAN USE Active Ingredients § 341.20 Nasal decongestant active ingredients....

  14. 21 CFR 341.20 - Nasal decongestant active ingredients.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Nasal decongestant active ingredients. 341.20 Section 341.20 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... OVER-THE-COUNTER HUMAN USE Active Ingredients § 341.20 Nasal decongestant active ingredients....

  15. Protocol for a human in vivo model of acute cigarette smoke inhalation challenge in smokers with COPD: monitoring the nasal and systemic immune response using a network biology approach

    PubMed Central

    Ross, Clare L; Galloway-Phillipps, Neil; Armstrong, Paul C; Mitchell, Jane A; Warner, Timothy D; Brearley, Christopher; Ito, Mari; Tunstall, Tanushree; Elkin, Sarah; Kon, Onn Min; Hansel, Trevor T; Paul-Clark, Mark J

    2015-01-01

    Introduction Cigarette smoke contributes to a diverse range of diseases including chronic obstructive pulmonary disease (COPD), cardiovascular disorders and many cancers. There currently is a need for human challenge models, to assess the acute effects of a controlled cigarette smoke stimulus, followed by serial sampling of blood and respiratory tissue for advanced molecular profiling. We employ precision sampling of nasal mucosal lining fluid by absorption to permit soluble mediators measurement in eluates. Serial nasal curettage was used for transcriptomic analysis of mucosal tissue. Methods and analysis Three groups of strictly defined patients will be studied: 12 smokers with COPD (GOLD Stage 2) with emphysema, 12 matched smokers with normal lung function and no evidence of emphysema, and 12 matched never smokers with normal spirometry. Patients in the smoking groups are current smokers, and will be given full support to stop smoking immediately after this study. In giving a controlled cigarette smoke stimulus, all patients will have abstained from smoking for 12 h, and will smoke two cigarettes with expiration through the nose in a ventilated chamber. Before and after inhalation of cigarette smoke, a series of samples will be taken from the blood, nasal mucosal lining fluid and nasal tissue by curettage. Analysis of plasma nicotine and metabolites in relation to levels of soluble inflammatory mediators in nasal lining fluid and blood, as well as assessing nasal transcriptomics, ex vivo blood platelet aggregation and leucocyte responses to toll-like receptor agonists will be undertaken. Implications Development of acute cigarette smoke challenge models has promise for the study of molecular effects of smoking in a range of pathological processes. Ethics and dissemination This study was approved by the West London National Research Ethics Committee (12/LO/1101). The study findings will be presented at conferences and will be reported in peer-reviewed journals

  16. The Effects of Gas Humidification with High-Flow Nasal Cannula on Cultured Human Airway Epithelial Cells

    PubMed Central

    Chidekel, Aaron; Zhu, Yan; Wang, Jordan; Mosko, John J.; Rodriguez, Elena; Shaffer, Thomas H.

    2012-01-01

    Humidification of inspired gas is important for patients receiving respiratory support. High-flow nasal cannula (HFNC) effectively provides temperature and humidity-controlled gas to the airway. We hypothesized that various levels of gas humidification would have differential effects on airway epithelial monolayers. Calu-3 monolayers were placed in environmental chambers at 37°C with relative humidity (RH) < 20% (dry), 69% (noninterventional comparator), and >90% (HFNC) for 4 and 8 hours with 10 L/min of room air. At 4 and 8 hours, cell viability and transepithelial resistance measurements were performed, apical surface fluid was collected and assayed for indices of cell inflammation and function, and cells were harvested for histology (n = 6/condition). Transepithelial resistance and cell viability decreased over time (P < 0.001) between HFNC and dry groups (P < 0.001). Total protein secretion increased at 8 hours in the dry group (P < 0.001). Secretion of interleukin (IL)-6 and IL-8 in the dry group was greater than the other groups at 8 hours (P < 0.001). Histological analysis showed increasing injury over time for the dry group. These data demonstrate that exposure to low humidity results in reduced epithelial cell function and increased inflammation. PMID:22988501

  17. Comparison of Nasal Acceleration and Nasalance across Vowels

    ERIC Educational Resources Information Center

    Thorp, Elias B.; Virnik, Boris T.; Stepp, Cara E.

    2013-01-01

    Purpose: The purpose of this study was to determine the performance of normalized nasal acceleration (NNA) relative to nasalance as estimates of nasalized versus nonnasalized vowel and sentence productions. Method: Participants were 18 healthy speakers of American English. NNA was measured using a custom sensor, and nasalance was measured using…

  18. Similarity and Enhancement: Nasality from Moroccan Arabic Pharyngeals and Nasals

    ERIC Educational Resources Information Center

    Zellou, Georgia Eve

    2012-01-01

    Experimental studies of the articulation, acoustics, and perception of nasal and pharyngeal consonants and adjacent vowels were conducted to investigate nasality in Moroccan Arabic (MA). The status of nasality in MA is described as coarticulatorily complex, where two phoneme types (pharyngeal segments and nasal segments) yield similar…

  19. Nasal PMN response to repeated challenge with endotoxin in healthy volunteers**

    EPA Science Inventory

    Abstract Rationale: We have employed nasal challenge with Iipopolysaccharid (lPS) followed by nasal lavage (NU to experimentally induce and examine upper airway inflammation in human volunteers.It is unclear however whether adaptation within individuals occurs following repeated ...

  20. Triclosan promotes Staphylococcus aureus nasal colonization.

    PubMed

    Syed, Adnan K; Ghosh, Sudeshna; Love, Nancy G; Boles, Blaise R

    2014-01-01

    The biocide triclosan is used in many personal care products, including toothpastes, soaps, clothing, and medical equipment. Consequently, it is present as a contaminant in the environment and has been detected in some human fluids, including serum, urine, and milk. Staphylococcus aureus is an opportunistic pathogen that colonizes the noses and throats of approximately 30% of the population. Colonization with S. aureus is known to be a risk factor for several types of infection. Here we demonstrate that triclosan is commonly found in the nasal secretions of healthy adults and the presence of triclosan trends positively with nasal colonization by S. aureus. We demonstrate that triclosan can promote the binding of S. aureus to host proteins such as collagen, fibronectin, and keratin, as well as inanimate surfaces such as plastic and glass. Lastly, triclosan-exposed rats are more susceptible to nasal colonization with S. aureus. These data reveal a novel factor that influences the ability of S. aureus to bind surfaces and alters S. aureus nasal colonization. IMPORTANCE Triclosan has been used as a biocide for over 40 years, but the broader effects that it has on the human microbiome have not been investigated. We demonstrate that triclosan is present in nasal secretions of a large portion of a test population and its presence correlates with Staphylococcus aureus nasal colonization. Triclosan also promotes the binding of S. aureus to human proteins and increases the susceptibility of rats to nasal colonization by S. aureus. These findings are significant because S. aureus colonization is a known risk factor for the development of several types of infections. Our data demonstrate the unintended consequences of unregulated triclosan use and contribute to the growing body of research demonstrating inadvertent effects of triclosan on the environment and human health. PMID:24713325

  1. Triclosan promotes Staphylococcus aureus nasal colonization.

    PubMed

    Syed, Adnan K; Ghosh, Sudeshna; Love, Nancy G; Boles, Blaise R

    2014-04-08

    The biocide triclosan is used in many personal care products, including toothpastes, soaps, clothing, and medical equipment. Consequently, it is present as a contaminant in the environment and has been detected in some human fluids, including serum, urine, and milk. Staphylococcus aureus is an opportunistic pathogen that colonizes the noses and throats of approximately 30% of the population. Colonization with S. aureus is known to be a risk factor for several types of infection. Here we demonstrate that triclosan is commonly found in the nasal secretions of healthy adults and the presence of triclosan trends positively with nasal colonization by S. aureus. We demonstrate that triclosan can promote the binding of S. aureus to host proteins such as collagen, fibronectin, and keratin, as well as inanimate surfaces such as plastic and glass. Lastly, triclosan-exposed rats are more susceptible to nasal colonization with S. aureus. These data reveal a novel factor that influences the ability of S. aureus to bind surfaces and alters S. aureus nasal colonization. IMPORTANCE Triclosan has been used as a biocide for over 40 years, but the broader effects that it has on the human microbiome have not been investigated. We demonstrate that triclosan is present in nasal secretions of a large portion of a test population and its presence correlates with Staphylococcus aureus nasal colonization. Triclosan also promotes the binding of S. aureus to human proteins and increases the susceptibility of rats to nasal colonization by S. aureus. These findings are significant because S. aureus colonization is a known risk factor for the development of several types of infections. Our data demonstrate the unintended consequences of unregulated triclosan use and contribute to the growing body of research demonstrating inadvertent effects of triclosan on the environment and human health.

  2. Young Scientists Explore the Human Body. Book 11 Primary Level.

    ERIC Educational Resources Information Center

    Penn, Linda

    Designed to present interesting facts about science and to heighten the curiosity of primary age students, this book contains activities about the natural world and numerous black and white illustrations. The activities specifically focus on the human body and encourage a positive self-concept. The theme of the first section is air--the breath of…

  3. Primary structure of the human M2 mitochondrial autoantigen of primary biliary cirrhosis: Dihydrolipoamide acetyltransferase

    SciTech Connect

    Coppel, R.L.; McNeilage, L.J.; Surh, C.D.; Van De Water, J.; Spithill, T.W.; Whittingham, S.; Gershwin, M.E. )

    1988-10-01

    Primary biliary cirrhosis is a chronic, destructive autoimmune liver disease of humans. Patient sera are characterized by a high frequency of autoantibodies to a M{sub r} 70,000 mitochondrial antigen a component of the M2 antigen complex. The authors have identified a human cDNA clone encoding the complete amino acid sequence of this autoantigen. The predicted structure has significant similarity with the dihydrolipoamide acetyltransferase of the Escherichia coli pyruvate dehydrogenase multienzyme complex. The human sequence preserves the Glu-Thr-Asp-Lys-Ala motif of the lipoyl-binding site and has two potential binding sites. Expressed fragments of the cDNA react strongly with sera from patients with primary biliary cirrhosis but not with sera from patients with autoimmune chronic active hepatitis or sera from healthy subjects.

  4. RANK and RANK ligand expression in primary human osteosarcoma.

    PubMed

    Branstetter, Daniel; Rohrbach, Kathy; Huang, Li-Ya; Soriano, Rosalia; Tometsko, Mark; Blake, Michelle; Jacob, Allison P; Dougall, William C

    2015-09-01

    Receptor activator of nuclear factor kappa-B ligand (RANKL) is an essential mediator of osteoclast formation, function and survival. In patients with solid tumor metastasis to the bone, targeting the bone microenvironment by inhibition of RANKL using denosumab, a fully human monoclonal antibody (mAb) specific to RANKL, has been demonstrated to prevent tumor-induced osteolysis and subsequent skeletal complications. Recently, a prominent functional role for the RANKL pathway has emerged in the primary bone tumor giant cell tumor of bone (GCTB). Expression of both RANKL and RANK is extremely high in GCTB tumors and denosumab treatment was associated with tumor regression and reduced tumor-associated bone lysis in GCTB patients. In order to address the potential role of the RANKL pathway in another primary bone tumor, this study assessed human RANKL and RANK expression in human primary osteosarcoma (OS) using specific mAbs, validated and optimized for immunohistochemistry (IHC) or flow cytometry. Our results demonstrate RANKL expression was observed in the tumor element in 68% of human OS using IHC. However, the staining intensity was relatively low and only 37% (29/79) of samples exhibited≥10% RANKL positive tumor cells. RANK expression was not observed in OS tumor cells. In contrast, RANK expression was clearly observed in other cells within OS samples, including the myeloid osteoclast precursor compartment, osteoclasts and in giant osteoclast cells. The intensity and frequency of RANKL and RANK staining in OS samples were substantially less than that observed in GCTB samples. The observation that RANKL is expressed in OS cells themselves suggests that these tumors may mediate an osteoclastic response, and anti-RANKL therapy may potentially be protective against bone pathologies in OS. However, the absence of RANK expression in primary human OS cells suggests that any autocrine RANKL/RANK signaling in human OS tumor cells is not operative, and anti-RANKL therapy

  5. In vivo microvascular imaging of human oral and nasal cavities using swept-source optical coherence tomography with a single forward/side viewing probe

    NASA Astrophysics Data System (ADS)

    Choi, Woo June; Wang, Ruikang K.

    2015-03-01

    We report three-dimensional (3D) imaging of microcirculation within human cavity tissues in vivo using a high-speed swept-source optical coherence tomography (SS-OCT) at 1.3 μm with a modified probe interface. Volumetric structural OCT images of the inner tissues of oral and nasal cavities are acquired with a field of view of 2 mm x 2 mm. Two types of disposable and detachable probe attachments are devised and applied to the port of the imaging probe of OCT system, enabling forward and side imaging scans for selective and easy access to specific cavity tissue sites. Blood perfusion is mapped with OCT-based microangiography from 3D structural OCT images, in which a novel vessel extraction algorithm is used to decouple dynamic light scattering signals, due to moving blood cells, from the background scattering signals due to static tissue elements. Characteristic tissue anatomy and microvessel architectures of various cavity tissue regions of a healthy human volunteer are identified with the 3D OCT images and the corresponding 3D vascular perfusion maps at a level approaching capillary resolution. The initial finding suggests that the proposed method may be engineered into a promising tool for evaluating and monitoring tissue microcirculation and its alteration within a wide-range of cavity tissues in the patients with various pathological conditions.

  6. Saline nasal washes

    MedlinePlus

    ... Be sure you only use distilled, boiled, or filtered water. While rare, some tap water may contain small ... pot or nasal bulb with distilled, boiled, or filtered water after every use and let it dry. Use ...

  7. Nicotine Nasal Spray

    MedlinePlus

    ... program, which may include support groups, counseling, or specific behavior change techniques. Nicotine nasal spray is in ... bottles at room temperature and away from excess heat and moisture (not in the bathroom). Discard used ...

  8. Triamcinolone Nasal Spray

    MedlinePlus

    Nasacort® Allergy 24HR ... watery eyes caused by hay fever or other allergies. Triamcinolone nasal spray should not be used to ... the release of certain natural substances that cause allergy symptoms.

  9. Naloxone Nasal Spray

    MedlinePlus

    ... is used along with emergency medical treatment to reverse the life-threatening effects of a known or ... this date passes.Naloxone nasal spray may not reverse the effects of certain opiates such as buprenorphine ( ...

  10. Nasal fracture (image)

    MedlinePlus

    A nasal fracture is a break in the bone over the ridge of the nose. It usually results from a blunt ... and is one of the most common facial fracture. Symptoms of a broken nose include pain, blood ...

  11. Nasal packing and stenting

    PubMed Central

    Weber, Rainer K.

    2011-01-01

    Nasal packs are indispensable in ENT practice. This study reviews current indications, effectiveness and risks of nasal packs and stents. In endoscopic surgery, nasal packs should always have smooth surfaces to minimize mucosal damage, improve wound healing and increase patient comfort. Functional endoscopic endonasal sinus surgery allows the use of modern nasal packs, since pressure is no longer required. So called hemostatic/resorbable materials are a first step in this direction. However, they may lead to adhesions and foreign body reactions in mucosal membranes. Simple occlusion is an effective method for creating a moist milieu for improved wound healing and avoiding dryness. Stenting of the frontal sinus is recommended if surgery fails to produce a wide, physiologically shaped drainage path that is sufficiently covered by intact tissue. PMID:22073095

  12. Measuring Nasal Obstruction.

    PubMed

    Keeler, Jarrod; Most, Sam P

    2016-08-01

    The nose and the nasal airway is highly complex with intricate 3-dimensional anatomy, with multiple functions in respiration and filtration of the respired air. Nasal airway obstruction (NAO) is a complex problem with no clearly defined "gold-standard" in measurement. There are 3 tools for the measurement of NAO: patient-derived measurements, physician-observed measurements, and objective measurements. We continue to work towards finding a link between subjective and objective nasal obstruction. The field of evaluation and surgical treatment for NAO has grown tremendously in the past 4-5 decades and will continue to grow as we learn more about the pathophysiology and treatment of nasal obstruction. PMID:27400845

  13. Fluticasone Nasal Spray

    MedlinePlus

    ... ingredients in fluticasone nasal spray. Check the package label for a list of the ingredients.tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking, or ...

  14. Oxymetazoline Nasal Spray

    MedlinePlus

    ... hour period. Follow the directions on the package label or on your prescription label carefully, and ask your doctor or pharmacist to ... prescribed by your doctor or directed on the label.If you use oxymetazoline nasal spray for more ...

  15. Humanization policy in primary health care: a systematic review

    PubMed Central

    Nora, Carlise Rigon Dalla; Junges, José Roque

    2013-01-01

    OBJECTIVE To analyze humanization practices in primary health care in the Brazilian Unified Health System according to the principles of the National Humanization Policy. METHODS A systematic review of the literature was carried out, followed by a meta-synthesis, using the following databases: BDENF (nursing database), BDTD (Brazilian digital library of theses and dissertations), CINAHL (Cumulative Index to nursing and allied health literature), LILACS (Latin American and Caribbean health care sciences literature), MedLine (International health care sciences literature), PAHO (Pan-American Health Care Organization Library) and SciELO (Scientific Electronic Library Online). The following descriptors were used: Humanization; Humanizing Health Care; Reception: Humanized care: Humanization in health care; Bonding; Family Health Care Program; Primary Care; Public Health and Sistema Único de Saúde (the Brazilian public health care system). Research articles, case studies, reports of experiences, dissertations, theses and chapters of books written in Portuguese, English or Spanish, published between 2003 and 2011, were included in the analysis. RESULTS Among the 4,127 publications found on the topic, 40 studies were evaluated and included in the analysis, producing three main categories: the first referring to the infrastructure and organization of the primary care service, made clear the dissatisfaction with the physical structure and equipment of the services and with the flow of attendance, which can facilitate or make difficult the access. The second, referring to the health work process, showed issues about the insufficient number of professionals, fragmentation of the work processes, the professional profile and responsibility. The third category, referring to the relational technologies, indicated the reception, bonding, listening, respect and dialog with the service users. CONCLUSIONS Although many practices were cited as humanizing they do not produce changes

  16. Diversity in primary palate ontogeny of amniotes revealed with 3D imaging.

    PubMed

    Abramyan, John; Thivichon-Prince, Beatrice; Richman, Joy Marion

    2015-05-01

    The amniote primary palate encompasses the upper lip and the nasal cavities. During embryonic development, the primary palate forms from the fusion of the maxillary, medial nasal and lateral nasal prominences. In mammals, as the primary palate fuses, the nasal and oral cavities become completely separated. Subsequently, the tissue demarcating the future internal nares (choanae) thins and becomes the bucconasal membrane, which eventually ruptures and allows for the essential connection of the oral and nasal cavities to form. In reptiles (including birds), the other major amniote group, primary palate ontogeny is poorly studied with respect to prominence fusion, especially the formation of a bucconasal membrane. Using 3D optical projection tomography, we found that the prominences that initiate primary palate formation are similar between mammals and crocodilians but distinct from turtles and lizards, which are in turn similar to each other. Chickens are distinct from all non-avian lineages and instead resemble human embryos in this aspect. The majority of reptiles maintain a communication between the oral and nasal cavities via the choanae during primary palate formation. However, crocodiles appear to have a transient separation between the oral and nasal cavities. Furthermore, the three lizard species examined here, exhibit temporary closure of their external nares via fusion of the lateral nasal prominences with the frontonasal mass, subsequently reopening them just before hatching. The mechanism of the persistent choanal opening was examined in chicken embryos. The mesenchyme posterior/dorsal to the choana had a significant decline in proliferation index, whereas the mesenchyme of the facial processes remained high. This differential proliferation allows the choana to form a channel between the oral and nasal cavities as the facial prominences grow and fuse around it. Our data show that primary palate ontogeny has been modified extensively to support the array of

  17. Nasal tip angiolipoma: the "Pinocchio" nasal deformity.

    PubMed

    De Poortere, David A; De Poortere, Boris M; Cohen, Noam A

    2012-10-01

    Angiolipoma is a rare, benign variant of lipoma; its distinctive feature is its prominent vascularity. It presents as a subcutaneous nodule of white adipose tissue; pain, which may be exacerbated by pressure, is the chief symptom. The anatomic distribution predominantly involves the trunk and extremities. Because of the rarity of this condition in otorhinolaryngology, our understanding of its diagnosis, treatment, and follow-up is limited. Microscopically, two different histopathologic forms of angiolipomas exist: circumscribed and infiltrating. The diagnosis of angiolipoma can be aided by ultrasound, computed tomography, or magnetic resonance imaging. Surgical excision remains the treatment of choice. Sites of previously reported otolaryngologic cases include the cheek, palate, mandible, nasal septum, and cervical area. We describe what we believe to be the second case of a nasal tip angiolipoma in a 78-year-old woman complaining of progressive aesthetic deformity.

  18. 21 CFR 868.5340 - Nasal oxygen cannula.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Nasal oxygen cannula. 868.5340 Section 868.5340 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5340 Nasal oxygen cannula....

  19. 21 CFR 868.5340 - Nasal oxygen cannula.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Nasal oxygen cannula. 868.5340 Section 868.5340 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5340 Nasal oxygen cannula....

  20. 21 CFR 868.5350 - Nasal oxygen catheter.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Nasal oxygen catheter. 868.5350 Section 868.5350 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5350 Nasal oxygen catheter....

  1. 21 CFR 868.5340 - Nasal oxygen cannula.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Nasal oxygen cannula. 868.5340 Section 868.5340 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5340 Nasal oxygen cannula....

  2. 21 CFR 868.5350 - Nasal oxygen catheter.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Nasal oxygen catheter. 868.5350 Section 868.5350 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5350 Nasal oxygen catheter....

  3. 21 CFR 868.5340 - Nasal oxygen cannula.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Nasal oxygen cannula. 868.5340 Section 868.5340 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5340 Nasal oxygen cannula....

  4. 21 CFR 868.5340 - Nasal oxygen cannula.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Nasal oxygen cannula. 868.5340 Section 868.5340 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5340 Nasal oxygen cannula....

  5. 21 CFR 868.5350 - Nasal oxygen catheter.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Nasal oxygen catheter. 868.5350 Section 868.5350 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5350 Nasal oxygen catheter....

  6. 21 CFR 868.5350 - Nasal oxygen catheter.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Nasal oxygen catheter. 868.5350 Section 868.5350 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5350 Nasal oxygen catheter....

  7. 21 CFR 868.5350 - Nasal oxygen catheter.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Nasal oxygen catheter. 868.5350 Section 868.5350 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5350 Nasal oxygen catheter....

  8. 21 CFR 874.5800 - External nasal splint.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false External nasal splint. 874.5800 Section 874.5800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Therapeutic Devices § 874.5800 External nasal splint....

  9. 21 CFR 874.5800 - External nasal splint.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false External nasal splint. 874.5800 Section 874.5800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Therapeutic Devices § 874.5800 External nasal splint....

  10. 21 CFR 874.5550 - Powered nasal irrigator.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Powered nasal irrigator. 874.5550 Section 874.5550 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Therapeutic Devices § 874.5550 Powered nasal irrigator....

  11. 21 CFR 874.5800 - External nasal splint.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false External nasal splint. 874.5800 Section 874.5800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Therapeutic Devices § 874.5800 External nasal splint....

  12. 21 CFR 874.5550 - Powered nasal irrigator.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Powered nasal irrigator. 874.5550 Section 874.5550 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Therapeutic Devices § 874.5550 Powered nasal irrigator....

  13. 21 CFR 874.5550 - Powered nasal irrigator.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Powered nasal irrigator. 874.5550 Section 874.5550 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Therapeutic Devices § 874.5550 Powered nasal irrigator....

  14. Primary pulmonary hypertension associated with human immunodeficiency virus infection.

    PubMed Central

    Golpe, R.; Fernandez-Infante, B.; Fernandez-Rozas, S.

    1998-01-01

    Several cardiorespiratory diseases can complicate human immunodeficiency virus infection. Primary pulmonary hypertension is a rare clinical disorder which carries a bad prognosis. More than 90 cases of HIV-associated primary pulmonary hypertension have been reported to date. Although its pathogenesis remains unknown, some evidence suggests a possible role for the virus itself in its development. Genetic susceptibility may also be implicated. The clinical and histopathologic features of this entity do not differ from those of classic primary pulmonary hypertension. The diagnosis requires a high degree of clinical suspicion and a careful evaluation to rule out causes of secondary pulmonary hypertension. In addition to supportive measures, anticoagulation and vasodilators have been used to treat this disorder, although sufficient data regarding long-term results with these therapies are lacking. PMID:9799910

  15. Arrhenius parameters for primary thermal injury in human tonsillar tissue

    NASA Astrophysics Data System (ADS)

    McMillan, Kathleen; Radabaugh, Rebecca; Coad, James E.

    2011-03-01

    Clinical implementation of a thermal therapy requires the ability to predict tissue injury following exposures to specific thermal histories. As part of an effort to develop a nonexcisional alternative to tonsillectomy, the degree of primary hyperthermic tissue injury in human tonsil was characterized. Fifteen fresh pediatric hypertrophic tonsillectomy specimens were sectioned and treated in a NIST-calibrated saline bath at temperatures of 40 to 70°C with hold times of one to seven minutes. The treated tissues were subsequently nitroblue tetrazolium (NBT) stained to assess for thermal respiratory enzyme inactivation as a marker of cellular injury/death. The NBT stains were quantitatively image analyzed and used to calculate Arrhenius parameters for primary thermal injury in human tonsils.

  16. Zinc oxide nanoparticle induced genotoxicity in primary human epidermal keratinocytes.

    PubMed

    Sharma, Vyom; Singh, Suman K; Anderson, Diana; Tobin, Desmond J; Dhawan, Alok

    2011-05-01

    Zinc oxide (ZnO) nanoparticles are widely used in cosmetics and sunscreens. Human epidermal keratinocytes may serve as the first portal of entry for these nanoparticles either directly through topically applied cosmetics or indirectly through any breaches in the skin integrity. Therefore, the objective of the present study was to assess the biological interactions of ZnO nanoparticles in primary human epidermal keratinocytes (HEK) as they are the most abundant cell type in the human epidermis. Cellular uptake of nanoparticles was investigated by scanning electron microscopy using back scattered electrons imaging as well as transmission electron microscopy. The electron microscopy revealed the internalization of ZnO nanoparticles in primary HEK after 6 h exposure at 14 microg/ml concentration. ZnO nanoparticles exhibited a time (6-24 h) as well as concentration (8-20 microg/ml) dependent inhibition of mitochondrial activity as evident by the MTT assay. A significant (p < 0.05) induction in DNA damage was observed in cells exposed to ZnO nanoparticles for 6 h at 8 and 14 microg/ml concentrations compared to control as evident in the Comet assay. This is the first study providing information on biological interactions of ZnO nanoparticles with primary human epidermal keratinocytes. Our findings demonstrate that ZnO nanoparticles are internalized by the human epidermal keratinocytes and elicit a cytotoxic and genotoxic response. Therefore, caution should be taken while using consumer products containing nanoparticles as any perturbation in the skin barrier could expose the underlying cells to nanoparticles.

  17. Transcriptional comparison of human induced and primary midbrain dopaminergic neurons

    PubMed Central

    Xia, Ninuo; Zhang, Pengbo; Fang, Fang; Wang, Zhengyuan; Rothstein, Megan; Angulo, Benjamin; Chiang, Rosaria; Taylor, James; Reijo Pera, Renee A.

    2016-01-01

    Generation of induced dopaminergic (iDA) neurons may provide a significant step forward towards cell replacement therapy for Parkinson’s disease (PD). To study and compare transcriptional programs of induced cells versus primary DA neurons is a preliminary step towards characterizing human iDA neurons. We have optimized a protocol to efficiently generate iDA neurons from human pluripotent stem cells (hPSCs). We then sequenced the transcriptomes of iDA neurons derived from 6 different hPSC lines and compared them to that of primary midbrain (mDA) neurons. We identified a small subset of genes with altered expression in derived iDA neurons from patients with Parkinson’s Disease (PD). We also observed that iDA neurons differ significantly from primary mDA neurons in global gene expression, especially in genes related to neuron maturation level. Results suggest iDA neurons from patient iPSCs could be useful for basic and translational studies, including in vitro modeling of PD. However, further refinement of methods of induction and maturation of neurons may better recapitulate full development of mDA neurons from hPSCs. PMID:26842779

  18. Nasal commensal Staphylococcus epidermidis counteracts influenza virus.

    PubMed

    Chen, Hui-Wen; Liu, Pei-Feng; Liu, Yu-Tsueng; Kuo, Sherwin; Zhang, Xing-Quan; Schooley, Robert T; Rohde, Holger; Gallo, Richard L; Huang, Chun-Ming

    2016-06-16

    Several microbes, including Staphylococcus epidermidis (S. epidermidis), a Gram-positive bacterium, live inside the human nasal cavity as commensals. The role of these nasal commensals in host innate immunity is largely unknown, although bacterial interference in the nasal microbiome may promote ecological competition between commensal bacteria and pathogenic species. We demonstrate here that S. epidermidis culture supernatants significantly suppressed the infectivity of various influenza viruses. Using high-performance liquid chromatography together with mass spectrometry, we identified a giant extracellular matrix-binding protein (Embp) as the major component involved in the anti-influenza effect of S. epidermidis. This anti-influenza activity was abrogated when Embp was mutated, confirming that Embp is essential for S. epidermidis activity against viral infection. We also showed that both S. epidermidis bacterial particles and Embp can directly bind to influenza virus. Furthermore, the injection of a recombinant Embp fragment containing a fibronectin-binding domain into embryonated eggs increased the survival rate of virus-infected chicken embryos. For an in vivo challenge study, prior Embp intranasal inoculation in chickens suppressed the viral titres and induced the expression of antiviral cytokines in the nasal tissues. These results suggest that S. epidermidis in the nasal cavity may serve as a defence mechanism against influenza virus infection.

  19. Nasal commensal Staphylococcus epidermidis counteracts influenza virus

    PubMed Central

    Chen, Hui-Wen; Liu, Pei-Feng; Liu, Yu-Tsueng; Kuo, Sherwin; Zhang, Xing-Quan; Schooley, Robert T.; Rohde, Holger; Gallo, Richard L.; Huang, Chun-Ming

    2016-01-01

    Several microbes, including Staphylococcus epidermidis (S. epidermidis), a Gram-positive bacterium, live inside the human nasal cavity as commensals. The role of these nasal commensals in host innate immunity is largely unknown, although bacterial interference in the nasal microbiome may promote ecological competition between commensal bacteria and pathogenic species. We demonstrate here that S. epidermidis culture supernatants significantly suppressed the infectivity of various influenza viruses. Using high-performance liquid chromatography together with mass spectrometry, we identified a giant extracellular matrix-binding protein (Embp) as the major component involved in the anti-influenza effect of S. epidermidis. This anti-influenza activity was abrogated when Embp was mutated, confirming that Embp is essential for S. epidermidis activity against viral infection. We also showed that both S. epidermidis bacterial particles and Embp can directly bind to influenza virus. Furthermore, the injection of a recombinant Embp fragment containing a fibronectin-binding domain into embryonated eggs increased the survival rate of virus-infected chicken embryos. For an in vivo challenge study, prior Embp intranasal inoculation in chickens suppressed the viral titres and induced the expression of antiviral cytokines in the nasal tissues. These results suggest that S. epidermidis in the nasal cavity may serve as a defence mechanism against influenza virus infection. PMID:27306590

  20. Cosmetic and Functional Nasal Deformities

    MedlinePlus

    ... Hay Fever) Headaches and Sinus Disease Disorders of Smell & Taste Upper Respiratory Infections Nasal Congestion & Snoring CSF ... Hay Fever) Headaches and Sinus Disease Disorders of Smell & Taste Upper Respiratory Infections Nasal Congestion & Snoring CSF ...

  1. Evaluation of nasal tip surgery.

    PubMed

    Friedman, W H; Biller, H F

    1975-09-01

    Nasal tip surgery has been evaluated with respect to correction of the lower lateral cartilages. Indications, techniques, results, and complications related to three generic approaches to the lower lateral cartilages are described. In 673 consecutive rhinoplasties the commonest type of nasal tip surgery was excisional, utilizing either a marginal or cartilage splitting technique. These techniques were utilized: 1. to accomplish debulking, and 2. to accomplish the installation of facets. The excisional technique found its greatest utility in primary rhinoplasties. The version technique, utilizing a change of direction of the thrust of the lower lateral cartilages was utilized in a variety of situations, particularly for the correction of moderately congenitally hypoplastic tip cartilages. It also found great utility in surgery of the Negro or cleft palate nose, increasing tip projection, correcting unacceptable bifidity, and in revision rhinoplasty. Augmentation rhinoplasty, utilizing conchal cartilage as an elastic strut was particularly useful for severe hypoplastic cartilage deficits, the Negro nose, columellar retraction, and alar rim deficits. The overall complication rate of lower lateral rhinoplasty was 17.4 percent. The rate of unacceptable complications related to lower lateral rhinoplasty was 2.7 percent.

  2. Human Bocavirus 1 Primary Infection and Shedding in Infants

    PubMed Central

    Martin, Emily T.; Kuypers, Jane; McRoberts, John P.; Englund, Janet A.; Zerr, Danielle M.

    2015-01-01

    Background. Human bocavirus 1 (HBoV-1) is frequently detected in young children. The role of HBoV-1 in respiratory illness is unclear, owing to frequent detection in asymptomatic children. Methods. Weekly oral fluid samples from a longitudinal cohort of infants were tested by quantitative polymerase chain reaction for HBoV-1 DNA. Symptoms during HBoV-1 primary shedding events were compared to those during 14-day control periods occurring 1 month prior to and following the primary event. Eight single-nucleotide polymorphisms were analyzed to assess HBoV-1 variants. Results. Sixty-six of 87 children (76%), followed for at least 18 months from birth, had a primary HBoV-1 infection. HBoV-1 was consistently detected for >1 month (maximum duration, 402 days) following 42 of 66 primary shedding events. Children were more likely to experience new cough symptoms (odds ratio [OR], 2.7; 95% confidence interval [CI], 1.4–5.5) and to visit a healthcare provider (OR, 2.8; 95% CI, 1.02–7.7) during the 14 days surrounding the time of initial detection of HBoV-1. Recurrent HBoV-1 shedding events were found in 33 children (50%). Twelve of 48 children with HBoV-1 variant data had multiple viral allelic patterns over time. Conclusions. HBoV-1 primary shedding events are associated with mild respiratory illness with subsequent prolonged detection of HBoV-1 DNA for up to a year. HBoV-1 reinfection contributes to long-term shedding. PMID:25632039

  3. Expression of androgen and progesterone receptors in primary human meningiomas.

    PubMed

    Maxwell, M; Galanopoulos, T; Neville-Golden, J; Antoniades, H N

    1993-03-01

    Meningiomas are common brain tumors that show a predilection for females and become more aggressive during pregnancy and menses. The existence of gender-specific hormone receptors in meningiomas has long been a matter of controversy; the recent cloning of androgen, estrogen, and progesterone receptors has facilitated their direct evaluation. The authors have demonstrated the expression of androgen and progesterone receptor messenger ribonucleic acid and protein product in nine primary human meningiomas by Northern blot analysis. Cellular localization was achieved by in situ hybridization analysis. Estrogen receptor expression was not detected. Normal adult meninges were shown to express very low levels of both androgen and progesterone receptors.

  4. Purification and primary structure determination of human lysosomal dipeptidase.

    PubMed

    Dolenc, Iztok; Mihelic, Marko

    2003-02-01

    The lysosomal metallopeptidase is an enzyme that acts preferentially on dipeptides with unsubstituted N- and C-termini. Its activity is highest in slightly acidic pH. Here we describe the isolation and characterization of lysosomal dipeptidase from human kidney. The isolated enzyme has the amino-terminal sequence DVAKAIINLAVY and is a homodimer with a molecular mass of 100 kDa. So far no amino acid sequence has been determined for this metallopeptidase. The complete primary structure as deduced from the nucleotide sequence revealed that the isolated dipeptidase is similar to blood plasma glutamate carboxypeptidase.

  5. Nasalance Norms in Greek Adults

    ERIC Educational Resources Information Center

    Okalidou, Areti; Karathanasi, Asimina; Grigoraki, Eleni

    2011-01-01

    The purposes of this study were to derive nasalance norms for monolingual Greek speakers, to examine nasalance scores as a function of gender and to draw cross-linguistic comparisons based on normative data. Participants read aloud a corpus of linguistic material, consisting of (1) a nasal text, an oral text and a balanced text; (2) a set of nasal…

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

    NASA Astrophysics Data System (ADS)

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

    2016-10-01

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

  7. A light microscopy study of the migration of Naegleria fowleri from the nasal submucosa to the central nervous system during the early stage of primary amebic meningoencephalitis in mice.

    PubMed

    Jarolim, K L; McCosh, J K; Howard, M J; John, D T

    2000-02-01

    The migratory pathway of Naegleria fowleri from the nasal submucosa to the central nervous system (CNS) during the early stage of primary amebic meningoencephalitis (PAM) was investigated in mice. Twenty-one-day-old CD-1 mice were inoculated by intranasal instillation of 1 x 10(6) amebas. Animals were divided into 3 groups of 5 and, after being anesthetized, were killed at intervals of 24, 32, and 48 hr postinoculation by transcardial perfusion with formaldehyde, acetic acid, and methanol. The heads were decalcified, divided in the midsagittal plane, and the area of the cribriform plate removed and embedded in paraffin. Serial sections were cut at 8 microm and stained with a combination of celestin blue, Harris' hematoxylin, and acid fuchsin for light microscopy. Focal inflammation and amebas were observed in the submucosal nerve plexus, olfactory nerves penetrating the cribriform plate, and the olfactory bulb of the brain as early as 24 hr postinoculation. The time periods selected assured that the disease process would not obliterate soft tissue structures. Earlier studies used moribund mice in which the inflammation and the number of amebas were overwhelming. The present study provides convincing evidence that amebas gain initial access to the CNS through olfactory nerves within the cribriform plate during the early stages of PAM.

  8. Zolmitriptan Nasal Spray

    MedlinePlus

    ... diarrhea and stomach pain caused by decreased blood flow to the intestines). Your doctor may tell you not to use zolmitriptan nasal spray.tell your doctor if you smoke or are overweight; if you have or have ever had high blood pressure, high cholesterol, diabetes, or liver or ...

  9. Sumatriptan Nasal Spray

    MedlinePlus

    ... diarrhea and stomach pain caused by decreased blood flow to the intestines). Your doctor may tell you not to use sumatriptan nasal spray.tell your doctor if you smoke or are overweight; if you have or have ever had high blood pressure, high cholesterol, diabetes, seizures, or liver ...

  10. Azelastine Nasal Spray

    MedlinePlus

    ... and replace with the pump unit. Prime the delivery system (pump unit) with four sprays or until a fine mist appears. If 3 days or more have elapsed since your last use of the nasal spray, reprime the pump with two sprays or until a fine mist appears.

  11. [Pharmacological and clinical evalutation of nasal obstruction: application to xylometazoline].

    PubMed

    Pradalier, André

    2006-01-01

    Nasal obstruction, a prominent feature of rhinitis, may be quantified in humans by haemodynamic techniques (measuring local blood flux), static methods (measuring the geometry of nasal cavities) and dynamic methods (assessing the patency of nasal airways through the measure of resistance to air flow). These methods demonstrated the nasal decongestant activity of xylometazoline in healthy volunteers and rhinitis patients. Controlled double-blind studies established the clinical efficacy of xylometazoline in infectious and allergic (seasonal and perennial) rhinitis versus placebo and in comparison with various reference substances. The effects on nasal epithelium ciliary activity which are observed in vitro are modest and even less pronounced in vivo owing to dilution in situ and protective physiological processes. PMID:16792148

  12. Regulation of human renin expression in chorion cell primary cultures

    SciTech Connect

    Duncan, K.G.; Haidar, M.A.; Baxter, J.D.; Reudelhuber, T.L. )

    1990-10-01

    The human renin gene is expressed in the kidney, placenta, and several other sites. The release of renin or its precursor, prorenin, can be affected by several regulatory agents. In this study, primary cultures of human placental cells were used to examine the regulation of prorenin release and renin mRNA levels and of the transfected human renin promoter linked to chloramphenicol acetyltransferase reporter sequences. Treatment of the cultures with a calcium ionophore alone, calcium ionophore plus forskolin (that activates adenylate cyclase), or forskolin plus a phorbol ester increased prorenin release and renin mRNA levels 1.3{endash} to 6{endash}fold, but several classes of steroids did not affect prorenin secretion or renin RNA levels. These results suggest that (i) the first 584 base pairs of the renin gene 5'{endash}flanking DNA do not contain functional glucocorticoid or estrogen response elements, (ii) placental prorenin release and renin mRNA are regulated by calcium ion and by the combinations of cAMP with either C kinase or calcium ion, and (iii) the first 100 base pairs of the human renin 5'{endash}flanking DNA direct accurate initiation of transcription and can be regulated by cAMP. Thus, some control of renin release in the placenta (and by inference in other tissues) occurs via transcriptional influences on its promoter.

  13. Primary human bronchial epithelial cells grown from explants.

    PubMed

    Yaghi, Asma; Zaman, Aisha; Dolovich, Myrna

    2010-01-01

    Human bronchial epithelial cells are needed for cell models of disease and to investigate the effect of excipients and pharmacologic agents on the function and structure of human epithelial cells. Here we describe in detail the method of growing bronchial epithelial cells from bronchial airway tissue that is harvested by the surgeon at the times of lung surgery (e.g. lung cancer or lung volume reduction surgery). With ethics approval and informed consent, the surgeon takes what is needed for pathology and provides us with a bronchial portion that is remote from the diseased areas. The tissue is then used as a source of explants that can be used for growing primary bronchial epithelial cells in culture. Bronchial segments about 0.5-1cm long and < or =1cm in diameter are rinsed with cold EBSS and excess parenchymal tissue is removed. Segments are cut open and minced into 2-3mm(3) pieces of tissue. The pieces are used as a source of primary cells. After coating 100mm culture plates for 1-2 hr with a combination of collagen (30 microg/ml), fibronectin (10 microg/ml), and BSA (10 microg/ml), the plates are scratched in 4-5 areas and tissue pieces are placed in the scratched areas, then culture medium (DMEM/Ham F-12 with additives) suitable for epithelial cell growth is added and plates are placed in an incubator at 37 degrees C in 5% CO(2) humidified air. The culture medium is changed every 3-4 days. The epithelial cells grow from the pieces forming about 1.5 cm diameter rings in 3-4 weeks. Explants can be re-used up to 6 times by moving them into new pre-coated plates. Cells are lifted using trypsin/EDTA, pooled, counted, and re-plated in T75 Cell Bind flasks to increase their numbers. T75 flasks seeded with 2-3 million cells grow to 80% confluence in 4 weeks. Expanded primary human epithelial cells can be cultured and allowed to differentiate on air-liquid interface. Methods described here provide an abundant source of human bronchial epithelial cells from freshly

  14. Development of a Transnasal Delivery System for Recombinant Human Growth Hormone (rhGH): Effects of the Concentration and Molecular Weight of Poly-L-arginine on the Nasal Absorption of rhGH in Rats.

    PubMed

    Kawashima, Ryo; Uchida, Masaki; Yamaki, Tsutomu; Ohtake, Kazuo; Hatanaka, Tomomi; Uchida, Hiroyuki; Ueda, Hideo; Kobayashi, Jun; Morimoto, Yasunori; Natsume, Hideshi

    2016-01-01

    A novel system for delivering recombinant human growth hormone (rhGH) that is noninvasive and has a simple method of administration is strongly desired to improve the compliance of children. The aim of this study was to investigate the potential for the intranasal (i.n.) co-administration of rhGH with poly-L-arginine (PLA) as a novel delivery system by evaluating the effects of the concentration and molecular weight of PLA on the nasal absorption of rhGH. The influence of the formation of insoluble aggregates and a soluble complex in the dosage formulation on nasal rhGH absorption was also evaluated by size-exclusion chromatography and ultrafiltration. PLA enhanced the nasal absorption of rhGH at each concentration and molecular weight examined. Nasal rhGH absorption increased dramatically when the PLA concentration was 1.0 % (w/v) due to the improved solubility of rhGH in the formulation. A delay in rhGH absorption was observed when the molecular weight of PLA was increased. This appeared to be because the increase in molecular weight caused the formation of a soluble complex. It seems that the PLA concentration affects the absorption-enhancing effect on rhGH, while the molecular weight of PLA affects the time when the maximum plasma rhGH concentration was reached (Tmax) of rhGH after i.n. administration, mainly because of the interactions among rhGH, PLA, and additives. Therefore, the transnasal rhGH delivery system using PLA is considered to be a promising alternative to subcutaneous (s.c.) injection if these interactions are sufficiently controlled.

  15. Primary human monocyte differentiation regulated by Nigella sativa pressed oil

    PubMed Central

    2011-01-01

    Background Oxidized low density lipoprotein plays an important role in development of foam cells in atherosclerosis. The study was focused on regulation of primary human monocyte growth and CD11b expression in presence of Nigella sativa oil. Methods Primary human monocytes were isolated from whole blood and grown at 37°C and 5% CO2 saturation for five days prior to treatment with Nigella sativa oil. The cells were plated and washed before treatment with ox-LDL (10 μg/ml) as positive control and combined treatment of ox-LDL (10 μg/ml) and (140 ng/ml) Nigella sativa oil. The growth progression was monitored every 24 hours for 3 days. Results Macrophages showed reduced growth in comparison to monocytes 24 hours after treatment with Nigella sativa oil. The mean cell diameter was significantly different between untreated and treated condition in monocytes and macrophages (p < 0.001). Similarly, intracellular lipid accumulation was hindered in combined treatment with Nigella sativa oil. This was further supported by cell surface expression analysis, where CD11b was markedly reduced in cells treated with combination oxLDL and Nigella sativa oil compared to oxLDL alone. More cells differentiated into macrophage-like cells when monocytes were supplemented with oxidized LDL alone. Conclusions The finding provides preliminary evidence on regulation of cell growth and differentiation in monocyte and monocyte-derived macrophages by Nigella sativa oil. Further investigations need to be conducted to explain its mechanism in human monocyte. PMID:22104447

  16. Rational design of nasal vaccines.

    PubMed

    Slütter, Bram; Hagenaars, Niels; Jiskoot, Wim

    2008-01-01

    Nasal vaccination is a promising alternative to classical parental vaccination, as it is non-invasive and, in principle, capable of eliciting strong systemic and local immune responses. However, the protective efficacy of nasally administered antigens is often impaired because of delivery problems: free antigens are readily cleared from the nasal cavity, poorly absorbed by nasal epithelial cells and generally have low intrinsic immunogenicity. In this review paper, we describe the main physiological hurdles to nasal vaccine delivery, survey the progress made in technological approaches to overcome these hurdles and discuss emerging opportunities for improving nasal vaccines. According to current insights, encapsulation of the antigen into bioadhesive (nano)particles is a promising approach towards successful nasal vaccine delivery. These antigen-loaded particles can be tailor made by supplying them with targeting ligands, adjuvants or endosomal escape mediators to form the desired vaccine that provides long-lasting protective immunity.

  17. Intracellular pH and its relationship to regulation of ion transport in normal and cystic fibrosis human nasal epithelia.

    PubMed

    Willumsen, N J; Boucher, R C

    1992-09-01

    1. Intracellular pH (pHi) of cultured human airway epithelial cells from normal and cystic fibrosis (CF) subjects were measured with double-barrelled pH-sensitive liquid exchanger microelectrodes. The cells, which were grown to confluence on a permeable collagen matrix support, were mounted in a modified miniature Ussing chamber. All studies were conducted under open circuit conditions. Values are given as means +/- S.E.M. and n refers to the number of preparations. 2. Normal preparations (n = 15) were characterized by a transepithelial potential difference (Vt) of -18 +/- 2 mV, an apical membrane potential (Va) of -19 +/- 2 mV, a basolateral membrane potential (Vb) of -37 +/- 2 mV, a transepithelial resistance (Rt) of 253 +/- 15 omega cm2, a fractional apical membrane resistance (fRa) of 0.40 +/- 0.04 and an equivalent short circuit current (Ieq) of -73 +/- 7 microA cm-2. 3. CF preparations (n = 13) were characterized by a Vt of -46 +/- 7 mV, a Va of 3 +/- 5 mV, a Vb of -43 +/- 3 mV, Rt of 373 +/- 47 omega cm2, fRa of 0.44 +/- 0.04 and an Ieq of -130 +/- 16 microA cm-2. All parameters except Vb and fRa were significantly different (P < 0.025) from those of normal preparations. 4. Despite large differences in electrochemical driving force for proton flow across the apical cell membranes between normal and CF preparations (-4 +/- 3 mV and 20 +/- 7 mV, respectively), pHi was similar (7.15 +/- 0.02 and 7.11 +/- 0.05, respectively). The driving force across the basolateral membrane was similar in normal and CF preparations (22 +/- 3 and 26 +/- 3 mV, respectively). 5. Intracellular alkalinization achieved by removal of CO2 from the luminal Ringer solution or by luminal ammonium prepulse led to stimulation of Ieq in both normal (from -58 to -70 microA cm-2, n = 4; P < 0.05) and CF (from -144 to -163 microA cm-2, n = 4; P < 0.005) preparations. The increase in Ieq was associated with a reduction of Rt, increase in fRa, and hyperpolarization of Vb. All changes in

  18. Nasal vasomotor responses in man to breath holding and hyperventilation recorded by means of intranasal balloons.

    PubMed

    Babatola, F D; Eccles, R

    1986-12-01

    Nasal vasomotor responses were recorded in conscious human subjects by means of water filled balloons. Hyperventilation caused an increase in intranasal balloon pressure associated with vasodilatation whereas breath holding caused a decrease associated with vasoconstriction. The amplitude of the nasal vasomotor response was influenced by the nasal cycle with the greatest response always observed on the congested or low airflow side of the nose. The results suggest that an elevated arterial level of carbon dioxide causes a pronounced vasoconstruction of the nasal blood vessels and that this response may be clinically relevant in controlling nasal bleeding.

  19. Zika virus productively infects primary human placenta-specific macrophages

    PubMed Central

    Jurado, Kellie Ann; Simoni, Michael K.; Tang, Zhonghua; Uraki, Ryuta; Hwang, Jesse; Householder, Sarah; Wu, Mingjie; Lindenbach, Brett D.; Abrahams, Vikki M.; Guller, Seth

    2016-01-01

    The strong association of Zika virus infection with congenital defects has led to questions of how a flavivirus is capable of crossing the placental barrier to reach the fetal brain. Here, we demonstrate permissive Zika virus infection of primary human placental macrophages, commonly referred to as Hofbauer cells, and placental villous fibroblasts. We also demonstrate Zika virus infection of Hofbauer cells within the context of the tissue ex vivo using term placental villous explants. In addition to amplifying infectious virus within a usually inaccessible area, the putative migratory activities of Hofbauer cells may aid in dissemination of Zika virus to the fetal brain. Understanding the susceptibility of placenta-specific cell types will aid future work around and understanding of Zika virus–associated pregnancy complications. PMID:27595140

  20. Zika virus productively infects primary human placenta-specific macrophages

    PubMed Central

    Jurado, Kellie Ann; Simoni, Michael K.; Tang, Zhonghua; Uraki, Ryuta; Hwang, Jesse; Householder, Sarah; Wu, Mingjie; Lindenbach, Brett D.; Abrahams, Vikki M.; Guller, Seth; Fikrig, Erol

    2016-01-01

    The strong association of Zika virus infection with congenital defects has led to questions of how a flavivirus is capable of crossing the placental barrier to reach the fetal brain. Here, we demonstrate permissive Zika virus infection of primary human placental macrophages, commonly referred to as Hofbauer cells, and placental villous fibroblasts. We also demonstrate Zika virus infection of Hofbauer cells within the context of the tissue ex vivo using term placental villous explants. In addition to amplifying infectious virus within a usually inaccessible area, the putative migratory activities of Hofbauer cells may aid in dissemination of Zika virus to the fetal brain. Understanding the susceptibility of placenta-specific cell types will aid future work around and understanding of Zika virus–associated pregnancy complications.

  1. Effect of silver nanoparticles on human primary keratinocytes.

    PubMed

    Szmyd, Radoslaw; Goralczyk, Anna Grazyna; Skalniak, Lukasz; Cierniak, Agnieszka; Lipert, Barbara; Filon, Francesca Larese; Crosera, Matteo; Borowczyk, Julia; Laczna, Eliza; Drukala, Justyna; Klein, Andrzej; Jura, Jolanta

    2013-01-01

    Silver nanoparticles (AgNPs) have many biological applications in biomedicine, biotechnology and other life sciences. Depending on the size, shape and the type of carrier, AgNPs demonstrate different physical and chemical properties. AgNPs have strong antimicrobial, antiviral and antifungal activity, thus they are used extensively in a range of medical settings, particularly in wound dressings but also in cosmetics. This study was undertaken to examine the potential toxic effects of 15 nm polyvinylpyrrolidone-coated AgNPs on primary normal human epidermal keratinocytes (NHEK). Cells were treated with different concentrations of AgNPs and then cell viability, metabolic activity and other biological and biochemical aspects of keratinocytes functioning were studied. We observed that AgNPs decrease keratinocyte viability, metabolism and also proliferatory and migratory potential of these cells. Moreover, longer exposure resulted in activation of caspase 3/7 and DNA damage. Our studies show for the first time, that AgNPs may present possible danger for primary keratinocytes, concerning activation of genotoxic and cytotoxic processes depending on the concentration.

  2. Youth who sexual offended: primary human goods and offense pathways.

    PubMed

    Chu, Chi Meng; Koh, Li Lian; Zeng, Gerald; Teoh, Jennifer

    2015-04-01

    There has been an increased focus on understanding youth sexual offending in recent years, but there has been limited empirical research on the causes, pathways, and treatment of youth who have sexually offended-especially within a non-Western context. The Good Lives and Self-Regulation Models have often been used to understand and rehabilitate adult sexual offenders, but (unfortunately) there is scant research on youth who sexually offended using these models. The present study aims to describe the different primary goods that are associated with youth sexual offending behaviors in an Asian context. In addition, the study sought to explore whether the age of victim (child vs. nonchild) and nature of sexual offense (penetrative vs. nonpenetrative) influenced the youth's engagement in offense pathways. The results suggest that pleasure, relatedness, and inner peace were the primary human goods that were most sought after by a sample of 168 youth who sexually offended in Singapore. In addition, offender classification (in relation to the age of victim and nature of sexual offense) influenced the pathways to sexual offending. Therefore, these findings have important clinical implications for assessment, management, and intervention planning for youth who sexually offended. PMID:24048701

  3. Youth who sexual offended: primary human goods and offense pathways.

    PubMed

    Chu, Chi Meng; Koh, Li Lian; Zeng, Gerald; Teoh, Jennifer

    2015-04-01

    There has been an increased focus on understanding youth sexual offending in recent years, but there has been limited empirical research on the causes, pathways, and treatment of youth who have sexually offended-especially within a non-Western context. The Good Lives and Self-Regulation Models have often been used to understand and rehabilitate adult sexual offenders, but (unfortunately) there is scant research on youth who sexually offended using these models. The present study aims to describe the different primary goods that are associated with youth sexual offending behaviors in an Asian context. In addition, the study sought to explore whether the age of victim (child vs. nonchild) and nature of sexual offense (penetrative vs. nonpenetrative) influenced the youth's engagement in offense pathways. The results suggest that pleasure, relatedness, and inner peace were the primary human goods that were most sought after by a sample of 168 youth who sexually offended in Singapore. In addition, offender classification (in relation to the age of victim and nature of sexual offense) influenced the pathways to sexual offending. Therefore, these findings have important clinical implications for assessment, management, and intervention planning for youth who sexually offended.

  4. Inverted papillomas and benign nonneoplastic lesions of the nasal cavity

    PubMed Central

    Casiano, Roy R.

    2012-01-01

    Background: Benign lesions of the nasal cavity represent a diverse group of pathologies. Furthermore, each of these disorders may present differently in any given patient as pain and discomfort, epistaxis, headaches, vision changes, or nasal obstruction. Although these nasal masses are benign, many of them have a significant capacity for local tissue destruction and symptomatology secondary to this destruction. Advances in office-based endoscopic nasendoscopy have equipped the otolaryngologist with a safe, inexpensive, and rapid means of directly visualizing lesions within the nasal cavity and the initiation of appropriate treatment. Methods: The purpose of this study is to review the diagnosis, management, and controversies of many of the most common benign lesions of the nasal cavity encountered by the primary care physician or otolaryngologist. Results: This includes discussion of inverted papilloma (IP), juvenile angiofibroma, squamous papilloma, pyogenic granuloma, hereditary hemorrhagic telangiectasia, schwannoma, benign fibro-osseous lesions, and other benign lesions of the nasal cavity, with particular emphasis on IP and juvenile angiofibroma. Conclusion: A diverse array of benign lesions occur within the nasal cavity and paranasal cavities. Despite their inability to metastasize, many of these lesions have significant capability for local tissue destruction and recurrence. PMID:22487294

  5. Steroid synthesis by primary human keratinocytes; implications for skin disease

    SciTech Connect

    Hannen, Rosalind F.; Michael, Anthony E.; Jaulim, Adil; Bhogal, Ranjit; Burrin, Jacky M.; Philpott, Michael P.

    2011-01-07

    Research highlights: {yields} Primary keratinocytes express the steroid enzymes required for cortisol synthesis. {yields} Normal primary human keratinocytes can synthesise cortisol. {yields} Steroidogenic regulators, StAR and MLN64, are expressed in normal epidermis. {yields} StAR expression is down regulated in eczema and psoriatic epidermis. -- Abstract: Cortisol-based therapy is one of the most potent anti-inflammatory treatments available for skin conditions including psoriasis and atopic dermatitis. Previous studies have investigated the steroidogenic capabilities of keratinocytes, though none have demonstrated that these skin cells, which form up to 90% of the epidermis are able to synthesise cortisol. Here we demonstrate that primary human keratinocytes (PHK) express all the elements required for cortisol steroidogenesis and metabolise pregnenolone through each intermediate steroid to cortisol. We show that normal epidermis and cultured PHK express each of the enzymes (CYP11A1, CYP17A1, 3{beta}HSD1, CYP21 and CYP11B1) that are required for cortisol synthesis. These enzymes were shown to be metabolically active for cortisol synthesis since radiometric conversion assays traced the metabolism of [7-{sup 3}H]-pregnenolone through each steroid intermediate to [7-{sup 3}H]-cortisol in cultured PHK. Trilostane (a 3{beta}HSD1 inhibitor) and ketoconazole (a CYP17A1 inhibitor) blocked the metabolism of both pregnenolone and progesterone. Finally, we show that normal skin expresses two cholesterol transporters, steroidogenic acute regulatory protein (StAR), regarded as the rate-determining protein for steroid synthesis, and metastatic lymph node 64 (MLN64) whose function has been linked to cholesterol transport in steroidogenesis. The expression of StAR and MLN64 was aberrant in two skin disorders, psoriasis and atopic dermatitis, that are commonly treated with cortisol, suggesting dysregulation of epidermal steroid synthesis in these patients. Collectively these data

  6. Effect of matrine on primary human hepatocytes in vitro.

    PubMed

    Gong, Xiaobing; Gao, Yuan; Guo, Guoqing; Vondran, Florian W R; Schwartlander, Ruth; Efimova, Ekaterina; Pless, Gesine; Sauera, Igor M; Neuhaus, Peter

    2015-03-01

    Matrine is a bioactive component of the traditional Chinese medical herb Sophora flavescens that has been used in China to treat various kinds of diseases including virus hepatitis. However, the molecular mechanisms underlying its hepatoprotective effects remains elusive. In the present study, primary human hepatocytes were employed to elucidate the protective effects and molecular mechanisms of matrine. We observed that low concentrations of matrine had no significant impact on albumin secretion, but high concentrations (>140 mg/L) of matrine decreased the albumin secretion in hepatocytes. Western blot data indicated that matrine at 140 mg/L at 72 h induced protein expression of CYP2A6, CYP2B6 and CYP3A4. Furthermore, high concentrations of matrine reduced LDH and AST levels and were cytotoxic to hepatocytes, leading to a decreased cell viability and total protein amount. Moreover, low concentrations of matrine, enhanced the ECOD activity and decreased the level of NO2 (-) induced by cytokines in human hepatocytes. Taken together, the present study sheds novel light on the molecular mechanisms of matrine and potential application of matrine in hepatic diseases.

  7. Transcranial focused ultrasound stimulation of human primary visual cortex

    PubMed Central

    Lee, Wonhye; Kim, Hyun-Chul; Jung, Yujin; Chung, Yong An; Song, In-Uk; Lee, Jong-Hwan; Yoo, Seung-Schik

    2016-01-01

    Transcranial focused ultrasound (FUS) is making progress as a new non-invasive mode of regional brain stimulation. Current evidence of FUS-mediated neurostimulation for humans has been limited to the observation of subjective sensory manifestations and electrophysiological responses, thus warranting the identification of stimulated brain regions. Here, we report FUS sonication of the primary visual cortex (V1) in humans, resulting in elicited activation not only from the sonicated brain area, but also from the network of regions involved in visual and higher-order cognitive processes (as revealed by simultaneous acquisition of blood-oxygenation-level-dependent functional magnetic resonance imaging). Accompanying phosphene perception was also reported. The electroencephalo graphic (EEG) responses showed distinct peaks associated with the stimulation. None of the participants showed any adverse effects from the sonication based on neuroimaging and neurological examinations. Retrospective numerical simulation of the acoustic profile showed the presence of individual variability in terms of the location and intensity of the acoustic focus. With exquisite spatial selectivity and capability for depth penetration, FUS may confer a unique utility in providing non-invasive stimulation of region-specific brain circuits for neuroscientific and therapeutic applications. PMID:27658372

  8. Transcranial focused ultrasound stimulation of human primary visual cortex

    NASA Astrophysics Data System (ADS)

    Lee, Wonhye; Kim, Hyun-Chul; Jung, Yujin; Chung, Yong An; Song, In-Uk; Lee, Jong-Hwan; Yoo, Seung-Schik

    2016-09-01

    Transcranial focused ultrasound (FUS) is making progress as a new non-invasive mode of regional brain stimulation. Current evidence of FUS-mediated neurostimulation for humans has been limited to the observation of subjective sensory manifestations and electrophysiological responses, thus warranting the identification of stimulated brain regions. Here, we report FUS sonication of the primary visual cortex (V1) in humans, resulting in elicited activation not only from the sonicated brain area, but also from the network of regions involved in visual and higher-order cognitive processes (as revealed by simultaneous acquisition of blood-oxygenation-level-dependent functional magnetic resonance imaging). Accompanying phosphene perception was also reported. The electroencephalo graphic (EEG) responses showed distinct peaks associated with the stimulation. None of the participants showed any adverse effects from the sonication based on neuroimaging and neurological examinations. Retrospective numerical simulation of the acoustic profile showed the presence of individual variability in terms of the location and intensity of the acoustic focus. With exquisite spatial selectivity and capability for depth penetration, FUS may confer a unique utility in providing non-invasive stimulation of region-specific brain circuits for neuroscientific and therapeutic applications.

  9. Human Rights Texts: Converting Human Rights Primary Source Documents into Data

    PubMed Central

    Fariss, Christopher J.; Linder, Fridolin J.; Jones, Zachary M.; Crabtree, Charles D.; Biek, Megan A.; Ross, Ana-Sophia M.; Kaur, Taranamol; Tsai, Michael

    2015-01-01

    We introduce and make publicly available a large corpus of digitized primary source human rights documents which are published annually by monitoring agencies that include Amnesty International, Human Rights Watch, the Lawyers Committee for Human Rights, and the United States Department of State. In addition to the digitized text, we also make available and describe document-term matrices, which are datasets that systematically organize the word counts from each unique document by each unique term within the corpus of human rights documents. To contextualize the importance of this corpus, we describe the development of coding procedures in the human rights community and several existing categorical indicators that have been created by human coding of the human rights documents contained in the corpus. We then discuss how the new human rights corpus and the existing human rights datasets can be used with a variety of statistical analyses and machine learning algorithms to help scholars understand how human rights practices and reporting have evolved over time. We close with a discussion of our plans for dataset maintenance, updating, and availability. PMID:26418817

  10. Human Rights Texts: Converting Human Rights Primary Source Documents into Data.

    PubMed

    Fariss, Christopher J; Linder, Fridolin J; Jones, Zachary M; Crabtree, Charles D; Biek, Megan A; Ross, Ana-Sophia M; Kaur, Taranamol; Tsai, Michael

    2015-01-01

    We introduce and make publicly available a large corpus of digitized primary source human rights documents which are published annually by monitoring agencies that include Amnesty International, Human Rights Watch, the Lawyers Committee for Human Rights, and the United States Department of State. In addition to the digitized text, we also make available and describe document-term matrices, which are datasets that systematically organize the word counts from each unique document by each unique term within the corpus of human rights documents. To contextualize the importance of this corpus, we describe the development of coding procedures in the human rights community and several existing categorical indicators that have been created by human coding of the human rights documents contained in the corpus. We then discuss how the new human rights corpus and the existing human rights datasets can be used with a variety of statistical analyses and machine learning algorithms to help scholars understand how human rights practices and reporting have evolved over time. We close with a discussion of our plans for dataset maintenance, updating, and availability.

  11. Differential response to bacteria, and TOLLIP expression, in the human respiratory tract

    PubMed Central

    Moncayo-Nieto, Olga Lucia; Wilkinson, Thomas S; Brittan, Mairi; McHugh, Brian J; Jones, Richard O; Conway Morris, Andrew; Walker, William S; Davidson, Donald J; Simpson, A John

    2014-01-01

    Objectives The observation that pathogenic bacteria are commonly tolerated in the human nose, yet drive florid inflammation in the lung, is poorly understood, partly due to limited availability of primary human cells from each location. We compared responses to bacterial virulence factors in primary human nasal and alveolar cells, and characterised the distribution of Toll-interacting protein (TOLLIP; an inhibitor of Toll-like receptor (TLR) signalling) in the human respiratory tract. Methods Primary cells were isolated from nasal brushings and lung tissue taken from patients undergoing pulmonary resection. Cells were exposed to lipopolysaccharide, lipoteichoic acid, peptidoglycan, CpG-C DNA or tumour necrosis factor (TNF). Cytokines were measured in cell supernatants. TOLLIP was characterised using quantitative real-time PCR and immunofluorescence. Results In primary alveolar, but not primary nasal, cells peptidoglycan significantly increased secretion of interleukin (IL)-1β, IL-6, IL-8, IL-10 and TNF. TLR2 expression was significantly higher in alveolar cells and correlated with IL-8 production. TOLLIP expression was significantly greater in nasal cells. Conclusion In conclusion, primary human alveolar epithelial cells are significantly more responsive to peptidoglycan than primary nasal epithelial cells. This may partly be explained by differential TLR2 expression. TOLLIP is expressed widely in the human respiratory tract, and may contribute to the regulation of inflammatory responses. PMID:25478190

  12. Ameloblastoma of the Nasal Septum Origin: A Case Report

    PubMed Central

    Zatoński, Tomasz; Roszkowska, Anna; Kręcicki, Tomasz

    2013-01-01

    Background. Ameloblastoma is the most common odontogenic tumor. It represents about 1% of all tumors of the jaw. Extragnathic location of the ameloblastoma is typical and extremely rare. Case Report. We report a case of ameloblastoma of the nasal septum origin, causing nasal obstruction. According to our information, this is the first reported case of ameloblastoma coming from the nasal septum as a primary tumor without maxillary sinus involvement. Conclusions. Ameloblastoma can not only locate in the maxilla and mandible, but also in other regions of the craniofacial. Ameloblastoma should be considered in the differential diagnosis of tumors causing nasal obstruction. Nonspecific clinical features of sinonasal ameloblastoma make it extremely important to perform accurate diagnostic imaging and histopathological examination. PMID:24171127

  13. Management of the Nasal Valve.

    PubMed

    Barrett, Dane M; Casanueva, Fernando J; Cook, Ted A

    2016-08-01

    The nasal valve is an important consideration in patients presenting with nasal obstruction. Controversy exists regarding the anatomy, terminology, evaluation, and management of the nasal valve. Innumerable techniques with variable effects have been described in the literature. The evidence qualifying these techniques has been plentiful, though often lacking in quality. This article reviews the controversial aspects of nasal valve management applying the best available evidence to help clarify potential areas of confusion. Future research using standardized definitions, consistent methodologies, and validated outcome measures are necessary to improve the quality of evidence and impact surgical decision-making. PMID:27400837

  14. [Design of the Rolling Type Nasal Feeding Perfusion Apparatus].

    PubMed

    Yu, Dong; Yang, Yonghuan; Hu, Huiqin; Luo, Hongjun; Feng, Yunhao; Hao, Xiali

    2015-09-01

    At present, the existing problem in nasal feeding perfusion apparatus is laborious and instability. Designing the rolling type perfusion apparatus by using a roller pump, the problem is solved. Compared with the traditional perfusion apparatus, the advantage lies in liquid carrying only need once and simulating human swallowing process. Through testing and verification, the apparatus can be used in nasal feeding perfusion for elderly or patients.

  15. Nasal septum injury in preterm infants using nasal prongs 1

    PubMed Central

    Bonfim, Suely de Fátima Santos Freire; de Vasconcelos, Maria Gorete Lucena; de Sousa, Nayara Francisca Cabral; da Silva, Daiana Vieira Câmara; Leal, Luciana Pedrosa

    2014-01-01

    OBJECTIVE: to assess the incidence and risk factors associated with nasal septum injury in premature infants using reused and new nasal prongs. METHOD: the study was a cohort from an open therapeutic intervention. The sample included 70 infants with a gestational age inferior to 37 weeks, who used nasal prongs and were hospitalized at the neonatal service of a hospital in Recife-PE, in the Northeast of Brazil. The data were collected in patient files through the assessment of the application of the device and of the nasal septum. Multinomial Logistic Regression and Survival analyses were applied. RESULTS: the incidence of nasal injury corresponded to 62.9%. In the multiple analysis, only the length of the infant's treatment was a determinant factor for the occurrence and severity of the injuries. CONCLUSION: the type of nasal prong does not serve as a risk factor for the nasal injury. The high incidence of nasal injury indicates the need to adapt the nursing care with emphasis on prevention. PMID:25493679

  16. Autoreactivity of primary human immunoglobulins ancestral to hypermutated human antibodies that neutralize HCMV.

    PubMed

    McLean, Gary R; Cho, Chin-wen; Schrader, John W

    2006-05-01

    The human antibody response to the AD-2S1 epitope of glycoprotein B (gB) of human cytomegalovirus (HCMV) is dominated by a family of closely related somatically mutated antibodies. These antibodies neutralize viral infectivity and the genes encoding them are derived from two commonly used germ-line variable (V) region genes, IGHV3-30 and IGKV3-11. Recombination of these V genes with the appropriate junctional diversity generates genes that encode primary immunoglobulins that bind to AD-2S1. To further understand the initial primary immunoglobulin response to AD-2S1 we synthesized the germ-line-based ancestor of one such family of antibodies and showed that it bound gB at the AD-2S1 epitope. Here we show that the germ-line ancestor of a second family of antibodies likewise binds to gB. We further show that one of the ancestral primary immunoglobulins, but not the other, also recognized autoantigens. In contrast, the hypermutated derivatives did not demonstrate autoreactivity and minor structural changes in the primary immunoglobulin were sufficient to generate or abolish autoreactivity or to change specificity. Thus, our demonstration that the ancestor of a highly mutated, non-autoreactive antiviral IgG antibody binds nuclear and cell-surface autoantigens indicates for the first time that self-reactivity is not necessarily a barrier to development into a follicular B lymphocyte that undergoes antigen-initiated affinity maturation.

  17. Noradrenaline release and the pathophysiology of primary human hypertension

    SciTech Connect

    Esler, M.; Jennings, G.; Lambert, G.

    1989-03-01

    Measurements of the overflow of norepinephrine to plasma from individual organs (using radiotracer methodology) were used to delineate the pattern of sympathetic nervous system activation present in primary human hypertension. Mean total norepinephrine (NE) spillover in hypertensive patients was 418 ng/min, 42% (124 ng/min) higher than in subjects with normal blood pressure (BP)(P less than .05). Norepinephrine spillover among hypertensive patients was a function of age, only being elevated in patients under 40 years of age. Half of the excess in total norepinephrine release in hypertensive patients was accounted for by increased cardiorenal spillover. Mean renal norepinephrine spillover was 120 ng/min, compared with 69 ng/min in healthy subjects (P less than .02). Renal spillover was highest in younger patients. Corresponding cardiac norepinephrine spillover values were 12.6 ng/min and 5.1 ng/min (P less than .01). The balance of the excess total norepinephrine spillover comes from undetermined sites, but not the lungs or hepatomesenteric circulation. These measurements of regional norepinephrine overflow suggest that sympathetic nervous outflow to the kidneys and heart is selectively activated in early hypertension. 21 references.

  18. Punicalagin promotes autophagy to protect primary human syncytiotrophoblasts from apoptosis.

    PubMed

    Wang, Ying; Chen, Baosheng; Longtine, Mark S; Nelson, D Michael

    2016-02-01

    Punicalagin is a prominent polyphenol in pomegranate juice that protects cultured syncytiotrophoblasts from stress-induced apoptosis. Here, we test the hypothesis that punicalagin has this effect by inhibiting the mTOR kinase pathway to enhance autophagic turnover and limit apoptosis in cultured primary human syncytiotrophoblasts. In syncytiotrophoblasts, starvation, rapamycin, or punicalagin all decreased the expression of phosphorylated ribosomal protein S6, a downstream target of the mTOR kinase, and of the autophagy markers, LC3-II and p62. In contrast, in the presence of bafilomycin, an inhibitor of late stages of autophagy and degradation in the autophagolysosome, syncytiotrophoblasts exposed to starvation, rapamycin, or punicalagin all showed increased levels of LC3-II and p62. The number of LC3-II punctae also increased in punicalagin-treated syncytiotrophoblasts exposed to chloroquine, another inhibitor of autophagic degradation, and punicalagin increased the number of lysosomes. The apoptosis-reducing effect of punicalagin was attenuated by inhibition of autophagy using bafilomycin or knockdown of the autophagy related gene, ATG16L1. Collectively, these data support the hypothesis that punicalagin modulates the crosstalk between autophagy and apoptosis to promote survival in cultured syncytiotrophoblasts. PMID:26659860

  19. Biased Allelic Expression in Human Primary Fibroblast Single Cells

    PubMed Central

    Borel, Christelle; Ferreira, Pedro G.; Santoni, Federico; Delaneau, Olivier; Fort, Alexandre; Popadin, Konstantin Y.; Garieri, Marco; Falconnet, Emilie; Ribaux, Pascale; Guipponi, Michel; Padioleau, Ismael; Carninci, Piero; Dermitzakis, Emmanouil T.; Antonarakis, Stylianos E.

    2015-01-01

    The study of gene expression in mammalian single cells via genomic technologies now provides the possibility to investigate the patterns of allelic gene expression. We used single-cell RNA sequencing to detect the allele-specific mRNA level in 203 single human primary fibroblasts over 133,633 unique heterozygous single-nucleotide variants (hetSNVs). We observed that at the snapshot of analyses, each cell contained mostly transcripts from one allele from the majority of genes; indeed, 76.4% of the hetSNVs displayed stochastic monoallelic expression in single cells. Remarkably, adjacent hetSNVs exhibited a haplotype-consistent allelic ratio; in contrast, distant sites located in two different genes were independent of the haplotype structure. Moreover, the allele-specific expression in single cells correlated with the abundance of the cellular transcript. We observed that genes expressing both alleles in the majority of the single cells at a given time point were rare and enriched with highly expressed genes. The relative abundance of each allele in a cell was controlled by some regulatory mechanisms given that we observed related single-cell allelic profiles according to genes. Overall, these results have direct implications in cellular phenotypic variability. PMID:25557783

  20. 3D Cultivation Techniques for Primary Human Hepatocytes

    PubMed Central

    Bachmann, Anastasia; Moll, Matthias; Gottwald, Eric; Nies, Cordula; Zantl, Roman; Wagner, Helga; Burkhardt, Britta; Sánchez, Juan J. Martínez; Ladurner, Ruth; Thasler, Wolfgang; Damm, Georg; Nussler, Andreas K.

    2015-01-01

    One of the main challenges in drug development is the prediction of in vivo toxicity based on in vitro data. The standard cultivation system for primary human hepatocytes is based on monolayer cultures, even if it is known that these conditions result in a loss of hepatocyte morphology and of liver-specific functions, such as drug-metabolizing enzymes and transporters. As it has been demonstrated that hepatocytes embedded between two sheets of collagen maintain their function, various hydrogels and scaffolds for the 3D cultivation of hepatocytes have been developed. To further improve or maintain hepatic functions, 3D cultivation has been combined with perfusion. In this manuscript, we discuss the benefits and drawbacks of different 3D microfluidic devices. For most systems that are currently available, the main issues are the requirement of large cell numbers, the low throughput, and expensive equipment, which render these devices unattractive for research and the drug-developing industry. A higher acceptance of these devices could be achieved by their simplification and their compatibility with high-throughput, as both aspects are of major importance for a user-friendly device.

  1. Proteomic and Bioinformatic Profile of Primary Human Oral Epithelial Cells

    PubMed Central

    Ghosh, Santosh K.; Yohannes, Elizabeth; Bebek, Gurkan; Weinberg, Aaron; Jiang, Bin; Willard, Belinda; Chance, Mark R.; Kinter, Michael T.; McCormick, Thomas S.

    2012-01-01

    Wounding of the oral mucosa occurs frequently in a highly septic environment. Remarkably, these wounds heal quickly and the oral cavity, for the most part, remains healthy. Deciphering the normal human oral epithelial cell (NHOEC) proteome is critical for understanding the mechanism(s) of protection elicited when the mucosal barrier is intact, as well as when it is breached. Combining 2D gel electrophoresis with shotgun proteomics resulted in identification of 1662 NHOEC proteins. Proteome annotations were performed based on protein classes, molecular functions, disease association and membership in canonical and metabolic signaling pathways. Comparing the NHOEC proteome with a database of innate immunity-relevant interactions (InnateDB) identified 64 common proteins associated with innate immunity. Comparison with published salivary proteomes revealed that 738/1662 NHOEC proteins were common, suggesting that significant numbers of salivary proteins are of epithelial origin. Gene ontology analysis showed similarities in the distributions of NHOEC and saliva proteomes with regard to biological processes, and molecular functions. We also assessed the inter-individual variability of the NHOEC proteome and observed it to be comparable with other primary cells. The baseline proteome described in this study should serve as a resource for proteome studies of the oral mucosa, especially in relation to disease processes. PMID:23035736

  2. Nasal Bridge Intramuscular Hemangioma

    PubMed Central

    Hamir Basah, Zulkifli; Ramza Ramli, Ramiza; Gayadh, Maha Khadum; Mutum, Samarendra Singh

    2015-01-01

    Intramuscular haemangioma (IMH) is a benign mesenchymal tumour. It appears as a deep, nontender mass within the soft tissue, particularly in the extremities. This tumour may not be obvious on clinical examination. Head and neck IMHs represent only 13.5% of the total IMHs. The most common site for a head and neck IMH is the masseter muscle, followed by trapezius, sternocleidomastoid, and very rarely temporalis muscle. We present a patient with left nasal bridge swelling which was excised and histologically confirmed as intramuscular hemangioma. PMID:25709848

  3. Virulent Coxiella burnetii pathotypes productively infect primary human alveolar macrophages.

    PubMed

    Graham, Joseph G; MacDonald, Laura J; Hussain, S Kauser; Sharma, Uma M; Kurten, Richard C; Voth, Daniel E

    2013-06-01

    The intracellular bacterial pathogen Coxiella burnetii is a category B select agent that causes human Q fever. In vivo, C. burnetii targets alveolar macrophages wherein the pathogen replicates in a lysosome-like parasitophorous vacuole (PV). In vitro, C. burnetii infects a variety of cultured cell lines that have collectively been used to model the pathogen's infectious cycle. However, differences in the cellular response to infection have been observed, and virulent C. burnetii isolate infection of host cells has not been well defined. Because alveolar macrophages are routinely implicated in disease, we established primary human alveolar macrophages (hAMs) as an in vitro model of C. burnetii-host cell interactions. C. burnetii pathotypes, including acute disease and endocarditis isolates, replicated in hAMs, albeit with unique PV properties. Each isolate replicated in large, typical PV and small, non-fused vacuoles, and lipid droplets were present in avirulent C. burnetii PV. Interestingly, a subset of small vacuoles harboured single organisms undergoing degradation. Prototypical PV formation and bacterial growth in hAMs required a functional type IV secretion system, indicating C. burnetii secretes effector proteins that control macrophage functions. Avirulent C. burnetii promoted sustained activation of Akt and Erk1/2 pro-survival kinases and short-termphosphorylation of stress-related p38. Avirulent organisms also triggered a robust, early pro-inflammatory response characterized by increased secretion of TNF-α and IL-6, while virulent isolates elicited substantially reduced secretion of these cytokines. A corresponding increase in pro- and mature IL-1β occurred in hAMs infected with avirulent C. burnetii, while little accumulation was observed following infection with virulent isolates. Finally, treatment of hAMs with IFN-γ controlled intracellular replication, supporting a role for this antibacterial insult in the host response to C

  4. Evaluation and comparison of nasal airway flow patterns among three subjects from Caucasian, Chinese and Indian ethnic groups using computational fluid dynamics simulation.

    PubMed

    Zhu, Jian Hua; Lee, Heow Pueh; Lim, Kian Meng; Lee, Shu Jin; Wang, De Yun

    2011-01-31

    Nasal airflow is one of the most important determinants for nasal physiology. During the long evolution of human beings, different races have developed their own attributes of nasal morphologies which result in variations of nasal airflow patterns and nasal functions. This study evaluated and compared the effects of differences of nasal morphology among three healthy male subjects from Caucasian, Chinese and Indian ethnic groups on nasal airflow patterns using computational fluid dynamics simulation. By examining the anterior nasal airway, the nasal indices and the nostril shapes of the three subjects were found to be similar to nasal cavities of respective ethnic groups. Computed tomography images of these three subjects were obtained to reconstruct 3-dimensional models of nasal cavities. To retain the flow characteristics around the nasal vestibules, a 40 mm-radius semi sphere was assembled around the human face for the prescription of zero ambient gauge pressure. The results show that more airflow tends to pass through the middle passage of the nasal airway in the Caucasian model, and through the inferior portion in the Indian model. The Indian model was found with extremely low flow flux flowing through the olfactory region. The sizes of vortexes near the anterior cavity were found to be correlated with the angles between the upper nasal valve wall and the anterior head of the nasal cavity. PMID:20854936

  5. Effects of nasalance on the acoustical properties of the tenor passaggio and the head voice

    NASA Astrophysics Data System (ADS)

    Perna, Nicholas Kevin

    This study aims to measure the effect that nasality has on the acoustical properties of the tenor passaggio and head voice. Not to be confused with forward resonance, nasality here will be defined as nasalance, the reading of a Nasometer, or the percentage of nasal and oral airflow during phonation. A previous study by Peer Birch et al. has shown that professional tenors used higher percentages of nasalance through their passaggio. They hypothesized that tenors used nasalance to make slight timbral adjustments as they ascended through passaggio. Other well respected authors including Richard Miller and William McIver have claimed that teaching registration issues is the most important component of training young tenors. It seemed logical to measure the acoustic effects of nasalance on the tenor passaggio and head voice. Eight professional operatic tenors participated as subjects performing numerous vocal exercises that demonstrated various registration events. These examples were recorded and analyzed using a Nasometer and Voce Vista Pro Software. Tenors did generally show an increase of nasalance during an ascending B-flat major scale on the vowels [i] and [u]. Perhaps the most revealing result was that six of seven tenors showed at least a 5-10% increase in nasalance on the note after their primary register transition on the vowel of [a]. It is suggested that this phenomenon receive further empirical scrutiny, because, if true, pedagogues could use nasalance as a tool for helping a young tenor ascend through his passaggio.

  6. Same Noses, Different Nasalance Scores: Data from Normal Subjects and Cleft Palate Speakers for Three Systems for Nasalance Analysis

    ERIC Educational Resources Information Center

    Bressmann, Tim; Klaiman, Paula; Fischbach, Simone

    2006-01-01

    Nasalance scores from the Nasometer, the NasalView and the OroNasal System were compared. The data was collected from 50 normal participants and 19 hypernasal patients with cleft palate. The Nasometer had the lowest nasalance scores for the non-nasal Zoo Passage and that the OroNasal System had the lowest nasalance scores for the Nasal Sentences.…

  7. Attachment of human primary osteoblast cells to modified polyethylene surfaces.

    PubMed

    Poulsson, Alexandra H C; Mitchell, Stephen A; Davidson, Marcus R; Johnstone, Alan J; Emmison, Neil; Bradley, Robert H

    2009-04-01

    Ultra-high-molecular-weight polyethylene (UHMWPE) has a long history of use in medical devices, primarily for articulating surfaces due to its inherent low surface energy which limits tissue integration. To widen the applications of UHMWPE, the surface energy can be increased. The increase in surface energy would improve the adsorption of proteins and attachment of cells to allow tissue integration, thereby allowing UHMWPE to potentially be used for a wider range of implants. The attachment and function of human primary osteoblast-like (HOB) cells to surfaces of UHMWPE with various levels of incorporated surface oxygen have been investigated. The surface modification of the UHMWPE was produced by exposure to a UV/ozone treatment. The resulting surface chemistry was studied using X-ray photoelectron spectroscopy (XPS), and the topography and surface structure were probed by atomic force microscopy (AFM) and scanning electron microscopy (SEM), which showed an increase in surface oxygen from 11 to 26 atom % with no significant change to the surface topography. The absolute root mean square roughness of both untreated and UV/ozone-treated surfaces was within 350-450 nm, and the water contact angles decreased with increasing oxygen incorporation, i.e., showing an increase in surface hydrophilicity. Cell attachment and functionality were assessed over a 21 day period for each cell-surface combination studied; these were performed using SEM and the alamarBlue assay to study cell attachment and proliferation and energy-dispersive X-ray (EDX) analysis to confirm extracellular mineral deposits, and total protein assay to examine the intra- and extracellular protein expressed by the cells. HOB cells cultured for 21 days on the modified UHMWPE surfaces with 19 and 26 atom % oxygen incorporated showed significantly higher cell densities compared to cells cultured on tissue culture polystyrene (TCPS) from day 3 onward. This indicated that the cells attached and proliferated more

  8. Inquiry-Based Learning in Teacher Education: A Primary Humanities Example

    ERIC Educational Resources Information Center

    Preston, Lou; Harvie, Kate; Wallace, Heather

    2015-01-01

    Inquiry-based learning features strongly in the new Australian Humanities and Social Sciences curriculum and increasingly in primary school practice. Yet, there is little research into, and few exemplars of, inquiry approaches in the primary humanities context. In this article, we outline and explain the implementation of a place-based simulation…

  9. Intravenous immunoglobulin treatment preserves and protects primary rat hippocampal neurons and primary human brain cultures against oxidative insults.

    PubMed

    Lahiri, Debomoy K; Ray, Balmiki

    2014-01-01

    Alzheimer's disease (AD) is characterized by deleterious accumulation of amyloid-β (Aβ) peptide into senile plaque, neurofibrillary tangles formed from hyperphosphorylated tau protein, and loss of cholinergic synapses in the cerebral cortex. The deposition of Aβ-loaded plaques results in microglial activation and subsequent production of reactive oxygen species (ROS), including free radicals. Neurons in aging and AD brains are particularly vulnerable to ROS and other toxic stimuli. Therefore, agents that decrease the vulnerability of neurons against ROS may provide therapeutic values for the treatment or prevention of AD. In the present study, our goal was to test whether intravenous immunoglobulin (IVIG) treatment could preserve as well as protect neurons from oxidative damage. We report that treatment with IVIG protects neuronal viability and synaptic proteins in primary rat hippocampal neurons. Further, we demonstrate the tolerability of IVIG treatment in the primary human fetal mixed brain cultures. Indeed, a high dose (20 mg/ml) of IVIG treatment was well-tolerated by primary human brain cultures that exhibit a normal neuronal phenotype. We also observed a potent neuropreservatory effect of IVIG against ROS-mediated oxidative insults in these human fetal brain cultures. These results indicate that IVIG treatment has great potential to preserve and protect primary human neuronal-enriched cultures and to potentially rescue dying neurons from oxidative insults. Therefore, our findings suggest that IVIG treatment may represent an important therapeutic agent for clinical trials designed to prevent and delay the onset of neurodegeneration as well as AD pathology. PMID:25115544

  10. Visualization of drug translocation in the nasal cavity and pharmacokinetic analysis on nasal drug absorption using positron emission tomography in the rat.

    PubMed

    Shingaki, Tomotaka; Katayama, Yumiko; Nakaoka, Takayoshi; Irie, Satsuki; Onoe, Kayo; Okauchi, Takashi; Hayashinaka, Emi; Yamaguchi, Masataka; Tanki, Nobuyoshi; Ose, Takayuki; Hayashi, Takuya; Wada, Yasuhiro; Furubayashi, Tomoyuki; Cui, Yilong; Sakane, Toshiyasu; Watanabe, Yasuyoshi

    2016-02-01

    We performed positron emission tomography (PET) using 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) to evaluate the pharmacokinetics of nasal drug absorption in the rat. The dosing solution of [(18)F]FDG was varied in volume (ranging from 5 to 25 μl) and viscosity (using 0% to 3% concentrations of hydroxypropylcellulose). We modeled the pharmacokinetic parameters regarding the nasal cavity and pharynx using mass balance equations, and evaluated the values that were obtained by fitting concentration-time profiles using WinNonlin® software. The regional nasal permeability was also estimated using the active surface area derived from the PET images. The translocation of [(18)F]FDG from the nasal cavity was visualized using PET. Analysis of the PET imaging data revealed that the pharmacokinetic parameters were independent of the dosing solution volume; however, the viscosity increased the absorption rate constant and decreased the mucociliary clearance rate constant. Nasal permeability was initially higher but subsequently decreased until the end of the study, indicating regional differences in permeability in the nasal cavity. We concluded that the visualization of drug translocation in the nasal cavity in the rat using PET enables quantitative analysis of nasal drug absorption, thereby facilitating the development of nasal formulations for human use.

  11. Contemporary Concepts for the Bilateral Cleft Lip and Nasal Repair

    PubMed Central

    Khosla, Rohit K.; McGregor, Jyoti; Kelley, Patrick K.; Gruss, Joseph S.

    2012-01-01

    The bilateral cleft lip and nasal deformity presents a complex challenge for repair. Surgical techniques continue to evolve and are focused on primary anatomic realignment of the tissues. This can be accomplished in a single-stage or two-stage repair early in infancy to provide a foundation for future growth of the lip and nasal tissue. Most cleft surgeons currently perform a single-stage repair for simplifying patient care. Certain institutions utilize presurgical orthopedics for alignment of the maxillary segments and nasal shaping. Methods for the bilateral cleft lip repair are combined with various open and closed rhinoplasty techniques to achieve improved correction of the primary nasal deformity. There is recent focus on shaping the nose for columellar and tip support, as well as alar contour and alar base position. The authors will present a new technique for closure of the nasal floor to prevent the alveolar cleft fistula. Although the alveolar fistula is closed, alveolar bone grafting is still required at the usual time in dental development to fuse the maxilla. It is paramount to try and minimize the stigmata of secondary deformities that historically have been characteristic of the repaired bilateral cleft lip. A properly planned and executed repair reduces the number of revisions and can spare a child from living with secondary deformities. PMID:24179448

  12. Keratoacanthoma: an unusual nasal mass.

    PubMed

    Sazafi, M S; Salina, H; Asma, A; Masir, N; Primuharsa Putra, S H A

    2013-12-01

    We report a case of keratoacanthoma in a non-sun-exposed nasal vestibule of an 84-year-old man. He presented with a progressively growing left nasal mass that had been present for 8 months. Examination showed a non-tender protruding mass arising from medial vestibular wall of the left nostril. Histopathology indicated it was a keratoacanthoma. In an elderly patient with a history of a progressively growing mass in the nose, a differential diagnosis of malignancy should be ruled out, and histological conformation is essential. To our knowledge, only a very small number of cases of nasal vestibular keratoacanthoma have been reported. PMID:24376301

  13. Mitek Suspension of the Lateral Nasal Wall.

    PubMed

    White, James R; Hamilton, Grant S

    2016-02-01

    The nasal valve has long been described as the anatomical boundary most likely to inhibit nasal airflow and lead to subsequent nasal obstruction. Although many procedures can address this area to improve the nasal airway, for over 20 years, suture lateralization of the external nasal valve has been described as a minimally invasive technique that can improve nasal breathing. We report our modification of the standard technique in which we lateralize the placement of the bone-anchored suture and incorporate Gore-Tex within the nasal vestibular incision to prevent tissue migration. PMID:26862966

  14. HIV-1 Interacts with Human Endogenous Retrovirus K (HML-2) Envelopes Derived from Human Primary Lymphocytes

    PubMed Central

    Brinzevich, Daria; Young, George R.; Sebra, Robert; Ayllon, Juan; Maio, Susan M.; Deikus, Gintaras; Chen, Benjamin K.; Fernandez-Sesma, Ana; Simon, Viviana

    2014-01-01

    ABSTRACT Human endogenous retroviruses (HERVs) are viruses that have colonized the germ line and spread through vertical passage. Only the more recently acquired HERVs, such as the HERV-K (HML-2) group, maintain coding open reading frames. Expression of HERV-Ks has been linked to different pathological conditions, including HIV infection, but our knowledge on which specific HERV-Ks are expressed in primary lymphocytes currently is very limited. To identify the most expressed HERV-Ks in an unbiased manner, we analyzed their expression patterns in peripheral blood lymphocytes using Pacific Biosciences (PacBio) single-molecule real-time (SMRT) sequencing. We observe that three HERV-Ks (KII, K102, and K18) constitute over 90% of the total HERV-K expression in primary human lymphocytes of five different donors. We also show experimentally that two of these HERV-K env sequences (K18 and K102) retain their ability to produce full-length and posttranslationally processed envelope proteins in cell culture. We show that HERV-K18 Env can be incorporated into HIV-1 but not simian immunodeficiency virus (SIV) particles. Moreover, HERV-K18 Env incorporation into HIV-1 virions is dependent on HIV-1 matrix. Taken together, we generated high-resolution HERV-K expression profiles specific for activated human lymphocytes. We found that one of the most abundantly expressed HERV-K envelopes not only makes a full-length protein but also specifically interacts with HIV-1. Our findings raise the possibility that these endogenous retroviral Env proteins could directly influence HIV-1 replication. IMPORTANCE Here, we report the HERV-K expression profile of primary lymphocytes from 5 different healthy donors. We used a novel deep-sequencing technology (PacBio SMRT) that produces the long reads necessary to discriminate the complexity of HERV-K expression. We find that primary lymphocytes express up to 32 different HERV-K envelopes, and that at least two of the most expressed Env proteins

  15. Interaction between arsenic trioxide and human primary cells: emphasis on human cells of myeloid origin.

    PubMed

    Binet, François; Antoine, Francis; Girard, Denis

    2009-03-01

    Arsenic trioxide (As(2)O(3); ATO) is considered to be one of the most potent drugs in cancer chemotherapy and is highly effective in the treatment of acute promyelocytic leukemia (APL). It is well established that treatment of APL patients with ATO is associated with the disappearance of the PML-RARalpha fusion transcript, the characteristic APL gene product of the chromosomal translocation t(15;17). Although its mode of action is still not fully understood, ATO is known to induce cell apoptosis via generation of reactive oxygen species and activation of caspases. Several reports have indicated that ATO acts principally by inducing cell apoptosis not only in APL, but in a variety of non-APL cells including myeloma cells, chronic myeloid leukemia cells and cells of immune origin, including B or T lymphocytes, macrophages and, more recently, neutrophils. There is an increasing amount of data, including some from our laboratory, concerning the interaction between ATO and human primary cells. The focus of this review will be to cover the role of ATO in human immune primary cells with special emphasis on cells of myeloid origin.

  16. 21 CFR 341.20 - Nasal decongestant active ingredients.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Nasal decongestant active ingredients. 341.20 Section 341.20 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS...

  17. Polymorphous low-grade adenocarcinoma of the nasal fossa.

    PubMed

    González-Lagunas, Javier; Alasà-Caparrós, Cristian; Vendrell-Escofet, Gerard; Huguet-Redecilla, Pere; Raspall-Martin, Guillermo

    2005-01-01

    An unusual case of a T4N2CMx polymorphous low grade adenocarcinoma located in the nasal fossae and extending to the pterygoid area is presented. The primary tumor was excised through a Lefort I maxillotomy and the neck was managed with a supraomohyoid neck dissection. Adjuntive postoperative radiotherapy was also administered to the patient.

  18. Primary human chorionic gonadotropin secreting germinoma of the corpus callosum

    PubMed Central

    Chuan Aaron, Foo Song; Dawn, Chong Q. Q.; Kenneth, Chang T. E.; Hoe, Ng Wai; Yen, Soh Shui; Chee Kian, Tham

    2013-01-01

    Background: Primary intracranial germinomas are a rare subset of intracranial tumors derived from mis-incorporated germ cells within the folding neural plate during embryogenesis. Though known to arise from midline structures in the central nervous system (CNS), occurrence within the corpus callosum is exceedingly rare. Case Description: We present a rare case of secreting primary intracranial germinoma with extensive intraventricular metastasis presenting as a multi-cystic butterfly lesion in the genu of the corpus callosum in a young boy. Conclusion: Intracranial germ cell tumors must be considered for any multi-cystic lesion arising from midline structures in the CNS in the preadult population. PMID:24233184

  19. Angioleiomyoma of the Nasal Cavity

    PubMed Central

    Arruda, Milena Moreira; Monteiro, Daniela Yasbek; Fernandes, Atilio Maximino; Menegatti, Vanessa; Thomazzi, Emerson; Hubner, Ricardo Arthur; Lima, Luiz Guilherme Cernaglia Aureliano de

    2014-01-01

    Introduction Vascular leiomyoma of the nasal cavity is an extremely rare tumor that represents less than 1% of all vascular leiomyomas. It is more prevalent in women between the fourth and sixth decades, reaching primarily the inferior nasal turbinates. Objectives Reporting and assisting the systematization of more accurate diagnostic methods in clinical and complementary investigation of vascular leiomyoma in the nasal cavity. Resumed Report We present the case of a 49-year-old woman diagnosed with vascular leiomyoma in the nasal cavity, which manifested mainly with nasal obstruction. During investigation, computer tomography was not diagnostic, the cytologic study was not conclusive, and according to the biopsy, it was a squamous papilloma. Conclusion We suggest that the technical difficulty in obtaining an adequate amount of material for preoperative biopsy, associated with the topography of the lesion in the vestibular nasal region, may have contributed to changing the postoperative diagnosis. Thus, pathologic study of the surgical fragment is the more accurate method for diagnosis. PMID:25992133

  20. Serodiagnosis of primary infections with human parvovirus 4, Finland.

    PubMed

    Lahtinen, Anne; Kivelä, Pia; Hedman, Lea; Kumar, Arun; Kantele, Anu; Lappalainen, Maija; Liitsola, Kirsi; Ristola, Matti; Delwart, Eric; Sharp, Colin; Simmonds, Peter; Söderlund-Venermo, Maria; Hedman, Klaus

    2011-01-01

    To determine the prevalence of parvovirus 4 infection and its clinical and sociodemographic correlations in Finland, we used virus-like particle-based serodiagnostic procedures (immunoglobulin [Ig] G, IgM, and IgG avidity) and PCR. We found 2 persons with parvovirus 4 primary infection who had mild or asymptomatic clinical features among hepatitis C virus-infected injection drug users.

  1. Overgrowth of a costochondral graft in nasal reconstruction.

    PubMed

    Baek, Rong-Min; Lee, Yoonho; Song, Yong-Tai

    2005-07-01

    Nasal reconstruction with autogenous costochondral graft has been one of the surgical managements in craniofacial clefts. We have recently seen one patient who underwent this operation and the graft had overgrown like as in Pinocchio's nose-overly projecting nasal tip for almost 7 years. This case supports the notion that the costochondral graft itself carries intrinsic factors and the growth of the graft depends mainly on the costochondral graft itself. Therefore we acknowledge "the primary growth center theory" rather than "the functional matrix theory".

  2. Is antibiotic prophylaxis in nasal packing for anterior epistaxis needed?

    PubMed

    Pérez, Francisco; Rada, Gabriel

    2016-01-07

    Epistaxis is an extremely common problem that sometimes requires anterior nasal packing. Antibiotics are frequently indicated to prevent infectious complications, although the role of this measure is controversial. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified one systematic review including three primary studies, none of them randomized. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded it is not clear whether prophylactic antibiotics reduce infectious complications in patients with nasal packing for anterior epistaxis because the certainty of the evidence is very low.

  3. Is antibiotic prophylaxis in nasal packing for anterior epistaxis needed?

    PubMed

    Pérez, Francisco; Rada, Gabriel

    2016-01-01

    Epistaxis is an extremely common problem that sometimes requires anterior nasal packing. Antibiotics are frequently indicated to prevent infectious complications, although the role of this measure is controversial. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified one systematic review including three primary studies, none of them randomized. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded it is not clear whether prophylactic antibiotics reduce infectious complications in patients with nasal packing for anterior epistaxis because the certainty of the evidence is very low. PMID:26817470

  4. Molecular profiling reveals primary mesothelioma cell lines recapitulate human disease.

    PubMed

    Chernova, T; Sun, X M; Powley, I R; Galavotti, S; Grosso, S; Murphy, F A; Miles, G J; Cresswell, L; Antonov, A V; Bennett, J; Nakas, A; Dinsdale, D; Cain, K; Bushell, M; Willis, A E; MacFarlane, M

    2016-07-01

    Malignant mesothelioma (MM) is an aggressive, fatal tumor strongly associated with asbestos exposure. There is an urgent need to improve MM patient outcomes and this requires functionally validated pre-clinical models. Mesothelioma-derived cell lines provide an essential and relatively robust tool and remain among the most widely used systems for candidate drug evaluation. Although a number of cell lines are commercially available, a detailed comparison of these commercial lines with freshly derived primary tumor cells to validate their suitability as pre-clinical models is lacking. To address this, patient-derived primary mesothelioma cell lines were established and characterized using complementary multidisciplinary approaches and bioinformatic analysis. Clinical markers of mesothelioma, transcriptional and metabolic profiles, as well as the status of p53 and the tumor suppressor genes CDKN2A and NF2, were examined in primary cell lines and in two widely used commercial lines. Expression of MM-associated markers, as well as the status of CDKN2A, NF2, the 'gatekeeper' in MM development, and their products demonstrated that primary cell lines are more representative of the tumor close to its native state and show a degree of molecular diversity, thus capturing the disease heterogeneity in a patient cohort. Molecular profiling revealed a significantly different transcriptome and marked metabolic shift towards a greater glycolytic phenotype in commercial compared with primary cell lines. Our results highlight that multiple, appropriately characterised, patient-derived tumor cell lines are required to enable concurrent evaluation of molecular profiles versus drug response. Furthermore, application of this approach to other difficult-to-treat tumors would generate improved cellular models for pre-clinical evaluation of novel targeted therapies.

  5. Molecular profiling reveals primary mesothelioma cell lines recapitulate human disease

    PubMed Central

    Chernova, T; Sun, X M; Powley, I R; Galavotti, S; Grosso, S; Murphy, F A; Miles, G J; Cresswell, L; Antonov, A V; Bennett, J; Nakas, A; Dinsdale, D; Cain, K; Bushell, M; Willis, A E; MacFarlane, M

    2016-01-01

    Malignant mesothelioma (MM) is an aggressive, fatal tumor strongly associated with asbestos exposure. There is an urgent need to improve MM patient outcomes and this requires functionally validated pre-clinical models. Mesothelioma-derived cell lines provide an essential and relatively robust tool and remain among the most widely used systems for candidate drug evaluation. Although a number of cell lines are commercially available, a detailed comparison of these commercial lines with freshly derived primary tumor cells to validate their suitability as pre-clinical models is lacking. To address this, patient-derived primary mesothelioma cell lines were established and characterized using complementary multidisciplinary approaches and bioinformatic analysis. Clinical markers of mesothelioma, transcriptional and metabolic profiles, as well as the status of p53 and the tumor suppressor genes CDKN2A and NF2, were examined in primary cell lines and in two widely used commercial lines. Expression of MM-associated markers, as well as the status of CDKN2A, NF2, the ‘gatekeeper' in MM development, and their products demonstrated that primary cell lines are more representative of the tumor close to its native state and show a degree of molecular diversity, thus capturing the disease heterogeneity in a patient cohort. Molecular profiling revealed a significantly different transcriptome and marked metabolic shift towards a greater glycolytic phenotype in commercial compared with primary cell lines. Our results highlight that multiple, appropriately characterised, patient-derived tumor cell lines are required to enable concurrent evaluation of molecular profiles versus drug response. Furthermore, application of this approach to other difficult-to-treat tumors would generate improved cellular models for pre-clinical evaluation of novel targeted therapies. PMID:26891694

  6. Characterization of primary human keratinocytes transformed by human papillomavirus type 18

    SciTech Connect

    Kaur, P.; McDougall, J.K. )

    1988-06-01

    Primary human epithelial cells were cotransfected with pHPV-18 and pSV2neo, and cell strains were generated by selecting in G418. Southern blot analysis revealed the presence of at least one intact, integrated viral genome in these cells. FE-A cells showed altered growth properties, characterized by a change in morphology, and clonal density. Differentiation markers analyzed by Western blotting (immunoblotting), such as cytokeratins and involucrin, indicated that the cells resembled a partially differentiated epithelial population. Increased expression of the 40-kilodalton cytokeratin was observed in FE-A cells, similar to that observed in simian virus 40-immortalized human keratinocytes. Calcium and 12-O-tetradecanoyl-phorbol-13-acetate treatment induced normal epithelial cells to differentiate, whereas the human papillomavirus 18 (HPV-18)-containing keratinocytes were resistant to these signals, indicating their partially transformed nature. These cells were not able to induce tumors in nude mice over a period of up to 8 months. A second cell strain, FE-H18L, also generated by transfecting HPV-18, also exhibited an extended life span and similar alterations in morphology. Viral RNA transcribed from the early region of HPV-18 was detected in both cell strains by Northern (RNA) blot analysis. These cell strains should provide a useful model for determining the role of HPV in carcinogenesis.

  7. Deposition of radon progeny in nonhuman primate nasal airways

    SciTech Connect

    Yeh, H.C.; Cheng, Y.S.; Su, Y.F. . Inhalation Toxicology Research Inst.); Morgan, K.T. )

    1991-01-01

    Information on aerosol deposition patterns in the human respiratory tract is needed to improve health risk estimates for exposure to airborne radon progeny. To investigate this, deposition of {sup 220}Rn progeny in Rhesus monkey nasal casts was examined. A substantial fraction of the inhaled ultrafine particles are deposited in the nasal cast. Deposition efficiency increases with decreasing particle size, reaching a maximum value of 80% for particles 1.7 nm in diameter. Breathing flow rate has a minimal effect on deposition efficiency. Deposition efficiencies for particles smaller than 100 nm in diameter are similar for monkey and human nasal casts. Equations based on turbulent diffusion can be fitted to these data for either inspirational or expirational flow. These mathematical expressions will be useful for modifying the inhaled particle deposition and dosimetry models. 20 refs., 9 figs., 1 tab (MHB)

  8. Chromosomal translocation engineering to recapitulate primary events of human cancer.

    PubMed

    Forster, A; Pannell, R; Drynan, L; Cano, F; Chan, N; Codrington, R; Daser, A; Lobato, N; Metzler, M; Nam, C-H; Rodriguez, S; Tanaka, T; Rabbitts, T

    2005-01-01

    Mouse models of human cancers are important for understanding determinants of overt disease and for "preclinical" development of rational therapeutic strategies; for instance, based on macrodrugs. Chromosomal translocations underlie many human leukemias, sarcomas, and epithelial tumors. We have developed three technologies based on homologous recombination in mouse ES cells to mimic human chromosome translocations. The first, called the knockin method, allows creation of fusion genes like those typical of translocations of human leukemias and sarcomas. Two new conditional chromosomal translocation mimics have been developed. The first is a method for generating reciprocal chromosomal translocations de novo using Cre-loxP recombination (translocator mice). In some cases, there is incompatible gene orientation and the translocator model cannot be applied. We have developed a different model (invertor mice) for these situations. This method consists of introducing an inverted cDNA cassette into the intron of a target gene and bringing the cassette into the correct transcriptional orientation by Cre-loxP recombination. We describe experiments using the translocator model to generate MLL-mediated neoplasias and the invertor method to generate EWS-ERG-mediated cancer. These methods mimic the situation found in human chromosome translocations and provide the framework for design and study of human chromosomal translocations in mice.

  9. Malignant solitary fibrous tumor of the nasal cavity.

    PubMed

    Zeitler, Daniel M; Kanowitz, Seth J; Har-El, Gady

    2007-07-01

    Solitary fibrous tumors (SFTs) are unusual mesenchymal tumors that were first described as primary spindle-cell neoplasms of the pleura. These tumors have been described in many other locations, including the urogenital system, orbit, mediastinum, and upper respiratory tract. Twenty-two cases of an SFT of the paranasal sinuses and nasal cavity have been reported, but none described a malignant SFT extending through the anterior skull base. A 70-year-old man had a 6-month history of unilateral left-sided epiphora and nasal obstruction. Computed tomography and magnetic resonance imaging showed a large left-sided nasal cavity mass with extension into the left extraconal orbit and intracranial extension through the left cribriform plate and ethmoid roof. The patient underwent preoperative embolization of the internal maxillary artery and a subsequent anterior craniofacial resection via a midfacial degloving approach and a left anterior craniotomy. Histopathological analysis of the specimen was consistent with a malignant SFT.

  10. Skin metastasis of hypopharyngeal carcinoma to the nasal tip.

    PubMed

    Shindo, Masahisa; Yoshida, Yuichi; Tominaga, Kyoko; Yamamoto, Osamu

    2013-06-01

    Head and neck squamous cell carcinoma (SCC) rarely metastasizes to the skin. Metastases to the nasal tip from hypopharyngeal malignancies are extremely rare. We present a patient with nasal tip metastasis from hypopharyngeal SCC. A 74-year-old man with hypopharyngeal and esophageal carcinomas had a red nodule on his nasal tip (so-called "clown nose"). Histopathologically, atypical squamoid cell nests had proliferated in a lobular fashion from the dermis to subcutaneous tissue. Those atypical cells were identical to primary tumor cells in the hypopharynx. Based on these findings, a diagnosis of skin metastasis from hypopharyngeal SCC was made. In patients with malignant disease, biopsy should be performed for any suspicious skin lesion. In a patient like ours, "clown nose" might be a symptom of cutaneous metastasis. When clinicians note a "clown nose", they should consider malignancies in the neck and chest areas.

  11. Treatment of nasal burns: analysis of 150 cases.

    PubMed

    Prousskaia, E; El-Muttardi, N; Philp, B; Dziewulski, P; Shelley, O P

    2015-06-30

    Nasal burns present a challenge for the plastic surgeon in terms of immediate management, choice of primary treatment and secondary reconstruction with the goals of good aesthetic and functional outcome. We present a retrospective analysis of the management of 150 patients with nasal burns treated in our center between July 2005 and July 2011. We rationalized our conservative and all surgical treatments of this subset of burns patients and organized them in a simple and structured way. The reconstructive options for most complex full thickness nasal injury is determined by the integrity of adjacent facial tissues which would always be preferred when available. Microsurgical free tissue transfer is dependent upon the fitness of the patient and the availability of unburned skin at the donor site. Secondary nasal reconstruction is based on an assessment of the residual functional and cosmetic problems. Airways narrowing from scar contracture or loss of support are managed using standard plastic surgical and rhinoplasty principles. Cosmetic refinements range from flap debulking to the importation of new tissue on to the nose. Our experience with this challenging group of patients has led us to develop a simple treatment algorithm for the management of nasal burns.

  12. Treatment of nasal burns: analysis of 150 cases

    PubMed Central

    Prousskaia, E.; El-Muttardi, N.; Philp, B.; Dziewulski, P.; Shelley, O.P.

    2015-01-01

    Summary Nasal burns present a challenge for the plastic surgeon in terms of immediate management, choice of primary treatment and secondary reconstruction with the goals of good aesthetic and functional outcome. We present a retrospective analysis of the management of 150 patients with nasal burns treated in our center between July 2005 and July 2011. We rationalized our conservative and all surgical treatments of this subset of burns patients and organized them in a simple and structured way. The reconstructive options for most complex full thickness nasal injury is determined by the integrity of adjacent facial tissues which would always be preferred when available. Microsurgical free tissue transfer is dependent upon the fitness of the patient and the availability of unburned skin at the donor site. Secondary nasal reconstruction is based on an assessment of the residual functional and cosmetic problems. Airways narrowing from scar contracture or loss of support are managed using standard plastic surgical and rhinoplasty principles. Cosmetic refinements range from flap debulking to the importation of new tissue on to the nose. Our experience with this challenging group of patients has led us to develop a simple treatment algorithm for the management of nasal burns. PMID:27252610

  13. Low-dose oxytocin delivered intranasally with Breath Powered device affects social-cognitive behavior: a randomized four-way crossover trial with nasal cavity dimension assessment

    PubMed Central

    Quintana, D S; Westlye, L T; Rustan, Ø G; Tesli, N; Poppy, C L; Smevik, H; Tesli, M; Røine, M; Mahmoud, R A; Smerud, K T; Djupesland, P G; Andreassen, O A

    2015-01-01

    Despite the promise of intranasal oxytocin (OT) for modulating social behavior, recent work has provided mixed results. This may relate to suboptimal drug deposition achieved with conventional nasal sprays, inter-individual differences in nasal physiology and a poor understanding of how intranasal OT is delivered to the brain in humans. Delivering OT using a novel ‘Breath Powered' nasal device previously shown to enhance deposition in intranasal sites targeted for nose-to-brain transport, we evaluated dose-dependent effects on social cognition, compared response with intravenous (IV) administration of OT, and assessed nasal cavity dimensions using acoustic rhinometry. We adopted a randomized, double-blind, double-dummy, crossover design, with 16 healthy male adults completing four single-dose treatments (intranasal 8 IU (international units) or 24 IU OT, 1 IU OT IV and placebo). The primary outcome was social cognition measured by emotional ratings of facial images. Secondary outcomes included the pharmacokinetics of OT, vasopressin and cortisol in blood and the association between nasal cavity dimensions and emotional ratings. Despite the fact that all the treatments produced similar plasma OT increases compared with placebo, there was a main effect of treatment on anger ratings of emotionally ambiguous faces. Pairwise comparisons revealed decreased ratings after 8 IU OT in comparison to both placebo and 24 IU OT. In addition, there was an inverse relationship between nasal valve dimensions and anger ratings of ambiguous faces after 8-IU OT treatment. These findings provide support for a direct nose-to-brain effect, independent of blood absorption, of low-dose OT delivered from a Breath Powered device. PMID:26171983

  14. Low-dose oxytocin delivered intranasally with Breath Powered device affects social-cognitive behavior: a randomized four-way crossover trial with nasal cavity dimension assessment.

    PubMed

    Quintana, D S; Westlye, L T; Rustan, Ø G; Tesli, N; Poppy, C L; Smevik, H; Tesli, M; Røine, M; Mahmoud, R A; Smerud, K T; Djupesland, P G; Andreassen, O A

    2015-01-01

    Despite the promise of intranasal oxytocin (OT) for modulating social behavior, recent work has provided mixed results. This may relate to suboptimal drug deposition achieved with conventional nasal sprays, inter-individual differences in nasal physiology and a poor understanding of how intranasal OT is delivered to the brain in humans. Delivering OT using a novel 'Breath Powered' nasal device previously shown to enhance deposition in intranasal sites targeted for nose-to-brain transport, we evaluated dose-dependent effects on social cognition, compared response with intravenous (IV) administration of OT, and assessed nasal cavity dimensions using acoustic rhinometry. We adopted a randomized, double-blind, double-dummy, crossover design, with 16 healthy male adults completing four single-dose treatments (intranasal 8 IU (international units) or 24 IU OT, 1 IU OT IV and placebo). The primary outcome was social cognition measured by emotional ratings of facial images. Secondary outcomes included the pharmacokinetics of OT, vasopressin and cortisol in blood and the association between nasal cavity dimensions and emotional ratings. Despite the fact that all the treatments produced similar plasma OT increases compared with placebo, there was a main effect of treatment on anger ratings of emotionally ambiguous faces. Pairwise comparisons revealed decreased ratings after 8 IU OT in comparison to both placebo and 24 IU OT. In addition, there was an inverse relationship between nasal valve dimensions and anger ratings of ambiguous faces after 8-IU OT treatment. These findings provide support for a direct nose-to-brain effect, independent of blood absorption, of low-dose OT delivered from a Breath Powered device. PMID:26171983

  15. A Study of the Infant Nasal Microbiome Development over the First Year of Life and in Relation to Their Primary Adult Caregivers Using cpn60 Universal Target (UT) as a Phylogenetic Marker.

    PubMed

    Peterson, Shelley W; Knox, Natalie C; Golding, George R; Tyler, Shaun D; Tyler, Andrea D; Mabon, Philip; Embree, Joanne E; Fleming, Fiona; Fanella, Sergio; Van Domselaar, Gary; Mulvey, Michael R; Graham, Morag R

    2016-01-01

    Whereas the infant gut microbiome is the subject of intense study, relatively little is known regarding the nares microbiome in newborns and during early life. This study aimed to survey the typical composition and diversity of human anterior nare microflora for developing infants over time, and to explore how these correlate to their primary caregivers. Single nare swabs were collected at five time points over a one-year period for each subject from infant-caregiver pairs. Our study comprised of 50 infants (recruited at 2 weeks, post delivery) and their 50 primary caregivers. Applying the chaperonin-60 (cpn60) universal target (UT) amplicon as our molecular barcoding marker to census survey the microbial communities, we longitudinally surveyed infant nares microbiota at 5 time points over the course of the first year of life. The inter- and intra-subject diversity was catalogued and compared, both longitudinally and relative to their adult primary caregivers. Although within-subject variability over time and inter-subject variability were both observed, the assessment detected only one or two predominant genera for individual infant samples, belonging mainly to phyla Actinobacteria, Firmicutes, and Proteobacteria. Consistent with previously observed microbial population dynamics in other body sites, the diversity of nares microflora increased over the first year of life and infants showed differential operational taxonomic units (OTUs) relative to their matched primary caregiver. The collected evidence also support that both temporal and seasonal changes occur with respect to carriage of potentially pathogenic bacteria (PPBs), which may influence host predisposition to infection. This pilot study surveying paired infant/caregiver nare microbiomes provides novel longitudinal diversity information that is pertinent to better understanding nare microbiome development in infants.

  16. A Study of the Infant Nasal Microbiome Development over the First Year of Life and in Relation to Their Primary Adult Caregivers Using cpn60 Universal Target (UT) as a Phylogenetic Marker

    PubMed Central

    Peterson, Shelley W.; Knox, Natalie C.; Golding, George R.; Tyler, Shaun D.; Tyler, Andrea D.; Mabon, Philip; Embree, Joanne E.; Fleming, Fiona; Fanella, Sergio; Van Domselaar, Gary; Mulvey, Michael R.; Graham, Morag R.

    2016-01-01

    Whereas the infant gut microbiome is the subject of intense study, relatively little is known regarding the nares microbiome in newborns and during early life. This study aimed to survey the typical composition and diversity of human anterior nare microflora for developing infants over time, and to explore how these correlate to their primary caregivers. Single nare swabs were collected at five time points over a one-year period for each subject from infant-caregiver pairs. Our study comprised of 50 infants (recruited at 2 weeks, post delivery) and their 50 primary caregivers. Applying the chaperonin-60 (cpn60) universal target (UT) amplicon as our molecular barcoding marker to census survey the microbial communities, we longitudinally surveyed infant nares microbiota at 5 time points over the course of the first year of life. The inter- and intra-subject diversity was catalogued and compared, both longitudinally and relative to their adult primary caregivers. Although within-subject variability over time and inter-subject variability were both observed, the assessment detected only one or two predominant genera for individual infant samples, belonging mainly to phyla Actinobacteria, Firmicutes, and Proteobacteria. Consistent with previously observed microbial population dynamics in other body sites, the diversity of nares microflora increased over the first year of life and infants showed differential operational taxonomic units (OTUs) relative to their matched primary caregiver. The collected evidence also support that both temporal and seasonal changes occur with respect to carriage of potentially pathogenic bacteria (PPBs), which may influence host predisposition to infection. This pilot study surveying paired infant/caregiver nare microbiomes provides novel longitudinal diversity information that is pertinent to better understanding nare microbiome development in infants. PMID:27019455

  17. Recombinant Subgroup B Human Respiratory Syncytial Virus Expressing Enhanced Green Fluorescent Protein Efficiently Replicates in Primary Human Cells and Is Virulent in Cotton Rats

    PubMed Central

    Lemon, Ken; Nguyen, D. Tien; Ludlow, Martin; Rennick, Linda J.; Yüksel, Selma; van Amerongen, Geert; McQuaid, Stephen; Rima, Bert K.; de Swart, Rik L.

    2014-01-01

    ABSTRACT Human respiratory syncytial virus (HRSV) is the most important viral cause of severe respiratory tract disease in infants. Two subgroups (A and B) have been identified, which cocirculate during, or alternate between, yearly epidemics and cause indistinguishable disease. Existing in vitro and in vivo models of HRSV focus almost exclusively on subgroup A viruses. Here, a recombinant (r) subgroup B virus (rHRSVB05) was generated based on a consensus genome sequence obtained directly from an unpassaged clinical specimen from a hospitalized infant. An additional transcription unit containing the gene encoding enhanced green fluorescent protein (EGFP) was introduced between the phosphoprotein and matrix genes (position 5) of the genome to generate rHRSVB05EGFP(5). The recombinant viruses replicated efficiently in both HEp-2 cells and in well-differentiated normal human bronchial cells grown at air-liquid interface. Intranasal infection of cotton rats (Sigmodon hispidus) resulted in high numbers of EGFP+ cells in epithelia of the nasal septum and conchae. When administered in a relatively large inoculum volume, the virus also replicated efficiently in bronchiolar epithelial cells and spread extensively in both the upper and lower respiratory tracts. Virus replication was not observed in ciliated epithelial cells of the trachea. This is the first virulent rHRSV strain with the genetic composition of a currently circulating wild-type virus. In vivo tracking of infected cells by means of EGFP fluorescence in the absence of cytopathic changes increases the sensitivity of virus detection in HRSV pathogenesis studies. IMPORTANCE Virology as a discipline has depended on monitoring cytopathic effects following virus culture in vitro. However, wild-type viruses isolated from patients often do not cause significant changes to infected cells, necessitating blind passage. This can lead to genetic and phenotypic changes and the generation of high-titer, laboratory

  18. Longitudinal distribution of ozone and chlorine in the human respiratory tract: simulation of nasal and oral breathing with the single-path diffusion model.

    PubMed

    Bush, M L; Zhang, W; Ben-Jebria, A; Ultman, J S

    2001-06-15

    In the single-path model of the respiratory system, gas transport occurs within a conduit of progressively increasing cross-sectional and surface areas by a combination of flow, longitudinal dispersion, and lateral absorption. The purpose of this study was to use bolus inhalation data previously obtained for chlorine (Cl(2)) and for ozone (O(3)) to test the predictive capability of the single-path model and to adjust input parameters for applying the model to other exposure conditions. The data, consisting of uptake fraction as a function of bolus penetration volume, were recorded on 10 healthy nonsmokers breathing orally as well as nasally at alternative air flows of 150, 250, and 1000 ml/s. By employing published data for airway anatomy, gas-phase dispersion coefficients, and gas-phase mass transfer coefficients while neglecting diffusion limitations in the mucus phase, the single-path model was capable of predicting the uptake distribution for O(3) but not the steeper distribution that was observed for Cl(2). To simultaneously explain the data for these two gases, it was necessary to increase gas-phase mass transfer coefficients and to include a finite diffusion resistance of O(3) within the mucous layer. The O(3) reaction rate constants that accounted for this diffusion resistance, 2 x 10(6) s(-1) in the mouth and 8 x 10(6) s(-1) in the nose and lower airways, were much greater than previously reported reactivities of individual substrates found in mucus.

  19. Primary Sources of Cognate Research in Human Performance Technology

    ERIC Educational Resources Information Center

    Johnsen, Liz V.; Huglin, Linda M.; Marker, Anthony

    2008-01-01

    This article is third in a series written to address questions regarding the need for more empirical research in the field of human performance technology (HPT) and the need to determine the future direction of HPT research. The call for more empirical research has been published in journals such as "Performance Improvement Quarterly" and…

  20. RTTN Mutations Cause Primary Microcephaly and Primordial Dwarfism in Humans

    PubMed Central

    Shamseldin, Hanan; Alazami, Anas M.; Manning, Melanie; Hashem, Amal; Caluseiu, Oana; Tabarki, Brahim; Esplin, Edward; Schelley, Susan; Innes, A. Micheil; Parboosingh, Jillian S.; Lamont, Ryan; Majewski, Jacek; Bernier, Francois P.; Alkuraya, Fowzan S.

    2015-01-01

    Primary microcephaly is a developmental brain anomaly that results from defective proliferation of neuroprogenitors in the germinal periventricular zone. More than a dozen genes are known to be mutated in autosomal-recessive primary microcephaly in isolation or in association with a more generalized growth deficiency (microcephalic primordial dwarfism), but the genetic heterogeneity is probably more extensive. In a research protocol involving autozygome mapping and exome sequencing, we recruited a multiplex consanguineous family who is affected by severe microcephalic primordial dwarfism and tested negative on clinical exome sequencing. Two candidate autozygous intervals were identified, and the second round of exome sequencing revealed a single intronic variant therein (c.2885+8A>G [p.Ser963∗] in RTTN exon 23). RT-PCR confirmed that this change creates a cryptic splice donor and thus causes retention of the intervening 7 bp of the intron and leads to premature truncation. On the basis of this finding, we reanalyzed the exome file of a second consanguineous family affected by a similar phenotype and identified another homozygous change in RTTN as the likely causal mutation. Combined linkage analysis of the two families confirmed that RTTN maps to the only significant linkage peak. Finally, through international collaboration, a Canadian multiplex family affected by microcephalic primordial dwarfism and biallelic mutation of RTTN was identified. Our results expand the phenotype of RTTN-related disorders, hitherto limited to polymicrogyria, to include microcephalic primordial dwarfism with a complex brain phenotype involving simplified gyration. PMID:26608784

  1. Investigation on the nasal airflow characteristics of anterior nasal cavity stenosis.

    PubMed

    Wang, T; Chen, D; Wang, P H; Chen, J; Deng, J

    2016-01-01

    We used a computational fluid dynamics (CFD) model to study the inspiratory airflow profiles of patients with anterior nasal cavity stenosis who underwent curative surgery, by comparing pre- and postoperative airflow characteristics. Twenty patients with severe anterior nasal cavity stenosis, including one case of bilateral stenosis, underwent computed tomography (CT) scans for CFD modelling. The pre- and postoperative airflow characteristics of the nasal cavity were simulated and analyzed. The narrowest area of the nasal cavity in all 20 patients was located within the nasal valve area, and the mean cross-sectional area increased from 0.39 cm2 preoperative to 0.78 cm2 postoperative (P<0.01). Meanwhile, the mean airflow velocity in the nasal valve area decreased from 6.19 m/s to 2.88 m/s (P<0.01). Surgical restoration of the nasal symmetry in the bilateral nasal cavity reduced nasal resistance in the narrow sides from 0.24 Pa.s/mL to 0.11 Pa.s/mL (P<0.01). Numerical simulation of the nasal cavity in patients with anterior nasal cavity stenosis revealed structural changes and the resultant patterns of nasal airflow. Surgery achieved balanced bilateral nasal ventilation and decreased nasal resistance in the narrow region of the nasal cavity. The correction of nasal valve stenosis is not only indispensable for reducing nasal resistance, but also the key to obtain satisfactory curative effect. PMID:27533764

  2. Investigation on the nasal airflow characteristics of anterior nasal cavity stenosis

    PubMed Central

    Wang, T.; Chen, D.; Wang, P.H.; Chen, J.; Deng, J.

    2016-01-01

    We used a computational fluid dynamics (CFD) model to study the inspiratory airflow profiles of patients with anterior nasal cavity stenosis who underwent curative surgery, by comparing pre- and postoperative airflow characteristics. Twenty patients with severe anterior nasal cavity stenosis, including one case of bilateral stenosis, underwent computed tomography (CT) scans for CFD modelling. The pre- and postoperative airflow characteristics of the nasal cavity were simulated and analyzed. The narrowest area of the nasal cavity in all 20 patients was located within the nasal valve area, and the mean cross-sectional area increased from 0.39 cm2 preoperative to 0.78 cm2 postoperative (P<0.01). Meanwhile, the mean airflow velocity in the nasal valve area decreased from 6.19 m/s to 2.88 m/s (P<0.01). Surgical restoration of the nasal symmetry in the bilateral nasal cavity reduced nasal resistance in the narrow sides from 0.24 Pa.s/mL to 0.11 Pa.s/mL (P<0.01). Numerical simulation of the nasal cavity in patients with anterior nasal cavity stenosis revealed structural changes and the resultant patterns of nasal airflow. Surgery achieved balanced bilateral nasal ventilation and decreased nasal resistance in the narrow region of the nasal cavity. The correction of nasal valve stenosis is not only indispensable for reducing nasal resistance, but also the key to obtain satisfactory curative effect. PMID:27533764

  3. Effects of Simulated Microgravity on Primary Human NK Cells

    PubMed Central

    Li, Qi; Mei, Qibing; Huyan, Ting; Xie, Li; Che, Su; Yang, Hui; Zhang, Mingjie

    2013-01-01

    Abstract The deleterious effects of microgravity on lymphocytes have been demonstrated in previous studies. However, research on the effects of microgravity on human natural killer (NK) cells remains exceedingly limited. In this study, we demonstrated that NK cell cytotoxicity was significantly decreased under simulated microgravity (SMG) conditions (p<0.05). Several processes, including apoptosis, receptor expression, and cytokine secretion, were investigated in human NK cells under SMG. We observed decreased cytotoxicity, concurrent with increased apoptosis and necrosis, in NK cells after exposure to SMG (p<0.05). Additionally, interferon (IFN)-γ and perforin expression decreased significantly, and the expression of granzyme-B was only slightly reduced. Meanwhile, SMG selectively inhibited the expression of certain surface receptors on NK cells. Specifically, the expression of NKG2A and NKG2D were significantly downregulated under SMG, but the expression of NKp30 and NKp44 was not affected. We also found that interleukin (IL)–15 alone or in combination with IL-12 could counteract the inhibition of NK cell cytotoxicity under SMG. Our findings indicate that human NK cells were sensitive to SMG, as reflected by their decreased cytotoxicity. Factors such as increased early apoptosis and late apoptosis/necrosis and the decreased expression of INF-γ, cytolytic proteins, and cell surface receptors may be responsible for the loss of cytotoxicity in human NK cells under SMG. A combination of IL-12 and IL-15 may be useful as a therapeutic strategy for overcoming the effects of microgravity on human NK cells during long space missions. Key Words: Simulated microgravity (SMG)—Natural killer (NK) cells—Cytotoxicity. Astrobiology 13, 703–714. PMID:23919749

  4. Devolution and human resources in primary healthcare in rural Mali

    PubMed Central

    2011-01-01

    Devolution, as other types of decentralization (e.g. deconcentration, delegation, privatization), profoundly changes governance relations in the health system. Devolution is meant to affect performance of the health system by transferring responsibilities and authority to locally elected governments. The key question of this article is: what does devolution mean for human resources for health in Mali? This article assesses the key advantages and dilemmas associated with devolution such as responsiveness to local needs, downward accountability and health worker retention. Challenges of politics and capacities are also addressed in relation to human resources for health at the local level. Examples are derived from experiences in Mali with a capacity development programme and from case studies of other countries. It is not research findings that are presented, but highlights of key issues at stake aimed at inspiring the debate in Mali and elsewhere. A first lesson from the discussion suggests that in the context of human resources for health, decentralization of authority and resources is not the main issue. The challenge is to develop or strengthen accountability of those who decide and act, whether they are local politicians, bureaucrats or community representatives. If decentralization policies do not address public accountability, they will not fundamentally change human resource management, quality and equity of staffing. A second lesson is that successful devolution requires innovations in capacity development of all actors involved and in designing effective incentive measures. A final key conclusion is that the topic of devolution policy and its effects on human resources for health, and vice versa, merit more attention. A better understanding may lead to more appropriate policy designs and better preparation for the actors involved in countries that are embarking on decentralization, as is the case in Mali. PMID:21651817

  5. Devolution and human resources in primary healthcare in rural Mali.

    PubMed

    Lodenstein, Elsbet; Dao, Dramane

    2011-06-08

    Devolution, as other types of decentralization (e.g. deconcentration, delegation, privatization), profoundly changes governance relations in the health system. Devolution is meant to affect performance of the health system by transferring responsibilities and authority to locally elected governments. The key question of this article is: what does devolution mean for human resources for health in Mali?This article assesses the key advantages and dilemmas associated with devolution such as responsiveness to local needs, downward accountability and health worker retention. Challenges of politics and capacities are also addressed in relation to human resources for health at the local level. Examples are derived from experiences in Mali with a capacity development programme and from case studies of other countries. It is not research findings that are presented, but highlights of key issues at stake aimed at inspiring the debate in Mali and elsewhere.A first lesson from the discussion suggests that in the context of human resources for health, decentralization of authority and resources is not the main issue. The challenge is to develop or strengthen accountability of those who decide and act, whether they are local politicians, bureaucrats or community representatives. If decentralization policies do not address public accountability, they will not fundamentally change human resource management, quality and equity of staffing. A second lesson is that successful devolution requires innovations in capacity development of all actors involved and in designing effective incentive measures. A final key conclusion is that the topic of devolution policy and its effects on human resources for health, and vice versa, merit more attention. A better understanding may lead to more appropriate policy designs and better preparation for the actors involved in countries that are embarking on decentralization, as is the case in Mali.

  6. Patterns of invasive growth in vitro. Human decidua graviditatis confronted with established human cell lines and primary human explants.

    PubMed

    Schleich, A B; Frick, M; Mayer, A

    1976-02-01

    Human decidua graviditatis was used as a receptor tissue to demonstrate invasive properties of human cells in vitro. In the confrontation between decidua and established cell lines of tumors and of normal origin as well as primary explanted cells, we noted differences in the cells' interactions with decidual tissue. The two original tumor cell lines, HeLa (carcinoma) and AFi (sarcoma), and a spontaneously transformed lymphoblastoid cell line showed aggressiveness, i.e., invasion, rapid proliferation, injury, and destruction of the decidual tissue. Strain HeLa S3 and two established cell lines, FL (amnion) and Girardi Heart, which are regarded as transformed cells because of their increased mitotic rate and polyploidy, exhibited various degrees of aggressiveness but did not invade. Freshly explanted fetal lung and endometrium caused no injury to the receptor tissue and were included in the decidual tissue.

  7. Management of the nasal dorsum.

    PubMed

    Sykes, Jonathan M; Tapias, Vanesa; Kim, Ji-Eon

    2011-04-01

    Profile alignment, including nasal dorsal reduction, is one of the most common maneuvers in aesthetic rhinoplasty. Techniques often include cartilaginous excision and bony hump reduction with a chisel or a rasp. Cartilaginous nasal vault excision can result in separation of the junction between the upper lateral cartilages and the dorsal septum. This separation can cause an inferior-medial repositioning of the upper lateral cartilages and overall weakening of middle vault infrastructure. Furthermore, surgical interruption of this key region can also damage the internal nasal valve configuration and function and create static and dynamic airway obstruction. This article outlines the anatomy and function of the middle nasal vault and internal nasal valve. In addition, it provides an overview of aesthetic complications of dorsal hump removal including inverted-V deformity, saddle nose deformity, hourglass deformity, and their functional consequences. Preoperative individual risk factors for middle-third deformities are mentioned. Preventive and corrective surgical techniques including cartilage grafting and reconstructive sutures are also detailed.

  8. Phenylephrine as an alternative to cocaine for nasal vasoconstriction before nasal surgery: A randomised trial

    PubMed Central

    AlHaddad, Sawsan T; Khanna, Ashish K; Mascha, Edward J; Abdelmalak, Basem B

    2013-01-01

    Background: Cocaine is often used topically to provide the profound vasoconstriction required for nasal surgery; however, it has been associated with intraoperative cardiac adverse effects. We compared cocaine with phenylephrine as an alternative to ascertain their relative efficacy as vasoconstrictors in nasal septoplasty. Methods: Adult patients, presenting for elective nasal septoplasty, of American Society of Anaesthesiologists physical status I-III, were randomised to either 0.5% phenylephrine or 4% cocaine. The primary outcome was quality of vasoconstriction on a 5-point scale (1=unacceptable, 5=excellent), rated by the surgeon at the end of the procedure. Results: Twenty-nine patients received phenylephrine and 26 received cocaine. The median rating for quality of the vasoconstriction was 4.0 (good) in both the phenylephrine and cocaine groups (P=0.84). Median blood loss was 50 ml in the phenylephrine group and 62.5 ml in the cocaine group (P=0.49). In secondary analyses, phenylephrine was shown to be non-inferior to cocaine on both quality of vasoconstriction (non-inferiority delta of 1 point, P=0.009) and estimated blood loss (non-inferiority delta of 25 ml, P=0.028). The frequency of ventricular ectopy, ST segment changes or blood pressure changes after nasal packing was not significantly different between the two groups. Conclusion: Phenylephrine in a concentration of 0.5% is not different from 4% cocaine on the quality of vasoconstriction in septoplasty. Given the abuse potential of cocaine and the added administrative burden associated with its handling, phenylephrine might serve as an alternative. PMID:23825816

  9. Expression of GD2 ganglioside by untreated primary human neuroblastomas.

    PubMed

    Wu, Z L; Schwartz, E; Seeger, R; Ladisch, S

    1986-01-01

    Primary neuroblastomas obtained before therapy from 36 patients were studied to determine the frequency of tumors expressing a specific glycosphingolipid, GD2 ganglioside. Total tissue gangliosides were purified by a new partition method, quantitated, and analyzed by high-performance thin-layer chromatography. All 36 neuroblastoma tumors, representing all clinical stages, contained GD2 ganglioside. The mean relative and absolute concentrations of GD2 were substantial (12% of the total tissue gangliosides and 50 nmol/g of tissue) and were independent of the clinical stage of the tumor. In contrast, 6 samples of related but more differentiated tumors (ganglioneuroblastoma and ganglioneuroma) had little or no detectable GD2 (less than or equal to 1.5% of total gangliosides and less than or equal to 4 nmol/g of tissue). These results suggest that GD2 is a sensitive marker for neuroblastoma tissue and may be an excellent target antigen for immunotherapy of this tumor.

  10. Interferon Alpha as a Primary Pathogenic Factor in Human Lupus

    PubMed Central

    2011-01-01

    Interferon alpha (IFN-α) is a critical mediator of human systemic lupus erythematosus (SLE). This review will summarize evidence supporting the role for IFN-α in the initiation of human SLE. IFN-α functions in viral immunity at the interface of innate and adaptive immunity, a position well suited to setting thresholds for autoimmunity. Some individuals treated with IFN-α for chronic viral infections develop de novo SLE, which frequently resolves when IFN-α is withdrawn, supporting the idea that IFN-α was causal. Abnormally high IFN-α levels are clustered within SLE families, suggesting that high serum IFN-α is a heritable risk factor for SLE. Additionally, SLE-risk genetic variants in the IFN-α pathway are gain of function in nature, resulting in either higher circulating IFN-α levels or greater sensitivity to IFN-α signaling in SLE patients. A recent genome-wide association study has identified additional novel genetic loci associated with high serum IFN-α in SLE patients. These data support the idea that genetically determined endogenous elevations in IFN-α predispose to human SLE. It is possible that some of these gain-of-function polymorphisms in the IFN-α pathway are useful in viral defense, and that risk of SLE is a burden we have taken on in the fight to defend ourselves against viral infection. PMID:21923413

  11. Nasal Reconstruction: Extending the Limits

    PubMed Central

    Corsten, Marcus; Haack, Sebastian; Gubisch, Wolfgang M.; Fischer, Helmut

    2016-01-01

    Summary: Reconstructing the 3-dimensional structure of the nose requires the maintenance of its aesthetic form and function. Restoration of the correct dimension, projection, skin quality, symmetrical contour, and function remains problematic. Consequently, modern approaches of nasal reconstruction aim at rebuilding the units rather than just covering the defect. However, revising or redoing a failed or insufficient reconstruction remains very challenging and requires experience and creativity. Here, we present a very particular case with a male patient, who underwent 37 operations elsewhere and presented with a failed nasal reconstruction. We describe and illustrate the complex steps of the nasal rereconstruction, including the reconstruction of the forehead donor site, surgical delay procedures for lining, and the coverage with a third paramedian forehead flap. PMID:27536483

  12. Surgery of the nasal septum.

    PubMed

    Mlynski, Gunter

    2006-11-01

    Long-term results after septoplasty are not satisfactory. Apart from a recurrence of deviation, there are various reasons for this: false preoperative analysis, complete straightening of the septum, and a disturbed nasal cycle. Preoperative functional diagnostics with a combination of rhinoresistometry, acoustic rhinometry, and long-term rhinoflowmetry are necessary for differentiating between "physiological" and "pathological" septal deviations and recognizing other causes for obstruction. The surgical procedure of septoplasty includes approach, mobilization, resection, reposition, and finally reconstruction of all three layers. The goal of the operation should not be complete straightening of the nasal septum. The space between the septum and turbinates is of utmost importance. It should not be enlarged as much as possible; rather, it must be shaped in such a way as to allow freely congestion and decongestion reciprocal on the two sides during the nasal cycle. PMID:17131264

  13. Nasal Reconstruction: Extending the Limits.

    PubMed

    Rezaeian, Farid; Corsten, Marcus; Haack, Sebastian; Gubisch, Wolfgang M; Fischer, Helmut

    2016-07-01

    Reconstructing the 3-dimensional structure of the nose requires the maintenance of its aesthetic form and function. Restoration of the correct dimension, projection, skin quality, symmetrical contour, and function remains problematic. Consequently, modern approaches of nasal reconstruction aim at rebuilding the units rather than just covering the defect. However, revising or redoing a failed or insufficient reconstruction remains very challenging and requires experience and creativity. Here, we present a very particular case with a male patient, who underwent 37 operations elsewhere and presented with a failed nasal reconstruction. We describe and illustrate the complex steps of the nasal rereconstruction, including the reconstruction of the forehead donor site, surgical delay procedures for lining, and the coverage with a third paramedian forehead flap. PMID:27536483

  14. Effect of nasal sprays on an in vitro survival and morphology of nasoseptal cartilage.

    PubMed

    Stoelzel, Katharina; Kohl, Benjamin; Hoyer, Mariann; Meier, Carola; Szczepek, Agnieszka J; Olze, Heidi; Schulze-Tanzil, Gundula

    2015-04-01

    Nasal sprays were introduced several years ago to support the treatment of allergic rhinitis. These sprays may come in direct contact with directly exposed nasoseptal cartilage (e.g. is case of nasoseptal perforation). To date, no studies investigated the effects of nasal sprays on cartilage tissues and cells. Therefore, our aim was to analyze the influence of two different nasal spray types (thixotropic and liposomal) on the vitality of nasoseptal chondrocytes. Human chondrocytes were isolated from surgically dissected tissues. Alternatively, nasal septa (porcine and human) tissue explants were used. The cell or explant cultures were treated with nasal sprays for 4-24 h. As a read-out, cell vitality and gene and protein expression profiles of type I and II collagen, SOX 9 and matrix metalloproteinase MMP-1 were compared to the untreated controls by means of real-time RT-PCR and immunostaining. Using the liposomal, but not thixotropic nasal spray in an explant or chondrocyte in vitro culture led to increased cell death, as compared to the untreated controls. A trend towards suppression of type II collagen and SOX 9 on protein level was found in cultures exposed to liposomal nasal spray, as compared to the controls. The thixotropic nasal spray has not affected the nasoseptal chondrocytes. Further studies with the use of viable nasoseptal cartilage explants and particularly using an in vivo animal model of exposed nasoseptal cartilage are necessary to clear the effect of liposomal spray on chondrocytes.

  15. Awake Measures of Nasal Resistance and Upper Airway Resistance on CPAP during Sleep

    PubMed Central

    Masdeu, Maria J.; Seelall, Vijay; Patel, Amit V.; Ayappa, Indu; Rapoport, David M.

    2011-01-01

    Study Objectives: Since on CPAP, the nose is the primary determinant of upper airway resistance, we assess utility of noninvasive measures of nasal resistance during wakefulness as a predictor of directly assessed upper airway resistance on CPAP during sleep in patients with obstructive sleep apnea/hypopnea syndrome. Methods: Patients with complaints of snoring and excessive daytime sleepiness were recruited. 14 subjects underwent daytime evaluations including clinical assessment, subjective questionnaires to assess nasal symptoms and evaluation of nasal resistance with acoustic rhinometry (AR) and active anterior rhinomanometry (RM) in the sitting and supine positions. Patients underwent nocturnal polysomnography on optimal CPAP with measurements of supraglottic pressure to evaluate upper airway resistance. Comparisons were made between nasal resistance using AR and RM during wakefulness, and between AR and RM awake and upper airway resistance during sleep. Results: Our study shows that measures of awake nasal resistance using AR and RM had little or no correlation to each other in the sitting position, whereas there was significant but weak correlation in the supine position. Upper airway resistance measured while on CPAP during sleep did not show significant relationships to any of the awake measures of nasal resistance (AR or RM). Conclusion: Awake measurements of nasal resistance do not seem to be predictive of upper airway resistance during sleep on CPAP. Citation: Masdeu MJ; Seelall V; Patel AV; Ayappa I; Rapoport DM. Awake Measures of Nasal Resistance and Upper Airway Resistance on CPAP during Sleep. J Clin Sleep Med 2011;7(1):31-40. PMID:21344056

  16. Nasal Retinoschisis Associated with Glaucoma.

    PubMed

    Hubschman, Jean-Pierre; Reddy, Shantan; Kaines, Andrew; Law, Simon

    2010-03-01

    The authors describe a case of nasal and macular retinoschisis in a patient with open angle glaucoma. A 75 year-old female with optic nerve head damage secondary to chronic open angle glaucoma developed macular schisis and a separate area of retinoschisis nasal to her optic disk. There were no other identifiable causes for her retinoschisis. Glaucoma related structural defects offer a plausible explanation for multiple cavities of retinoschisis in favor of multiple occult congenital pits of the optic nerve head. PMID:20337311

  17. Molecular genetics of human primary microcephaly: an overview.

    PubMed

    Faheem, Muhammad; Naseer, Muhammad Imran; Rasool, Mahmood; Chaudhary, Adeel G; Kumosani, Taha A; Ilyas, Asad Muhammad; Pushparaj, Peter; Ahmed, Farid; Algahtani, Hussain A; Al-Qahtani, Mohammad H; Saleh Jamal, Hasan

    2015-01-01

    Autosomal recessive primary microcephaly (MCPH) is a neurodevelopmental disorder that is characterised by microcephaly present at birth and non-progressive mental retardation. Microcephaly is the outcome of a smaller but architecturally normal brain; the cerebral cortex exhibits a significant decrease in size. MCPH is a neurogenic mitotic disorder, though affected patients demonstrate normal neuronal migration, neuronal apoptosis and neural function. Twelve MCPH loci (MCPH1-MCPH12) have been mapped to date from various populations around the world and contain the following genes: Microcephalin, WDR62, CDK5RAP2, CASC5, ASPM, CENPJ, STIL, CEP135, CEP152, ZNF335, PHC1 and CDK6. It is predicted that MCPH gene mutations may lead to the disease phenotype due to a disturbed mitotic spindle orientation, premature chromosomal condensation, signalling response as a result of damaged DNA, microtubule dynamics, transcriptional control or a few other hidden centrosomal mechanisms that can regulate the number of neurons produced by neuronal precursor cells. Additional findings have further elucidated the microcephaly aetiology and pathophysiology, which has informed the clinical management of families suffering from MCPH. The provision of molecular diagnosis and genetic counselling may help to decrease the frequency of this disorder. PMID:25951892

  18. SEASONAL EFFECTS OF ULTRAFINE, FINE, AND COARSE PARTICULATE MATTER (PM) ON HUMAN PRIMARY AIRWAY EPITHELIAL CELLS

    EPA Science Inventory

    SEASONAL EFFECTS OF ULTRAFINE, FINE, AND COARSE PARTICULATE MATTER (PM) ON HUMAN PRIMARY AIRWAY EPITHELIAL CELLS

    Exposure of humans to PM results in increased mortality and morbidity. Recent toxicology studies have shown a number of pathophysiological pulmonary and car...

  19. Quantification of regenerative potential in primary human mammary epithelial cells

    PubMed Central

    Linnemann, Jelena R.; Miura, Haruko; Meixner, Lisa K.; Irmler, Martin; Kloos, Uwe J.; Hirschi, Benjamin; Bartsch, Harald S.; Sass, Steffen; Beckers, Johannes; Theis, Fabian J.; Gabka, Christian; Sotlar, Karl; Scheel, Christina H.

    2015-01-01

    We present an organoid regeneration assay in which freshly isolated human mammary epithelial cells are cultured in adherent or floating collagen gels, corresponding to a rigid or compliant matrix environment. In both conditions, luminal progenitors form spheres, whereas basal cells generate branched ductal structures. In compliant but not rigid collagen gels, branching ducts form alveoli at their tips, express basal and luminal markers at correct positions, and display contractility, which is required for alveologenesis. Thereby, branched structures generated in compliant collagen gels resemble terminal ductal-lobular units (TDLUs), the functional units of the mammary gland. Using the membrane metallo-endopeptidase CD10 as a surface marker enriches for TDLU formation and reveals the presence of stromal cells within the CD49fhi/EpCAM− population. In summary, we describe a defined in vitro assay system to quantify cells with regenerative potential and systematically investigate their interaction with the physical environment at distinct steps of morphogenesis. PMID:26071498

  20. Quantification of regenerative potential in primary human mammary epithelial cells.

    PubMed

    Linnemann, Jelena R; Miura, Haruko; Meixner, Lisa K; Irmler, Martin; Kloos, Uwe J; Hirschi, Benjamin; Bartsch, Harald S; Sass, Steffen; Beckers, Johannes; Theis, Fabian J; Gabka, Christian; Sotlar, Karl; Scheel, Christina H

    2015-09-15

    We present an organoid regeneration assay in which freshly isolated human mammary epithelial cells are cultured in adherent or floating collagen gels, corresponding to a rigid or compliant matrix environment. In both conditions, luminal progenitors form spheres, whereas basal cells generate branched ductal structures. In compliant but not rigid collagen gels, branching ducts form alveoli at their tips, express basal and luminal markers at correct positions, and display contractility, which is required for alveologenesis. Thereby, branched structures generated in compliant collagen gels resemble terminal ductal-lobular units (TDLUs), the functional units of the mammary gland. Using the membrane metallo-endopeptidase CD10 as a surface marker enriches for TDLU formation and reveals the presence of stromal cells within the CD49f(hi)/EpCAM(-) population. In summary, we describe a defined in vitro assay system to quantify cells with regenerative potential and systematically investigate their interaction with the physical environment at distinct steps of morphogenesis.

  1. Denervation of nasal mucosa induced by posterior nasal neurectomy suppresses nasal secretion, not hypersensitivity, in an allergic rhinitis rat model.

    PubMed

    Nishijima, Hironobu; Kondo, Kenji; Toma-Hirano, Makiko; Iwasaki, Shinichi; Kikuta, Shu; Fujimoto, Chisato; Ueha, Rumi; Kagoya, Ryoji; Yamasoba, Tatsuya

    2016-09-01

    The posterior nasal nerve is the dominant source of the parasympathetic, sympathetic, and sensory fibers that innervate the nasal respiratory mucosa. Therefore, a posterior nasal neurectomy (PNN) is thought to induce denervation of the nasal mucosa and relieve the nasal symptoms of allergic rhinitis. However, the underlying mechanisms and therapeutic action of PNN remain unknown. To investigate the impact of PNN-induced denervation of the nasal mucosa on allergic rhinitis, we developed a rat model of PNN and examined the effects of PNN on allergic rhinitis in ovalbumin-sensitized rats. This rat model of PNN was characterized by the depletion of nerve fibers, choline acetyltransferase, and neuropeptides (eg, substance P, calcitonin gene-related peptide, vasoactive intestinal peptide, and neuropeptide Y) in the nasal respiratory mucosa. These animals exhibited nasal gland and goblet cell hypertrophy in the septal mucosa and atrophy of the submucosal gland in the lateral nasal wall, as well as reduced nasal secretion due to deficient acetylcholine synthesis. In an ovalbumin-sensitized model of allergic rhinitis, PNN also induced the depletion of nerve fibers, choline acetyltransferase, and neuropeptides in the nasal mucosa and suppressed nasal secretion. However, PNN did not affect mucosal thickening, eosinophil and mast cell infiltration, interleukin-4 and interferon-γ mRNA expression, and allergic symptoms (ie, sneezing and nasal scratching). These results suggest that the peripheral nerves and corresponding neuropeptides regulate nasal secretion, but not hypersensitivity, in allergic rhinitis, and that allergic rhinitis-related mucosal reactions occur in a highly denervated mucosa after PNN. Posterior nasal neurectomy may be a therapeutic option for the treatment of hyperrhinorrhea, but not allergic rhinitis hypersensitivity. PMID:27322954

  2. Pinocchio nasal deformity secondary to lymphangioma circumscriptum.

    PubMed

    Uysal, Afşin; Yildiz, Kaya; Kankaya, Yüksel; Oruç, Melike; Sungur, Nezih; Koçer, Uğur; Ozer, Elif

    2007-11-01

    Pinocchio or Cyrano nasal tip deformity is a rare situation that develops secondary to the soft tissue tumors underneath. In literature, there is only one case reported with Pinocchio nasal deformity secondary to cavernous lymphangioma. In this study, we present a Pinocchio or Cyrano nasal deformity with skin involvement secondary to lymphangioma circumscriptum.

  3. Does post septoplasty nasal packing reduce complications?

    PubMed

    Naghibzadeh, Bijan; Peyvandi, Ali Asghar; Naghibzadeh, Ghazal

    2011-01-01

    The main issues in nasal surgery are to stabilize the nose in the good position after surgery and preserve the cartilages and bones in the favorable situation and reduce the risk of deviation recurrence. Also it is necessary to avoid the synechia formation, nasal valve narrowing, hematoma and bleeding. Due to the above mentioned problems and in order to solve and minimize them nasal packing, nasal splint and nasal mold have been advised. Patients for whom the nasal packing used may faced to some problems like naso-pulmonary reflex, intractable pain, sleep disorder, post operation infection and very dangerous complication like toxic shock syndrome. We have two groups of patients and three surgeons (one of the surgeons used post operative nasal packing in his patients and the two others surgeons did not).Complications and morbidities were compared in these two groups. Comparing the two groups showed that the rate of complication and morbidities between these two groups were same and the differences were not valuable, except the pain and discomfort post operatively and at the time of its removal. Nasal packing has several risks for the patients while its effects are not studied. Septoplasty can be safely performed without postoperative nasal packing. Nasal packing had no main findings that compensated its usage. Septal suture is one of the procedures that can be used as alternative method to nasal packing. Therefore the nasal packing after septoplasty should be reserved for the patients with increased risk of bleeding. PMID:21425063

  4. Experience in primary culture of human peritoneal mesothelial cell.

    PubMed

    Chen, Kuo-Su; Chen, Wen-Shiang

    2012-08-31

    To compare the growth condition between different sources and different culture environments, mesothelial cells were isolated from omentum and peritoneal dialysate effluent (PDE), seeded at different densities (5 × 10⁵, 1 × 10⁵, 5 × 10⁴, 1 × 10⁴, 5 × 10³, 1 × 10³ and 5 × 10² cells/cm², respectively), supported with different fetal calf serum (FCS) concentrations (3%, 6%, 10% and 15%) and grown in dishes with and without gelatin pre-coating. Growth condition was evaluated by simple morphological observation. Cells phenotype was examined by immunofluorescent staining. The results showed that omentum-derived mesothelial cells generally showed a uniform growth pattern with good quality. Alternatively, there was a wide patient-to-patient variation in PDE-derived culture. Heterogeneous colonies composed of a mixture of large, small or abortive mesothelial colonies as well as fibroblastoid colonies were frequently observed. A minimum seeding density of 5 × 10³ cells/cm² is required for the omentum-derived mesothelial cells to grow to confluent monolayer (1-5 × 10⁴ cells/cm² for initial culture from fresh PDE). Appropriate seeding density is always associated with successful culture in omentumbased culture, but not in PDE-based culture. Mesothelial cells could grow to confluency regardless of FCS concentration and gelatin pre-coating. However, growth rate was slower in lower FCS concentrations and on dishes without gelatin coating. Most cells in culture expressed cytokeratin and vimentin, but not VWF. Alpha-smooth muscle actin frequently appeared in cytokeratin+ mesothelial cells, especially in higher FCS concentrations and in PDE-derived culture. Our data demonstrate that PDE, in contrast to omentum, provides a source of mesothelial cells with poor and unstable quality for primary culture. Healthy cell quality and sufficient seeding density seem to be the most important factors for successful culture of mesothelial cells. The frequent occurrence

  5. Secreted primary human malignant mesothelioma exosome signature reflects oncogenic cargo.

    PubMed

    Greening, David W; Ji, Hong; Chen, Maoshan; Robinson, Bruce W S; Dick, Ian M; Creaney, Jenette; Simpson, Richard J

    2016-01-01

    Malignant mesothelioma (MM) is a highly-aggressive heterogeneous malignancy, typically diagnosed at advanced stage. An important area of mesothelioma biology and progression is understanding intercellular communication and the contribution of the secretome. Exosomes are secreted extracellular vesicles shown to shuttle cellular cargo and direct intercellular communication in the tumour microenvironment, facilitate immunoregulation and metastasis. In this study, quantitative proteomics was used to investigate MM-derived exosomes from distinct human models and identify select cargo protein networks associated with angiogenesis, metastasis, and immunoregulation. Utilising bioinformatics pathway/network analyses, and correlation with previous studies on tumour exosomes, we defined a select mesothelioma exosomal signature (mEXOS, 570 proteins) enriched in tumour antigens and various cancer-specific signalling (HPGD/ENO1/OSMR) and secreted modulators (FN1/ITLN1/MAMDC2/PDGFD/GBP1). Notably, such circulating cargo offers unique insights into mesothelioma progression and tumour microenvironment reprogramming. Functionally, we demonstrate that oncogenic exosomes facilitate the migratory capacity of fibroblast/endothelial cells, supporting the systematic model of MM progression associated with vascular remodelling and angiogenesis. We provide biophysical and proteomic characterisation of exosomes, define a unique oncogenic signature (mEXOS), and demonstrate the regulatory capacity of exosomes in cell migration/tube formation assays. These findings contribute to understanding tumour-stromal crosstalk in the context of MM, and potential new diagnostic and therapeutic extracellular targets.

  6. Secreted primary human malignant mesothelioma exosome signature reflects oncogenic cargo

    NASA Astrophysics Data System (ADS)

    Greening, David W.; Ji, Hong; Chen, Maoshan; Robinson, Bruce W. S.; Dick, Ian M.; Creaney, Jenette; Simpson, Richard J.

    2016-09-01

    Malignant mesothelioma (MM) is a highly-aggressive heterogeneous malignancy, typically diagnosed at advanced stage. An important area of mesothelioma biology and progression is understanding intercellular communication and the contribution of the secretome. Exosomes are secreted extracellular vesicles shown to shuttle cellular cargo and direct intercellular communication in the tumour microenvironment, facilitate immunoregulation and metastasis. In this study, quantitative proteomics was used to investigate MM-derived exosomes from distinct human models and identify select cargo protein networks associated with angiogenesis, metastasis, and immunoregulation. Utilising bioinformatics pathway/network analyses, and correlation with previous studies on tumour exosomes, we defined a select mesothelioma exosomal signature (mEXOS, 570 proteins) enriched in tumour antigens and various cancer-specific signalling (HPGD/ENO1/OSMR) and secreted modulators (FN1/ITLN1/MAMDC2/PDGFD/GBP1). Notably, such circulating cargo offers unique insights into mesothelioma progression and tumour microenvironment reprogramming. Functionally, we demonstrate that oncogenic exosomes facilitate the migratory capacity of fibroblast/endothelial cells, supporting the systematic model of MM progression associated with vascular remodelling and angiogenesis. We provide biophysical and proteomic characterisation of exosomes, define a unique oncogenic signature (mEXOS), and demonstrate the regulatory capacity of exosomes in cell migration/tube formation assays. These findings contribute to understanding tumour-stromal crosstalk in the context of MM, and potential new diagnostic and therapeutic extracellular targets.

  7. Secreted primary human malignant mesothelioma exosome signature reflects oncogenic cargo

    PubMed Central

    Greening, David W.; Ji, Hong; Chen, Maoshan; Robinson, Bruce W. S.; Dick, Ian M.; Creaney, Jenette; Simpson, Richard J.

    2016-01-01

    Malignant mesothelioma (MM) is a highly-aggressive heterogeneous malignancy, typically diagnosed at advanced stage. An important area of mesothelioma biology and progression is understanding intercellular communication and the contribution of the secretome. Exosomes are secreted extracellular vesicles shown to shuttle cellular cargo and direct intercellular communication in the tumour microenvironment, facilitate immunoregulation and metastasis. In this study, quantitative proteomics was used to investigate MM-derived exosomes from distinct human models and identify select cargo protein networks associated with angiogenesis, metastasis, and immunoregulation. Utilising bioinformatics pathway/network analyses, and correlation with previous studies on tumour exosomes, we defined a select mesothelioma exosomal signature (mEXOS, 570 proteins) enriched in tumour antigens and various cancer-specific signalling (HPGD/ENO1/OSMR) and secreted modulators (FN1/ITLN1/MAMDC2/PDGFD/GBP1). Notably, such circulating cargo offers unique insights into mesothelioma progression and tumour microenvironment reprogramming. Functionally, we demonstrate that oncogenic exosomes facilitate the migratory capacity of fibroblast/endothelial cells, supporting the systematic model of MM progression associated with vascular remodelling and angiogenesis. We provide biophysical and proteomic characterisation of exosomes, define a unique oncogenic signature (mEXOS), and demonstrate the regulatory capacity of exosomes in cell migration/tube formation assays. These findings contribute to understanding tumour-stromal crosstalk in the context of MM, and potential new diagnostic and therapeutic extracellular targets. PMID:27605433

  8. Secreted primary human malignant mesothelioma exosome signature reflects oncogenic cargo.

    PubMed

    Greening, David W; Ji, Hong; Chen, Maoshan; Robinson, Bruce W S; Dick, Ian M; Creaney, Jenette; Simpson, Richard J

    2016-01-01

    Malignant mesothelioma (MM) is a highly-aggressive heterogeneous malignancy, typically diagnosed at advanced stage. An important area of mesothelioma biology and progression is understanding intercellular communication and the contribution of the secretome. Exosomes are secreted extracellular vesicles shown to shuttle cellular cargo and direct intercellular communication in the tumour microenvironment, facilitate immunoregulation and metastasis. In this study, quantitative proteomics was used to investigate MM-derived exosomes from distinct human models and identify select cargo protein networks associated with angiogenesis, metastasis, and immunoregulation. Utilising bioinformatics pathway/network analyses, and correlation with previous studies on tumour exosomes, we defined a select mesothelioma exosomal signature (mEXOS, 570 proteins) enriched in tumour antigens and various cancer-specific signalling (HPGD/ENO1/OSMR) and secreted modulators (FN1/ITLN1/MAMDC2/PDGFD/GBP1). Notably, such circulating cargo offers unique insights into mesothelioma progression and tumour microenvironment reprogramming. Functionally, we demonstrate that oncogenic exosomes facilitate the migratory capacity of fibroblast/endothelial cells, supporting the systematic model of MM progression associated with vascular remodelling and angiogenesis. We provide biophysical and proteomic characterisation of exosomes, define a unique oncogenic signature (mEXOS), and demonstrate the regulatory capacity of exosomes in cell migration/tube formation assays. These findings contribute to understanding tumour-stromal crosstalk in the context of MM, and potential new diagnostic and therapeutic extracellular targets. PMID:27605433

  9. The role of arginine vasopressin in electroacupuncture treatment of primary sciatica in human.

    PubMed

    Zhao, Xue-Yan; Zhang, Qi-Shun; Yang, Jun; Sun, Fang-Jie; Wang, Da-Xin; Wang, Chang-Hong; He, Wei-Ya

    2015-08-01

    It has been implicated that electroacupuncture can relieve the symptoms of sciatica with the increase of pain threshold in human, and arginine vasopressin (AVP) in the brain rather than the spinal cord and blood circulation participates in antinociception. Our previous study has proven that AVP in the brain played a role in the process of electroacupuncture analgesia in rat. The goal of the present study was to investigate the role of AVP in electroacupuncture in treating primary sciatica in human. The results showed that (1) AVP concentration of cerebrospinal fluid (CSF) (7.5 ± 2.5 pg/ml), not plasma (13.2 ± 4.2 pg/ml) in primary sciatica patients was lower than that in health volunteers (16.1 ± 3.8 pg/ml and 12.3 ± 3.4 pg/ml), although the osmotic pressure in CSF and plasma did not change; (2) electroacupuncture of the bilateral "Zusanli" points (St. 36) for 60 min relieved the pain sensation in primary sciatica patients; (3) electroacupuncture increased the AVP level of CSF, not plasma in primary sciatica patients; and (4) there was the positive correlation between the effect of electroacupuncture relieving the pain and the AVP level of CSF in the primary sciatica patients. The data suggested that central AVP, not peripheral AVP might improve the effect of electroacupuncture treatment of primary sciatica in human, i.e., central AVP might take part in the electroacupuncture relieving the pain sensation in primary sciatica patients.

  10. [Study of nasal and tonsillar mucosal microbiocenoses as one of the health indices].

    PubMed

    Khusnutdinova, L M; Usviatsov, B Ia; Soboleva, Iu V; Bukharin, O V

    2009-01-01

    The qualitative and quantitative compositions of nasal and tonsillar mucosal biocenoses were studied in healthy individuals and patients with chronic tonsillitis as an ecological criterion for assessing the stability of biocenosis and human health. The qualitative composition of tonsillar mucosal biocenosis turned out to be steady-state both in health and disease. The human nasal mucosa showed itself as an indicator system. Staphylococcal strains with a high persistent potential and polyantibiotic resistance, which may cause an exacerbation of the inflammatory process on translocation to the tonsillar mucosa, were selected on the nasal mucosa of patients with chronic tonsillitis. PMID:19799231

  11. Nasal spray flu vaccine (image)

    MedlinePlus

    The flu vaccine can also be administered as a nasal spray instead of the usual injection method. It is an ... 49 who want to be protected from the flu virus. Unlike the regular vaccine, it is a live virus. Therefore, it is ...

  12. Orientation anisotropies in human primary visual cortex depend on contrast.

    PubMed

    Maloney, Ryan T; Clifford, Colin W G

    2015-10-01

    Orientation processing in visual cortex appears matched to the environment, such that larger neural populations are tuned to cardinal (horizontal/vertical) than oblique orientations. This may be manifested perceptually as a cardinal bias: poorer sensitivity to oblique compared to cardinal orientations (the "oblique effect"). However, a growing body of psychophysical data reveals the opposite pattern of anisotropy: a bias towards the oblique over the cardinal orientations (the "horizontal effect"), something matched by recent functional magnetic resonance imaging (fMRI) studies that have found an increased response to the oblique over the cardinal orientations in early visual cortex. This may reveal the operation of an efficient coding strategy optimised to the diet of orientations encountered during natural viewing. From consideration of coding efficiency, it might be expected that the anisotropies would change as the quality/strength of the oriented stimulus changes. In two experiments, fMRI response modulations were measured in retinotopically-defined human early visual cortex as a function of the contrast and orientation of sinusoidal gratings. Both experiments revealed a marked change in the V1 response from a cardinal (vertical) bias at low contrast to an oblique bias at high contrast. In Experiment 2, this was also apparent in areas V2 and V3. On average, there was no systematic "radial bias" (a preference for orientations aligned with the visual field meridian) in V1, although it was present in some individual subjects. The change in orientation anisotropies with contrast is consistent with an adaptive stimulus coding strategy in cortex that shifts according to the strength of the sensory inputs. PMID:26093331

  13. Matrigel improves functional properties of primary human salivary gland cells.

    PubMed

    Maria, Ola M; Zeitouni, Anthony; Gologan, Olga; Tran, Simon D

    2011-05-01

    Currently, there is no effective treatment available to patients with irreversible loss of functional salivary acini caused by Sjogren's syndrome or after radiotherapy for head and neck cancer. A tissue-engineered artificial salivary gland would help these patients. The graft cells for this device must establish tight junctions in addition to being of fluid-secretory nature. This study analyzed a graft source from human salivary glands (huSG) cultured on Matrigel. Cells were obtained from parotid and submandibular glands, expanded in vitro, and then plated on either Matrigel-coated (2 mg/mL) or uncoated culture dish. Immunohistochemistry, transmission electron microscopy, quantitative real-time-polymerase chain reaction, Western blot, and transepithelial electrical resistance were employed. On Matrigel, huSG cells adopted an acinar phenotype by forming three-dimensional acinar-like units (within 24 h of plating) as well as a monolayer of cells. On uncoated surfaces (plastic), huSG cells only formed monolayers of ductal cells. Both types of culture conditions allowed huSG cells to express tight junction proteins (claudin-1, -2, -3, -4; occludin; JAM-A; and ZO-1) and adequate transepithelial electrical resistance. Importantly, 99% of huSG cells on Matrigel expressed α-amylase and the water channel protein Aquaporin-5, as compared to <5% of huSG cells on plastic. Transmission electron microscopy confirmed an acinar phenotype with many secretory granules. Matrigel increased the secretion of α-amylase two to five folds into the media, downregulated certain salivary genes, and regulated the translation of acinar proteins. This three-dimensional in vitro serum-free cell culture method allows the organization and differentiation of huSG cells into salivary cells with an acinar phenotype.

  14. Broad nasal bridge

    MedlinePlus

    ... Jones KL, Jones MC, Del Campo MD, eds. Smith's Recognizable Patterns of Human Malformation . 7th ed. Philadelphia, PA: Elsevier Saunders; 2013:chap H. Olitsky SE, Hug D, Plummer LS, Stahl ED, Ariss MM, Lindquist TP. Disorders of ...

  15. The total nasal defect and reconstruction.

    PubMed

    Cannady, Steven B; Cook, Ted A; Wax, Mark K

    2009-05-01

    The structures of the nose are arguably the most complex within the face to reconstitute when absent. Total nasal reconstruction has evolved to encompass advanced surgical techniques in an effort to achieve increasingly satisfactory cosmetic results while restoring nasal function that mimics the function of a patient's natural nose. In this article, the history of total nasal defects and their reconstruction, relevant nasal anatomy, etiologies of the defect, and the surgical approaches to reconstructing each of the three-layered structure of the nose (ie, nasal skin, cartilage/bone, and lining mucosa) are explored.

  16. Thiolated polycarbophil as an adjuvant for permeation enhancement in nasal delivery of antisense oligonucleotides.

    PubMed

    Vetter, A; Martien, R; Bernkop-Schnürch, A

    2010-03-01

    The purpose of this study was to investigate the effect of thiolated polycarbophil as an adjuvant to enhance the permeation and improve the stability of a phosphorothioate antisense oligonucleotide (PTO-ODN) on the nasal mucosa. Polycarbophil-cysteine (PCP-Cys) was synthesized by the covalent attachment of L-cysteine to the polymeric backbone. Cytotoxicity tests were examined on human nasal epithelial cells from surgery of nasal polyps confirmed by histological studies. Deoxyribonuclease I activity in respiratory region of the porcine nasal cavity was analyzed by an enzymatic assay. The enzymatic degradation of PTO-ODNs on freshly excised porcine nasal mucosa was analyzed and protection of PCP-cysteine toward DNase I degradation was evaluated. Permeation studies were performed in Ussing-type diffusion chambers. PCP-Cys/GSH did not arise a remarkable mortal effect. Porcine respiratory mucosa was shown to possess nuclease activity corresponding to 0.69 Kunitz units/mL. PTO-ODNs were degraded by incubation with nasal mucosa. In the presence of 0.45% thiolated polycarbophil and 0.5% glutathione (GSH), this degradation process could be lowered. In the presence of thiolated polycarbophil and GSH the uptake of PTO-ODNs from the nasal mucosa was 1.7-fold improved. According to these results thiolated polycarbophil/GSH might be a promising excipient for nasal administration of PTO-ODNs.

  17. Lexical confusability and nasal coarticulation in French

    NASA Astrophysics Data System (ADS)

    Scarborough, Rebecca

    2005-09-01

    Previous research has revealed a relationship between lexical confusability and degree of coarticulation [Brown (2001); Scarborough (2004)]. In particular, English speakers produce confusable, or ``hard'' words with more nasal and vowel-to-vowel coarticulation than less confusable, ``easy'' ones. Thus, it has been suggested that speakers produce additional coarticulation in order to increase the intelligibility of ``hard'' words. Here, the relation between nasal coarticulation and lexical confusability is investigated for French, a language in which vowel nasality is phonemically contrastive (at least for a subset of vowels) and might constrain such a lexical effect. Acoustic measures of nasality show that ``hard'' words (those with low usage frequencies and many frequent, phonologically similar neighbors) exhibit more nasal coarticulation than ``easy'' ones (those with high frequencies and few, low-frequency neighbors) in French as well. Interestingly, however, the effect emerges only for words containing vowels that can exhibit phonemic oral-nasal contrasts (oral vowels with nasal counterparts). Thus, where the use of nasality in phonological contrast is constrained, coarticulatory nasality is constrained, too. But the existence of phonological contrast does not itself constrain the lexical confusability effect: increased coarticulatory nasality contributes to lexically motivated phonetic enhancement in French, while even more nasality provides the basis for phonemic contrast.

  18. Nasal NK/T cell lymphoma presents with long-term nasal blockage and fever: a rare case report and literature review

    PubMed Central

    Zou, Hai; Pan, Ke-Hua; Wu, Liang; Pan, Hong-Ying; Ding, Ya-Hui; Zheng, Ming-Hua

    2016-01-01

    NK/T cell lymphoma (NKTCL) is a common disease which is a threat to human health. Nasal NKTCL is a rare but serious type of systemic lymphoma because of its high mortality rate and serious complications. In this case report, we describe a male who presented with nasal blockage in the right side, a fever of one month duration and a soy-like, painless and gradually increasing mass in the right submandibular region due to nasal NKTCL. The patient had no significant medical history and the initial clinical symptoms were nasal blockage. Contrast computed tomography showed that the nasopharyngeal mucosa was thickened and that the celiac and retroperitoneal lymphaden was intumescent. Finally a biopsy, guided by nasal endoscopy and examined using flow cytometry confirmed a diagnosis of NKTCL. Nasal NKTCL is rare and has no unique characteristics at first presentation, such as epidemiology and obvious clinical manifestation. As no effective therapy is currently available for this disease, early diagnosis and therapy of nasal NKTCL remains challenging. PMID:26885897

  19. Squamous cell carcinoma of the nasal vestibule.

    PubMed

    Horsmans, J D; Godballe, C; Jørgensen, K E; Bastholt, L; Løntoft, E

    1999-09-01

    From 1978 to 1992, 66 patients (32 women and 34 men) were treated for carcinoma of the nasal vestibule at Odense University Hospital. The treatment was radiotherapy (41 patients), surgery (13 patients) or a combination of the two modalities (12 patients). Twenty-one patients (32%) developed recurrence. Of these, 17 (81%) were diagnosed within the first two years of follow up. The recurrence rate was found to be correlated to the anatomic site of the tumour-origin; septal site of origin meant higher risk of recurrence. Five-year disease specific and crude survival of all patients were 87.0% and 58.5%, respectively. Several variables (sex, age, anatomic site of origin, Wang-classification, tumour volume and regional lymphnode metastases at time of diagnosis) were evaluated as possible prognostic indicators. In univariate analysis, regional lymph node metastases at the time of diagnosis and anatomic site of origin of the tumour showed a significant influence on survival. In multivariate analysis, septal origin of primary tumour was a significant, independent predictive factor of recurrence and the presence of lymph node metastases at the time of diagnosis showed to be a highly significant prognosticator of both disease specific and crude survival (p < 0.0001). We conclude that patients with primary lymph node metastases and septal location of primary tumour need intensive primary treatment and close follow up. PMID:10567990

  20. Human enamel veneer restoration: an alternative technique to restore anterior primary teeth.

    PubMed

    Oliveira, Luciana Butini; Tamay, Tereza Keiko; Oliveira, Marta Dutra Machado; Rodrigues, Célia Martins Delgado; Wanderley, Marcia Turolla

    2006-01-01

    Restoration of severely decayed primary teeth is a clinical challenge in Pediatric Dentistry. Among the restorative treatment options, the use of prefabricated crowns and resin composite restorations, either by means of direct or indirect techniques is mentioned in the literature. The purpose of this article is to describe the rehabilitation of primary anterior teeth in a 5-year-old patient. Dental treatment consisted on an anterior space maintainer prosthesis made with natural primary teeth, plus human dental enamel veneer (facet) restorations. The advantages of this technique are better esthetics and the natural enamel has physiologic wear and offers superficial smoothness and cervical adaptation compatible with those of the surrounding teeth.

  1. Human enamel veneer restoration: an alternative technique to restore anterior primary teeth.

    PubMed

    Oliveira, Luciana Butini; Tamay, Tereza Keiko; Oliveira, Marta Dutra Machado; Rodrigues, Célia Martins Delgado; Wanderley, Marcia Turolla

    2006-01-01

    Restoration of severely decayed primary teeth is a clinical challenge in Pediatric Dentistry. Among the restorative treatment options, the use of prefabricated crowns and resin composite restorations, either by means of direct or indirect techniques is mentioned in the literature. The purpose of this article is to describe the rehabilitation of primary anterior teeth in a 5-year-old patient. Dental treatment consisted on an anterior space maintainer prosthesis made with natural primary teeth, plus human dental enamel veneer (facet) restorations. The advantages of this technique are better esthetics and the natural enamel has physiologic wear and offers superficial smoothness and cervical adaptation compatible with those of the surrounding teeth. PMID:16937849

  2. Septic arthritis: a unique complication of nasal septal abscess.

    PubMed

    Olsen, Steven M; Koch, Cody A; Ekbom, Dale C

    2015-03-01

    Nasal septal abscesses (NSAs) occur between the mucoperichondrium and the nasal septum. They most often arise when an untreated septal hematoma becomes infected. The most commonly reported sequela is a loss of septal cartilage support, which can result in a nasal deformity. Other sequelae include potentially life-threatening conditions such as meningitis, cavernous sinus thrombosis, brain abscess, and subarachnoid empyema. We report the case of a 17-year-old boy who developed an NSA after he had been struck in the face with a basketball. He presented to his primary care physician 5 days after the injury and again the next day, but his condition was not correctly diagnosed. Finally, 7 days after his injury, he presented to an emergency department with more serious symptoms, and he was correctly diagnosed with NSA. He was admitted to the intensive care unit, and he remained hospitalized for 6 days. Among the abscess sequelae he experienced was septic arthritis, which has heretofore not been reported as a complication of NSA. He responded well to appropriate treatment, although he lost a considerable amount of septal cartilage. He was discharged home on intravenous antibiotic therapy, and his condition improved. Reconstruction of the nasal septum will likely need to be pursued in the future. PMID:25738728

  3. Septic arthritis: a unique complication of nasal septal abscess.

    PubMed

    Olsen, Steven M; Koch, Cody A; Ekbom, Dale C

    2015-03-01

    Nasal septal abscesses (NSAs) occur between the mucoperichondrium and the nasal septum. They most often arise when an untreated septal hematoma becomes infected. The most commonly reported sequela is a loss of septal cartilage support, which can result in a nasal deformity. Other sequelae include potentially life-threatening conditions such as meningitis, cavernous sinus thrombosis, brain abscess, and subarachnoid empyema. We report the case of a 17-year-old boy who developed an NSA after he had been struck in the face with a basketball. He presented to his primary care physician 5 days after the injury and again the next day, but his condition was not correctly diagnosed. Finally, 7 days after his injury, he presented to an emergency department with more serious symptoms, and he was correctly diagnosed with NSA. He was admitted to the intensive care unit, and he remained hospitalized for 6 days. Among the abscess sequelae he experienced was septic arthritis, which has heretofore not been reported as a complication of NSA. He responded well to appropriate treatment, although he lost a considerable amount of septal cartilage. He was discharged home on intravenous antibiotic therapy, and his condition improved. Reconstruction of the nasal septum will likely need to be pursued in the future.

  4. Bile acid-induced necrosis in primary human hepatocytes and in patients with obstructive cholestasis

    SciTech Connect

    Woolbright, Benjamin L.; Dorko, Kenneth; Antoine, Daniel J.; Clarke, Joanna I.; Gholami, Parviz; Li, Feng; Kumer, Sean C.; Schmitt, Timothy M.; Forster, Jameson; Fan, Fang; Jenkins, Rosalind E.; Park, B. Kevin; Hagenbuch, Bruno; Olyaee, Mojtaba; Jaeschke, Hartmut

    2015-03-15

    Accumulation of bile acids is a major mediator of cholestatic liver injury. Recent studies indicate bile acid composition between humans and rodents is dramatically different, as humans have a higher percent of glycine conjugated bile acids and increased chenodeoxycholate content, which increases the hydrophobicity index of bile acids. This increase may lead to direct toxicity that kills hepatocytes, and promotes inflammation. To address this issue, this study assessed how pathophysiological concentrations of bile acids measured in cholestatic patients affected primary human hepatocytes. Individual bile acid levels were determined in serum and bile by UPLC/QTOFMS in patients with extrahepatic cholestasis with, or without, concurrent increases in serum transaminases. Bile acid levels increased in serum of patients with liver injury, while biliary levels decreased, implicating infarction of the biliary tracts. To assess bile acid-induced toxicity in man, primary human hepatocytes were treated with relevant concentrations, derived from patient data, of the model bile acid glycochenodeoxycholic acid (GCDC). Treatment with GCDC resulted in necrosis with no increase in apoptotic parameters. This was recapitulated by treatment with biliary bile acid concentrations, but not serum concentrations. Marked elevations in serum full-length cytokeratin-18, high mobility group box 1 protein (HMGB1), and acetylated HMGB1 confirmed inflammatory necrosis in injured patients; only modest elevations in caspase-cleaved cytokeratin-18 were observed. These data suggest human hepatocytes are more resistant to human-relevant bile acids than rodent hepatocytes, and die through necrosis when exposed to bile acids. These mechanisms of cholestasis in humans are fundamentally different to mechanisms observed in rodent models. - Highlights: • Cholestatic liver injury is due to cytoplasmic bile acid accumulation in hepatocytes. • Primary human hepatocytes are resistant to BA-induced injury

  5. Impaired Air Conditioning within the Nasal Cavity in Flat-Faced Homo.

    PubMed

    Nishimura, Takeshi; Mori, Futoshi; Hanida, Sho; Kumahata, Kiyoshi; Ishikawa, Shigeru; Samarat, Kaouthar; Miyabe-Nishiwaki, Takako; Hayashi, Misato; Tomonaga, Masaki; Suzuki, Juri; Matsuzawa, Tetsuro; Matsuzawa, Teruo

    2016-03-01

    We are flat-faced hominins with an external nose that protrudes from the face. This feature was derived in the genus Homo, along with facial flattening and reorientation to form a high nasal cavity. The nasal passage conditions the inhaled air in terms of temperature and humidity to match the conditions required in the lung, and its anatomical variation is believed to be evolutionarily sensitive to the ambient atmospheric conditions of a given habitat. In this study, we used computational fluid dynamics (CFD) with three-dimensional topology models of the nasal passage under the same simulation conditions, to investigate air-conditioning performance in humans, chimpanzees, and macaques. The CFD simulation showed a horizontal straight flow of inhaled air in chimpanzees and macaques, contrasting with the upward and curved flow in humans. The inhaled air is conditioned poorly in humans compared with nonhuman primates. Virtual modifications to the human external nose topology, in which the nasal vestibule and valve are modified to resemble those of chimpanzees, change the airflow to be horizontal, but have little influence on the air-conditioning performance in humans. These findings suggest that morphological variation of the nasal passage topology was only weakly sensitive to the ambient atmosphere conditions; rather, the high nasal cavity in humans was formed simply by evolutionary facial reorganization in the divergence of Homo from the other hominin lineages, impairing the air-conditioning performance. Even though the inhaled air is not adjusted well within the nasal cavity in humans, it can be fully conditioned subsequently in the pharyngeal cavity, which is lengthened in the flat-faced Homo. Thus, the air-conditioning faculty in the nasal passages was probably impaired in early Homo members, although they have survived successfully under the fluctuating climate of the Plio-Pleistocene, and then they moved "Out of Africa" to explore the more severe climates of

  6. Impaired Air Conditioning within the Nasal Cavity in Flat-Faced Homo

    PubMed Central

    Nishimura, Takeshi; Mori, Futoshi; Hanida, Sho; Kumahata, Kiyoshi; Ishikawa, Shigeru; Samarat, Kaouthar; Miyabe-Nishiwaki, Takako; Hayashi, Misato; Tomonaga, Masaki; Suzuki, Juri; Matsuzawa, Tetsuro; Matsuzawa, Teruo

    2016-01-01

    We are flat-faced hominins with an external nose that protrudes from the face. This feature was derived in the genus Homo, along with facial flattening and reorientation to form a high nasal cavity. The nasal passage conditions the inhaled air in terms of temperature and humidity to match the conditions required in the lung, and its anatomical variation is believed to be evolutionarily sensitive to the ambient atmospheric conditions of a given habitat. In this study, we used computational fluid dynamics (CFD) with three-dimensional topology models of the nasal passage under the same simulation conditions, to investigate air-conditioning performance in humans, chimpanzees, and macaques. The CFD simulation showed a horizontal straight flow of inhaled air in chimpanzees and macaques, contrasting with the upward and curved flow in humans. The inhaled air is conditioned poorly in humans compared with nonhuman primates. Virtual modifications to the human external nose topology, in which the nasal vestibule and valve are modified to resemble those of chimpanzees, change the airflow to be horizontal, but have little influence on the air-conditioning performance in humans. These findings suggest that morphological variation of the nasal passage topology was only weakly sensitive to the ambient atmosphere conditions; rather, the high nasal cavity in humans was formed simply by evolutionary facial reorganization in the divergence of Homo from the other hominin lineages, impairing the air-conditioning performance. Even though the inhaled air is not adjusted well within the nasal cavity in humans, it can be fully conditioned subsequently in the pharyngeal cavity, which is lengthened in the flat-faced Homo. Thus, the air-conditioning faculty in the nasal passages was probably impaired in early Homo members, although they have survived successfully under the fluctuating climate of the Plio-Pleistocene, and then they moved “Out of Africa” to explore the more severe climates of

  7. Impaired Air Conditioning within the Nasal Cavity in Flat-Faced Homo.

    PubMed

    Nishimura, Takeshi; Mori, Futoshi; Hanida, Sho; Kumahata, Kiyoshi; Ishikawa, Shigeru; Samarat, Kaouthar; Miyabe-Nishiwaki, Takako; Hayashi, Misato; Tomonaga, Masaki; Suzuki, Juri; Matsuzawa, Tetsuro; Matsuzawa, Teruo

    2016-03-01

    We are flat-faced hominins with an external nose that protrudes from the face. This feature was derived in the genus Homo, along with facial flattening and reorientation to form a high nasal cavity. The nasal passage conditions the inhaled air in terms of temperature and humidity to match the conditions required in the lung, and its anatomical variation is believed to be evolutionarily sensitive to the ambient atmospheric conditions of a given habitat. In this study, we used computational fluid dynamics (CFD) with three-dimensional topology models of the nasal passage under the same simulation conditions, to investigate air-conditioning performance in humans, chimpanzees, and macaques. The CFD simulation showed a horizontal straight flow of inhaled air in chimpanzees and macaques, contrasting with the upward and curved flow in humans. The inhaled air is conditioned poorly in humans compared with nonhuman primates. Virtual modifications to the human external nose topology, in which the nasal vestibule and valve are modified to resemble those of chimpanzees, change the airflow to be horizontal, but have little influence on the air-conditioning performance in humans. These findings suggest that morphological variation of the nasal passage topology was only weakly sensitive to the ambient atmosphere conditions; rather, the high nasal cavity in humans was formed simply by evolutionary facial reorganization in the divergence of Homo from the other hominin lineages, impairing the air-conditioning performance. Even though the inhaled air is not adjusted well within the nasal cavity in humans, it can be fully conditioned subsequently in the pharyngeal cavity, which is lengthened in the flat-faced Homo. Thus, the air-conditioning faculty in the nasal passages was probably impaired in early Homo members, although they have survived successfully under the fluctuating climate of the Plio-Pleistocene, and then they moved "Out of Africa" to explore the more severe climates of

  8. Cutting Edge: Inflammasome Activation in Primary Human Macrophages Is Dependent on Flagellin

    PubMed Central

    Kortmann, Jens; Brubaker, Sky W.

    2015-01-01

    Murine NLR family, apoptosis inhibitory protein (Naip)1, Naip2, and Naip5/6 are host sensors that detect the cytosolic presence of needle and rod proteins from bacterial type III secretion systems and flagellin, respectively. Previous studies using human-derived macrophage-like cell lines indicate that human macrophages sense the cytosolic needle protein, but not bacterial flagellin. In this study, we show that primary human macrophages readily sense cytosolic flagellin. Infection of primary human macrophages with Salmonella elicits robust cell death and IL-1β secretion that is dependent on flagellin. We show that flagellin detection requires a full-length isoform of human Naip. This full-length Naip isoform is robustly expressed in primary macrophages from healthy human donors, but it is drastically reduced in monocytic tumor cells, THP-1, and U937, rendering them insensitive to cytosolic flagellin. However, ectopic expression of full-length Naip rescues the ability of U937 cells to sense flagellin. In conclusion, human Naip functions to activate the inflammasome in response to flagellin, similar to murine Naip5/6. PMID:26109648

  9. The catalytic and the RNA subunits of human telomerase are required to immortalize equid primary fibroblasts.

    PubMed

    Vidale, Pamela; Magnani, Elisa; Nergadze, Solomon G; Santagostino, Marco; Cristofari, Gael; Smirnova, Alexandra; Mondello, Chiara; Giulotto, Elena

    2012-10-01

    Many human primary somatic cells can be immortalized by inducing telomerase activity through the exogenous expression of the human telomerase catalytic subunit (hTERT). This approach has been extended to the immortalization of cell lines from several mammals. Here, we show that hTERT expression is not sufficient to immortalize primary fibroblasts from three equid species, namely donkey, Burchelli's zebra and Grevy's zebra. In vitro analysis of a reconstituted telomerase composed by hTERT and an equid RNA component of telomerase (TERC) revealed a low activity of this enzyme compared to human telomerase, suggesting a low compatibility of equid and human telomerase subunits. This conclusion was also strengthened by comparison of human and equid TERC sequences, which revealed nucleotide differences in key regions for TERC and TERT interaction. We then succeeded in immortalizing equid fibroblasts by expressing hTERT and hTERC concomitantly. Expression of both human telomerase subunits led to telomerase activity and telomere elongation, indicating that human telomerase is compatible with the other equid telomerase subunits and proteins involved in telomere metabolism. The immortalization procedure described herein could be extended to primary cells from other mammals. The availability of immortal cells from endangered species could be particularly useful for obtaining new information on the organization and function of their genomes, which is relevant for their preservation.

  10. Cutting Edge: Inflammasome Activation in Primary Human Macrophages Is Dependent on Flagellin.

    PubMed

    Kortmann, Jens; Brubaker, Sky W; Monack, Denise M

    2015-08-01

    Murine NLR family, apoptosis inhibitory protein (Naip)1, Naip2, and Naip5/6 are host sensors that detect the cytosolic presence of needle and rod proteins from bacterial type III secretion systems and flagellin, respectively. Previous studies using human-derived macrophage-like cell lines indicate that human macrophages sense the cytosolic needle protein, but not bacterial flagellin. In this study, we show that primary human macrophages readily sense cytosolic flagellin. Infection of primary human macrophages with Salmonella elicits robust cell death and IL-1β secretion that is dependent on flagellin. We show that flagellin detection requires a full-length isoform of human Naip. This full-length Naip isoform is robustly expressed in primary macrophages from healthy human donors, but it is drastically reduced in monocytic tumor cells, THP-1, and U937, rendering them insensitive to cytosolic flagellin. However, ectopic expression of full-length Naip rescues the ability of U937 cells to sense flagellin. In conclusion, human Naip functions to activate the inflammasome in response to flagellin, similar to murine Naip5/6. PMID:26109648

  11. Mechanical loading and the synthesis of 1,25(OH)2D in primary human osteoblasts.

    PubMed

    van der Meijden, K; Bakker, A D; van Essen, H W; Heijboer, A C; Schulten, E A J M; Lips, P; Bravenboer, N

    2016-02-01

    The metabolite 1,25-dihydroxyvitamin D (1,25(OH)2D) is synthesized from its precursor 25-hydroxyvitamin D (25(OH)D) by human osteoblasts leading to stimulation of osteoblast differentiation in an autocrine or paracrine way. Osteoblast differentiation is also stimulated by mechanical loading through activation of various responses in bone cells such as nitric oxide signaling. Whether mechanical loading affects osteoblast differentiation through an enhanced synthesis of 1,25(OH)2D by human osteoblasts is still unknown. We hypothesized that mechanical loading stimulates the synthesis of 1,25(OH)2D from 25(OH)D in primary human osteoblasts. Since the responsiveness of bone to mechanical stimuli can be altered by various endocrine factors, we also investigated whether 1,25(OH)2D or 25(OH)D affect the response of primary human osteoblasts to mechanical loading. Primary human osteoblasts were pre-incubated in medium with/without 25(OH)D3 (400 nM) or 1,25(OH)2D3 (100 nM) for 24h and subjected to mechanical loading by pulsatile fluid flow (PFF). The response of osteoblasts to PFF was quantified by measuring nitric oxide, and by PCR analysis. The effect of PFF on the synthesis of 1,25(OH)2D3 was determined by subjecting osteoblasts to PFF followed by 24h post-incubation in medium with/without 25(OH)D3 (400 nM). We showed that 1,25(OH)2D3 reduced the PFF-induced NO response in primary human osteoblasts. 25(OH)D3 did not significantly alter the NO response of primary human osteoblasts to PFF, but 25(OH)D3 increased osteocalcin and RANKL mRNA levels, similar to 1,25(OH)2D3. PFF did not increase 1,25(OH)2D3 amounts in our model, even though PFF did increase CYP27B1 mRNA levels and reduced VDR mRNA levels. CYP24 mRNA levels were not affected by PFF, but were strongly increased by both 25(OH)D3 and 1,25(OH)2D3. In conclusion, 1,25(OH)2D3 may affect the response of primary human osteoblasts to mechanical stimuli, at least with respect to NO production. Mechanical stimuli may affect

  12. Flame Retardant BDE-47 Effectively Activates Nuclear Receptor CAR in Human Primary Hepatocytes

    PubMed Central

    Sueyoshi, Tatsuya

    2014-01-01

    Polybrominated diphenyl ether BDE-47 (2,2′,4,4′-tetrabromodiphenyl ether) is a thyroid hormone disruptor in mice; hepatic induction of various metabolic enzymes and transporters has been suggested as the mechanism for this disruption. Utilizing Car −/− and Pxr −/− mice as well as human primary hepatocytes, here we have demonstrated that BDE-47 activated both mouse and human nuclear receptor constitutive activated/androstane receptor (CAR). In mouse livers, CAR, not PXR, was responsible for Cyp2b10 mRNA induction by BDE-47. In human primary hepatocytes, BDE-47 was able to induce translocation of YFP-tagged human CAR from the cytoplasm to the nucleus andCYP2B6 and CYP3A4 mRNAs expressions. BDE-47 activated human CAR in a manner akin to the human CAR ligand CITCO (6-(4-Chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde-O-(3,4-dichlorobenzyl)oxime) in luciferase-reporter assays using Huh-7 cells. In contrast, mouse CAR was not potently activated by BDE-47 in the same reporter assays. Furthermore, human pregnane X receptor (PXR) was effectively activated by BDE-47 while mouse PXR was weakly activated in luciferase-reporter assays. Our results indicate that BDE-47 induces CYP genes through activation of human CAR in addition to the previously identified pathway through human PXR. PMID:24218150

  13. Lysozyme: primary bactericidin in human plasma serum active against Bacillus subtilis.

    PubMed Central

    Selsted, M E; Martinez, R J

    1978-01-01

    The in vitro bactericidal reaction of human plasma serum against Bacillus subtilis was investigated. Human lysozyme was purified to homogeneity, and antiserum was prepared against the enzyme. The anti-lysozyme immunoglobulin G was used as a specific inhibitor in bactericidal and bacteriolytic reactions. It was found that at low serum concentrations lysozyme was the primary bactericide active against B. subtilis. At appreciably higher serum concentrations, a lysozyme-independent bactericidal activity was also demonstrated. Images PMID:97236

  14. Unilateral and bilateral nasal resistances: a supplement.

    PubMed

    Naito, K; Cole, P; Humphrey, D

    1990-06-01

    Three hundred and thirty-four measurements of bilateral and unilateral nasal resistance (at delta P 1.0 cm H2O and by time averaging) in 233 adults were carried out by posterior rhinomanometry with a head-out body plethysmograph. Total nasal resistances, calculated by the equation of Ohm's Law for parallel resistors from measured unilateral resistances, were compared with measured total nasal resistances. The time averaged total nasal resistances calculated by use of Ohm's Law for parallel resistors were closer to direct measurements than resistances at delta P 1.0 cm H2O calculated from the same equation. We attempted to fit calculated total nasal resistance with direct measurements by modification of the equation of Ohm's Law for parallel resistors to T = 0.96[R x L/(R + L)]0.92 in the time averaged nasal resistance and T = 1.07[R x L/(R + L)]0.77 in resistance at delta P 1.0 cm H2O (T: total nasal resistance, R: nasal resistance on the right side, L: nasal resistance on the left side). Calculated total nasal resistances from the above equations agreed closely with direct measurements.

  15. Smart Polymers in Nasal Drug Delivery

    PubMed Central

    Chonkar, Ankita; Nayak, Usha; Udupa, N.

    2015-01-01

    Nasal drug delivery has now been recognized as a promising route for drug delivery due to its capability of transporting a drug to systemic circulation and central nervous system. Though nasal mucosa offers improved bioavailability and quick onset of action of the drug, main disadvantage associated with nasal drug delivery is mucocilliary clearance due to which drug particles get cleared from the nose before complete absorption through nasal mucosa. Therefore, mucoadhesive polymeric approach can be successfully used to enhance the retention of the drug on nasal mucosal surface. Here, some of the aspects of the stimuli responsive polymers have been discussed which possess liquid state at the room temperature and in response to nasal temperature, pH and ions present in mucous, can undergo in situ gelation in nasal cavity. In this review, several temperature responsive, pH responsive and ion responsive polymers used in nasal delivery, their gelling mechanisms have been discussed. Smart polymers not only able to enhance the retention of the drug in nasal cavity but also provide controlled release, ease of administration, enhanced permeation of the drug and protection of the drug from mucosal enzymes. Thus smart polymeric approach can be effectively used for nasal delivery of peptide drugs, central nervous system dugs and hormones. PMID:26664051

  16. Characterization of a primary brown adipocyte culture system derived from human fetal interscapular fat

    PubMed Central

    Seiler, Sarah E; Xu, Dan; Ho, Jia-Pei; Lo, Kinyui Alice; Buehrer, Benjamin M; Ludlow, Y John W; Kovalik, Jean-Paul; Sun, Lei

    2015-01-01

    Brown fat has gained widespread attention as a potential therapeutic target to treat obesity and associated metabolic disorders. Indeed, the anti-obesity potential of multiple targets to stimulate both brown adipocyte differentiation and recruitment have been verified in rodent models. However, their therapeutic potential in humans is unknown due to the lack of a human primary brown adipocyte cell culture system. Likewise, the lack of a well-characterized human model has limited the discovery of novel targets for the activation of human brown fat. To address this current need, we aimed to identify and describe the first primary brown adipocyte cell culture system from human fetal interscapular brown adipose tissue. Pre-adipocytes isolated from non-viable human fetal interscapular tissue were expanded and cryopreserved. Cells were then thawed and plated alongside adult human subcutaneous and omental pre-adipocytes for subsequent differentiation and phenotypic characterization. Interscapular pre-adipocytes in cell culture differentiated into mature adipocytes that were morphologically indistinguishable from the adult white depots. Throughout differentiation, cultured human fetal interscapular adipocytes demonstrated increased expression of classical brown fat markers compared to subcutaneous and omental cells. Further, functional analysis revealed an elevation in fatty acid oxidation as well as maximal and uncoupled oxygen consumption in interscapular brown adipocytes compared to white control cells. These data collectively identify the brown phenotype of these cells. Thus, our primary cell culture system derived from non-viable human fetal interscapular brown adipose tissue provides a valuable tool for the study of human brown adipocyte biology and for the development of anti-obesity therapeutics. PMID:26451287

  17. Phylogenetic analysis of nasal avian schistosomes (Trichobilharzia) from aquatic birds in Mazandaran Province, northern Iran.

    PubMed

    Fakhar, Mahdi; Ghobaditara, Maryam; Brant, Sara V; Karamian, Mehdi; Gohardehi, Shaban; Bastani, Reza

    2016-04-01

    Nasal schistosomes are trematodes in the family Schistosomatidae, many members of which are causative agents of human cercarial dermatitis (HCD). Little is known about the species diversity and distribution of nasal dwelling schistosomes of water birds, particularly in countries outside of Europe; even less is known in countries like Iran. Nasal schistosomes are of particular interest since these species migrate via the central nervous system to the nasal cavity once they penetrate their host. Thus, there must be efforts to determine the incidence of HCD due to nasal schistosomes. HCD outbreaks are reported seasonally in Mazandaran Province, northern Iran, an area well known for rice cultivation leading to increased person contact with water and infected snails. Such places include favorable habitat for both domestic ducks year round, and wild migratory ducks in the winter through spring. Recent reports have detected the presence of both nasal and visceral schistosomes in ducks in this area but with little species characterization. In this study, we examine a diversity of aquatic birds to determine the distribution, prevalence and bird host use of nasal schistosomes. We apply for the first time a molecular identification and phylogenetic analysis of these schistosomes. From 2012 to 2014, the nasal cavity of 508 aquatic birds from Mazandaran Province were examined that included species in Anseriformes, Gruiformes, Charadriiformes and Phoenicopteriformes. Nasal schistosomes were found in 45 (8.9%) birds belonging to Anseriformes (Anas platyrhynchos and Anas clypeata). Phylogenetic analysis of the nuclear internal transcribed spacer 1 rDNA and the mitochondrial cytochrome oxidase1 gene of isolated eggs revealed that all samples grouped in a sister clade to the European Trichobilharzia regenti. However, Trichobilharzia from this study were more similar to a unique haplotype of Trichobilharzia, isolated from the nasals of an A. clypeata in France. The genetic and

  18. Nasal diseases and psychological distress.

    PubMed

    Wang, Deping; Luo, Wenlong

    2016-01-01

    A high rate of ENT doctors were murdered by nasal disordered patients in China recently. It is obviously important and urgent to find out whether there is any potential relationship between nasal diseases (ND) and psychological distress that might contribute to violent behavior. For this purpose, we carried out this literature review. There is a complex relationship between ND and psychiatric distress, which is mainly considered as a bidirectional causal relationship with other controversy opinions. However, most of the previous studies were found to be focused on allergic rhinitis and chronic rhinosinusitis, while reports about other ND were rare. Further study is still needed to uncover the secret aspects in this field, and more attentions need to be paid to other ND. PMID:26095351

  19. Resolvin D1 Polarizes Primary Human Macrophages toward a Proresolution Phenotype through GPR32.

    PubMed

    Schmid, Mattia; Gemperle, Claudio; Rimann, Nicole; Hersberger, Martin

    2016-04-15

    Resolvin D1 (RvD1) was shown to be a potent anti-inflammatory and proresolution lipid mediator in several animal models of inflammation, but its mechanism of action in humans is not clear. We show that the RvD1 receptor GPR32 is present on resting, proinflammatory M(LPS) and alternatively activated primary human M(IL-4) macrophages, whereas TGF-β and IL-6 reduce its membrane expression. Accordingly, stimulation of resting primary human macrophages with 10 nM RvD1 for 48 h maximally reduced the secretion of the proinflammatory cytokines IL-1β and IL-8; abolished chemotaxis to several chemoattractants like chemerin, fMLF, and MCP-1; and doubled the phagocytic activity of these macrophages toward microbial particles. In contrast, these functional changes were not accompanied by surface expression of markers specific for alternatively activated M(IL-4) macrophages. Similar proresolution effects of RvD1 were observed when proinflammatory M(LPS) macrophages were treated with RvD1. In addition, we show that these RvD1-mediated effects are GPR32 dependent because reduction of GPR32 expression by small interfering RNA, TGF-β, and IL-6 treatment ablated these proresolution effects in primary human macrophages. Taken together, our results indicate that in humans RvD1 triggers GPR32 to polarize and repolarize macrophages toward a proresolution phenotype, supporting the role of this mediator in the resolution of inflammation in humans.

  20. Nasal airway responses to nasal continuous positive airway pressure breathing: An in-vivo pilot study.

    PubMed

    White, David E; Bartley, Jim; Shakeel, Muhammad; Nates, Roy J; Hankin, Robin K S

    2016-06-14

    The nasal cycle, through variation in nasal airflow partitioning, allows the upper airway to accommodate the contrasting demands of air conditioning and removal of entrapped air contaminants. The purpose of this study was to investigate the influence of nasal continuous positive airway pressure (nCPAP) breathing has on both nasal airflow partitioning and nasal geometry. Using a custom-made nasal mask, twenty healthy participants had the airflow in each naris measured during normal nasal breathing followed by nCPAP breathing. Eight participants also underwent magnetic resonance imaging (MRI) of the nasal region during spontaneous nasal breathing, and then nCPAP breathing over a range of air pressures. During nCPAP breathing, a simultaneous reduction in airflow through the patent airway together with a corresponding increase in airway flow within the congested nasal airway were observed in sixteen of the twenty participants. Nasal airflow resistance is inversely proportional to airway cross-sectional area. MRI data analysis during nCPAP breathing confirmed airway cross-sectional area reduced along the patent airway while the congested airway experienced an increase in this parameter. During awake breathing, nCPAP disturbs the normal inter-nasal airflow partitioning. This could partially explain the adverse nasal drying symptoms frequently reported by many users of this therapy. PMID:27173595

  1. Primary human cervical carcinoma cells require human papillomavirus E6 and E7 expression for ongoing proliferation

    SciTech Connect

    Magaldi, Thomas G.; Almstead, Laura L.; Bellone, Stefania; Prevatt, Edward G.; Santin, Alessandro D.; DiMaio, Daniel

    2012-01-05

    Repression of human papillomavirus (HPV) E6 and E7 oncogenes in established cervical carcinoma cell lines causes senescence due to reactivation of cellular tumor suppressor pathways. Here, we determined whether ongoing expression of HPV16 or HPV18 oncogenes is required for the proliferation of primary human cervical carcinoma cells in serum-free conditions at low passage number after isolation from patients. We used an SV40 viral vector expressing the bovine papillomavirus E2 protein to repress E6 and E7 in these cells. To enable efficient SV40 infection and E2 gene delivery, we first incubated the primary cervical cancer cells with the ganglioside GM1, a cell-surface receptor for SV40 that is limiting in these cells. Repression of HPV in primary cervical carcinoma cells caused them to undergo senescence, but the E2 protein had little effect on HPV-negative primary cells. These data suggest that E6 and E7 dependence is an inherent property of human cervical cancer cells.

  2. Primary Human Ovarian Epithelial Cancer Cells Broadly Express HER2 at Immunologically-Detectable Levels

    PubMed Central

    Lanitis, Evripidis; Dangaj, Denarda; Hagemann, Ian S.; Song, De-Gang; Best, Andrew; Sandaltzopoulos, Raphael; Coukos, George; Powell, Daniel J.

    2012-01-01

    The breadth of HER2 expression by primary human ovarian cancers remains controversial, which questions its suitability as a universal antigen in this malignancy. To address these issues, we performed extensive HER2 expression analysis on a wide panel of primary tumors as well as established and short-term human ovarian cancer cell lines. Conventional immunohistochemical (IHC) analysis of multiple tumor sites in 50 cases of high-grade ovarian serous carcinomas revealed HER2 overexpression in 29% of evaluated sites. However, more sensitive detection methods including flow cytometry, western blot analysis and q-PCR revealed HER2 expression in all fresh tumor cells derived from primary ascites or solid tumors as well as all established and short-term cultured cancer cell lines. Cancer cells generally expressed HER2 at higher levels than that found in normal ovarian surface epithelial (OSE) cells. Accordingly, genetically-engineered human T cells expressing an HER2-specific chimeric antigen receptor (CAR) recognized and reacted against all established or primary ovarian cancer cells tested with minimal or no reactivity against normal OSE cells. In conclusion, all human ovarian cancers express immunologically-detectable levels of HER2, indicating that IHC measurement underestimates the true frequency of HER2-expressing ovarian cancers and may limit patient access to otherwise clinically meaningful HER2-targeted therapies. PMID:23189165

  3. Humanities-Oriented Accents in Teaching Mathematics to Prospective Primary School Teachers

    ERIC Educational Resources Information Center

    Tabov, Jordan; Gortcheva, Iordanka

    2016-01-01

    Our research includes undergraduate students who major in primary school education. Their academic background is prevailingly in the humanities. This poses specific demands on their mathematics instruction at university. To attract them to their mathematics course and raise its effectiveness, we use a series of activities. Writing assignments…

  4. MiR-191 Regulates Primary Human Fibroblast Proliferation and Directly Targets Multiple Oncogenes.

    PubMed

    Polioudakis, Damon; Abell, Nathan S; Iyer, Vishwanath R

    2015-01-01

    miRNAs play a central role in numerous pathologies including multiple cancer types. miR-191 has predominantly been studied as an oncogene, but the role of miR-191 in the proliferation of primary cells is not well characterized, and the miR-191 targetome has not been experimentally profiled. Here we utilized RNA induced silencing complex immunoprecipitations as well as gene expression profiling to construct a genome wide miR-191 target profile. We show that miR-191 represses proliferation in primary human fibroblasts, identify multiple proto-oncogenes as novel miR-191 targets, including CDK9, NOTCH2, and RPS6KA3, and present evidence that miR-191 extensively mediates target expression through coding sequence (CDS) pairing. Our results provide a comprehensive genome wide miR-191 target profile, and demonstrate miR-191's regulation of primary human fibroblast proliferation.

  5. Risk Factors for Primary Middle East Respiratory Syndrome Coronavirus Illness in Humans, Saudi Arabia, 2014

    PubMed Central

    Alraddadi, Basem M.; Watson, John T.; Almarashi, Abdulatif; Abedi, Glen R.; Turkistani, Amal; Sadran, Musallam; Housa, Abeer; Almazroa, Mohammad A.; Alraihan, Naif; Banjar, Ayman; Albalawi, Eman; Alhindi, Hanan; Choudhry, Abdul Jamil; Meiman, Jonathan G.; Paczkowski, Magdalena; Curns, Aaron; Mounts, Anthony; Feikin, Daniel R.; Marano, Nina; Swerdlow, David L.; Gerber, Susan I.; Hajjeh, Rana

    2016-01-01

    Risk factors for primary Middle East respiratory syndrome coronavirus (MERS-CoV) illness in humans are incompletely understood. We identified all primary MERS-CoV cases reported in Saudi Arabia during March–November 2014 by excluding those with history of exposure to other cases of MERS-CoV or acute respiratory illness of unknown cause or exposure to healthcare settings within 14 days before illness onset. Using a case–control design, we assessed differences in underlying medical conditions and environmental exposures among primary case-patients and 2–4 controls matched by age, sex, and neighborhood. Using multivariable analysis, we found that direct exposure to dromedary camels during the 2 weeks before illness onset, as well as diabetes mellitus, heart disease, and smoking, were each independently associated with MERS-CoV illness. Further investigation is needed to better understand animal-to-human transmission of MERS-CoV. PMID:26692185

  6. Risk Factors for Primary Middle East Respiratory Syndrome Coronavirus Illness in Humans, Saudi Arabia, 2014.

    PubMed

    Alraddadi, Basem M; Watson, John T; Almarashi, Abdulatif; Abedi, Glen R; Turkistani, Amal; Sadran, Musallam; Housa, Abeer; Almazroa, Mohammad A; Alraihan, Naif; Banjar, Ayman; Albalawi, Eman; Alhindi, Hanan; Choudhry, Abdul Jamil; Meiman, Jonathan G; Paczkowski, Magdalena; Curns, Aaron; Mounts, Anthony; Feikin, Daniel R; Marano, Nina; Swerdlow, David L; Gerber, Susan I; Hajjeh, Rana; Madani, Tariq A

    2016-01-01

    Risk factors for primary Middle East respiratory syndrome coronavirus (MERS-CoV) illness in humans are incompletely understood. We identified all primary MERS-CoV cases reported in Saudi Arabia during March-November 2014 by excluding those with history of exposure to other cases of MERS-CoV or acute respiratory illness of unknown cause or exposure to healthcare settings within 14 days before illness onset. Using a case-control design, we assessed differences in underlying medical conditions and environmental exposures among primary case-patients and 2-4 controls matched by age, sex, and neighborhood. Using multivariable analysis, we found that direct exposure to dromedary camels during the 2 weeks before illness onset, as well as diabetes mellitus, heart disease, and smoking, were each independently associated with MERS-CoV illness. Further investigation is needed to better understand animal-to-human transmission of MERS-CoV. PMID:26692185

  7. Neisseria gonorrhoeae phagosomes delay fusion with primary granules to enhance bacterial survival inside human neutrophils.

    PubMed

    Johnson, M Brittany; Criss, Alison K

    2013-08-01

    Symptomatic infection with Neisseria gonorrhoeae (Gc) promotes inflammation driven by polymorphonuclear leucocytes (PMNs, neutrophils), yet some Gc survive PMN exposure during infection. Here we report a novel mechanism of gonococcal resistance to PMNs: Gc phagosomes avoid maturation into phagolysosomes by delayed fusion with primary (azurophilic) granules, which contain antimicrobial components including serine proteases. Reduced phagosome-primary granule fusion was observed in gonorrheal exudates and human PMNs infected ex vivo. Delayed phagosome-granule fusion could be overcome by opsonizing Gc with immunoglobulin. Using bacterial viability dyes along with antibodies to primary granules revealed that Gc survival in PMNs correlated with early residence in primary granule-negative phagosomes. However, when Gc was killed prior to PMN exposure, dead bacteria were also found in primary granule-negative phagosomes. These results suggest that Gc surface characteristics, rather than active bacterial processes, influence phagosome maturation and that Gc death inside PMNs occurs after phagosome-granule fusion. Ectopically increasing primary granule-phagosome fusion, by immunoglobulin opsonization or PMN treatment with lysophosphatidylcholine, reduced intracellular Gc viability, which was attributed in part to serine protease activity. We conclude that one method for Gc to avoid PMN clearance in acute gonorrhoea is by delaying primary granule-phagosome fusion, thus preventing formation of a degradative phagolysosome. PMID:23374609

  8. [Unilateral nasal obstruction in children: Pai syndrome].

    PubMed

    Zanetta, Adrián; Cuestas, Giselle; Oviedo, Maricruz; Tiscorni, Carlos

    2011-10-01

    Unilateral obstruction of the nasal cavity in children is mainly caused by the introduction of foreign bodies further stated with rhinorrhea and fetid odor. Less commonly, it can be traumatic, neoplastic, due to congenital malformation or iatrogenic. Symptoms of congenital intranasal mass may present at birth, or go unnoticed and be a finding in a routine pediatric examination. Patient evaluation should include imaging studies to guide the diagnosis and rule out intracranial extension. A syndrome associated with congenital nasal tumor should be suspected when other abnormalities are present. Pai syndrome is a rare genetic disorder. Its manifestations are craniofacial being congenital nasal polyp his main marker. We present a patient with unilateral nasal respiratory failure secondary to congenital nasal lipoma, with craniofacial anomalies belonging to Pai syndrome. Nasal obstruction was successfully surgically resolved. PMID:22042063

  9. Quantifying and mapping the human appropriation of net primary production in earth's terrestrial ecosystems

    PubMed Central

    Haberl, Helmut; Erb, K. Heinz; Krausmann, Fridolin; Gaube, Veronika; Bondeau, Alberte; Plutzar, Christoph; Gingrich, Simone; Lucht, Wolfgang; Fischer-Kowalski, Marina

    2007-01-01

    Human appropriation of net primary production (HANPP), the aggregate impact of land use on biomass available each year in ecosystems, is a prominent measure of the human domination of the biosphere. We present a comprehensive assessment of global HANPP based on vegetation modeling, agricultural and forestry statistics, and geographical information systems data on land use, land cover, and soil degradation that localizes human impact on ecosystems. We found an aggregate global HANPP value of 15.6 Pg C/yr or 23.8% of potential net primary productivity, of which 53% was contributed by harvest, 40% by land-use-induced productivity changes, and 7% by human-induced fires. This is a remarkable impact on the biosphere caused by just one species. We present maps quantifying human-induced changes in trophic energy flows in ecosystems that illustrate spatial patterns in the human domination of ecosystems, thus emphasizing land use as a pervasive factor of global importance. Land use transforms earth's terrestrial surface, resulting in changes in biogeochemical cycles and in the ability of ecosystems to deliver services critical to human well being. The results suggest that large-scale schemes to substitute biomass for fossil fuels should be viewed cautiously because massive additional pressures on ecosystems might result from increased biomass harvest. PMID:17616580

  10. Quantifying and mapping the human appropriation of net primary production in earth's terrestrial ecosystems.

    PubMed

    Haberl, Helmut; Erb, K Heinz; Krausmann, Fridolin; Gaube, Veronika; Bondeau, Alberte; Plutzar, Christoph; Gingrich, Simone; Lucht, Wolfgang; Fischer-Kowalski, Marina

    2007-07-31

    Human appropriation of net primary production (HANPP), the aggregate impact of land use on biomass available each year in ecosystems, is a prominent measure of the human domination of the biosphere. We present a comprehensive assessment of global HANPP based on vegetation modeling, agricultural and forestry statistics, and geographical information systems data on land use, land cover, and soil degradation that localizes human impact on ecosystems. We found an aggregate global HANPP value of 15.6 Pg C/yr or 23.8% of potential net primary productivity, of which 53% was contributed by harvest, 40% by land-use-induced productivity changes, and 7% by human-induced fires. This is a remarkable impact on the biosphere caused by just one species. We present maps quantifying human-induced changes in trophic energy flows in ecosystems that illustrate spatial patterns in the human domination of ecosystems, thus emphasizing land use as a pervasive factor of global importance. Land use transforms earth's terrestrial surface, resulting in changes in biogeochemical cycles and in the ability of ecosystems to deliver services critical to human well being. The results suggest that large-scale schemes to substitute biomass for fossil fuels should be viewed cautiously because massive additional pressures on ecosystems might result from increased biomass harvest.

  11. [Clinical analysis of nasal sinus mucocele with eye symptoms as main manifestation: 3 cases report].

    PubMed

    Gu Qingjia; Li Jingxian; Fan Jiangang

    2015-04-01

    Endoscopic sinus surgery is effective to nasal sinus mucocele with eye symptoms as main manifestation. It is very importment to raise the awareness of the disease and to prompt imaging examination. Three cases were reviewed. One mucocele was found in the frontal sinus ethmoid sinus,1 in the fronto-ethmoid sinus and 1 in the spheno-ethmoid sinus. All cases were preoperatively diagnosed by CT, MRI or intranasal endoscopy. Nasal sinus mucocele with eye symptoms as main manifestation should be early diagnosed. Endoscopic sinus surgery is a safe and effective method for the treatment of nasal sinus mucocele,and could be the primary choice for it. All cases were treated by nasal endoscopic sinus surgery. The majority of symptoms, such as exophthalmos, epiphora and diplopia, disappeared in all patients. However, vision recovery was observed only in some patients.

  12. Vasomotor rhinitis: neglected cause of nasal congestion.

    PubMed

    Stewart, T W

    1980-01-01

    Vasomotor rhinitis is a condition of chronic nasal congestion which is noninfectious and nonallergic. Its cause is thought to be an imbalance of autonomic control to the nasal mucosa. This disorder is a diagnosis of exclusion, and other causes of chronic nasal obstruction must be considered first. Treatment measures include avoidance of nonspecific stimuli which exacerbate symptoms and, for symptomatic relief, use of oral sympathomimetics. Antihistamine-decongestant combinations may be effective in some patients. Topical vasoconstrictors should not be used.

  13. Lessening the Misery of Nasal Polyps

    PubMed Central

    Martin, G.F.

    1991-01-01

    Nasal polyps are characterized by progressive nasal obstruction, postnasal drip, rhinorrhea, and anosmia. Although their pathogenesis is unknown, key diagnostic signs include appearance, bilaterality, mobility, and insensitivity. Treating allergies and infections is important, while surgery is aimed at maintaining normal nasal structure and improving the airway so that intranasal steroids can be administered to keep the chronic disease under control. ImagesFigure 1Figure 2Figure 3 PMID:21229039

  14. Does oral prednisolone increase the efficacy of subsequent nasal steroids in treating nasal polyposis?

    PubMed Central

    Wongsritrang, Krongthong; Ruttanaphol, Suwalee

    2012-01-01

    Background: Although combined oral and nasal steroid therapy is widely used in nasal polyposis, a subset of patients show an unfavorable therapeutic outcome. This study aimed to evaluate whether oral prednisolone produces any additive effects on subsequent nasal steroid therapy and to evaluate if any clinical variables can predict therapeutic outcome. Methods: Using a 3:2 randomization ratio, 67 patients with nasal polyposis received 50 mg of prednisolone and 47 patients received placebo daily for 2 weeks, followed by mometasone furoate nasal spray (MFNS) at 200 micrograms twice daily for 10 weeks. Clinical response was evaluated by nasal symptom score (NSS), peak expiratory flow index (PEFI), and total nasal polyps score (TNPS). Potential predictor variables were assessed by clinical history, nasal endoscopy, allergy skin test, and sinus radiography. Results: At the end of the 2-week oral steroid phase, the prednisolone group showed significantly greater improvements in all nasal symptoms, nasal airflow, and polyp size than the placebo group. In the nasal steroid phase, while the MFNS maintained the outcome improvements in the prednisolone group, all outcome variables in the placebo group showed continuing improvements. At the end of the nasal steroid phase, there were no significant differences of most outcome improvements between the two groups, except in hyposmia, PEFI, and TNPS (p = 0.049, p = 0.029, and p = 0.005, respectively). In the prednisolone group, patients with polyps grade 3 and endoscopic signs of meatal discharge showed significantly less improvement in total NSS, PEFI, and TNPS than patients with grade 1–2 size and negative metal discharge. Conclusion: In the 12-week treatment evaluation of nasal polyposis, pretreatment with oral steroids had no significant advantage for most nasal symptoms other than earlier relief; however, combined oral and nasal steroid therapy more effectively improved hyposmia, polyps size, and nasal airflow. Polyps size

  15. Safety and efficacy of once-daily treatment with beclomethasone dipropionate nasal aerosol in subjects with perennial allergic rhinitis.

    PubMed

    Meltzer, Eli O; Jacobs, Robert L; LaForce, Craig F; Kelley, C Leith; Dunbar, Stephanie A; Tantry, Sudeesh K

    2012-01-01

    Intranasal corticosteroids are recommended as first-line therapy for the treatment of the symptoms of persistent allergic rhinitis (AR). Since the phase-out of chlorofluorocarbon nasal aerosols, intranasal corticosteroids have been available only as aqueous nasal sprays. This study was designed to assess the efficacy, safety, and quality-of-life benefits of beclomethasone dipropionate (BDP) hydrofluoroalkane nasal aerosol in subjects with perennial AR (PAR). After a 7- to 21-day placebo run-in period, eligible subjects aged ≥12 years with PAR were randomized to 6 weeks of once-daily treatment with BDP nasal aerosol at 320 μg or placebo. Reflective and instantaneous total nasal symptom scores (rTNSS and iTNSS, respectively), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score, and physician-assessed total nasal symptom score were evaluated. The primary end point was change from baseline in average morning (A.M.) and evening (P.M.) subject-reported rTNSS over the 6-week treatment period. Safety and tolerability were also assessed. Treatment with BDP nasal aerosol showed significantly greater improvement in average A.M. and P.M. rTNSS compared with placebo (mean treatment difference, -0.84; 95% confidence interval, -1.2, -0.5; p < 0.001). Greater improvements in rTNSS were reported as early as day 1 and were maintained throughout the 6-week treatment period with the exception of day 2. Greater improvements were seen for all four individual nasal symptoms (nasal congestion, nasal itching, rhinorrhea, and sneezing) with BDP nasal aerosol compared with placebo. Similarly, significant improvements were seen in average A.M. and P.M. iTNSS (p < 0.001) and RQLQ score (p = 0.001) with BDP nasal aerosol compared with placebo. In addition, BDP nasal aerosol treatment was well tolerated, and its safety profile was comparable to that of placebo. This clinical study indicated that treatment with BDP nasal aerosol provides statistically significant and clinically

  16. Nasal Myiasis in Hinduism and Contemporary Otorhinolaryngology.

    PubMed

    Bosmia, Anand N; Zimmermann, Terence M; Griessenauer, Christoph J; Shane Tubbs, R; Rosenthal, Eben L

    2014-01-01

    Various case reports on nasal myiasis written during the 1990s and 2000s state that nasal myiasis, which is known as peenash among South Asian natives, is a form of divine punishment in Hindu mythology, but do not provide citations from Hindu scriptures that would suggest this interpretation. This paper aims to discuss the phenomenon of peenash in a historical context by examining medical literature written during the nineteenth and early twentieth centuries, to identify Hindu texts contributing to the belief of some Hindus that nasal myiasis is a form of divine punishment, and to provide an overview of contemporary treatment for and management of nasal myiasis. PMID:24385004

  17. Endoscopic laser treatment for pediatric nasal allergy.

    PubMed

    Araki, S; Suzuki, N; Sato, H; Yamaguchi, T; Fujita, H; Umezawa, Y; Suzuki, M

    2000-01-01

    We have used the carbon dioxide (CO(2)) laser and the gallium aluminium arsenide (GaAlAs) diode laser with flexible fiber delivery instruments for vaporization of the inferior nasal turbinate in pediatric patients since 1993. Under endoscopic control, the whole inferior turbinate was vaporized by 5-10 W laser output delivered via an optical fiber. Generally, the nasal mucosa changes into normal mucosa, and symptoms improve. The greatest symptomatic improvement was in nasal obstruction. The results obtained by the two laser devices were similar although they have had different characteristics. Endoscopic laser surgery is effective in the treatment of pediatric nasal allergy.

  18. Multidimensional Genome-wide Analyses Show Accurate FVIII Integration by ZFN in Primary Human Cells

    PubMed Central

    Sivalingam, Jaichandran; Kenanov, Dimitar; Han, Hao; Nirmal, Ajit Johnson; Ng, Wai Har; Lee, Sze Sing; Masilamani, Jeyakumar; Phan, Toan Thang; Maurer-Stroh, Sebastian; Kon, Oi Lian

    2016-01-01

    Costly coagulation factor VIII (FVIII) replacement therapy is a barrier to optimal clinical management of hemophilia A. Therapy using FVIII-secreting autologous primary cells is potentially efficacious and more affordable. Zinc finger nucleases (ZFN) mediate transgene integration into the AAVS1 locus but comprehensive evaluation of off-target genome effects is currently lacking. In light of serious adverse effects in clinical trials which employed genome-integrating viral vectors, this study evaluated potential genotoxicity of ZFN-mediated transgenesis using different techniques. We employed deep sequencing of predicted off-target sites, copy number analysis, whole-genome sequencing, and RNA-seq in primary human umbilical cord-lining epithelial cells (CLECs) with AAVS1 ZFN-mediated FVIII transgene integration. We combined molecular features to enhance the accuracy and activity of ZFN-mediated transgenesis. Our data showed a low frequency of ZFN-associated indels, no detectable off-target transgene integrations or chromosomal rearrangements. ZFN-modified CLECs had very few dysregulated transcripts and no evidence of activated oncogenic pathways. We also showed AAVS1 ZFN activity and durable FVIII transgene secretion in primary human dermal fibroblasts, bone marrow- and adipose tissue-derived stromal cells. Our study suggests that, with close attention to the molecular design of genome-modifying constructs, AAVS1 ZFN-mediated FVIII integration in several primary human cell types may be safe and efficacious. PMID:26689265

  19. Consistency of the Proteome in Primary Human Keratinocytes With Respect to Gender, Age, and Skin Localization*

    PubMed Central

    Sprenger, Adrian; Weber, Sebastian; Zarai, Mostafa; Engelke, Rudolf; Nascimento, Juliana M.; Gretzmeier, Christine; Hilpert, Martin; Boerries, Melanie; Has, Cristina; Busch, Hauke; Bruckner-Tuderman, Leena; Dengjel, Jörn

    2013-01-01

    Keratinocytes account for 95% of all cells of the epidermis, the stratified squamous epithelium forming the outer layer of the skin, in which a significant number of skin diseases takes root. Immortalized keratinocyte cell lines are often used as research model systems providing standardized, reproducible, and homogenous biological material. Apart from that, primary human keratinocytes are frequently used for medical studies because the skin provides an important route for drug administration and is readily accessible for biopsies. However, comparability of these cell systems is not known. Cell lines may undergo phenotypic shifts and may differ from the in vivo situation in important aspects. Primary cells, on the other hand, may vary in biological functions depending on gender and age of the donor and localization of the biopsy specimen. Here we employed metabolic labeling in combination with quantitative mass spectrometry-based proteomics to assess A431 and HaCaT cell lines for their suitability as model systems. Compared with cell lines, comprehensive profiling of the primary human keratinocyte proteome with respect to gender, age, and skin localization identified an unexpected high proteomic consistency. The data were analyzed by an improved ontology enrichment analysis workflow designed for the study of global proteomics experiments. It enables a quick, comprehensive and unbiased overview of altered biological phenomena and links experimental data to literature. We guide through our workflow, point out its advantages compared with other methods and apply it to visualize differences of cell lines compared with primary human keratinocytes. PMID:23722187

  20. The psychiatric sequelae of human rights violations: a challenge for primary health care.

    PubMed

    Zungu-Dirwayi, Nompumelelo; Kaminer, Debra; Mbanga, Irene; Stein, Dan J

    2004-04-01

    High rates of psychiatric morbidity have been documented in survivors of gross human rights abuses. Nevertheless, there has been relatively little focus on such patients in the context of primary care medicine. A sample of 134 survivors of gross human rights violations was assessed using a structured interview to determine exposure to violations and psychiatric status. In addition, psychiatric treatment history was probed with an open-ended interview. The study found that of the 95 of 134 (72%) participants who were assessed and found to have a current psychiatric diagnosis, only three were receiving treatment for such a disorder. Many subjects had presented to primary care clinics with somatic symptoms and had been prescribed benzodiazepines. Reasons for not reporting trauma or not seeking treatment included issues revolving around fear and mistrust, privacy and confidentiality, re-experiencing the trauma, and lack of awareness. Misdiagnosis and ineffective treatment of survivors of human rights abuses are likely to pose a significant drain on primary care resources. Accurate diagnosis and appropriate treatment are important challenges in primary care settings.

  1. Effective Connectivity within Human Primary Visual Cortex Predicts Interindividual Diversity in Illusory Perception

    PubMed Central

    Schwarzkopf, D. Samuel; Lutti, Antoine; Li, Baojuan; Kanai, Ryota; Rees, Geraint

    2013-01-01

    Visual perception depends strongly on spatial context. A classic example is the tilt illusion where the perceived orientation of a central stimulus differs from its physical orientation when surrounded by tilted spatial contexts. Here we show that such contextual modulation of orientation perception exhibits trait-like interindividual diversity that correlates with interindividual differences in effective connectivity within human primary visual cortex. We found that the degree to which spatial contexts induced illusory orientation perception, namely, the magnitude of the tilt illusion, varied across healthy human adults in a trait-like fashion independent of stimulus size or contrast. Parallel to contextual modulation of orientation perception, the presence of spatial contexts affected effective connectivity within human primary visual cortex between peripheral and foveal representations that responded to spatial context and central stimulus, respectively. Importantly, this effective connectivity from peripheral to foveal primary visual cortex correlated with interindividual differences in the magnitude of the tilt illusion. Moreover, this correlation with illusion perception was observed for effective connectivity under tilted contextual stimulation but not for that under iso-oriented contextual stimulation, suggesting that it reflected the impact of orientation-dependent intra-areal connections. Our findings revealed an interindividual correlation between intra-areal connectivity within primary visual cortex and contextual influence on orientation perception. This neurophysiological-perceptual link provides empirical evidence for theoretical proposals that intra-areal connections in early visual cortices are involved in contextual modulation of visual perception. PMID:24285885

  2. Nasal and Oral Consonant Similarity in Speech Errors: Exploring Parallels with Nasal Consonant Harmony

    ERIC Educational Resources Information Center

    Walker, Rachel

    2007-01-01

    Previous research has found that "similar" sounds interact in phonological nasal consonant harmony, wherein certain consonants become nasals when the word contains a nasal (e.g., Kikongo: /-kun-idi/ [right arrow] [-kun-ini] "planted"). Across languages, stops and approximants are chiefly affected, especially voiced consonants and ones that match…

  3. Visualization of nasal airflow patterns in a patient affected with atrophic rhinitis using particle image velocimetry

    NASA Astrophysics Data System (ADS)

    Garcia, G. J. M.; Mitchell, G.; Bailie, N.; Thornhill, D.; Watterson, J.; Kimbell, J. S.

    2007-10-01

    The relationship between airflow patterns in the nasal cavity and nasal function is poorly understood. This paper reports an experimental study of the interplay between symptoms and airflow patterns in a patient affected with atrophic rhinitis. This pathology is characterized by mucosal dryness, fetor, progressive atrophy of anatomical structures, a spacious nasal cavity, and a paradoxical sensation of nasal congestion. A physical replica of the patient's nasal geometry was made and particle image velocimetry (PIV) was used to visualize and measure the flow field. The nasal replica was based on computed tomography (CT) scans of the patient and was built in three steps: three-dimensional reconstruction of the CT scans; rapid prototyping of a cast; and sacrificial use of the cast to form a model of the nasal passage in clear silicone. Flow patterns were measured by running a water-glycerol mixture through the replica and evaluating the displacement of particles dispersed in the liquid using PIV. The water-glycerol flow rate used corresponded to an air flow rate representative of a human breathing at rest. The trajectory of the flow observed in the left passage of the nose (more affected by atrophic rhinitis) differed markedly from what is considered normal, and was consistent with patterns of epithelial damage observed in cases of the condition. The data are also useful for validation of computational fluid dynamics predictions.

  4. Unsteady flow in the nasal cavity with high flow therapy measured by stereoscopic PIV

    NASA Astrophysics Data System (ADS)

    Spence, C. J. T.; Buchmann, N. A.; Jermy, M. C.

    2012-03-01

    Nasal high flow (NHF) cannulae are used to deliver heated and humidified air to patients at steady flows ranging from 5 to 50 l/min. In this study, the flow velocities in the nasal cavity across the complete respiratory cycle during natural breathing and with NHF has been mapped in vitro using time-resolved stereoscopic particle image velocimetry (SPIV). An anatomically accurate silicone resin model of a complete human nasal cavity was constructed using CT scan data and rapid prototyping. Physiological breathing waveforms were reproduced in vitro using Reynolds and Womersley number matching and a piston pump driven by a ball screw and stepper motor. The flow pattern in the nasal cavity with NHF was found to differ significantly from natural breathing. Velocities of 2.4 and 3.3 ms-1 occurred in the nasal valve during natural breathing at peak expiration and inspiration, respectively; however, on expiration, the maximum velocity of 3.8 ms-1 occurred in the nasopharynx. At a cannula flow rate of 30 l/min, maximal velocities of 13.6 and 16.5 ms-1 at peak expiration and inspiration, respectively, were both located in the cannula jet within the nasal valve. Results are presented that suggest the quasi-steady flow assumption is invalid in the nasal cavity during natural breathing; however, it was valid with NHF. Cannula flow has been found to continuously flush the nasopharyngeal dead space, which may enhance carbon dioxide removal and increase oxygen fraction.

  5. Maintenance of Hepatic Functions in Primary Human Hepatocytes Cultured on Xeno-Free and Chemical Defined Human Recombinant Laminins.

    PubMed

    Watanabe, Masaaki; Zemack, Helen; Johansson, Helene; Hagbard, Louise; Jorns, Carl; Li, Meng; Ellis, Ewa

    2016-01-01

    Refined methods for maintaining specific functions of isolated hepatocytes under xeno-free and chemical defined conditions is of great importance for the development of hepatocyte research and regenerative therapy. Laminins, a large family of heterotrimeric basement membrane adhesion proteins, are highly cell and tissue type specific components of the extracellular matrix and strongly influence the behavior and function of associated cells and/or tissues. However, detailed biological functions of many laminin isoforms are still to be evaluated. In this study, we determined the distribution of laminin isoforms in human liver tissue and isolated primary human hepatocytes by western blot analysis, and investigated the efficacy of different human recombinant laminin isoforms on hepatic functions during culture. Protein expressions of laminin-chain α2, α3, α4, β1, β3, γ1, and γ2 were detected in both isolated human hepatocytes and liver tissue. No α1 and α5 expression could be detected in liver tissue or hepatocytes. Hepatocytes were isolated from five different individual livers, and cultured on human recombinant laminin isoforms -111, -211, -221, -332, -411, -421, -511, and -521 (Biolamina AB), matrigel (extracted from Engelbreth-Holm-Swarm sarcoma), or collagen type IV (Collagen). Hepatocytes cultured on laminin showed characteristic hexagonal shape in a flat cell monolayer. Viability, double stranded DNA concentration, and Ki67 expression for hepatocytes cultured for six days on laminin were comparable to those cultured on EHS and Collagen. Hepatocytes cultured on laminin also displayed production of human albumin, alpha-1-antitrypsin, bile acids, and gene expression of liver-enriched factors, such as hepatocyte nuclear factor 4 alpha, glucose-6-phosphate, cytochrome P450 3A4, and multidrug resistance-associated protein 2. We conclude that all forms of human recombinant laminin tested maintain cell viability and liver-specific functions of primary human

  6. Maintenance of Hepatic Functions in Primary Human Hepatocytes Cultured on Xeno-Free and Chemical Defined Human Recombinant Laminins

    PubMed Central

    Watanabe, Masaaki; Zemack, Helen; Johansson, Helene; Hagbard, Louise; Jorns, Carl; Li, Meng; Ellis, Ewa

    2016-01-01

    Refined methods for maintaining specific functions of isolated hepatocytes under xeno-free and chemical defined conditions is of great importance for the development of hepatocyte research and regenerative therapy. Laminins, a large family of heterotrimeric basement membrane adhesion proteins, are highly cell and tissue type specific components of the extracellular matrix and strongly influence the behavior and function of associated cells and/or tissues. However, detailed biological functions of many laminin isoforms are still to be evaluated. In this study, we determined the distribution of laminin isoforms in human liver tissue and isolated primary human hepatocytes by western blot analysis, and investigated the efficacy of different human recombinant laminin isoforms on hepatic functions during culture. Protein expressions of laminin-chain α2, α3, α4, β1, β3, γ1, and γ2 were detected in both isolated human hepatocytes and liver tissue. No α1 and α5 expression could be detected in liver tissue or hepatocytes. Hepatocytes were isolated from five different individual livers, and cultured on human recombinant laminin isoforms -111, -211, -221, -332, -411, -421, -511, and -521 (Biolamina AB), matrigel (extracted from Engelbreth-Holm-Swarm sarcoma), or collagen type IV (Collagen). Hepatocytes cultured on laminin showed characteristic hexagonal shape in a flat cell monolayer. Viability, double stranded DNA concentration, and Ki67 expression for hepatocytes cultured for six days on laminin were comparable to those cultured on EHS and Collagen. Hepatocytes cultured on laminin also displayed production of human albumin, alpha-1-antitrypsin, bile acids, and gene expression of liver-enriched factors, such as hepatocyte nuclear factor 4 alpha, glucose-6-phosphate, cytochrome P450 3A4, and multidrug resistance-associated protein 2. We conclude that all forms of human recombinant laminin tested maintain cell viability and liver-specific functions of primary human

  7. Thrombopoietin receptor expression in human cancer cell lines and primary tissues.

    PubMed

    Columbyova, L; Loda, M; Scadden, D T

    1995-08-15

    c-mpl is the receptor for the recently identified megakaryocyte growth and differentiation factor thrombopoietin. Thrombopoietin has been shown to be capable of raising platelet counts in animals and is about to enter clinical trials in humans. In anticipation of its likely use in the care of patients receiving cancer chemotherapy, we evaluated the expression of human c-mpl by reverse transcription PCR on 39 human cell lines and 20 primary human tissue samples derived from both normal and malignant sources. c-mpl transcripts were found in all megakaryocytic cell lines tested (CMK, CMK-2B, CMK-2D, SO, and DAMI), the CD34+ leukemia cell line KMT-2, and a hepatocellular carcinoma cell line (Hep3B). Among primary tissues, fetal liver cells and brain had detectable levels of c-mpl message, and among primary tumors, none were found to express c-mpl. These data support the conclusion that c-mpl has restricted expression that is primarily, but not exclusively, related to megakaryocytopoiesis. These observations suggest that thrombopoietin is unlikely to have direct effects on other malignant or normal tissue should it have a clinical role in the treatment of chemotherapy-induced thrombocytopenia. PMID:7627956

  8. Retroviral-mediated gene transfer and expression of human phenylalanine hydroxylase in primary mouse hepatocytes

    SciTech Connect

    Peng, H.; Armentano, D.; Mackenzie-Graham, L.; Shen, R.F.; Darlington, G.; Ledley, F.D.; Woo, S.L.C. )

    1988-11-01

    Genetic therapy for phenylketonuria (severe phenylalanine hydroxylase deficiency) may require introduction of a normal phenylalanine hydroxylase gene into hepatic cells of patients. The authors report development of a recombinant retrovirus based on the N2 vector for gene transfer and expression of human phenylalanine hydroxylase cDNA in primary mouse hepatocytes. This construct contains an internal promoter of the human {alpha}{sub 1}-antitrypsin gene driving transcription of the phenylalanine hydroxylase cDNA. Primary mouse hepatocytes were isolated from newborn mice, infected with the recombinant virus, and selected for expression of the neomycin-resistance gene. Hepatocytes transformed with the recombinant virus contained high levels of human phenylalanine hydroxylase mRNA transcripts originating from the retroviral and internal promoters. These results demonstrate that the transcriptional regulatory elements of the {alpha}{sub 1} antitrypsin gene retain their tissue-specific function in the recombinant provirus and establish a method for efficient transfer and high-level expression of human phenylalanine hydroxylase in primary hepatocytes.

  9. Three-Dimensional Mapping of Ozone-Induced Injury in the Nasal Airways of Monkeys Using Magnetic Resonance Imaging and Morphometric Techniques

    SciTech Connect

    Carey, Stephen A.; Minard, Kevin R.; Trease, Lynn L.; Wagner, James G.; Garcia, Guilherme M.; Ballinger, Carol A.; Kimbell, Julia; Plopper, Charles G.; Corley, Rick A.; Postlewait, Ed; Harkema, Jack R.

    2007-03-01

    ABSTRACT Age-related changes in gross and microscopic structure of the nasal cavity can alter local tissue susceptibility as well as the dose of inhaled toxicant delivered to susceptible sites. This article describes a novel method for the use of magnetic resonance imaging, 3-dimensional airway modeling, and morphometric techniques to characterize the distribution and magnitude of ozone-induced nasal injury in infant monkeys. Using this method, we are able to generate age-specific, 3-dimensional, epithelial maps of the nasal airways of infant Rhesus macaques. The principal nasal lesions observed in this primate model of ozone-induced nasal toxicology were neutrophilic rhinitis, along with necrosis and exfoliation of the epithelium lining the anterior maxilloturbinate. These lesions, induced by acute or cyclic (episodic) exposures, were examined by light microscopy, quantified by morphometric techniques, and mapped on 3-dimensional models of the nasal airways. Here, we describe the histopathologic, imaging, and computational biology methods developed to efficiently characterize, localize, quantify, and map these nasal lesions. By combining these techniques, the location and severity of the nasal epithelial injury were correlated with epithelial type, nasal airway geometry, and local biochemical and molecular changes on an individual animal basis. These correlations are critical for accurate predictive modeling of exposure-dose-response relationships in the nasal airways, and subsequent extrapolation of nasal findings in animals to humans for developing risk assessment.

  10. Marine Collagen Scaffolds for Nasal Cartilage Repair: Prevention of Nasal Septal Perforations in a New Orthotopic Rat Model Using Tissue Engineering Techniques

    PubMed Central

    Bermueller, Christian; Elsaesser, Alexander F.; Sewing, Judith; Baur, Nina; von Bomhard, Achim; Scheithauer, Marc; Notbohm, Holger; Rotter, Nicole

    2013-01-01

    Autologous grafts are frequently needed for nasal septum reconstruction. Because they are only available in limited amounts, there is a need for new cartilage replacement strategies. Tissue engineering based on the use of autologous chondrocytes and resorbable matrices might be a suitable option. So far, an optimal material for nasal septum reconstruction has not been identified. The aim of our study was to provide the first evaluation of marine collagen for use in nasal cartilage repair. First, we studied the suitability of marine collagen as a cartilage replacement matrix in the context of in vitro three dimensional cultures by analyzing cell migration, cytotoxicity, and extracellular matrix formation using human and rat nasal septal chondrocytes. Second, we worked toward developing a suitable orthotopic animal model for nasal septum repair, while simultaneously evaluating the biocompatibility of marine collagen. Seeded and unseeded scaffolds were transplanted into nasal septum defects in an orthotopic rat model for 1, 4, and 12 weeks. Explanted scaffolds were histologically and immunohistochemically evaluated. Scaffolds did not induce any cytotoxic reactions in vitro. Chondrocytes were able to adhere to marine collagen and produce cartilaginous matrix proteins, such as collagen type II. Treating septal cartilage defects in vivo with seeded and unseeded scaffolds led to a significant reduction in the number of nasal septum perforations compared to no replacement. In summary, we demonstrated that marine collagen matrices provide excellent properties for cartilage tissue engineering. Marine collagen scaffolds are able to prevent septal perforations in an autologous, orthotopic rat model. This newly described experimental surgical procedure is a suitable way to evaluate new scaffold materials for their applicability in the context of nasal cartilage repair. PMID:23621795

  11. Nasal obstruction in neonates and infants.

    PubMed

    Chirico, G; Beccagutti, F

    2010-10-01

    The main functions of the nasal airway are respiration and olfaction. The nose and sinuses condition air before reaching the lower respiratory tract by providing almost 100% humidification, warming, filtering and trapping of foreign particles. The airway epithelium contributes to the host defense system. Any alteration of this clearance system may produce significant problems, particularly in neonates, who are obligate nasal breathers until they are at least two months old. Nasal obstruction, and the inability to remove nasal secretion by nose blowing, may have serious consequences, such as respiratory distress or discomfort, altered sleep cycle, increased risk of obstructive apnoea and feeding difficulties. Most cases of nasal obstruction in neonates and infants are due to generalized nasal airway obstruction associated with neonatal rhinitis, viral upper respiratory tract infections, and possibly milk/soy allergies. Saline nasal lavage is recommended as an adjunct therapy for rhinosinusitis and allergic rhinitis, and in most cases of nasal congestion or obstruction in newborns, infants and children. In two recent experiences, was deemed to be the Narhinel method safe and effective for treatment of nasal congestion in babies with viral infections of the upper respiratory tract, or for the prevention of acute otitis media (AOM) and acute rhinosinusitis (AR) in children. Due to the efficacy, ease of use, tolerability and the lack of alternative medications in children younger than 12 years of age, nasal irrigation with physiological saline solution, followed by gentle aspiration, represent an effective method for the prevention and control of nasal congestion or obstruction in term or preterm neonates, infants and children.

  12. Numbered nasal discs for waterfowl

    USGS Publications Warehouse

    Bartonek, J.C.; Dane, C.W.

    1964-01-01

    Numbered nasal discs were successfully used in studies requiring large numbers of individually marked waterfowl. The procedure for constructing these discs is outlined. Blue-winged teal (Anas discors) with 5/8-inch discs, and canvasback (Aythya valisineria) and redhead (A. americana) with 3/4-inch discs can be individually identified up to 50 and 80 yards, respectively, with a gunstock-mounted, 20-power spotting scope. The particular value of these markers is their durability, the number of combinations possible, and the apparent absence of behavioral or mortality influence among such species as the blue-winged teal.

  13. High-affinity nasal extraction of vinyl acetate vapor is carboxylesterase dependent.

    PubMed

    Bogdanffy, M S; Manning, L A; Sarangapani, R

    1999-10-01

    Vinyl acetate induces nasal tumors in rats, but not mice. Species differences in airflow patterns, physiology, and biochemistry complicate extrapolation of nasal dosimetry from rats to humans. Physiologically based pharmacokinetic modeling of vinyl acetate dosimetry in rats suggested the presence of a saturable metabolic removal pathway in rat nasal mucus. We explored the possibility that this pathway is either a cytochrome P-450 2E1 (CYP2E1) or high-affinity carboxylesterase. Nasal extraction of vinyl acetate vapor (150 ppm) was measured in the surgically isolated nasal cavity of anesthetized rats. Vinyl acetate (150 ppm) was extracted with 73% efficiency in controls. Pretreatment of rats with the CYP2E1 inhibitor diallyl sulfide (DAS) had no effect on extraction, despite significantly reducing CYP2E1 activity. Pretreatment with bis(p-nitrophenyl) phosphate (BNPP), a carboxylesterase inhibitor, reduced extraction to approximately 41%. Acetaldehyde production was similarly unaffected by DAS but was reduced to 55% of control by BNPP. Rat nasal mucus carboxylesterase activity had a K(m) value (32 microM) similar, within a factor of 2, to the value predicted by the physiologically based model, although V(max) was significantly lower than the model prediction. Histochemical observations support the inference that the high-affinity carboxylesterase is bound to the luminal plasma membrane of nasal tissue and is not readily released by nasal lavage, providing an explanation for the low V(max) of the lavage enzyme. This high-affinity isoenzyme could be important in the removal of odorants from the sensory cell-rich nasal olfactory epithelium.

  14. What is normal nasal airflow? A computational study of 22 healthy adults

    PubMed Central

    Zhao, Kai; Jiang, Jianbo

    2014-01-01

    Objective Nasal airflow is essential for functioning of the human nose. Given individual variation in nasal anatomy, there is yet no consensus what constitutes normal nasal airflow patterns. We attempt to obtain such information that is essential to differentiate disease-related variations. Methods Computational fluid dynamics (CFD) simulated nasal airflow in 22 healthy subjects during resting breathing. Streamline patterns, airflow distributions, velocity profiles, pressure, wall stress, turbulence, and vortical flow characteristics under quasi-steady state were analyzed. Patency ratings, acoustically measured minimum cross-sectional area (MCA), and rhinomanometric nasal resistance (NR) were examined for potential correlations with morphological and airflow-related variables. Results Common features across subjects included: >50% total pressure-drop reached near the inferior turbinate head; wall shear stress, NR, turbulence energy, and vorticity were lower in the turbinate than in the nasal valve region. However, location of the major flow path and coronal velocity distributions varied greatly across individuals. Surprisingly, on average, more flow passed through the middle than the inferior meatus and correlated with better patency ratings (r=-0.65, p<0.01). This middle flow percentage combined with peak post-vestibule nasal heat loss and MCA accounted for >70% of the variance in subjective patency ratings and predicted patency categories with 86% success. Nasal index correlated with forming of the anterior dorsal vortex. Expected for resting breathing, the functional impact for local and total turbulence, vorticity, and helicity was limited. As validation, rhinomanometric NR significantly correlated with CFD simulations (r=0.53, p<0.01). Conclusion Significant variations of nasal airflow found among healthy subjects; Key features may have clinically relevant applications. PMID:24664528

  15. Acute effect of glucan-spiked office dust on nasal and pulmonary inflammation in guinea pigs.

    PubMed

    Straszek, S P; Adamcakova-Dodd, A; Metwali, N; Pedersen, O F; Sigsgaard, T; Thorne, P S

    2007-11-01

    The acute effects of pure inhaled glucan on respiratory inflammation remain inconclusive and not sufficiently examined with regards to the simultaneous interaction of glucan, endotoxin (lipopolysaccharide, LPS), and house dust in airway inflammation. This study aims at determining effects of simultaneous exposure to office dust and glucan on nasal and pulmonary inflammation. This is relevant for humans with occupational exposure in waste handling and farming and buildings with mold problems. Office dust collected from Danish offices was spiked with 1% (1-3)-beta-glucan (curdlan). Guinea pig nasal cavity volume was measured by acoustic rhinometry (AR) and animals were exposed by inhalation for 4 h to curdlan-spiked dust, unspiked dust, purified air (negative controls), or LPS (positive controls). After exposure (+5 h) or the following day (+18 h), measurements were repeated by AR and followed by bronchoalveolar lavage (BAL). Total and differential cell counts, interleukin (IL)-8 in BAL fluid, and change in nasal volume were compared between groups. A 5-10% increase in nasal volume was seen for all groups including clean air except for a significant 5% decrease for spiked-dust inhalation (+18 h). No marked differences were observed in BAL cells or IL-8 except in LPS-exposed controls. The delayed decrease of nasal cavity volume after exposure to glucan spiked dust suggests a slow effect on the upper airways for curdlan and office dust together, though no pulmonary response or direct signs of inflammation were observed. Glucan-spiked office dust exposures produced a delayed nasal subacute congestion in guinea pigs compared to office dust alone, but extrapolated to nasal congestion in humans, paralleling the nasal congestion seen in human volunteers exposed to the same dust, this may not have clinical importance. PMID:17966063

  16. Pharmacologic inhibition of tpl2 blocks inflammatory responses in primary human monocytes, synoviocytes, and blood.

    PubMed

    Hall, J Perry; Kurdi, Yahya; Hsu, Sang; Cuozzo, John; Liu, Julie; Telliez, Jean-Baptiste; Seidl, Katherine J; Winkler, Aaron; Hu, Yonghan; Green, Neal; Askew, G Roger; Tam, Steve; Clark, James D; Lin, Lih-Ling

    2007-11-16

    Tumor necrosis factor alpha (TNFalpha) is a pro-inflammatory cytokine that controls the initiation and progression of inflammatory diseases such as rheumatoid arthritis. Tpl2 is a MAPKKK in the MAPK (i.e. ERK) pathway, and the Tpl2-MEK-ERK signaling pathway is activated by the pro-inflammatory mediators TNFalpha, interleukin (IL)-1beta, and bacterial endotoxin (lipopolysaccharide (LPS)). Moreover, Tpl2 is required for TNFalpha expression. Thus, pharmacologic inhibition of Tpl2 should be a valid approach to therapeutic intervention in the pathogenesis of rheumatoid arthritis and other inflammatory diseases in humans. We have developed a series of highly selective and potent Tpl2 inhibitors, and in the present study we have used these inhibitors to demonstrate that the catalytic activity of Tpl2 is required for the LPS-induced activation of MEK and ERK in primary human monocytes. These inhibitors selectively target Tpl2 in these cells, and they block LPS- and IL-1beta-induced TNFalpha production in both primary human monocytes and human blood. In rheumatoid arthritis fibroblast-like synoviocytes these inhibitors block ERK activation, cyclooxygenase-2 expression, and the production of IL-6, IL-8, and prostaglandin E(2), and the matrix metalloproteinases MMP-1 and MMP-3. Taken together, our results show that inhibition of Tpl2 in primary human cell types can decrease the production of TNFalpha and other pro-inflammatory mediators during inflammatory events, and they further support the notion that Tpl2 is an appropriate therapeutic target for rheumatoid arthritis and other human inflammatory diseases. PMID:17848581

  17. Telomerase-mediated life-span extension of human primary fibroblasts by human artificial chromosome (HAC) vector

    SciTech Connect

    Shitara, Shingo; Kakeda, Minoru; Nagata, Keiko; Hiratsuka, Masaharu; Sano, Akiko; Osawa, Kanako; Okazaki, Akiyo; Katoh, Motonobu; Kazuki, Yasuhiro; Oshimura, Mitsuo; Tomizuka, Kazuma

    2008-05-09

    Telomerase-mediated life-span extension enables the expansion of normal cells without malignant transformation, and thus has been thought to be useful in cell therapies. Currently, integrating vectors including the retrovirus are used for human telomerase reverse transcriptase (hTERT)-mediated expansion of normal cells; however, the use of these vectors potentially causes unexpected insertional mutagenesis and/or activation of oncogenes. Here, we established normal human fibroblast (hPF) clones retaining non-integrating human artificial chromosome (HAC) vectors harboring the hTERT expression cassette. In hTERT-HAC/hPF clones, we observed the telomerase activity and the suppression of senescent-associated SA-{beta}-galactosidase activity. Furthermore, the hTERT-HAC/hPF clones continued growing beyond 120 days after cloning, whereas the hPF clones retaining the silent hTERT-HAC senesced within 70 days. Thus, hTERT-HAC-mediated episomal expression of hTERT allows the extension of the life-span of human primary cells, implying that gene delivery by non-integrating HAC vectors can be used to control cellular proliferative capacity of primary cultured cells.

  18. Antiadipogenic properties of retinol in primary cultured differentiating human adipocyte precursor cells.

    PubMed

    Garcia, E; Lacasa, D; Agli, B; Giudicelli, Y; Castelli, D

    2000-04-01

    The aim of this study was to investigate the effect of retinol on the human adipose conversion process using primary cultured human adipocyte precursor cells. When these cells were seeded in a medium containing retinol (concentrations ranging from 3.5 nM to 3.5 muM), cell proliferation was slightly inhibited by high concentrations of retinol, as demonstrated by cell counting and [(3)H]-thymidine incorporation. Moreover, the differentiation capacities of these cells were markedly and dose-dependently inhibited by retinol, as shown by the reduced expression of the lipogenic enzyme glycerol-3-phosphate dehydrogenase and by microscopic morphological analysis. These results strongly suggest that retinol, by inhibiting the ability of human preadipocytes to convert into mature adipocytes, could be of potential interest in the prevention of human adipose tissue development in general and of cellulitis in particular. PMID:18503465

  19. Rearrangement of a common cellular DNA domain on chromosome 4 in human primary liver tumors

    SciTech Connect

    Pasquinelli, C.; Garreau, F.; Bougueleret, L.; Cariani, E.; Thiers, V.; Croissant, O.; Hadchouel, M.; Tiollais, P.; Brechot, C. ); Grzeschik, K.H. )

    1988-02-01

    Hepatitis B virus (HBV) DNA integration has been shown to occur frequently in human hepatocellular carcinomas. The authors have investigated whether common cellular DNA domains might be rearranged, possibly by HBV integration, in human primary liver tumors. Unique cellular DNA sequences adjacent to an HBV integration site were isolated from a patient with hepatitis B surface antigen-positive hepatocellular carcinoma. These probes detected rearrangement of this cellular region of chromosomal DNA in 3 of 50 additional primary liver tumors studied. Of these three tumor samples, two contained HBV DNA, without an apparent link between the viral DNA and the rearranged allele; HBV DNA sequences were not detected in the third tumor sample. By use of a panel of somatic cell hybrids, these unique cellular DNA sequences were shown to be located on chromosome 4. Therefore, this region of chromosomal DNA might be implicated in the formation of different tumors at one step of liver cell transformation, possible related to HBV integration.

  20. Production and Concentration of Lentivirus for Transduction of Primary Human T Cells.

    PubMed

    Kennedy, Alan; Cribbs, Adam P

    2016-01-01

    Lentiviral vectors have emerged as efficient tools for investigating T cell biology through their ability to efficiently deliver transgene expression into both dividing and nondividing cells. Such lentiviral vectors have the potential to infect a wide variety of cell types. However, despite this advantage, the ability to transduce primary human T cells remains challenging and methods to achieve efficient gene transfer are often time consuming and expensive. We describe a method for generating lentivirus that is simple to perform and does not require the purchase of non-standard equipment to transduce primary human T cells. Therefore, we provide an optimized protocol that is easy to implement and allow transduction with high efficiency and reproducibility. PMID:27317175

  1. Human T Follicular Helper Cells in Primary Immunodeficiency: Quality Just as Important as Quantity.

    PubMed

    Ma, Cindy S

    2016-05-01

    T follicular helper (Tfh) cells are a subset of effector CD4(+) T cells specialised to induce Ab production by B cells. This review highlights some of the recent advances in the field of human Tfh cells that have come from the study of primary immunodeficiencies. In particular it is increasingly evident that the quality of the Tfh cells that are generated, is just as important as the quantity.

  2. Human Immunodeficiency Virus Type 1 Coat Protein Neurotoxicity Mediated by Nitric Oxide in Primary Cortical Cultures

    NASA Astrophysics Data System (ADS)

    Dawson, Valina L.; Dawson, Ted M.; Uhl, George R.; Snyder, Solomon H.

    1993-04-01

    The human immunodeficiency virus type 1 coat protein, gp120, kills neurons in primary cortical cultures at low picomolar concentrations. The toxicity requires external glutamate and calcium and is blocked by glutamate receptor antagonists. Nitric oxide (NO) contributes to gp120 toxicity, since nitroarginine, an inhibitor of NO synthase, prevents toxicity as does deletion of arginine from the incubation medium and hemoglobin, which binds NO. Superoxide dismutase also attenuates toxicity, implying a role for superoxide anions.

  3. Preventing Cleavage of the Respiratory Syncytial Virus Attachment Protein in Vero Cells Rescues the Infectivity of Progeny Virus for Primary Human Airway Cultures

    PubMed Central

    Corry, Jacqueline; Johnson, Sara M.; Cornwell, Jessica

    2015-01-01

    ABSTRACT All live attenuated respiratory syncytial virus (RSV) vaccines that have advanced to clinical trials have been produced in Vero cells. The attachment (G) glycoprotein in virions produced in these cells is smaller than that produced in other immortalized cells due to cleavage. These virions are 5-fold less infectious for primary well-differentiated human airway epithelial (HAE) cell cultures. Because HAE cells are isolated directly from human airways, Vero cell-grown vaccine virus would very likely be similarly inefficient at initiating infection of the nasal epithelium following vaccination, and therefore, a larger inoculum would be required for effective vaccination. We hypothesized that Vero cell-derived virus containing an intact G protein would be more infectious for HAE cell cultures. Using protease inhibitors with increasing specificity, we identified cathepsin L to be the protease responsible for cleavage. Our evidence suggests that cleavage occurs in the late endosome or lysosome during endocytic recycling. Cathepsin L activity was 100-fold greater in Vero cells than in HeLa cells. In addition, cathepsin L was able to cleave the G protein in Vero cell-grown virions but not in HeLa cell-grown virions, suggesting a difference in G-protein posttranslational modification in the two cell lines. We identified by mutagenesis amino acids important for cleavage, and these amino acids included a likely cathepsin L cleavage site. Virus containing a modified, noncleavable G protein produced in Vero cells was 5-fold more infectious for HAE cells in culture, confirming our hypothesis and indicating the value of including such a mutation in future live attenuated RSV vaccines. IMPORTANCE Worldwide, RSV is the second leading infectious cause of infant death, but no vaccine is available. Experimental live attenuated RSV vaccines are grown in Vero cells, but during production the virion attachment (G) glycoprotein is cleaved. Virions containing a cleaved G protein

  4. Pythiosis in the Nasal Cavity of Horses.

    PubMed

    Souto, E P F; Maia, L A; Olinda, R G; Galiza, G J N; Kommers, G D; Miranda-Neto, E G; Dantas, A F M; Riet-Correa, F

    2016-01-01

    Two cases of nasal pythiosis are reported in horses from the semi-arid region of northeastern Brazil. From January 1986 to December 2015, the Laboratory of Animal Pathology, Federal University of Campina Grande received 830 equine samples, 156 (18.79%) of which were diagnosed with pythiosis. Of these, two horses (1.28%), a male and a female adult cross-breed, had lesions in the nasal cavity. Both horses had access to water reservoirs. Clinically, they had swelling in the rhinofacial region and a serosanguineous nasal discharge. Macroscopically, in case 1, the lesion affected the nasal vestibule, extending to the alar cartilage and nasal septum. In case 2, the lesion extended through the turbinates and the meatuses of the nasal cavity, as well as the ethmoid region. In both cases, the lesions were characterized by having a yellow-grey granular surface with cavitations of different sizes containing coral-like masses of necrotic tissue (kunkers). Histologically, multifocal necrotizing eosinophilic rhinitis associated with hyphae (2-8 μm) similar to Pythium insidiosum were observed. In case 2, the lesions extended to the muscle, cartilage and bone adjacent to the nasal cavity and lungs. The diagnosis was confirmed by immunohistochemistry. It is concluded that nasal pythiosis occurs sporadically in horses in the semi-arid region of northeastern Brazil where cutaneous pythiosis is prevalent. PMID:27406311

  5. Nasal Airway Resistance: Its Measurement and Regulation.

    ERIC Educational Resources Information Center

    Hamilton, Lyle H.

    1979-01-01

    Reviews studies of regulation of nasal airway resistance (Rn). Describes methods of calculating Rn by measuring pressure-flow relationship. Data are presented on improved methods for measuring Rn and effects for expiratory and inspiratory Rn after topical application of phenylephrine nasal decongestant spray. (Author/SA)

  6. Chronic Rhinosinusitis without Nasal Polyps.

    PubMed

    Cho, Seong Ho; Kim, Dae Woo; Gevaert, Philippe

    2016-01-01

    Chronic rhinosinusitis without nasal polyps (CRSsNP) is more prevalent than chronic rhinosinusitis with nasal polyps (CRSwNP). Certain diseases predispose to whereas others are associated with CRSsNP. Predisposing diseases include allergic and nonallergic upper and lower airway diseases, epithelial cell disorders, immunodeficiencies, autoimmune diseases, and some infectious diseases. In addition, environmental and host factors, examples of which include smoking, a higher incidence of abnormal biofilms, and innate immune defects, play a role in the pathogenesis of this disease. CRSsNP is characterized by histologic abnormalities, including basement membrane thickening (fibrosis) and goblet cell hyperplasia. Neutrophils and several chemokines, TGF-β and C-X-C motif chemokine ligand (CXCL)-8, play a role in CRSsNP remodeling. However, there are conflicting data about CRSsNP endotypes, for example, whether it is characterized by neutrophilia or eosinophilia or both. In spite of advancements and the understanding of the pathogenesis of this disease, additional study is necessary to better comprehend its underlying mechanisms, endotypes, and evidence-based treatment strategies. PMID:27393771

  7. Gene modification of primary tumor cells for active immunotherapy of human breast and ovarian cancer.

    PubMed

    Philip, R; Clary, B; Brunette, E; Kilinski, L; Murugesh, D; Sorich, M; Yau, J; Lebkowski, J; Lyerly, H K; Philip, M

    1996-01-01

    We have previously shown that cationic liposomes facilitate adeno-associated virus (AAV) plasmid transfections of primary and cultured cell types. To test the clinical feasibility of using genetically modified tumor vaccines for the treatment of breast and ovarian cancers, we have constructed an expression plasmid pMP6IL2 and investigated the use of liposome-mediated gene delivery into primary, uncultured human breast and ovarian tumor cells to produce interleukin 2 (IL-2)-secreting tumor cells. We have demonstrated significant levels of IL-2 expression in tumor cell lines and primary breast and ovarian tumor cells using this AAV-based expression plasmid complexed to cationic liposomes. Transfections with the non-AAV plasmid containing the identical expression cassette as the AAV plasmid induced IL-2 expression in the tumor cell line but failed to produce IL-2 in primary tumor cells. Significant levels of IL-2 were induced with the AAV plasmid regardless of liposome compositions used for transfection. The transfected breast cell line and primary tumor cells were able to express the transgene product for up to 28 days after lethal radiation. The transfection efficiency was comparable for both the tumor cell line and primary tumor cells and ranged from 20 to 50% for both cell types as assessed by intracellular IL-2 staining. Although the primary tumor cell preparations consist of mixed population of cells, at least 40% of the tumor cells expressed the transgene as assessed by immunostaining for IL-2. The ability to efficiently express transgenes in freshly isolated, nondividing tumor cells may potentiate active immunotherapy strategies for gene-based cancer treatment.

  8. Numerical model of a nasal septal perforation.

    PubMed

    Grant, Orla; Bailie, Neil; Watterson, John; Cole, Jonathan; Gallagher, Geraldine; Hanna, Brendan

    2004-01-01

    This paper describes numerical simulation of airflow in a nose with a nasal septal perforation. Diseased airflow is compared to airflow in a healthy nasal model. The healthy model has been generated from CT scans from the Antrim Area Hospital ENT clinic and is close to being anatomically accurate. The nasal septal perforation has been superimposed on the healthy geometry using image manipulation software. The flow is modeled as laminar, steady state, with the flow rates corresponding to quiet breathing at rest approximately 165 ml/sec. Healthy flow patterns show that the majority of the flow travels close to nasal septum, in the region close to the middle turbinate. In the diseased case, high shear stresses concentrated at the posterior region of the perforation explain bleeding associated with nasal perforations.

  9. Safety and efficacy of a novel nasal spray for maxillary dental anesthesia.

    PubMed

    Ciancio, S G; Hutcheson, M C; Ayoub, F; Pantera, E A; Pantera, C T; Garlapo, D A; Sobieraj, B D; Almubarak, S A

    2013-07-01

    This study examines the efficacy, safety, and tolerability of a nasal spray to induce anesthesia of maxillary teeth. Forty-five healthy adults requiring restoration of one maxillary tooth were randomized in a 1:2 ratio to receive (1) an intra-oral lidocaine-epinephrine injection with buffered saline nasal spray bilaterally, or (2) a tetracaine hydrochloride-oxymetazoline hydrochloride nasal spray bilaterally with sham injection. Primary endpoints were use of rescue anesthesia and patient global pain assessment. Secondary outcomes included vital sign changes, soft-tissue anesthesia, and treatment-emergent adverse events. In intent-to-treat analysis, 25 of 30 patients given nasal spray (83.3%) did not require rescue anesthesia. Proportion of anesthesia successes for nasal spray was significantly different from the hypothesized placebo anesthesia success of 30% (one-sided p value < .0001 by exact binomial test). Mean duration of soft-tissue anesthesia did not differ significantly by treatment for 3 of 4 sites assessed. No serious adverse events or systemic effects were observed. Tetracaine hydrochloride-oxymetazoline nasal spray appears to provide adequate and safe anesthesia for the majority of maxillary dental procedures. Based on the results from this Phase 2 study, pivotal trials are warranted to validate these findings in an expanded patient population.

  10. Bile Acid-Induced Necrosis in Primary Human Hepatocytes and in Patients with Obstructive Cholestasis

    PubMed Central

    Woolbright, Benjamin L.; Dorko, Kenneth; Antoine, Daniel J.; Clarke, Joanna I.; Gholami, Parviz; Li, Feng; Kumer, Sean C.; Schmitt, Timothy M.; Forster, Jameson; Fan, Fang; Jenkins, Rosalind E.; Park, B. Kevin; Hagenbuch, Bruno; Olyaee, Mojtaba; Jaeschke, Hartmut

    2015-01-01

    Accumulation of bile acids is a major mediator of cholestatic liver injury. Recent studies indicate bile acid composition between humans and rodents is dramatically different, as humans have a higher percent of glycine conjugated bile acids and increased chenodeoxycholate content, which increases the hydrophobicity index of bile acids. This increase may lead to direct toxicity that kills hepatocytes, and promotes inflammation. To address this issue, this study assessed how pathophysiological concentrations of bile acids measured in cholestatic patients affected primary human hepatocytes. Individual bile acid levels were determined in serum and bile by UPLC/QTOFMS in patients with extrahepatic cholestasis with, or without, concurrent increases in serum transaminases. Bile acid levels increased in serum of patients with liver injury, while biliary levels decreased, implicating infarction of the biliary tracts. To assess bile acid-induced toxicity in man, primary human hepatocytes were treated with relevant concentrations, derived from patient data, of the model bile acid glycochenodeoxycholic acid (GCDC). Treatment with GCDC resulted in necrosis with no increase in apoptotic parameters. This was recapitulated by treatment with biliary bile acid concentrations, but not serum concentrations. Marked elevations in serum full-length cytokeratin-18, high mobility group box1 protein (HMGB1), and acetylated HMGB1 confirmed inflammatory necrosis in injured patients; only modest elevations in caspase-cleaved cytokeratin-18 were observed. These data suggest human hepatocytes are more resistant to human-relevant bile acids than rodent hepatocytes, and die through necrosis when exposed to bile acids. These mechanisms of cholestasis in humans are fundamentally different to mechanisms observed in rodent models. PMID:25636263

  11. Subjective Nasal Fullness and Objective Congestion

    PubMed Central

    Baraniuk, James N.

    2011-01-01

    How well do subjective descriptions of the sensation of nasal closure or absence of nasal patency agree with objective measures of nasal geometry and airflow? Problems with this concept begin with terminology. “Congestion” has been applied to both the subjective and objective measures. Therefore, the term “fullness” will be used to describe perceptions of nasal mucosal heaviness or blockage that subjects with allergic rhinitis articulate. “Congestion” will refer to the objective measures used to assess patency. Sensations attributed to the nasal mucosa are highly integrated interpretations summed from multiple subsets of nociceptive and other neurons. Activation of sensor systems is required to depolarize afferent neurons. These sensors and other receptor proteins can be modulated by inflammation as part of the neural plasticity that leads to increased sensitivity to nasal stimuli. This plasticity and hyperalgesia may extend from the afferent neuron to spinal cord dorsal horn synapses, and regulatory and analytical regions of the brainstem and cerebrum. Although glandular hypersecretion can deliver obstructing material into the nasal cavities, the dilation of deep venous sinusoids is the strongest factor regulating nasal airspace volumes. There is a long history of attempts to correlate subjective sensations to objective measurements such as airflow resistance (rhinomanometry), nasal wall geometry (acoustic rhinometry), and peak nasal inspiratory flow. The medical evidence supporting each method has been analyzed on the basis of the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) system. These results provide a starting point for linking the outcomes of pathophysiological processes with a patient's psychometrically calibrated sensation of airflow. PMID:21364223

  12. Nasal Drug Delivery in Traditional Persian Medicine

    PubMed Central

    Zarshenas, Mohammad Mehdi; Zargaran, Arman; Müller, Johannes; Mohagheghzadeh, Abdolali

    2013-01-01

    Background Over one hundred different pharmaceutical dosage forms have been recorded in literatures of Traditional Persian Medicine among which nasal forms are considerable. Objectives This study designed to derive the most often applied nasal dosage forms together with those brief clinical administrations. Materials and Methods In the current study remaining pharmaceutical manuscripts of Persia during 9th to 18th century AD have been studied and different dosage forms related to nasal application of herbal medicines and their therapeutic effects were derived. Results By searching through pharmaceutical manuscripts of medieval Persia, different nasal dosage forms involving eleven types related to three main groups are found. These types could be derived from powder, solution or liquid and gaseous forms. Gaseous form were classified into fumigation (Bakhoor), vapor bath (Enkebab), inhalation (Lakhlakheh), aroma agents (Ghalieh) and olfaction or smell (Shomoom). Nasal solutions were as drops (Ghatoor), nasal snuffing drops (Saoot) and liquid snuff formulations (Noshoogh). Powders were as nasal insufflation or snorting agents (Nofookh) and errhine or sternutator medicine (Otoos). Nasal forms were not applied only for local purposes. Rather systemic disorders and specially CNS complications were said to be a target for these dosage forms. Discussion While this novel type of drug delivery is known as a suitable substitute for oral and parenteral administration, it was well accepted and extensively mentioned in Persian medical and pharmaceutical manuscripts and other traditional systems of medicine as well. Accordingly, medieval pharmaceutical standpoints on nasal dosage forms could still be an interesting subject of study. Therefore, the current work can briefly show the pharmaceutical knowledge on nasal formulations in medieval Persia and clarify a part of history of traditional Persian pharmacy. PMID:24624204

  13. Trehalose-Mediated Autophagy Impairs the Anti-Viral Function of Human Primary Airway Epithelial Cells

    PubMed Central

    Wu, Qun; Jiang, Di; Huang, Chunjian; van Dyk, Linda F.; Li, Liwu; Chu, Hong Wei

    2015-01-01

    Human rhinovirus (HRV) is the most common cause of acute exacerbations of chronic lung diseases including asthma. Impaired anti-viral IFN-λ1 production and increased HRV replication in human asthmatic airway epithelial cells may be one of the underlying mechanisms leading to asthma exacerbations. Increased autophagy has been shown in asthmatic airway epithelium, but the role of autophagy in anti-HRV response remains uncertain. Trehalose, a natural glucose disaccharide, has been recognized as an effective autophagy inducer in mammalian cells. In the current study, we used trehalose to induce autophagy in normal human primary airway epithelial cells in order to determine if autophagy directly regulates the anti-viral response against HRV. We found that trehalose-induced autophagy significantly impaired IFN-λ1 expression and increased HRV-16 load. Inhibition of autophagy via knockdown of autophagy-related gene 5 (ATG5) effectively rescued the impaired IFN-λ1 expression by trehalose and subsequently reduced HRV-16 load. Mechanistically, ATG5 protein interacted with retinoic acid-inducible gene I (RIG-I) and IFN-β promoter stimulator 1 (IPS-1), two critical molecules involved in the expression of anti-viral interferons. Our results suggest that induction of autophagy in human primary airway epithelial cells inhibits the anti-viral IFN-λ1 expression and facilitates HRV infection. Intervention of excessive autophagy in chronic lung diseases may provide a novel approach to attenuate viral infections and associated disease exacerbations. PMID:25879848

  14. A Three-dimensional Tissue Culture Model to Study Primary Human Bone Marrow and its Malignancies

    PubMed Central

    Parikh, Mukti R.; Belch, Andrew R.; Pilarski, Linda M; Kirshner, Julia

    2014-01-01

    Tissue culture has been an invaluable tool to study many aspects of cell function, from normal development to disease. Conventional cell culture methods rely on the ability of cells either to attach to a solid substratum of a tissue culture dish or to grow in suspension in liquid medium. Multiple immortal cell lines have been created and grown using such approaches, however, these methods frequently fail when primary cells need to be grown ex vivo. Such failure has been attributed to the absence of the appropriate extracellular matrix components of the tissue microenvironment from the standard systems where tissue culture plastic is used as a surface for cell growth. Extracellular matrix is an integral component of the tissue microenvironment and its presence is crucial for the maintenance of physiological functions such as cell polarization, survival, and proliferation. Here we present a 3-dimensional tissue culture method where primary bone marrow cells are grown in extracellular matrix formulated to recapitulate the microenvironment of the human bone (rBM system). Embedded in the extracellular matrix, cells are supplied with nutrients through the medium supplemented with human plasma, thus providing a comprehensive system where cell survival and proliferation can be sustained for up to 30 days while maintaining the cellular composition of the primary tissue. Using the rBM system we have successfully grown primary bone marrow cells from normal donors and patients with amyloidosis, and various hematological malignancies. The rBM system allows for direct, in-matrix real time visualization of the cell behavior and evaluation of preclinical efficacy of novel therapeutics. Moreover, cells can be isolated from the rBM and subsequently used for in vivo transplantation, cell sorting, flow cytometry, and nucleic acid and protein analysis. Taken together, the rBM method provides a reliable system for the growth of primary bone marrow cells under physiological conditions

  15. Chemosensitivity of primary human fibroblasts with defective unhooking of DNA interstrand cross-links.

    PubMed

    Clingen, Peter H; Arlett, Colin F; Hartley, John A; Parris, Christopher N

    2007-02-15

    Xeroderma pigmentosum (XP) is characterised by defects in nucleotide excision repair, ultraviolet (UV) radiation sensitivity and increased skin carcinoma. Compared to other complementation groups, XP-F patients show relatively mild cutaneous symptoms. DNA interstrand cross-linking agents are a highly cytotoxic class of DNA damage induced by common cancer chemotherapeutics such as cisplatin and nitrogen mustards. Although the XPF-ERCC1 structure-specific endonuclease is required for the repair of ICLs cellular sensitivity of primary human XP-F cells has not been established. In clonogenic survival assays, primary fibroblasts from XP-F patients were moderately sensitive to both UVC and HN2 compared to normal cells (2- to 3-fold and 3- to 5-fold, respectively). XP-A fibroblasts were considerably more sensitive to UVC (10- to 12-fold) but not sensitive to HN2. The sensitivity of XP-F fibroblasts to HN2 correlated with the defective incision or 'unhooking' step of ICL repair. Using the comet assay, XP-F cells exhibited only 20% residual unhooking activity over 24 h. Over the same time, normal and XP-A cells unhooked greater than 95% and 62% of ICLs, respectively. After HN2 treatment, ICL-associated DNA double-strand breaks (DSBs) are detected by pulse field gel electrophoresis in dividing cells. Induction and repair of DNA DSBs was normal in XP-F fibroblasts. These findings demonstrate that in primary human fibroblasts, XPF is required for the unhooking of ICLs and not for the induction or repair of ICL-associated DNA DSBs induced by HN2. In terms of cancer chemotherapy, people with mild DNA repair defects affecting ICL repair may be more prevalent in the general population than expected. Since cellular sensitivity of primary human fibroblasts usually reflects clinical sensitivity such patients with cancer would be at risk of increased toxicity. PMID:17188678

  16. Chemosensitivity of primary human fibroblasts with defective unhooking of DNA interstrand cross-links

    SciTech Connect

    Clingen, Peter H. . E-mail: p.clingen@ucl.ac.uk; Arlett, Colin F.; Hartley, John A.; Parris, Christopher N.

    2007-02-15

    Xeroderma pigmentosum (XP) is characterised by defects in nucleotide excision repair, ultraviolet (UV) radiation sensitivity and increased skin carcinoma. Compared to other complementation groups, XP-F patients show relatively mild cutaneous symptoms. DNA interstrand cross-linking agents are a highly cytotoxic class of DNA damage induced by common cancer chemotherapeutics such as cisplatin and nitrogen mustards. Although the XPF-ERCC1 structure-specific endonuclease is required for the repair of ICLs cellular sensitivity of primary human XP-F cells has not been established. In clonogenic survival assays, primary fibroblasts from XP-F patients were moderately sensitive to both UVC and HN2 compared to normal cells (2- to 3-fold and 3- to 5-fold, respectively). XP-A fibroblasts were considerably more sensitive to UVC (10- to 12-fold) but not sensitive to HN2. The sensitivity of XP-F fibroblasts to HN2 correlated with the defective incision or 'unhooking' step of ICL repair. Using the comet assay, XP-F cells exhibited only 20% residual unhooking activity over 24 h. Over the same time, normal and XP-A cells unhooked greater than 95% and 62% of ICLs, respectively. After HN2 treatment, ICL-associated DNA double-strand breaks (DSBs) are detected by pulse field gel electrophoresis in dividing cells. Induction and repair of DNA DSBs was normal in XP-F fibroblasts. These findings demonstrate that in primary human fibroblasts, XPF is required for the unhooking of ICLs and not for the induction or repair of ICL-associated DNA DSBs induced by HN2. In terms of cancer chemotherapy, people with mild DNA repair defects affecting ICL repair may be more prevalent in the general population than expected. Since cellular sensitivity of primary human fibroblasts usually reflects clinical sensitivity such patients with cancer would be at risk of increased toxicity.

  17. Sulforaphane induces SLPI secretion in the nasal mucosa

    PubMed Central

    Meyer, Megan; Kesic, Matthew J.; Clarke, John; Ho, Emily; Simmen, Rosalia C.M.; Diaz-Sanchez, David; Noah, Terry L.; Jaspers, Ilona

    2012-01-01

    Summary Cells lining the respiratory tract are equipped with mechanisms that dampen the effects of oxidative stress. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a mediator involved in regulating oxidative stress. Recent data indicate Nrf2 also controls expression of secretory leukocyte protease inhibitor (SLPI). Sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables, enhances Nrf2 activity. Therefore, we hypothesized that SFN supplementation induces SLPI secretion in the nasal mucosa in an Nrf2 dependent manner. Healthy nonsmoking adults ingested SFN-containing broccoli shake homogenate (BSH) for 3 consecutive days. Nasal lavage fluid (NLF) was collected before and after BSH ingestion and analyzed for SLPI protein levels. In follow up in vitro experiments, differentiated primary nasal epithelial cells were used to evaluate the relationship between SFN, Nrf2, and SLPI. Epithelial cells were transduced with Nrf2-specific shRNA to examine the regulatory role of Nrf2 on SLPI expression. Supplementation with BSH significantly increased SLPI levels in NLF. SFN supplementation in vitro significantly enhanced SLPI secretion and these effects were significantly decreased in cells transduced with Nrf2-specific shRNA. PMID:23195333

  18. Fibulin-5 is upregulated in decidualized human endometrial stromal cells and promotes primary human extravillous trophoblast outgrowth.

    PubMed

    Winship, Amy; Cuman, Carly; Rainczuk, Katarzyna; Dimitriadis, Evdokia

    2015-12-01

    Interactions between the highly invasive trophoblasts and the maternal uterine decidual extracellular matrix (ECM) are crucial in the determination of a successful pregnancy. Fibulin-5 (FBLN5) is a member of the fibulin family that alters cell adhesive and invasive properties and is expressed in human villous cytotrophoblasts. We aimed to determine the expression and immunolocalization of FBLN5 in human first trimester decidua and examine the effect of FBLN5 in trophoblast invasion in vitro using a first trimester placental villous outgrowth assay. We demonstrated that FBLN5 mRNA expression is upregulated in response to cAMP-mediated decidualization of primary human endometrial stromal cells, although FBLN5 itself does not enhance decidualization. We reported for the first time, FBLN5 protein production in first trimester decidual cells and also co-localization to HLAG-positive EVTs in first trimester decidua. Consequently, we investigated the effects of exogenous FBLN5 on placental villous outgrowth in vitro and demonstrated that FBLN5 promotes EVT migration/invasion. This is the first study to identify FBLN5 in decidualized human endometrial stromal cells, first trimester decidua and EVT and determine a functional role for FBLN5 in human EVTs, suggesting that decidual and or EVT-derived FBLN5 regulates EVT invasion and placentation in women. PMID:26506560

  19. Astrocytes As the Main Players in Primary Degenerative Disorders of the Human Central Nervous System.

    PubMed

    Capani, Francisco; Quarracino, Cecilia; Caccuri, Roberto; Sica, Roberto E P

    2016-01-01

    Along the last years it has been demonstrated that non-neural cells play a major role in the pathogenesis of the primary degenerative disorders (PDDs) of the human central nervous system. Among them, astrocytes coordinate and participate in many different and complex metabolic processes, in close interaction with neurons. Moreover, increasing experimental evidence hints an early astrocytic dysfunction in these diseases. In this mini review we summarize the astrocytic behavior in PDDs, with special consideration to the experimental observations where astrocytic pathology precedes the development of neuronal dysfunction. We also suggest a different approach that could be consider in human investigations in Alzheimer's and Parkinson's disease. We believe that the study of PDDs with human brain samples may hold the key of a paradigmatic physiopathological process in which astrocytes might be the main players. PMID:26973519

  20. Genotoxicity test of self-renovated ceramics in primary human peripheral lymphocytes.

    PubMed

    Hua, Nan; Zhu, Huifang; Zhuang, Jing; Chen, Liping

    2014-12-01

    Zirconia-based ceramics is widely used in dentistry. Different compositions of ceramics have different features. Our self-renovated ceramics become more machinable without scarifying its dental restoration properties after adjusting ratio of lanthanum phosphate (LaPO4)/yttrium oxide (Y2O3). In order to evaluate its safety, here, we tested its genotoxicity in primary human peripheral lymphocytes. The human lymphocytes cultured on three groups of different ratios of LaPO4/Y2O3 diphase ceramics for 6 days showed little effect of growth inhibition and similar effect of growth trend to the negative control. Furthermore, single-cell gel electrophoresis (comet assay) indicated that there was no significant difference of the value of tail moment between the tested ceramics and negative control, the IPS Empress II (P > 0.05). Our findings implicate that our self-renovated ceramics do not induce DNA damages in human peripheral lymphocytes and support their future clinic application.

  1. Evaluating the Effect of Sinex® (0.05% Oxymetazoline) Nasal Spray on Reduction of Nasal Congestion Using Computational Fluid Dynamics.

    PubMed

    Kishore, Aravind; Blake, Lauren; Wang, Chengming; Ba, Shan; Gross, Gary

    2015-08-01

    Computational fluid dynamics (CFD) was used to simulate air flow changes in reconstructed nasal passages based on magnetic resonance imaging (MRI) data from a previous clinical study of 0.05% Oxymetazoline (Vicks Sinex Micromist®). Total-pressure boundary conditions were uniquely applied to accommodate low patency subjects. Net nasal resistance, the primary simulation outcome, was determined using a parallel-circuit analogy and compared across treatments. Relative risk (RR) calculations show that for a 50% reduction in nasal resistance, subjects treated with Sinex® are 9.1 times more likely to achieve this after 8 hr, and 3.2 times more likely after 12 hr compared to Sham.

  2. Characterizing primary human microglia: A comparative study with myeloid subsets and culture models.

    PubMed

    Melief, J; Sneeboer, M A M; Litjens, M; Ormel, P R; Palmen, S J M C; Huitinga, I; Kahn, R S; Hol, E M; de Witte, L D

    2016-11-01

    The biology of microglia has become subject to intense study, as they are widely recognized as crucial determinants of normal and pathologic brain functioning. While they are well studied in animal models, it is still strongly debated what specifies most accurately the phenotype and functioning of microglia in the human brain. In this study, we therefore isolated microglia from postmortem human brain tissue of corpus callosum (CC) and frontal cortex (CTX). The cells were phenotyped for a panel of typical microglia markers and genes involved in myeloid cell biology. Furthermore, their response to pro- and anti-inflammatory stimuli was assessed. The microglia were compared to key human myeloid cell subsets, including monocytes, monocyte-derived macrophages and monocyte-derived dendritic cells, and several commonly used microglial cell models. Protein and mRNA expression profiles partly differed between microglia isolated from CC and frontal cortex and were clearly distinct from other myeloid subsets. Microglia responded to both pro- (LPS or poly I:C) and anti-inflammatory (IL-4 or dexamethasone) stimuli. Interestingly, pro-inflammatory responses differed between microglia and monocyte-derived macrophages, as the former responded more strongly to poly I:C and the latter more strongly to LPS. Furthermore, we defined a large phenotypic discrepancy between primary human microglia and currently used microglial cell models and cell lines. In conclusion, we further delineated the unique and specific features that discriminate human microglia from other myeloid subsets, and we show that currently used cellular models only partly reflect the phenotype of primary human microglia. GLIA 2016;64:1857-1868.

  3. Bisphenol S Induces Adipogenesis in Primary Human Preadipocytes From Female Donors.

    PubMed

    Boucher, Jonathan G; Ahmed, Shaimaa; Atlas, Ella

    2016-04-01

    Human exposure to bisphenol A has been associated with negative health outcomes in humans and its use is now regulated in a number of countries. Bisphenol S (BPS) is increasingly used as a replacement for bisphenol A; however, its effects on cellular metabolism and potential role as an endocrine disruptor have not been fully characterized. In the current study, we evaluated the effect of BPS on adipogenesis in primary human preadipocytes. The effect of BPS on the differentiation of human preadipocytes was determined after treatment with BPS at concentrations ranging from 0.1 nM to 25 μM by quantifying lipid accumulation and mRNA and protein levels of key adipogenic markers. Treatment of preadipocytes with 25 μM BPS induced lipid accumulation and increased the mRNA and protein levels of several adipogenic markers including lipoprotein lipase and adipocyte protein 2 (aP2). Cotreatment of cells with the estrogen receptor antagonist ICI-182,780 significantly inhibited BPS-induced lipid accumulation and affected aP2 but not lipoprotein lipase protein levels. Cotreatment of cells with the glucocorticoid receptor antagonist RU486 had no effect on BPS-induced lipid accumulation or protein levels. Furthermore, reporter gene assays using a synthetic promoter containing peroxisome proliferator-activated receptor-γ (PPARG)-response elements and a PPARG-responsive human aP2 promoter region showed that BPS was able to activate PPARG. To our knowledge, this study is the first to show that BPS induces lipid accumulation and differentiation of primary human preadipocytes, and this effect may be mediated through a PPARG pathway.

  4. Global human appropriation of net primary production doubled in the 20th century

    PubMed Central

    Krausmann, Fridolin; Erb, Karl-Heinz; Gingrich, Simone; Haberl, Helmut; Bondeau, Alberte; Gaube, Veronika; Lauk, Christian; Plutzar, Christoph; Searchinger, Timothy D.

    2013-01-01

    Global increases in population, consumption, and gross domestic product raise concerns about the sustainability of the current and future use of natural resources. The human appropriation of net primary production (HANPP) provides a useful measure of human intervention into the biosphere. The productive capacity of land is appropriated by harvesting or burning biomass and by converting natural ecosystems to managed lands with lower productivity. This work analyzes trends in HANPP from 1910 to 2005 and finds that although human population has grown fourfold and economic output 17-fold, global HANPP has only doubled. Despite this increase in efficiency, HANPP has still risen from 6.9 Gt of carbon per y in 1910 to 14.8 GtC/y in 2005, i.e., from 13% to 25% of the net primary production of potential vegetation. Biomass harvested per capita and year has slightly declined despite growth in consumption because of a decline in reliance on bioenergy and higher conversion efficiencies of primary biomass to products. The rise in efficiency is overwhelmingly due to increased crop yields, albeit frequently associated with substantial ecological costs, such as fossil energy inputs, soil degradation, and biodiversity loss. If humans can maintain the past trend lines in efficiency gains, we estimate that HANPP might only grow to 27–29% by 2050, but providing large amounts of bioenergy could increase global HANPP to 44%. This result calls for caution in refocusing the energy economy on land-based resources and for strategies that foster the continuation of increases in land-use efficiency without excessively increasing ecological costs of intensification. PMID:23733940

  5. Generation of knock-in primary human T cells using Cas9 ribonucleoproteins

    SciTech Connect

    Schumann, Kathrin; Lin, Steven; Boyer, Eric; Simeonov, Dimitre R.; Subramaniam, Meena; Gate, Rachel E.; Haliburton, Genevieve E.; Ye, Chun J.; Bluestone, Jeffrey A.; Doudna, Jennifer A.; Marson, Alexander

    2015-07-27

    T-cell genome engineering holds great promise for cell-based therapies for cancer, HIV, primary immune deficiencies, and autoimmune diseases, but genetic manipulation of human T cells has been challenging. Improved tools are needed to efficiently “knock out” genes and “knock in” targeted genome modifications to modulate T-cell function and correct disease-associated mutations. CRISPR/Cas9 technology is facilitating genome engineering in many cell types, but in human T cells its efficiency has been limited and it has not yet proven useful for targeted nucleotide replacements. Here we report efficient genome engineering in human CD4+ T cells using Cas9:single-guide RNA ribonucleoproteins (Cas9 RNPs). Cas9 RNPs allowed ablation of CXCR4, a coreceptor for HIV entry. Cas9 RNP electroporation caused up to ~40% of cells to lose high-level cell-surface expression of CXCR4, and edited cells could be enriched by sorting based on low CXCR4 expression. Importantly, Cas9 RNPs paired with homology-directed repair template oligonucleotides generated a high frequency of targeted genome modifications in primary T cells. Targeted nucleotide replacement was achieved in CXCR4 and PD-1 (PDCD1), a regulator of T-cell exhaustion that is a validated target for tumor immunotherapy. Deep sequencing of a target site confirmed that Cas9 RNPs generated knock-in genome modifications with up to ~20% efficiency, which accounted for up to approximately one-third of total editing events. These results establish Cas9 RNP technology for diverse experimental and therapeutic genome engineering applications in primary human T cells.

  6. Generation of knock-in primary human T cells using Cas9 ribonucleoproteins.

    PubMed

    Schumann, Kathrin; Lin, Steven; Boyer, Eric; Simeonov, Dimitre R; Subramaniam, Meena; Gate, Rachel E; Haliburton, Genevieve E; Ye, Chun J; Bluestone, Jeffrey A; Doudna, Jennifer A; Marson, Alexander

    2015-08-18

    T-cell genome engineering holds great promise for cell-based therapies for cancer, HIV, primary immune deficiencies, and autoimmune diseases, but genetic manipulation of human T cells has been challenging. Improved tools are needed to efficiently "knock out" genes and "knock in" targeted genome modifications to modulate T-cell function and correct disease-associated mutations. CRISPR/Cas9 technology is facilitating genome engineering in many cell types, but in human T cells its efficiency has been limited and it has not yet proven useful for targeted nucleotide replacements. Here we report efficient genome engineering in human CD4(+) T cells using Cas9:single-guide RNA ribonucleoproteins (Cas9 RNPs). Cas9 RNPs allowed ablation of CXCR4, a coreceptor for HIV entry. Cas9 RNP electroporation caused up to ∼40% of cells to lose high-level cell-surface expression of CXCR4, and edited cells could be enriched by sorting based on low CXCR4 expression. Importantly, Cas9 RNPs paired with homology-directed repair template oligonucleotides generated a high frequency of targeted genome modifications in primary T cells. Targeted nucleotide replacement was achieved in CXCR4 and PD-1 (PDCD1), a regulator of T-cell exhaustion that is a validated target for tumor immunotherapy. Deep sequencing of a target site confirmed that Cas9 RNPs generated knock-in genome modifications with up to ∼20% efficiency, which accounted for up to approximately one-third of total editing events. These results establish Cas9 RNP technology for diverse experimental and therapeutic genome engineering applications in primary human T cells.

  7. Generation of knock-in primary human T cells using Cas9 ribonucleoproteins

    DOE PAGES

    Schumann, Kathrin; Lin, Steven; Boyer, Eric; Simeonov, Dimitre R.; Subramaniam, Meena; Gate, Rachel E.; Haliburton, Genevieve E.; Ye, Chun J.; Bluestone, Jeffrey A.; Doudna, Jennifer A.; et al

    2015-07-27

    T-cell genome engineering holds great promise for cell-based therapies for cancer, HIV, primary immune deficiencies, and autoimmune diseases, but genetic manipulation of human T cells has been challenging. Improved tools are needed to efficiently “knock out” genes and “knock in” targeted genome modifications to modulate T-cell function and correct disease-associated mutations. CRISPR/Cas9 technology is facilitating genome engineering in many cell types, but in human T cells its efficiency has been limited and it has not yet proven useful for targeted nucleotide replacements. Here we report efficient genome engineering in human CD4+ T cells using Cas9:single-guide RNA ribonucleoproteins (Cas9 RNPs). Cas9more » RNPs allowed ablation of CXCR4, a coreceptor for HIV entry. Cas9 RNP electroporation caused up to ~40% of cells to lose high-level cell-surface expression of CXCR4, and edited cells could be enriched by sorting based on low CXCR4 expression. Importantly, Cas9 RNPs paired with homology-directed repair template oligonucleotides generated a high frequency of targeted genome modifications in primary T cells. Targeted nucleotide replacement was achieved in CXCR4 and PD-1 (PDCD1), a regulator of T-cell exhaustion that is a validated target for tumor immunotherapy. Deep sequencing of a target site confirmed that Cas9 RNPs generated knock-in genome modifications with up to ~20% efficiency, which accounted for up to approximately one-third of total editing events. These results establish Cas9 RNP technology for diverse experimental and therapeutic genome engineering applications in primary human T cells.« less

  8. [Nasal endoscope surgery of acinic cell carcinoma of salivary gland on nasal septum: a case report].

    PubMed

    Tang, Yuanyuan; Sun, Xiuzhen; Wang, Jizhe

    2016-02-01

    A 67-year-old male patient was admitted because of "the right side nasal obstruction repeatedly for 4 years". He got nasal obstruction 4 years ago, especially for the right side nasal cavity, sometimes got blood in his nasal discharge, then the symptom relieved after accepting treatment in local hospital. During the 4 years, the symptom repeatedly occurrence. Three days before hospitalization, the CT examination indicated abnormal things in his nasal cavity and the bone of his nasal sinus had been destroyed. Some abnormal organism were sent to pathological examination, and the report indicated it is acinic cell carcinoma of salivary gland. During the nasal endoscope surgery, a red goiter was found in his nose with its surface crude and brittle. Then we cut the goiter by nasal endoscope, during the operation we find the bottom of the goiter is on the nasal septum. Two weeks after the operation, the patient received the radiation therapy. One year after the operation he doesn't get the abnormal symptom and the nasal MRI not found recidivation. PMID:27373103

  9. Effectiveness of azelastine nasal solution in seasonal allergic rhinitis.

    PubMed

    Storms, W W; Pearlman, D S; Chervinsky, P; Grossman, J; Halverson, P C; Freitag, J J; Widlitz, M D

    1994-06-01

    Azelastine is a novel antiallergy medication currently under investigation for the treatment of allergic rhinitis and asthma. Pharmacologic studies in laboratory animals and in vitro model systems indicate that azelastine exerts multiple actions including modulation of airways smooth muscle response, interference with inflammatory processes, and inhibition of allergic reactions. In a previous controlled clinical trial, azelastine nasal solution (ASTELIN N.S.) demonstrated effectiveness in controlling symptoms of seasonal allergic rhinitis (SAR). The objective of this 2-week double-blind, parallel-group study was to further assess the effectiveness of azelastine nasal solution in improving allergic rhinitis symptoms. Two hundred forty-seven patients (> or = 12 years) with symptomatic SAR who satisfied a minimum symptoms score during a 1-week, single-blind, baseline evaluation period were randomized to receive azelastine 2 sprays per nostril bid, azelastine 2 sprays per nostril qd, chlorpheniramine 12 mg bid, or placebo using a double-dummy technique to insure blinding. The primary efficacy variables were changes in Major Symptom Complex (nose blows, sneezes, runny nose/sniffles, itch nose, and watery eyes) and Total Symptom Complex (Major plus itchy eyes/ears/throat/palate, cough, and postnasal drip) severity scores. Patients treated with azelastine nasal solution qd and bid had mean percent improvements in the Total and Major Symptom Complex severity scores that were clinically significant (> or = 50% improvement over placebo) after both weeks, at endpoint, and overall. The improvements for the azelastine bid group were statistically significant (P < or = .05) at all evaluation points. Adverse experiences occurred infrequently, and none was considered serious or potentially limiting to the clinical utility of the nasal solution.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Houttuynia cordata Thunb extract inhibits cell growth and induces apoptosis in human primary colorectal cancer cells.

    PubMed

    Lai, Kuang-Chi; Chiu, Yu-Jen; Tang, Yih-Jing; Lin, Kuei-Li; Chiang, Jo-Hua; Jiang, Yi-Lin; Jen, Hsiu-Fang; Kuo, Yueh-Hsiung; Agamaya, Sakae; Chung, Jing-Gung; Yang, Jai-Sing

    2010-09-01

    It is reported that Houttuynia cordata Thunb. (HCT), a traditional Chinese herbal medicine, has many biological properties such as antiviral, antibacterial and antileukemic activities. However, the molecular mechanisms of cytotoxicity and apoptosis in human primary colorectal cancer cells are not clear. In this study, whether HCT induced cytotoxicity in primary colorectal cancer cells obtained from three patients was investigated. The results indicated that HCT inhibited growth of cancer cells in a dose-dependent manner. After treatment with HCT (250 μg/ml) for 24 h, cells exhibited chromatin condensation (an apoptotic characteristic). HCT increased reactive oxygen species (ROS) production and decreased the mitochondrial membrane potential (ΔΨ(m)) in examined cells. Mitochondria-dependent apoptotic signaling pathway was shown to be involved as determined by increase in the levels of cytochrome c, Apaf-1, and caspase-3 and -9. The decrease in the level of ΔΨ(m) was associated with an increase in the BAX/BCL-2 ratio which led to activation of caspase-9 and -3. Based on our results, HCT induced apoptotic cell death in human primary colorectal cancer cells through a mitochondria-dependent signaling pathway. PMID:20944136

  11. Gene expression profiling of dengue infected human primary cells identifies secreted mediators in vivo

    PubMed Central

    Becerra, Aniuska; Warke, Rajas V.; Martin, Katherine; Xhaja, Kris; de Bosch, Norma; Rothman, Alan L.; Bosch, Irene

    2009-01-01

    We used gene expression profiling of human primary cells infected in vitro with dengue virus (DENV) as a tool to identify secreted mediators induced in response to the acute infection. Affymetrix Genechip analysis of human primary monocytes, B cells and dendritic cells infected with DENV in vitro revealed a strong induction of monocyte chemotactic protein 2 (MCP-2/CCL8), interferon gamma-induced protein 10 (IP-10/CXCL10) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/TNFSF10). The expression of these genes was confirmed in dendritic cells infected with DENV in vitro at mRNA and protein levels. A prospectively enrolled cohort of DENV-infected Venezuelan patients was used to measure the levels of these proteins in serum during three different periods of the disease. Results showed significant increase of MCP-2, IP-10 and TRAIL levels in DENV-infected patients during the febrile period, when compared to healthy donors and patients with other febrile illnesses. MCP-2 and IP-10 levels were still elevated during the post-febrile period while TRAIL levels dropped close to normal after defervescense. Patients with primary infections had higher TRAIL levels than patients with secondary infections during the febrile period of the disease. Increased levels of IP-10, TRAIL and MCP-2 in acute DENV infections suggest a role for these mediators in the immune response to the infection. PMID:19551822

  12. Activation of Notch1 signaling is required for β-catenin–mediated human primary melanoma progression

    PubMed Central

    Balint, Klara; Xiao, Min; Pinnix, Chelsea C.; Soma, Akinobu; Veres, Imre; Juhasz, Istvan; Brown, Eric J.; Capobianco, Anthony J.; Herlyn, Meenhard; Liu, Zhao-Jun

    2005-01-01

    Notch is a highly conserved transmembrane receptor that determines cell fate. Notch signaling denotes cleavage of the Notch intracellular domain, its translocation to the nucleus, and subsequent activation of target gene transcription. Involvement of Notch signaling in several cancers is well known, but its role in melanoma remains poorly characterized. Here we show that the Notch1 pathway is activated in human melanoma. Blocking Notch signaling suppressed whereas constitutive activation of the Notch1 pathway enhanced primary melanoma cell growth both in vitro and in vivo yet had little effect on metastatic melanoma cells. Activation of Notch1 signaling enabled primary melanoma cells to gain metastatic capability. Furthermore, the oncogenic effect of Notch1 on primary melanoma cells was mediated by β-catenin, which was upregulated following Notch1 activation. Inhibiting β-catenin expression reversed Notch1-enhanced tumor growth and metastasis. Our data therefore suggest a β-catenin–dependent, stage-specific role for Notch1 signaling in promoting the progression of primary melanoma. PMID:16239965

  13. Disorders of the nasal valve area

    PubMed Central

    Bloching, Marc Boris

    2008-01-01

    The nasal valve area is not a singular structure, but a complex three-dimensional construct consisting of several morphological structures. From the physiologic point of view, it is the place of maximum nasal flow resistance (“flow limiting segment”). Therefore, according to Poiseuille’s law, even minor constrictions of this area result in a clinically relevant impairment of nasal breathing for the patient. This narrow passage, also called “ostium internum nasi”, is formed by the mobile lateral nasal wall, the anterior septum with the swell body, the head of the inferior turbinate and the osseous piriform aperture. Within the framework of aetiology, static and dynamic disorders of the nasal valve area have to be distinguished since they result in different therapeutic measures. In the context of diagnosis, the exploration of the case history for assessing the patient’s extent of suffering and the clinical examination are very important. In addition to the presentation of the basics of disorders of the nasal valves, this paper focuses on the treatment of dynamic disorders that mainly constitute the more important therapeutic issue. In this context, we distinguish between stabilisation techniques through grafts or implants and stabilising suture techniques. Following a thorough analysis, the correction of static nasal valve disorders requires various plastic-reconstructive measures using transposition grafting and skin or composite grafts. PMID:22073083

  14. Reduced nasal transport of insulin-like growth factor-1 to the mouse cerebrum with olfactory bulb resection.

    PubMed

    Shiga, Hideaki; Nagaoka, Mikiya; Washiyama, Kohshin; Yamamoto, Junpei; Yamada, Kentaro; Noda, Takuya; Harita, Masayuki; Amano, Ryohei; Miwa, Takaki

    2014-09-01

    Although the olfactory nerve is involved in nasal transport of insulin-like growth factor-1 (IGF-1) to the brain, to our knowledge there have been no direct assessments of the effects of olfactory nerve damage on this transport. To determine whether olfactory bulb resection resulted in reduced transport of nasally administered human recombinant IGF-1 (hIGF-1) to the cerebrum, we measured the uptake of nasally administered iodine-125 hIGF-1 ((125)I-hIGF-1) in the cerebrum as a percentage of that in the blood in male ICR mice subjected to left olfactory bulb resection (model mice) and in sham-operated male ICR mice (control mice). Phosphorylated extracellular signal-regulated kinase (ERK) 1/2 (Thr202/Tyr204)/(Thr185/Tyr187) as a percentage of total ERK 1/2 in the left cerebrum was also assessed by using enzyme-linked immunosorbent assay after nasal administration of hIGF-1. Uptake of nasally administered (125)I-hIGF-1 in the cerebrum as a percentage of that in the blood was significantly lower in the model group than in the control group 30min after nasal administration of hIGF-1. Unilateral olfactory bulb resection prevented nasally administered hIGF-1 from increasing the phosphorylation of ERK 1/2 in the mouse cerebrum in vivo. These findings suggest that olfactory bulb damage reduces nasal transport of hIGF-1 to the brain in vivo.

  15. Dosimetry of nasal uptake of water-soluble and reactive gases: a first study of interhuman variability.

    PubMed

    Garcia, Guilherme J M; Schroeter, Jeffry D; Segal, Rebecca A; Stanek, John; Foureman, Gary L; Kimbell, Julia S

    2009-06-01

    Certain inhaled chemicals, such as reactive, water-soluble gases, are readily absorbed by the nasal mucosa upon inhalation and may cause damage to the nasal epithelium. Comparisons of the spatial distribution of nasal lesions in laboratory animals exposed to formaldehyde with gas uptake rates predicted by computational models reveal that lesions usually occur in regions of the susceptible epithelium where gas absorption is highest. Since the uptake patterns are influenced by air currents in the nose, interindividual variability in nasal anatomy and ventilation rates due to age, body size, and gender will affect the patterns of gas absorption in humans, potentially putting some age groups at higher risk when exposed to toxic gases. In this study, interhuman variability in the nasal dosimetry of reactive, water-soluble gases was investigated by means of computational fluid dynamics (CFD) models in 5 adults and 2 children, aged 7 and 8 years old. Airflow patterns were investigated for allometrically scaled inhalation rates corresponding to resting breathing. The spatial distribution of uptake at the airway walls was predicted to be nonuniform, with most of the gas being absorbed in the anterior portion of the nasal passages. Under the conditions of these simulations, interhuman variability in dose to the whole nose (mass per time per nasal surface area) due to differences in anatomy and ventilation was predicted to be 1.6-fold among the 7 individuals studied. Children and adults displayed very similar patterns of nasal gas uptake; no significant differences were noted between the two age groups.

  16. Does nasal decongestion improve obstructive sleep apnea?

    PubMed

    Clarenbach, Christian F; Kohler, Malcolm; Senn, Oliver; Thurnheer, Robert; Bloch, Konrad E

    2008-12-01

    Whether nasal congestion promotes obstructive sleep apnea is controversial. Therefore, we performed a randomized placebo-controlled cross-over trial on the effects of topical nasal decongestion in patients with obstructive sleep apnea syndrome (OSA) and nasal congestion. Twelve OSA patients with chronic nasal congestion (mean +/- SD age 49.1 +/- 11.1 years, apnea/hypopnea index 32.6 +/- 24.5/h) were treated with nasal xylometazoline or placebo for 1 week each. At the end of treatment periods, polysomnography including monitoring of nasal conductance by an unobtrusive technique, vigilance by the OSLER test, and symptom scores were assessed. Data from xylometazoline and placebo treatments were compared. Mean nocturnal nasal conductance on xylometazoline was significantly higher than on placebo (8.6 +/- 5.3 versus 6.3 +/- 5.8 mL s(-1)Pa(-1), P < 0.05) but the apnea/hypopnea index was similar (29.3 +/- 32.5/h versus 33.2 +/- 32.8/h, P = NS). However, 30-210 min after application of xylometazoline, at the time of the maximal pharmacologic effect, the apnea/hypopnea index was slightly reduced (27.3 +/- 30.5/h versus 33.2 +/- 33.9/h, P < 0.05). Xylometazoline did not alter sleep quality, sleep resistance time (33.6 +/- 8.8 versus 33.4 +/- 10.1 min, P = NS) and subjective sleepiness (Epworth score 10.5 +/- 3.8 versus 11.8 +/- 4.4, P = NS). The reduced apnea/hypopnea index during maximal nasal decongestion by xylometazoline suggests a pathophysiologic link but the efficacy of nasal decongestion was not sufficient to provide a clinically substantial improvement of OSA. PMID:18710420

  17. Two methods for establishing primary human endometrial stromal cells from hysterectomy specimens.

    PubMed

    Jividen, Kasey; Movassagh, Mercedeh Javanbakht; Jazaeri, Amir; Li, Hui

    2014-01-01

    Many efforts have been devoted to establish in vitro cell culture systems. These systems are designed to model a vast number of in vivo processes. Cell culture systems arising from human endometrial samples are no exception. Applications range from normal cyclic physiological processes to endometrial pathologies such as gynecological cancers, infectious diseases, and reproductive deficiencies. Here, we provide two methods for establishing primary endometrial stromal cells from surgically resected endometrial hysterectomy specimens. The first method is referred to as "the scraping method" and incorporates mechanical scraping using surgical or razor blades whereas the second method is termed "the trypsin method." This latter method uses the enzymatic activity of trypsin to promote the separation of cells and primary cell outgrowth. We illustrate step-by-step methodology through digital images and microscopy. We also provide examples for validating endometrial stromal cell lines via quantitative real time polymerase chain reactions (qPCR) and immunofluorescence (IF). PMID:24894444

  18. Hyperoside protects human primary melanocytes against H2O2-induced oxidative damage

    PubMed Central

    YANG, BIN; YANG, QIN; YANG, XIN; YAN, HONG-BO; LU, QI-PING

    2016-01-01

    Cuscutae semen has been shown to have beneficial effects in the treatment of vitiligo, recorded in the Chinese Pharmacopoeia, whereas the effects of its constituent compounds remains to be elucidated. Using a tetrazolium bromide assay, the present study found that hyperoside (0.5–200 µg/ml) significantly increased the viability of human melanocytes in a time- and dose-dependent manner. The present study used a cell model of hydrogen peroxide (H2O2)-induced oxidative damage to examine the effect of hyperoside on human primary melanocytes. The results demonstrated that hyperoside pretreatment for 2 h decreased cell apoptosis from 54.03±9.11 to 17.46±3.10% in the H2O2-injured melanocytes. The levels of oxidative stress in the mitochondrial membrane potential of the melanocytes increased following hyperoside pretreatment. The mRNA and protein levels of B-cell lymphoma-2/Bcl-2-associated X protein and caspase 3 were regulated by hyperoside, and phosphoinositide 3-kinase/AKT and mitogen-activated protein kinase signaling were also mediated by hyperoside. In conclusion, the results of the present study demonstrated that hyperoside protected the human primary melanocytes against oxidative damage. PMID:27082158

  19. Electrotransfection and lipofection show comparable efficiency for in vitro gene delivery of primary human myoblasts.

    PubMed

    Mars, Tomaz; Strazisar, Marusa; Mis, Katarina; Kotnik, Nejc; Pegan, Katarina; Lojk, Jasna; Grubic, Zoran; Pavlin, Mojca

    2015-04-01

    Transfection of primary human myoblasts offers the possibility to study mechanisms that are important for muscle regeneration and gene therapy of muscle disease. Cultured human myoblasts were selected here because muscle cells still proliferate at this developmental stage, which might have several advantages in gene therapy. Gene therapy is one of the most sought-after tools in modern medicine. Its progress is, however, limited due to the lack of suitable gene transfer techniques. To obtain better insight into the transfection potential of the presently used techniques, two non-viral transfection methods--lipofection and electroporation--were compared. The parameters that can influence transfection efficiency and cell viability were systematically approached and compared. Cultured myoblasts were transfected with the pEGFP-N1 plasmid either using Lipofectamine 2000 or with electroporation. Various combinations for the preparation of the lipoplexes and the electroporation media, and for the pulsing protocols, were tested and compared. Transfection efficiency and cell viability were inversely proportional for both approaches. The appropriate ratio of Lipofectamine and plasmid DNA provides optimal conditions for lipofection, while for electroporation, RPMI medium and a pulsing protocol using eight pulses of 2 ms at E = 0.8 kV/cm proved to be the optimal combination. The transfection efficiencies for the optimal lipofection and optimal electrotransfection protocols were similar (32 vs. 32.5%, respectively). Both of these methods are effective for transfection of primary human myoblasts; however, electroporation might be advantageous for in vivo application to skeletal muscle.

  20. Oxidative Stress Kills Human Primary Oligodendrocytes Via Neutral Sphingomyelinase: Implications for Multiple Sclerosis

    PubMed Central

    Jana, Arundhati

    2007-01-01

    Multiple sclerosis (MS) is the most common human demyelinating disease of the central nervous system where oxidative stress has been proposed to play an important role in oligodendroglial death. However, molecular mechanisms that couple oxidative stress to the loss of oligodendrocytes are poorly understood. This study underlines the importance of neutral sphingomyelinase–ceramide pathway in mediating oxidative stress-induced apoptosis and cell death of human primary oligodendrocytes. Various oxidative stress-inducing agents, such as, superoxide radical produced by hypoxanthine and xanthine oxidase, hydrogen peroxide, aminotriazole capable of inhibiting catalase and increasing intracellular level of H2O2, or reduced glutathione-depleting diamide induced the activation of neutral sphingomyelinase and the production of ceramide. It is interesting to note that antisense knockdown of neutral but not acidic sphingomyelinase ablated oxidative stress-induced apoptosis and cell death in human primary oligodendrocytes. This study identifies neutral but not acidic sphingomyelinase as a target for possible therapeutic intervention in MS. PMID:18040843

  1. Human prion protein-induced autophagy flux governs neuron cell damage in primary neuron cells

    PubMed Central

    Moon, Ji-Hong; Lee, Ju-Hee; Nazim, Uddin MD; Lee, You-Jin; Seol, Jae-Won; Eo, Seong-Kug; Lee, John-hwa; Park, Sang-Youel

    2016-01-01

    An unusual molecular structure of the prion protein, PrPsc is found only in mammals with transmissible prion diseases. Prion protein stands for either the infectious pathogen itself or a main component of it. Recent studies suggest that autophagy is one of the major functions that keep cells alive and has a protective effect against the neurodegeneration. In this study, we investigated that the effect of human prion protein on autophagy-lysosomal system of primary neuronal cells. The treatment of human prion protein induced primary neuron cell death and decreased both LC3-II and p62 protein amount indicating autophagy flux activation. Electron microscope pictures confirmed the autophagic flux activation in neuron cells treated with prion protein. Inhibition of autophagy flux using pharmacological and genetic tools prevented neuron cell death induced by human prion protein. Autophagy flux induced by prion protein is more activated in prpc expressing cells than in prpc silencing cells. These data demonstrated that prion protein-induced autophagy flux is involved in neuron cell death in prion disease and suggest that autophagy flux might play a critical role in neurodegenerative diseases including prion disease. PMID:27102156

  2. 21 CFR 874.5550 - Powered nasal irrigator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Therapeutic Devices § 874.5550 Powered nasal irrigator. (a) Identification. A powered nasal irrigator is an AC-powered device intended to wash the nasal cavity by means of a... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Powered nasal irrigator. 874.5550 Section...

  3. 21 CFR 874.5550 - Powered nasal irrigator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Therapeutic Devices § 874.5550 Powered nasal irrigator. (a) Identification. A powered nasal irrigator is an AC-powered device intended to wash the nasal cavity by means of a... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Powered nasal irrigator. 874.5550 Section...

  4. Molecular cloning, primary structure, and expression of the human platelet/erythroleukemia cell 12-lipoxygenase

    SciTech Connect

    Funk, C.D.; Furci, L.; FitzGerald, G.A. )

    1990-08-01

    The major pathway of arachidonic acid metabolism in human platelets proceeds via a 12-lipoxygenase enzyme; however, the biological role of the product of this reaction, 12-hydro(pero)xyeicosatetraenoic acid (12-H(P)ETE), is unknown. Using a combination of the polymerase chain reaction and conventional screening procedures, the authors have isolated cDNA clones encoding the human platelet/human erythroleukemia (HEL) cell 12-lipoxygenase. From the deduced primary structure, human platelet/HEL 12-lipoxygenase would encode a M{sub r} 75,000 protein consisting of 663 amino acids. The cDNA encoding the full-length protein (pCDNA-12lx) under the control of the cytomegalovirus promoter was expressed in simian COS-M6 cells. Intact cells and lysed-cell supernatants were able to synthesize 12-H(P)ETE from arachidonic acid, whereas no 12-H(P)ETE synthesis was detected in mock-transfected cells. A single 2.4-kilobase mRNA was detected in erythroleukemia cells but not in several other tissues and cell lines evaluated by Northern blot analysis. Comparison of the human platelet/HEL 12-lipoxygenase sequence with that of porcine leukocyte 12-lipoxygenase and human reticulocyte 15-lipoxygenase revealed 65% amino acid identity to both enzymes. By contrast, the leukocyte 12-lipoxygenase is 86% identical to human reticulocyte 15-lipoxygenase. Sequence data and previously demonstrated immunochemical and biochemical evidence support the existence of distinct 12-lipoxygenase isoforms. The availability of cDNA probes for human platelet/HEL cell 12-lipoxygenase should facilitate elucidation of the biological role of this pathway.

  5. Bisphenol A and Bisphenol S Induce Distinct Transcriptional Profiles in Differentiating Human Primary Preadipocytes

    PubMed Central

    Boucher, Jonathan G.; Gagné, Rémi; Rowan-Carroll, Andrea; Boudreau, Adèle; Yauk, Carole L.; Atlas, Ella

    2016-01-01

    Bisphenol S (BPS) is increasingly used as a replacement plasticizer for bisphenol A (BPA) but its effects on human health have not been thoroughly examined. Recent evidence indicates that both BPA and BPS induce adipogenesis, although the mechanisms leading to this effect are unclear. In an effort to identify common and distinct mechanisms of action in inducing adipogenesis, transcriptional profiles of differentiating human preadipocytes exposed to BPA or BPS were compared. Human subcutaneous primary preadipocytes were differentiated in the presence of either 25 μM BPA or BPS for 2 and 4 days. Poly-A RNA-sequencing was used to identify differentially expressed genes (DEGs). Functional analysis of DEGs was undertaken in Ingenuity Pathway Analysis. BPA-treatment resulted in 472 and 176 DEGs on days 2 and 4, respectively, affecting pathways such as liver X receptor (LXR)/retinoid X receptor (RXR) activation, hepatic fibrosis and cholestasis. BPS-treatment resulted in 195 and 51 DEGs on days 2 and 4, respectively, revealing enrichment of genes associated with adipogenesis and lipid metabolism including the adipogenesis pathway and cholesterol biosynthesis. Interestingly, the transcription repressor N-CoR was identified as a negative upstream regulator in both BPA- and BPS-treated cells. This study presents the first comparison of BPA- and BPS-induced transcriptional profiles in human differentiating preadipocytes. While we previously showed that BPA and BPS both induce adipogenesis, the results from this study show that BPS affects adipose specific transcriptional changes earlier than BPA, and alters the expression of genes specifically related to adipogenesis and lipid metabolism. The findings provide insight into potential BPS and BPA-mediated mechanisms of action in inducing adipogenesis in human primary preadipocytes. PMID:27685785

  6. Case report: unilateral mydriasis following nasal cautery.

    PubMed

    Koo Ng, Nigel K F; Calder, Nick

    2010-12-01

    We report a case of unilateral mydriasis following nasal electrocautery presumed to be the result of retrograde flow of adrenaline and/or xylometazoline hydrochloride (Otrivine) through the nasolacrimal duct into the eye. We review the literature and highlight the importance of correct interpretation of finding a dilated pupil post-operatively. To our knowledge. we report the first such case involving xylometazoline hydrochloride and also following nasal electrocautery. Unilateral mydriasis is alarming after nasal surgery but must be interpreted with caution. During minimally invasive procedures it is likely to be due to the effects of topical medication to the nose rather than surgical trauma. PMID:21158576

  7. Dynamic Changes in Heart Rate Variability and Nasal Airflow Resistance during Nasal Allergen Provocation Test.

    PubMed

    Seppänen, Tiina M; Alho, Olli-Pekka; Seppänen, Tapio

    2016-01-01

    Allergic rhinitis is a major chronic respiratory disease and an immunoneuronal disorder. We aimed at providing further knowledge on the function of the neural system in nasal allergic reaction. Here, a method to assess simultaneously the nasal airflow resistance and the underlying function of autonomic nervous system (ANS) is presented and used during the nasal provocation of allergic and nonallergic subjects. Continuous nasal airflow resistance and spectral heart rate variability parameters show in detail the timing and intensity differences in subjects' reactions. After the provocation, the nasal airflow resistance of allergic subjects showed a positive trend, whereas LF/HF (Low Frequency/High Frequency) ratio and LF power showed a negative trend. This could imply a gradual sympathetic withdrawal in allergic subjects after the allergen provocation. The groups differed significantly by these physiological descriptors. The proposed method opens entirely new opportunities to research accurately concomitant changes in nasal breathing function and ANS. PMID:27196870

  8. Immunophenotypic and Clinical Differences Between the Nasal and Extranasal Subtypes of Upper Aerodigestive Tract Natural Killer/T-Cell Lymphoma

    SciTech Connect

    Liu, Qing-Feng; Wang, Wei-Hu; Wang, Shu-Lian; Liu, Yue-Ping; Huang, Wen-Ting; Lu, Ning; Zhou, Li-Qiang; Ouyang, Han; Jin, Jing; Li, Ye-Xiong

    2014-03-15

    Purpose: To investigate, in a large cohort of patients, the immunophenotypic and clinical differences of nasal and extranasal extranodal nasal-type natural killer/T-cell lymphoma of the upper aerodigestive tract (UADT-NKTCL) and examine the relevance of the immunophenotype on the clinical behavior, prognosis, and treatment. Methods and Materials: A total of 231 patients with UADT-NKTCL were recruited. One hundred eighty-one patients had primary location in the nasal cavity (nasal UADT-NKTCL), and 50 patients had primary extranasal UADT-NKTCL. Results: Patients with extranasal UADT-NKTCL had more adverse clinical features, including advanced-stage disease, regional lymph node involvement, B symptoms, and poor performance status, than patients with nasal UADT-NKTCL. In addition, CD56 and granzyme B were less frequently expressed in extranasal UADT-NKTCL. The 5-year overall survival rate was 74.1% for the entire group and 76.0% for early-stage disease. The 5-year overall survival rate for extranasal UADT-NKTCL was similar or superior to that of nasal UADT-NKTCL for all disease stages (76.9% vs 73.4%, P=.465), stage I disease (75.9% vs 79.2%, P=.786), and stage II disease (83.3% vs 50.3%, P=.018). CD56 expression and a Ki-67 proliferation rate ≥50% predicted poorer survival for extranasal UADT-NKTCL but not for nasal UADT-NKTCL. Conclusions: Patients with nasal and extranasal UADT-NKTCL have significantly different clinical features, immunophenotypes, and prognosis. Extranasal UADT-NKTCL should be considered as a distinct subgroup apart from the most commonly diagnosed prototype of nasal UADT-NKTCL.

  9. A transcriptional sketch of a primary human breast cancer by 454 deep sequencing

    PubMed Central

    Guffanti, Alessandro; Iacono, Michele; Pelucchi, Paride; Kim, Namshin; Soldà, Giulia; Croft, Larry J; Taft, Ryan J; Rizzi, Ermanno; Askarian-Amiri, Marjan; Bonnal, Raoul J; Callari, Maurizio; Mignone, Flavio; Pesole, Graziano; Bertalot, Giovanni; Bernardi, Luigi Rossi; Albertini, Alberto; Lee, Christopher; Mattick, John S; Zucchi, Ileana; De Bellis, Gianluca

    2009-01-01

    Background The cancer transcriptome is difficult to explore due to the heterogeneity of quantitative and qualitative changes in gene expression linked to the disease status. An increasing number of "unconventional" transcripts, such as novel isoforms, non-coding RNAs, somatic gene fusions and deletions have been associated with the tumoral state. Massively parallel sequencing techniques provide a framework for exploring the transcriptional complexity inherent to cancer with a limited laboratory and financial effort. We developed a deep sequencing and bioinformatics analysis protocol to investigate the molecular composition of a breast cancer poly(A)+ transcriptome. This method utilizes a cDNA library normalization step to diminish the representation of highly expressed transcripts and biology-oriented bioinformatic analyses to facilitate detection of rare and novel transcripts. Results We analyzed over 132,000 Roche 454 high-confidence deep sequencing reads from a primary human lobular breast cancer tissue specimen, and detected a range of unusual transcriptional events that were subsequently validated by RT-PCR in additional eight primary human breast cancer samples. We identified and validated one deletion, two novel ncRNAs (one intergenic and one intragenic), ten previously unknown or rare transcript isoforms and a novel gene fusion specific to a single primary tissue sample. We also explored the non-protein-coding portion of the breast cancer transcriptome, identifying thousands of novel non-coding transcripts and more than three hundred reads corresponding to the non-coding RNA MALAT1, which is highly expressed in many human carcinomas. Conclusion Our results demonstrate that combining 454 deep sequencing with a normalization step and careful bioinformatic analysis facilitates the discovery and quantification of rare transcripts or ncRNAs, and can be used as a qualitative tool to characterize transcriptome complexity, revealing many hitherto unknown

  10. Nasal mass removal in the koala (Phascolarctos cinereus).

    PubMed

    Bercier, Marjorie; Wynne, Janna; Klause, Stephen; Stadler, Cynthia K; Gorow, April; Pye, Geoffrey W

    2012-12-01

    Nasal masses in the koala (Phascolarctos cinereus) are not uncommon and can be challenging to diagnose and treat. Differential diagnoses for nasal masses in the koala are cryptococcal granulomas, nasal polyps, nasal adenocarcinoma, and osteochondromatosis. This report describes successful surgical approaches for two adult koalas with nasal masses and includes photodocumentation and description of the anatomy of the koala nasal passages from the postmortem transverse sectioning of a normal koala head. Surgical removal of the nasal masses in these koalas resulted in a rapid resolution of clinical signs.

  11. Use of primary high-risk human papillomavirus testing for cervical cancer screening: interim clinical guidance.

    PubMed

    Huh, Warner K; Ault, Kevin A; Chelmow, David; Davey, Diane D; Goulart, Robert A; Garcia, Francisco A R; Kinney, Walter K; Massad, L Stewart; Mayeaux, Edward J; Saslow, Debbie; Schiffman, Mark; Wentzensen, Nicolas; Lawson, Herschel W; Einstein, Mark H

    2015-02-01

    In 2011, the American Cancer Society, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology updated screening guidelines for the early detection of cervical cancer and its precursors. Recommended screening strategies were cytology or cotesting (cytology in combination with high-risk human papillomavirus [hrHPV] testing). These guidelines also addressed the use of hrHPV testing alone as a primary screening approach, which was not recommended for use at that time. There is now a growing body of evidence for screening with primary hrHPV testing, including a prospective U.S.-based registration study. Thirteen experts, including representatives from the Society of Gynecologic Oncology, the American Society for Colposcopy and Cervical Pathology, the American College of Obstetricians and Gynecologists, the American Cancer Society, the American Society of Cytopathology, the College of American Pathologists, and the American Society for Clinical Pathology, convened to provide interim guidance for primary hrHPV screening. This guidance panel was specifically triggered by an application to the U.S. Food and Drug Administration (FDA) for a currently marketed HPV test to be labeled for the additional indication of primary cervical cancer screening. Guidance was based on literature review and review of data from the FDA registration study, supplemented by expert opinion. This document aims to provide information for health care providers who are interested in primary hrHPV testing and an overview of the potential advantages and disadvantages of this strategy for screening as well as to highlight areas in need of further investigation.

  12. Primary Ciliary Dyskinesia.

    PubMed

    Knowles, Michael R; Zariwala, Maimoona; Leigh, Margaret

    2016-09-01

    Primary ciliary dyskinesia (PCD) is a recessive genetically heterogeneous disorder of motile cilia with chronic otosinopulmonary disease and organ laterality defects in ∼50% of cases. The prevalence of PCD is difficult to determine. Recent diagnostic advances through measurement of nasal nitric oxide and genetic testing has allowed rigorous diagnoses and determination of a robust clinical phenotype, which includes neonatal respiratory distress, daily nasal congestion, and wet cough starting early in life, along with organ laterality defects. There is early onset of lung disease in PCD with abnormal airflow mechanics and radiographic abnormalities detected in infancy and early childhood. PMID:27514592

  13. Catecholamine concentrations in rat nasal mucus are modulated by trigeminal stimulation of the nasal cavity.

    PubMed

    Lucero, M T; Squires, A

    1998-10-01

    Olfactory mucus provides the perireceptor environment in which the initial steps of olfactory signal transduction occur [5]. Extrinsic autonomic and trigeminal innervation controls mucus secretion and may release neurotransmitters into nasal mucus [13]. We quantitated catecholamines in rat nasal mucus and found that catecholamine levels first increased and then declined with trigeminal stimulation. These data indicate that catecholamine levels are regulated in nasal mucus and could modulate the odor sensitivity of olfactory sensory neurons.

  14. Comparative nasal absorption of allergens in atopic and nonatopic subjects.

    PubMed

    Kontou-Karakitsos, K; Salvaggio, J E; Mathews, K P

    1975-04-01

    Based on sensitization following intranasal antigen administration, previous investigations have suggested greater absorption of allergens through the nasal mucous membranes of atopic than of nonatopic subjects. In this study mucosal absorption was assessed more directly by determining the capacity of allergens applied intranasally to elicit cutaneous Prausnitz-Küstner (P-K) reactions in nonatopic persons as compared with asymptomatic atopic subjects sensitive to other allergens. Two series of reaginic human serum dilutions were injected intracutaneously in recipients backs, and 48 hours later one series was challenged intracutaneously with test allergen. After the responses had been recorded, concentrated allergenic extract was sprayed into the nose and the second series of P-K sites observed for reactivity. Sometimes these P-K sites were rechallenged intracutaneously the following day to determine passive transfer neutralization. Two allergens were studied: bovine ribonuclease (RNase) and peanut extract. Two sera containing peanut reagins and one with RNase antibodies were each used in 10 to 11 atopic and 9 to 11 nonatopic recipients. The atopic group failed to show greater or more rapid absorption of either allergen through the nose based on the highest serum dilution reacting after nasal challenge. the speed of the reaction, the ratio of the titer by nasal challenge to the intracutaneous titer, or passive transfer neutralization. Controls showed that the results were not influenced by systemic absorption of allergen employed for intracutaneous tests. Drinking the amount of peanut extract applied intranasally did not elicit P-K reactions.

  15. Nasal absorption of interferon: Enhancement by surfactant agents

    SciTech Connect

    Baglioni, C.; Phipps, R.J. )

    1990-10-01

    The effect of spraying the nasal mucosa with an aerosol of recombinant human interferon-alpha (IFN-alpha 2a) was studied in an animal model, the sheep, because cultures of sheep cells were found to be responsive to the antiviral activity of this IFN. Binding assays with {sup 125}I-labeled IFN-alpha 2a detected very few receptors in sheep nasal mucosa, but a membrane fraction prepared from this mucosa had abundant high-affinity receptors. Nasal mucosa homogenates were prepared from the turbinates of sheep that had been sprayed with IFN-alpha 2a aerosols, and the 2',5'-oligoadenylate (2-5A) activity induced in response was measured. To try to enhance the permeability of the mucosa, surfactant agents were added to the IFN and aerosols generated. There were measurable levels of 2-5A synthetase after aerosols with added sodium deoxycholate or, better, polyoxyethylene 9-lauryl ether. This latter surfactant was well tolerated in previous studies with intranasally administered insulin. The level of 2-5A synthetase induced was related to the dose of IFN, and the increased activity persisted up to 72 h after an IFN aerosol. These studies suggest that surfactant agents may make IFN aerosols much more effective for the prophylaxis of respiratory virus infections.

  16. [Disturbances of nasal aerodynamics in patients with the curved nasal septum and the rationale for its surgical correction].

    PubMed

    Tulebaev, R K; Mustafin, A A; Zholdybaeva, Z T

    2011-01-01

    Serious disturbances of nasal aerodynamics contribute to the development of diseases of the broncho-pulmonary apparatus. The early recognition of ventilation problems in patients with the curved nasal septum is paramount for the efficacious prevention and treatment of respiratory complications. The authors describe principles of rhinosurgical correction of affected nasal aerodynamics in patients with the curved nasal septum.

  17. 21 CFR 341.80 - Labeling of nasal decongestant drug products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Labeling of nasal decongestant drug products. 341.80 Section 341.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC...

  18. Rabbit muscle creatine phosphokinase. CDNA cloning, primary structure and detection of human homologues.

    PubMed

    Putney, S; Herlihy, W; Royal, N; Pang, H; Aposhian, H V; Pickering, L; Belagaje, R; Biemann, K; Page, D; Kuby, S

    1984-12-10

    A cDNA library was constructed from rabbit muscle poly(A) RNA. Limited amino acid sequence information was obtained on rabbit muscle creatine phosphokinase and this was the basis for design and synthesis of two oligonucleotide probes complementary to a creatine kinase cDNA sequence which encodes a pentapeptide. Colony hybridizations with the probes and subsequent steps led to isolation of two clones, whose cDNA segments partially overlap and which together encode the entire protein. The primary structure was established from the sequence of two cDNA clones and from independently determined sequences of scattered portions of the polypeptide. The reactive cysteine has been located to position 282 within the 380 amino acid polypeptide. The rabbit cDNA hybridizes to digests of human chromosomal DNA. This reveals a restriction fragment length polymorphism associated with the human homologue(s) which hybridizes to the rabbit cDNA.

  19. Complexity of the primary genetic response to mitogenic activation of human T cells

    SciTech Connect

    Zipfel, P.F.; Siebenlist, U. ); Irving, S.G.; Kelly, K. )

    1989-03-01

    The authors describe the isolation and characterization of more than 60 novel cDNA clones that constitute part of the immediate genetic response to resting human peripheral blood T cells after mitogen activation. This primary response was highly complex, both in the absolute number of inducible genes and in the diversity of regulation. Although most of the genes expressed in activated T cells were shared with the activation response of normal human fibroblasts, a significant number were more restricted in tissue specificity and thus likely encode or effect the differentiated functions of activated T cells. The activatable genes could be further differentiated on the basis of kinetics of induction, response to cycloheximide, and sensitivity to the immunosuppressive drug cylcosporin A. It is of note that cyclosporin A inhibited the expression of more than 10 inducible genes, which suggests that this drug has a broad genetic mechanism of action.

  20. Neurotoxic potential and cellular uptake of T-2 toxin in human astrocytes in primary culture.

    PubMed

    Weidner, Maria; Lenczyk, Marlies; Schwerdt, Gerald; Gekle, Michael; Humpf, Hans-Ulrich

    2013-03-18

    The trichothecene mycotoxin T-2 toxin, which is produced by fungi of the Fusarium species, is a worldwide occurring contaminant of cereal based food and feed. The cytotoxic properties of T-2 toxin are already well described with apoptosis being a major mechanism of action in various cell lines as well as in primary cells of different origin. However, only few data on neurotoxic properties of T-2 toxin are reported so far, but in vivo studies showed different effects of T-2 toxin on behavior as well as on levels of brain amines in animals. To further investigate the cytotoxic properties of T-2 toxin on cells derived from brain tissue, normal human astrocytes in primary culture (NHA) were used in this study. Besides studies of cytotoxicity, apoptosis (caspase-3-activation, Annexin V) and necrosis (LDH-release), the cellular uptake and metabolism of T-2 toxin in NHA was analyzed and compared to the uptake in an established human cell line (HT-29). The results show that human astrocytes were highly sensitive to the cytotoxic properties of T-2 toxin, and apoptosis, induced at low concentrations, was identified for the first time as the mechanism of toxic action in NHA. Furthermore, a strong accumulation of T-2 toxin in NHA and HT-29 cells was detected, and T-2 toxin was subjected to metabolism leading to HT-2 toxin, a commonly found metabolite after T-2 toxin incubation in both cell types. This formation seems to occur within the cells since incubations of T-2 toxin with cell depleted culture medium did not lead to any degradation of the parent toxin. The results of this study emphasize the neurotoxic potential of T-2 toxin in human astrocytes at low concentrations after short incubation times. PMID:23363530

  1. 1,25 Dihydroxyvitamin D3 Inhibits TGFβ1-Mediated Primary Human Cardiac Myofibroblast Activation

    PubMed Central

    Meredith, Anna; Boroomand, Seti; Carthy, Jon; Luo, Zongshu; McManus, Bruce

    2015-01-01

    Aims Epidemiological and interventional studies have suggested a protective role for vitamin D in cardiovascular disease, and basic research has implicated vitamin D as a potential inhibitor of fibrosis in a number of organ systems; yet little is known regarding direct effects of vitamin D on human cardiac cells. Given the critical role of fibrotic responses in end stage cardiac disease, we examined the effect of active vitamin D treatment on fibrotic responses in primary human adult ventricular cardiac fibroblasts (HCF-av), and investigated the relationship between circulating vitamin D (25(OH)D3) and cardiac fibrosis in human myocardial samples. Methods and Results Interstitial cardiac fibrosis in end stage HF was evaluated by image analysis of picrosirius red stained myocardial sections. Serum 25(OH)D3 levels were assayed using mass spectrometry. Commercially available HCF-av were treated with transforming growth factor (TGF)β1 to induce activation, in the presence or absence of active vitamin D (1,25(OH)2D3). Functional responses of fibroblasts were analyzed by in vitro collagen gel contraction assay. 1,25(OH)2D3 treatment significantly inhibited TGFβ1-mediated cell contraction, and confocal imaging demonstrated reduced stress fiber formation in the presence of 1,25(OH)2D3. Treatment with 1,25(OH)2D3 reduced alpha-smooth muscle actin expression to control levels and inhibited SMAD2 phosphorylation. Conclusions Our results demonstrate that active vitamin D can prevent TGFβ1-mediated biochemical and functional pro-fibrotic changes in human primary cardiac fibroblasts. An inverse relationship between vitamin D status and cardiac fibrosis in end stage heart failure was observed. Collectively, our data support an inhibitory role for vitamin D in cardiac fibrosis. PMID:26061181

  2. Isolation and genetic characterization of human coronavirus NL63 in primary human renal proximal tubular epithelial cells obtained from a commercial supplier, and confirmation of its replication in two different types of human primary kidney cells

    PubMed Central

    2013-01-01

    Background Cryopreserved primary human renal proximal tubule epithelial cells (RPTEC) were obtained from a commercial supplier for studies of Simian virus 40 (SV40). Within twelve hrs after cell cultures were initiated, cytoplasmic vacuoles appeared in many of the RPTEC. The RPTEC henceforth deteriorated rapidly. Since SV40 induces the formation of cytoplasmic vacuoles, this batch of RPTEC was rejected for the SV40 study. Nevertheless, we sought the likely cause(s) of the deterioration of the RPTEC as part of our technology development efforts. Methods Adventitious viruses in the RPTEC were isolated and/or detected and identified by isolation in various indicator cell lines, observation of cytopathology, an immunoflurorescence assay, electron microscopy, PCR, and sequencing. Results Cytomegalovirus (CMV) was detected in some RPTEC by cytology, an immunofluorescence assay, and PCR. Human Herpesvirus 6B was detected by PCR of DNA extracted from the RPTEC, but was not isolated. Human coronavirus NL63 was isolated and identified by RT-PCR and sequencing, and its replication in a fresh batch of RPTEC and another type of primary human kidney cells was confirmed. Conclusions At least 3 different adventitious viruses were present in the batch of contaminated RPTEC. Whereas we are unable to determine whether the original RPTEC were pre-infected prior to their separation from other kidney cells, or had gotten contaminated with HCoV-NL63 from an ill laboratory worker during their preparation for commercial sale, our findings are a reminder that human-derived biologicals should always be considered as potential sources of infectious agents. Importantly, HCoV-NL63 replicates to high titers in some primary human kidney cells. PMID:23805916

  3. Nasal Chondromesenchymal Hamartoma in a Child

    SciTech Connect

    Finitsis, Stefanos; Giavroglou, Constantinos; Potsi, Stamatia; Constantinidis, Ioannis; Mpaltatzidis, Angelos; Rachovitsas, Dimitrios; Tzioufa, Valentini

    2009-05-15

    Nasal chondromesenchymal hamartoma (NCMH) is a benign tumor that was described in 1998. The occurrence of this lesion in the nasal cavity of infants and children is especially rare, with only 21 cases reported in the international literature. We report a 12-month-old boy with respiratory distress due to nasal obstruction. Computed tomographic scan and magnetic resonance imaging examination demonstrated a soft-tissue mass obstructing the left nasal cavity. Digital subtraction angiography and preoperative superselective embolization with microparticles were also performed. The tumor was completely resected surgically. Histopathology and immunohistochemical analyses of the tumor disclosed a NCMH. The imaging characteristics of the tumor are described and the radiology literature is reviewed.

  4. Nasal toxicity of cocaine: a hypercoagulable effect?

    PubMed Central

    Patel, R.; Shah, R.; Baredes, S.; Spillert, C. R.; Lazaro, E. J.

    2000-01-01

    Nasal insufflation of cocaine injures the nasal mucosa and can perforate the septum. Cocaine-induced vasoconstriction resulting in ischemia is one of the methods that may be responsible for this damage. We are determining whether cocaine also produces a hypercoagulable state that may compound factors which have been previously established to cause damage to the nasal mucosa and septum. This study uses Modified Recalcification Time (MRT), a test developed in our laboratory that has the ability to measure the overall coagulation process. Our study revealed no connection between cocaine and enhanced platelet function or monocyte-released tissue factor. The coagulation process was unaffected by the addition of the drug, so we conclude that cocaine does not cause a hypercoagulable state and cannot assist in the explanation regarding the ischemic changes of the nasal septum. PMID:10800286

  5. Nasal foreign body: an unexpected discovery.

    PubMed

    Yasny, Jeffrey S; Stewart, Stacy

    2011-01-01

    Abstract Nasal foreign bodies may result from the abundant availability of tiny objects in our society and a curious child exploring his or her nasal cavities. An inserted object that is not witnessed or retrieved can remain relatively asymptomatic or cause local tissue damage and potentially yield more serious consequences. An unusual case of a young child who presented for dental rehabilitation under general anesthesia is described. Immediately prior to the nasotracheal intubation, an unanticipated foreign body was detected and safely removed before any injury occurred. This case report discusses the presentation and pathophysiology of nasal foreign bodies. Moreover, applicable suggestions are provided to aid in the prevention and management of the unexpected discovery of a nasal foreign body after the induction of general anesthesia.

  6. Nasal Mucociliary Transport Before and After Jogging.

    ERIC Educational Resources Information Center

    Cederlund, Anna; And Others

    1987-01-01

    A study of nasal mucociliary transport in 11 healthy subjects before and after they jogged 8-10 kilometers indicated that the transport time was significantly longer after jogging than before jogging. (Author/CB)

  7. Development of the cetacean nasal skull.

    PubMed

    Klima, M

    1999-01-01

    The adaptation of cetaceans to aquatic life habits is reflected, in their nasal region, in three marked changes from the original relations found in land mammals. These changes include (1) the loss of the sense of smell, (2) translocation of the nostrils from the tip of the rostrum to the vertex of the head, and (3) elongation of the anterior head to form a rostrum protruding far towards anterior. The morphogenetic processes taking place during embryogenesis of the nasal skull play a decisive part in the development of all these changes. The lateral parts of the embryonic nasal capsule, encompassing the nasal passages, change their position from horizontal to vertical. At the same time, the structures of the original nasal floor (the solum nasi) are shifted in front of the nasal passages towards the rostrum. The structures of the original nasal roof (the tectum nasi) and of the nasal side wall (the paries nasi) are translocated behind the nasal passages towards the neurocranium. The medial nasal septum (the septum nasi) mostly loses its connection to the nasal passages and is produced into a point protruding far towards anterior. The transformed embryonic nasal skull of the Cetacea can be divided into three sections: 1. The median structures. These include the cartilaginous structures, viz., the rostrum nasi, the septum interorbitale and the spina mesethmoidalis, which are accompanied by the dermal bones, the vomer and the praemaxillare. In adult cetaceans the rostrum nasi is mostly preserved as a robust cartilage of the skull, which may possibly serve as a sound transmitting structure of the sonar system, or it may be responsible for the sensing of water streams and vibrations. 2. The posterior side wall structures. These include the following cartilaginous structures that are mostly heavily reduced or mutually fused: the cupula nasi anterior, the tectum nasi, the lamina cribrosa, the paries nasi, the commissura orbitonasalis, the cupula nasi posterior, the

  8. Microstructured zirconia surfaces modulate osteogenic marker genes in human primary osteoblasts.

    PubMed

    Bergemann, Claudia; Duske, Kathrin; Nebe, J Barbara; Schöne, André; Bulnheim, Ulrike; Seitz, Hermann; Fischer, Jens

    2015-01-01

    In dentistry, zirconia has been used since the early 1990s for endodontic posts, more recently for implant abutments and frameworks for fixed dental prostheses. Zirconia is biocompatible and mechanically strong enough to serve as implant material for oral implants. Although several zirconia implant systems are available, currently the scientific and clinical data for zirconia implants are not sufficient to recommend them for routine clinical use. Here the influence of microstructured yttria-stabilized zirconia (YZ) on human primary osteoblast (HOB) behavior was determined. YZ surfaces were treated by sandblasting (YZ-S), acid etching (YZ-SE) and additionally heat treatment (YZ-SEH). Morphological changes of HOB were determined by scanning electron microscopy. Actin cytoskeleton was investigated by laser scanning microscopy and analyzed by novel actin quantification software. Differentiation of HOB was determined by real time RT-PCR. Improved mechanical interlocking of primary HOB into the porous microstructure of the acid etched and additionally heat treated YZ-surfaces correlates with drastically increased osteocalcin (OCN) gene expression. In particular, OCN was considerably elevated in primary HOB after 3 days on YZ-SE (13-fold) as well as YZ-SEH (12-fold) surfaces. Shorter actin filaments without any favored orientation on YZ-SE and YZ-SEH surfaces are associated with higher roughness (Ra) values. Topographically modified yttria-stabilized zirconia is a likely material for dental implants with cell stimulating properties achieving or actually exceeding those of titanium. PMID:25578704

  9. Phenotypic differentiation does not affect tumorigenicity of primary human colon cancer initiating cells.

    PubMed

    Dubash, Taronish D; Hoffmann, Christopher M; Oppel, Felix; Giessler, Klara M; Weber, Sarah; Dieter, Sebastian M; Hüllein, Jennifer; Zenz, Thorsten; Herbst, Friederike; Scholl, Claudia; Weichert, Wilko; Werft, Wiebke; Benner, Axel; Schmidt, Manfred; Schneider, Martin; Glimm, Hanno; Ball, Claudia R

    2016-02-28

    Within primary colorectal cancer (CRC) a subfraction of all tumor-initiating cells (TIC) drives long-term progression in serial xenotransplantation. It has been postulated that efficient maintenance of TIC activity in vitro requires serum-free spheroid culture conditions that support a stem-like state of CRC cells. To address whether tumorigenicity is indeed tightly linked to such a stem-like state in spheroids, we transferred TIC-enriched spheroid cultures to serum-containing adherent conditions that should favor their differentiation. Under these conditions, primary CRC cells did no longer grow as spheroids but formed an adherent cell layer, up-regulated colon epithelial differentiation markers, and down-regulated TIC-associated markers. Strikingly, upon xenotransplantation cells cultured under either condition equally efficient formed serially transplantable tumors. Clonal analyses of individual lentivirally marked TIC clones cultured under either culture condition revealed no systematic differences in contributing clone numbers, indicating that phenotypic differentiation does not select for few individual clones adapted to unfavorable culture conditions. Our results reveal that CRC TIC can be propagated under conditions previously thought to induce their elimination. This phenotypic plasticity allows addressing primary human CRC TIC properties in experimental settings based on adherent cell growth.

  10. [Diagnostic methods of nasal respiratory function].

    PubMed

    Mlynski, G; Beule, A

    2008-01-01

    Objective assessment of nasal obstruction may help with preoperative planning for rhinosurgery and indicate different aspects of endonasal pathology. To improve quality control, preoperative and postoperative objective assessment is desirable. This review presents objective functional diagnostic tools and explains their appropriate uses, the information obtained, and their limitations. An algorithm is presented for analysing nasal obstruction by means of objective functional assessment. Examples illustrate how to use this information for preoperative planning in rhinosurgery. PMID:18210011

  11. Necrotizing sialometaplasia of the nasal cavity.

    PubMed

    Chen, K T

    1982-01-01

    A case of necrotizing sialometaplasia involving the mucous membrane of a nasal turbinate is described. Necrotizing sialometaplasia is a benign, self-limited process characterized by necrosis and squamous metaplasia of the salivary or mucous glands. Typically, the lesion manifests as an ulcer of the hard palate. Nonulcerated lesions and involvement of sites other than the hard palate have also been reported. This case appears to be the second reported case of involvement of the nasal cavity by necrotizing sialometaplasia.

  12. Origin and primary dispersal of the Mycobacterium tuberculosis Beijing genotype: Clues from human phylogeography

    PubMed Central

    Mokrousov, Igor; Ly, Ho Minh; Otten, Tatiana; Lan, Nguyen Ngoc; Vyshnevskyi, Boris; Hoffner, Sven; Narvskaya, Olga

    2005-01-01

    We suggest that the evolution of the population structure of microbial pathogens is influenced by that of modern humans. Consequently, the timing of hallmark changes in bacterial genomes within the last 100,000 yr may be attempted by comparison with relevant human migrations. Here, we used a lineage within Mycobacterium tuberculosis, a Beijing genotype, as a model and compared its phylogeography with human demography and Y chromosome-based phylogeography. We hypothesize that two key events shaped the early history of the Beijing genotype: (1) its Upper Palaeolithic origin in the Homo sapiens sapiens K-M9 cluster in Central Asia, and (2) primary Neolithic dispersal of the secondary Beijing NTF::IS6110 lineage by Proto-Sino-Tibetan farmers within east Asia (human O-M214/M122 haplogroup). The independent introductions of the Beijing strains from east Asia to northern Eurasia and South Africa were likely historically recent, whereas their differential dissemination within these areas has been influenced by demographic and climatic factors. PMID:16169923

  13. Microtubule plus end–associated CLIP-170 initiates HSV-1 retrograde transport in primary human cells

    PubMed Central

    Jovasevic, Vladimir

    2015-01-01

    Dynamic microtubules (MTs) continuously explore the intracellular environment and, through specialized plus end–tracking proteins (+TIPs), engage a variety of targets. However, the nature of cargoes that require +TIP-mediated capture for their movement on MTs remains poorly understood. Using RNA interference and dominant-negative approaches, combined with live cell imaging, we show that herpes simplex virus particles that have entered primary human cells exploit a +TIP complex comprising end-binding protein 1 (EB1), cytoplasmic linker protein 170 (CLIP-170), and dynactin-1 (DCTN1) to initiate retrograde transport. Depletion of these +TIPs completely blocked post-entry long-range transport of virus particles and suppressed infection ∼5,000-fold, whereas transferrin uptake, early endosome organization, and dynein-dependent movement of lysosomes and mitochondria remained unaffected. These findings provide the first insights into the earliest stages of viral engagement of MTs through specific +TIPs, akin to receptors, with therapeutic implications, and identify herpesvirus particles as one of a very limited number of cargoes absolutely dependent on CLIP-170–mediated capture to initiate transport in primary human cells. PMID:26504169

  14. Spatiotemporal analysis of RhoA/B/C activation in primary human endothelial cells

    PubMed Central

    Reinhard, Nathalie R.; van Helden, Suzanne F.; Anthony, Eloise C.; Yin, Taofei; Wu, Yi I.; Goedhart, Joachim; Gadella, Theodorus W. J.; Hordijk, Peter L.

    2016-01-01

    Endothelial cells line the vasculature and are important for the regulation of blood pressure, vascular permeability, clotting and transendothelial migration of leukocytes and tumor cells. A group of proteins that that control the endothelial barrier function are the RhoGTPases. This study focuses on three homologous (>88%) RhoGTPases: RhoA, RhoB, RhoC of which RhoB and RhoC have been poorly characterized. Using a RhoGTPase mRNA expression analysis we identified RhoC as the highest expressed in primary human endothelial cells. Based on an existing RhoA FRET sensor we developed new RhoB/C FRET sensors to characterize their spatiotemporal activation properties. We found all these RhoGTPase sensors to respond to physiologically relevant agonists (e.g. Thrombin), reaching transient, localized FRET ratio changes up to 200%. These RhoA/B/C FRET sensors show localized GEF and GAP activity and reveal spatial activation differences between RhoA/C and RhoB. Finally, we used these sensors to monitor GEF-specific differential activation of RhoA/B/C. In summary, this study adds high-contrast RhoB/C FRET sensors to the currently available FRET sensor toolkit and uncover new insights in endothelial and RhoGTPase cell biology. This allows us to study activation and signaling by these closely related RhoGTPases with high spatiotemporal resolution in primary human cells. PMID:27147504

  15. Spatiotemporal analysis of RhoA/B/C activation in primary human endothelial cells.

    PubMed

    Reinhard, Nathalie R; van Helden, Suzanne F; Anthony, Eloise C; Yin, Taofei; Wu, Yi I; Goedhart, Joachim; Gadella, Theodorus W J; Hordijk, Peter L

    2016-01-01

    Endothelial cells line the vasculature and are important for the regulation of blood pressure, vascular permeability, clotting and transendothelial migration of leukocytes and tumor cells. A group of proteins that that control the endothelial barrier function are the RhoGTPases. This study focuses on three homologous (>88%) RhoGTPases: RhoA, RhoB, RhoC of which RhoB and RhoC have been poorly characterized. Using a RhoGTPase mRNA expression analysis we identified RhoC as the highest expressed in primary human endothelial cells. Based on an existing RhoA FRET sensor we developed new RhoB/C FRET sensors to characterize their spatiotemporal activation properties. We found all these RhoGTPase sensors to respond to physiologically relevant agonists (e.g. Thrombin), reaching transient, localized FRET ratio changes up to 200%. These RhoA/B/C FRET sensors show localized GEF and GAP activity and reveal spatial activation differences between RhoA/C and RhoB. Finally, we used these sensors to monitor GEF-specific differential activation of RhoA/B/C. In summary, this study adds high-contrast RhoB/C FRET sensors to the currently available FRET sensor toolkit and uncover new insights in endothelial and RhoGTPase cell biology. This allows us to study activation and signaling by these closely related RhoGTPases with high spatiotemporal resolution in primary human cells. PMID:27147504

  16. Rapid Reprogramming of Primary Human Astrocytes into Potent Tumor-Initiating Cells with Defined Genetic Factors.

    PubMed

    Li, Fang; Liu, Xinjian; Sampson, John H; Bigner, Darell D; Li, Chuan-Yuan

    2016-09-01

    Cancer stem-like cells (CSC) are thought to drive brain cancer, but their cellular and molecular origins remain uncertain. Here, we report the successful generation of induced CSC (iCSC) from primary human astrocytes through the expression of defined genetic factors. Combined transduction of four factors, Myc, Oct-4, p53DD, and Ras, induced efficient transformation of primary human astrocytes into malignant cells with powerful tumor-initiating capabilities. Notably, transplantation of 100 transduced cells into nude mice was sufficient for tumor formation. The cells showed unlimited self-renewal ability with robust telomerase activities. In addition, they expressed typical glioma stem-like cell markers, such as CD133, CD15, and CD90. Moreover, these cells could form spheres in culture and differentiate into neuron-like, astrocyte-like, and oligodendrocyte-like cells. Finally, they also displayed resistance to the widely used brain cancer drug temozolomide. These iCSCs could provide important tools for studies of glioma biology and therapeutics development. Cancer Res; 76(17); 5143-50. ©2016 AACR. PMID:27364552

  17. In vivo functional and myeloarchitectonic mapping of human primary auditory areas

    PubMed Central

    Dick, Frederic; Tierney, Adam Taylor; Lutti, Antoine; Josephs, Oliver; Sereno, Martin I.; Weiskopf, Nikolaus

    2012-01-01

    In contrast to vision, where retinotopic mapping alone can define areal borders, primary auditory areas such as A1 are best delineated by combining in vivo tonotopic mapping with post mortem cyto- or myelo-architectonics from the same individual. We combined high-resolution (800 μm) quantitative T1 mapping with phase-encoded tonotopic methods to map primary auditory areas (A1 and R) within the ‘auditory core’ of human volunteers. We first quantitatively characterize the highly myelinated auditory core in terms of shape, area, cortical depth profile, and position, with our data showing considerable correspondence to post-mortem myeloarchitectonic studies, both in cross-participant averages and in individuals. The core region contains two ‘mirror-image‘ tonotopic maps oriented along the same axis as observed in macaque and owl monkey. We suggest that thee two maps within the core are the human analogues of primate auditory areas A1 and R. The core occupies a much smaller portion of tonotopically organized cortex on the superior temporal plane and gyrus than is generally supposed. The multi-modal approach to defining the auditory core will facilitate investigations of structure-function relationships, comparative neuroanatomical studies, and promises new biomarkers for diagnosis and clinical studies. PMID:23152594

  18. On the relation between surface roughness of metallic substrates and adhesion of human primary bone cells.

    PubMed

    Anselme, K; Bigerelle, M

    2014-01-01

    Surface characteristics of materials, whether their topography, chemistry, or surface energy, play an essential part in osteoblast adhesion on biomaterials. Thus, the quality of cell adhesion will influence the cell's capacity to proliferate and differentiate in contact with a biomaterial. We have developed for more than ten years numerous studies on the influence of topography and chemistry of metallic substrates on the response of primary human bone cells. The originality of our approach is that contrary to most of other authors, we quantified the adhesion of primary human bone cells on metallic substrates with perfectly characterized surface topography after some hours but also over 21 days. Moreover, we have developed original statistical approaches for characterizing the relation between surface roughness and cell-adhesion parameters. In this article, we will illustrate different studies we did these last ten years concerning the development of a new adhesion parameter, the adhesion power; the correlation between short-term adhesion, long-term adhesion, and proliferation; the influence of roughness organization on cell adhesion and the development of the order parameter; our modeling approach of cell adhesion on surface topography; the relative influence of surface chemistry and topography on cell adhesion and contact angle; the relation between surface features dimensions and cell adhesion. Further, some considerations will be given on the methods for scanning surface topography for cell-adhesion studies. Finally, perspectives will be given to elucidate these intracellular mechanotransduction mechanisms induced by the deformation of cells on model sinusoidal peaks-or-valleys surfaces.

  19. Standardized 3D Bioprinting of Soft Tissue Models with Human Primary Cells.

    PubMed

    Rimann, Markus; Bono, Epifania; Annaheim, Helene; Bleisch, Matthias; Graf-Hausner, Ursula

    2016-08-01

    Cells grown in 3D are more physiologically relevant than cells cultured in 2D. To use 3D models in substance testing and regenerative medicine, reproducibility and standardization are important. Bioprinting offers not only automated standardizable processes but also the production of complex tissue-like structures in an additive manner. We developed an all-in-one bioprinting solution to produce soft tissue models. The holistic approach included (1) a bioprinter in a sterile environment, (2) a light-induced bioink polymerization unit, (3) a user-friendly software, (4) the capability to print in standard labware for high-throughput screening, (5) cell-compatible inkjet-based printheads, (6) a cell-compatible ready-to-use BioInk, and (7) standard operating procedures. In a proof-of-concept study, skin as a reference soft tissue model was printed. To produce dermal equivalents, primary human dermal fibroblasts were printed in alternating layers with BioInk and cultured for up to 7 weeks. During long-term cultures, the models were remodeled and fully populated with viable and spreaded fibroblasts. Primary human dermal keratinocytes were seeded on top of dermal equivalents, and epidermis-like structures were formed as verified with hematoxylin and eosin staining and immunostaining. However, a fully stratified epidermis was not achieved. Nevertheless, this is one of the first reports of an integrative bioprinting strategy for industrial routine application.

  20. Chemokine-Targeted Mouse Models of Human Primary and Metastatic Colorectal Cancer

    PubMed Central

    Chen, Huanhuan Joyce; Sun, Jian; Huang, Zhiliang; Hou, Harry; Arcilla, Myra; Rakhilin, Nikolai; Joe, Daniel J.; Choi, Jiahn; Gadamsetty, Poornima; Milsom, Jeff; Nandakumar, Govind; Longman, Randy; Zhou, Xi Kathy; Edwards, Robert; Chen, Jonlin; Chen, Kai Yuan; Bu, Pengcheng; Wang, Lihua; Xu, Yitian; Munroe, Robert; Abratte, Christian; Miller, Andrew D.; Gümüş, Zeynep H.; Shuler, Michael; Nishimura, Nozomi; Edelmann, Winfried; Shen, Xiling; Lipkin, Steven M.

    2015-01-01

    Current orthotopic xenograft models of human colorectal cancer (CRC) require surgery and do not robustly form metastases in the liver, the most common site clinically. CCR9 traffics lymphocytes to intestine and colorectum. We engineered use of the chemokine receptor CCR9 in CRC cell lines and patient-derived cells to create primary gastrointestinal (GI) tumors in immunodeficient mice by tail-vein injection rather than surgery. The tumors metastasize inducibly and robustly to the liver. Metastases have higher DKK4 and NOTCH signaling levels and are more chemoresistant than paired sub-cutaneous xenografts. Using this approach, we generated 17 chemokine-targeted mouse models (CTMMs) that recapitulate the majority of common human somatic CRC mutations. We also show that primary tumors can be modeled in immunocompetent mice by microinjecting CCR9-expressing cancer cell lines into early-stage mouse blastocysts, which induces central immune tolerance. We expect that CTMMs will facilitate investigation of the biology of CRC metastasis and drug screening. PMID:26006007