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Sample records for primary human nasal

  1. 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

  2. Primary nasal tuberculosis: a case report.

    PubMed

    Nayar, Ravi C; Al Kaabi, Juma; Ghorpade, Kanchanmala

    2004-03-01

    During the past 2 decades, tuberculosis--both pulmonary and extrapulmonary--has re-emerged as a major health problem worldwide. Nasal tuberculosis--either primary or secondary to pulmonary tuberculosis or facial lupus--is rare, but it should be considered in the differential diagnosis of nasal granulomas. We describe a case of primary nasal tuberculosis in an adult male who presented with a polypoid lesion in one nasal cavity. The diagnosis was based on histopathology and the patient's successful response to antituberculous drug treatment. Given the rising incidence of tuberculosis, it is prudent that otolaryngologists remain cognizant of this infection as a potential cause of unusual lesions in the head and neck.

  3. Depicting the inner and outer nose: the representation of the nose and the nasal mucosa on the human primary somatosensory cortex (SI).

    PubMed

    Gastl, Mareike; Brünner, Yvonne F; Wiesmann, Martin; Freiherr, Jessica

    2014-09-01

    The nose is important not only for breathing, filtering air, and perceiving olfactory stimuli. Although the face and hands have been mapped, the representation of the internal and external surface of the nose on the primary somatosensory cortex (SI) is still poorly understood. To fill this gap functional magnetic resonance imaging (fMRI) was used to localize the nose and the nasal mucosa in the Brodman areas (BAs) 3b, 1, and 2 of the human postcentral gyrus (PG). Tactile stimulation during fMRI was applied via a customized pneumatically driven device to six stimulation sites: the alar wing of the nose, the lateral nasal mucosa, and the hand (serving as a reference area) on the left and right side of the body. Individual representations could be discriminated for the left and right hand, for the left nasal mucosa and left alar wing of the nose in BA 3b and BA 1 by comparing mean activation maxima and Euclidean distances. Right-sided nasal conditions and conditions in BA 2 could further be separated by different Euclidean distances. Regarding the alar wing of the nose, the results concurred with the classic sensory homunculus proposed by Penfield and colleagues. The nasal mucosa was not only determined an individual and bilateral representation, its position on the somatosensory cortex is also situated closer to the caudal end of the PG compared to that of the alar wing of the nose and the hand. As SI is commonly activated during the perception of odors, these findings underscore the importance of the knowledge of the representation of the nasal mucosa on the primary somatosensory cortex, especially for interpretation of results of functional imaging studies about the sense of smell.

  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. Nasal obstruction and human communication.

    PubMed

    Malinoff, R; Moreno, C

    1989-04-01

    Nasal obstruction may cause a variety of communication disorders, particularly in children. The effects of nasal obstruction on hearing, speech, language, and voice are examined. Methods for assessing the effects of nasal obstruction are delineated, and recommendations for therapeutic interventions are described.

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

    PubMed

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

    2015-10-01

    The distribution of cilia and the respiratory syncytial virus (RSV) nucleocapsid (N) protein, fusion (F) protein, attachment (G) protein, and M2-1 protein in human ciliated nasal epithelial cells was examined at between 1 and 5 days post-infection (dpi). All virus structural proteins were localized at cell surface projections that were distinct from cilia. The F protein was also trafficked into the cilia, and while its presence increased as the infection proceeded, the N protein was not detected in the cilia at any time of infection. The presence of the F protein in the cilia correlated with cellular changes in the cilia and reduced cilia function. At 5dpi 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.

  7. 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.

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

    PubMed Central

    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

  9. 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.

  10. Exploring the bacterial assemblages along the human nasal passage.

    PubMed

    Wos-Oxley, Melissa L; Chaves-Moreno, Diego; Jáuregui, Ruy; Oxley, Andrew P A; Kaspar, Ursula; Plumeier, Iris; Kahl, Silke; Rudack, Claudia; Becker, Karsten; Pieper, Dietmar H

    2016-07-01

    The human nasal passage, from the anterior nares through the nasal vestibule to the nasal cavities, is an important habitat for opportunistic pathogens and commensals alike. This work sampled four different anatomical regions within the human nasal passage across a large cohort of individuals (n = 79) comprising individuals suffering from chronic nasal inflammation clinically known as chronic rhinosinusitis (CRS) and individuals not suffering from inflammation (CRS-free). While individuals had their own unique bacterial fingerprint that was consistent across the anatomical regions, these bacterial fingerprints formed into distinct delineated groups comprising core bacterial members, which were consistent across all four swabbed anatomical regions irrespective of health status. The most significant observed pattern was the difference between the global bacterial profiles of swabbed and tissue biopsy samples from the same individuals, being also consistent across different anatomical regions. Importantly, no statistically significant differences could be observed concerning the global bacterial communities, any of the bacterial species or the range of diversity indices used to compare between CRS and CRS-free individuals, and between two CRS phenotypes (without nasal polyps and with nasal polyps). Thus, the role of bacteria in the pathogenesis of sinusitis remains uncertain.

  11. 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

  12. Measuring and Characterizing the Human Nasal Cycle.

    PubMed

    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.

  13. The ontogeny of nasal floor shape variation in extant humans.

    PubMed

    Nicholas, Christina L; Franciscus, Robert G

    2014-11-01

    Variation in nasal floor topography has generated both neontological and paleontological interest. Three categories of nasal floor shape (Franciscus: J Hum Evol 44 (2003) 699-727) have been used when analyzing this trait in extant humans and fossil Homo: flat, sloped, and depressed (or "bi-level"). Variation in the frequency of these configurations within and among extant and fossil humans has been well-documented (Franciscus: J Hum Evol 44 (2003) 699-727; Wu et al.: Anthropol Sci 120 (2012) 217-226). However, variation in this trait in Homo has been observed primarily in adults, with comparatively small subadult sample sizes and/or large age gradients that may not sufficiently track key ontogenetic changes. In this study, we investigate the ontogeny of nasal floor shape in a relatively large cross-sectional age sample of extant humans (n = 382) ranging from 4.0 months fetal to 21 years post-natal. Results indicate that no fetal or young infant individuals possess a depressed nasal floor, and that a depressed nasal floor, when present (ca. 21% of the sample), does not occur until 3.0 years postnatal. A canonical variates analysis of maxillary shape revealed that individuals with depressed nasal floors were also characterized by relatively taller anterior alveolar regions. This suggests that palate remodeling at about 3.0-3.5 years after birth, under the influence of tooth development, strongly influences nasal floor variation, and that various aspects of dental development, including larger crown/root size, may contribute to the development of a depressed nasal floor. These results in extant humans may help explain the high frequency of this trait found in Neandertal and other archaic Homo maxillae.

  14. LPS may enhance expression and release of HMGB1 in human nasal epithelial cells in vitro.

    PubMed

    Chen, D; Bellussi, L M; Passali, D; Chen, L

    2013-12-01

    Chronic rhinosinusitis with nasal polyps is a common disease with still unclear pathophysiologic mechanisms. The airway epithelial barrier has been shown to be involved in different chronic disorders, including rhinitis, nasal polyposis and asthma. High mobility group box 1 (HMGB1), a primarily nuclear protein, is involved in the induction of airway inflammation in patients with chronic rhinosinusitis, allergy, asthma and COPD. Pathogen-derived lipopolysaccharide is widely used as a trigger for inflammation. However, the molecular dialogue between LPS and HMGB1 in the delayed inflammatory processes remains to be explored, and the regulation of HMGB1 release through LPS from epithelial cells has not been extensively studied in patients with chronic rhinosinusitis and nasal polyps. The objective of the present study was to investigate the relocation of HMGB1 in LPS-induced human nasal epithelial cells in vitro. We obtained epithelial cells of nasal polyps from 10 patients requiring surgery for sinusitis at the ENT Department of the Chinese PLA General Hospital. The primary cultured human nasal epithelial (HNE) cells were stimulated with LPS. The expression and translocation of HMGB1 in intracellular and culture supernatants were determined using Western blot and immunofluorescence assay. HMGB1 protein was released in a time-dependent fashion in culture supernatants: in fact, expression of HMGB1 protein in HNE cells showed no significant changes at 0-24 h after exposure to 100 μg/ml LPS, but increased significantly at 48 and 72 hr. Immunofluorescence analysis revealed the transfer of HMGB1 from nuclei to cytoplasm in response to LPS exposure after 24 hr. These data reveal a hitherto unrecognized association between HMGB1 and LPS in human nasal epithelial cells. LPS can affect HMGB1 translocation and release, suggesting the involvement of HMGB1, through inflammatory mediators, in chronic rhinosinusitis with nasal polyps.

  15. 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.

  16. Hypoxia Increases Epithelial Permeability in Human Nasal Epithelia

    PubMed Central

    Min, Hyun Jin; Kim, Tae Hoon; Yoon, Joo-Heon

    2015-01-01

    Purpose The nasal mucosa is the first site to encounter pathogens, and it forms continuous barriers to various stimuli. This barrier function is very important in the innate defense mechanism. Additionally, inflammation of the nasal sinus is known to be a hypoxic condition. Here, we studied the effect of hypoxia on barrier function in normal human nasal epithelial (NHNE) cells. Materials and Methods The expression levels of various junction complex proteins were assessed in hypoxia-stimulated NHNE cells and human nasal mucosal tissues. We performed real-time polymerase chain reaction analysis, western blotting, and immunofluorescence assays to examine differences in the mRNA and protein expression of ZO-1, a tight junction protein, and E-cadherin in NHNE cells. Moreover, we evaluated the trans-epithelial resistance (TER) of NHNE cells under hypoxic conditions to check for changes in permeability. The expression of ZO-1 and E-cadherin was measured in human nasal mucosa samples by western blotting. Results Hypoxia time-dependently decreased the expression of ZO-1 and E-cadherin at the gene and protein levels. In addition, hypoxia decreased the TER of NHNE cells, which indicates increased permeability. Human nasal mucosa samples, which are supposed to be hypoxic, showed significantly decreased levels of ZO-1 and E-cadherin expression compared with control. Conclusion Our results demonstrate that hypoxia altered the expression of junction complex molecules and increased epithelial permeability in human nasal epithelia. This suggests that hypoxia causes barrier dysfunction. Furthermore, it may be associated with innate immune dysfunction after encountering pathogens. PMID:25837192

  17. 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.

  18. 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

  19. Primary Tuberculosis of Nose Causing Bilateral Nasal Obstruction and Halitosis in a 25-Year-Old Woman

    PubMed Central

    Rajam, Leena; Kumar, Sabitha Hari

    2017-01-01

    Primary or secondary nasal tuberculosis is rare and usually, it is considered as an extra pulmonary form of tuberculosis. Nasal tuberculosis infection may spread to maxillary palatal region by contagious or haematogenous route causing palatal perforation. In some instance, it may cause septal perforation with nasal obstruction which may give rise to halitosis. We report a case where, there was bilateral nasal mucosal involvement leading to severe nasal obstruction. This rare manifestation should be considered in areas where the disease is prevalent as delay in diagnosis and treatment could lead to serious and life threatening complications due to local spread from the nose to the para nasal sinuses and brain. PMID:28384990

  20. Nasal Immunization Confers High Avidity Neutralizing Antibody Response and Immunity to Primary and Recurrent Genital Herpes in Guinea Pigs

    PubMed Central

    Persson, Josefine; Zhang, Yuan; Olafsdottir, Thorunn A.; Thörn, Karolina; Cairns, Tina M.; Wegmann, Frank; Sattentau, Quentin J.; Eisenberg, Roselyn J.; Cohen, Gary H.; Harandi, Ali M.

    2016-01-01

    Genital herpes is one of the most prevalent sexually transmitted infections in both the developing and developed world. Following infection, individuals experience life-long latency associated with sporadic ulcerative outbreaks. Despite many efforts, no vaccine has yet been licensed for human use. Herein, we demonstrated that nasal immunization with an adjuvanted HSV-2 gD envelope protein mounts significant protection to primary infection as well as the establishment of latency and recurrent genital herpes in guinea pigs. Nasal immunization was shown to elicit specific T cell proliferative and IFN-γ responses as well as systemic and vaginal gD-specific IgG antibody (Ab) responses. Furthermore, systemic IgG Abs displayed potent HSV-2 neutralizing properties and high avidity. By employing a competitive surface plasmon resonance (SPR) analysis combined with a battery of known gD-specific neutralizing monoclonal Abs (MAbs), we showed that nasal immunization generated IgG Abs directed to two major discontinuous neutralizing epitopes of gD. These results highlight the potential of nasal immunization with an adjuvanted HSV-2 envelope protein for induction of protective immunity to primary and recurrent genital herpes. PMID:28082979

  1. Nasal Immunization Confers High Avidity Neutralizing Antibody Response and Immunity to Primary and Recurrent Genital Herpes in Guinea Pigs.

    PubMed

    Persson, Josefine; Zhang, Yuan; Olafsdottir, Thorunn A; Thörn, Karolina; Cairns, Tina M; Wegmann, Frank; Sattentau, Quentin J; Eisenberg, Roselyn J; Cohen, Gary H; Harandi, Ali M

    2016-01-01

    Genital herpes is one of the most prevalent sexually transmitted infections in both the developing and developed world. Following infection, individuals experience life-long latency associated with sporadic ulcerative outbreaks. Despite many efforts, no vaccine has yet been licensed for human use. Herein, we demonstrated that nasal immunization with an adjuvanted HSV-2 gD envelope protein mounts significant protection to primary infection as well as the establishment of latency and recurrent genital herpes in guinea pigs. Nasal immunization was shown to elicit specific T cell proliferative and IFN-γ responses as well as systemic and vaginal gD-specific IgG antibody (Ab) responses. Furthermore, systemic IgG Abs displayed potent HSV-2 neutralizing properties and high avidity. By employing a competitive surface plasmon resonance (SPR) analysis combined with a battery of known gD-specific neutralizing monoclonal Abs (MAbs), we showed that nasal immunization generated IgG Abs directed to two major discontinuous neutralizing epitopes of gD. These results highlight the potential of nasal immunization with an adjuvanted HSV-2 envelope protein for induction of protective immunity to primary and recurrent genital herpes.

  2. Particle Image Velocimetry Measurements Inside the Human Nasal Passage

    NASA Astrophysics Data System (ADS)

    Kelly, James; Hopkins, Lisa; Sreenivas, K. R.; Wexler, Anthony; Prasad, Ajay

    1998-11-01

    In some applications (such as biological flows) the flow passage exhibits a highly complex geometry. A method is described by which such a flow passage is rendered as a three-dimensional model. A computer model of an adult human nasal cavity was generated from digitized computed tomography (CT) scan images, using the I-DEAS modeling package, and was converted to a stereolithographic file for rapid prototyping. Rapid prototyping yielded a water soluble negative of the airway. Silicone elastomer was poured over the negative, which was washed out after the silicone hardened. This technique can be used to obtain an accurate, transparent, silicone, replicate model of any arbitrary geometry. If the working fluid is refractive-index matched to the silicone, it is possible to obtain PIV measurements in any cross-section. We demonstrate the technique by creating a double-scale model of the human nasal passage, and obtaining PIV measurements.

  3. Primary Nasal Tuberculosis: Resurgence or Coincidence − A Report of Four Cases with Review of Literature

    PubMed Central

    Khan, Sabina; Pujani, Mukta; Jetley, Sujata

    2017-01-01

    Background: Primary nasal tuberculosis (TB) is a rare form of TB even in areas with high TB incidence. It is timely diagnosis and proper management are often delayed due to its rarity and nonspecific clinical presentation. Aim: The aim of the study was to review histopathologically diagnosed cases of nasal TB over a period of 1 year and to describe its clinical presentation, diagnostic workup, the importance of histopathological diagnosis along with a brief review of the literature. Materials and Methods: This was a retrospective study done in the Department of Pathology of a Tertiary Care Hospital of Delhi over a period of 1 year where all the cases with histopathological diagnosis of nasal TB were reviewed. Patients' clinical details, investigations and treatment details along with follow-up were obtained from the medical records section. For each case, routine hematoxylin and eosin stain were studied along with Ziehl–Neelson staining. Results: A total of four patients were diagnosed with nasal TB histopathologically. Patients' age ranged from 5 to 34 with an equal male to female ratio. All patients were immunocompetent. Primary nasal TB was seen in all of the four cases. None of the cases, it was clinically suspected, and histopathology was the mainstay of diagnosis. All the cases were treated with antituberculous treatment and showed considerable improvement. Conclusions: Although nasal TB is rare, it should be considered in the differential diagnosis of chronic nasal symptoms and granulomatous lesions of the nose. Histopathology plays an important role in the diagnosis of these clinically unsuspecting cases of nasal TB. PMID:28042213

  4. Computational fluid dynamics simulations of respiratory airflow in human nasal cavity and its characteristic dimension study

    NASA Astrophysics Data System (ADS)

    Zhang, Jun; Liu, Yingxi; Sun, Xiuzhen; Yu, Shen; Yu, Chi

    2008-04-01

    To study the airflow distribution in human nasal cavity during respiration and the characteristic parameters of nasal structure, three-dimensional, anatomically accurate representations of 30 adult nasal cavity models were reconstructed based on processed tomography images collected from normal people. The airflow fields in nasal cavities were simulated by fluid dynamics with finite element software ANSYS. The results showed that the difference of human nasal cavity structure led to different airflow distribution in the nasal cavities and variation of the main airstream passing through the common nasal meatus. The nasal resistance in the regions of nasal valve and nasal vestibule accounted for more than half of the overall resistance. The characteristic model of nasal cavity was extracted on the basis of characteristic points and dimensions deduced from the original models. It showed that either the geometric structure or the airflow field of the two kinds of models was similar. The characteristic dimensions were the characteristic parameters of nasal cavity that could properly represent the original model in model studies on nasal cavity.

  5. Primary NK/T cell lymphoma nasal type of the colon.

    PubMed

    Mahuad, Carolina Valeria; Bilbao, Erica Rojas; Garate, Gonzalo Martín; de Los Ángeles Vicente Repáraz, María; Del Olmo, Mercedes; Casali, Claudia Érica; Zerga, Marta Elisa; Chirife, Ana María; Cicco, Juan Alberto

    2013-02-11

    Since nasal NK/T-cell lymphoma and NK/T-cell lymphoma nasal type are rare diseases, colonic involvement has seldom been seen. We report a case of a patient with a primary NK/T-cell lymphoma nasal type of the colon. The patient had no history of malignant diseases and was diagnosed after exhaustive study in the context of fever of unknown origin. The first therapeutic approach followed the DA-EPOCH-protocol: etoposide, prednisone, doxor-rubicin, vincristine and cyclophosphamide. The persistence of constitutional symptoms after the first treatment course motivated the switch to a second line following the SMILE-protocol: dexamethasone, metotrexate, ifosfamide, E.coli L-asparaginase, and etoposide. Despite intensive chemotherapy, the patient died 2 months after the diagnose of an extranodal NK/T-cell lymphoma of the colon and 4 months after the first symptomatic appearance of disease.

  6. Primary NK/T cell lymphoma nasal type of the colon

    PubMed Central

    Mahuad, Carolina Valeria; Bilbao, Érica Rojas; Garate, Gonzalo Martín; de los Ángeles Vicente Repáraz, María; del Olmo, Mercedes; Casali, Claudia Érica; Zerga, Marta Elisa; Chirife, Ana María; Cicco, Juan Alberto

    2013-01-01

    Since nasal NK/T-cell lymphoma and NK/T-cell lymphoma nasal type are rare diseases, colonic involvement has seldom been seen. We report a case of a patient with a primary NK/T-cell lymphoma nasal type of the colon. The patient had no history of malignant diseases and was diagnosed after exhaustive study in the context of fever of unknown origin. The first therapeutic approach followed the DA-EPOCH-protocol: etoposide, prednisone, doxor-rubicin, vincristine and cyclophosphamide. The persistence of constitutional symptoms after the first treatment course motivated the switch to a second line following the SMILE-protocol: dexamethasone, metotrexate, ifosfamide, E.coli L-asparaginase, and etoposide. Despite intensive chemotherapy, the patient died 2 months after the diagnose of an extranodal NK/T-cell lymphoma of the colon and 4 months after the first symptomatic appearance of disease. PMID:23772308

  7. Swelling of Erectile Nasal Tissue Induced by Human Sexual Pheromone.

    PubMed

    Mazzatenta, Andrea; De Luca, C; Di Tano, A; Cacchio, M; Di Giulio, C; Pokorski, Mieczyslaw

    2016-01-01

    Most chemically mediated sexual communication in humans remains uncharacterized. Yet the study of sexual communication is decisive for understanding sexual behavior and evolutive mechanisms in our species. Here we provide the evidence to consider 4,16-androstadien-3-one (AND) as a man's sexual pheromone. Our experiment provides support for the physiological effect of AND on nasal airway resistance (Rna) in women, as assessed by anterior rhinomanometry. We found that AND administration increased the area of turbinate during the ovulatory phase, resulting in an increase of Rna. Thus, we discovered that minute amounts of AND, acting through neuroendocrine brain control, regulate Rna and consequently affect the sexual physiology and behavior. Fascinatingly, this finding provides the evidence of the preservation of chemosexual communication in humans, which it has been largely neglected due to its unconscious perception and concealed nature. Therefore, chemical communication is a plesiomorphic evolutive phenomenon in humans.

  8. 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

  9. Unilateral nasal obstruction affects motor representation development within the face primary motor cortex in growing rats.

    PubMed

    Abe, Yasunori; Kato, Chiho; Uchima Koecklin, Karin Harumi; Okihara, Hidemasa; Ishida, Takayoshi; Fujita, Koichi; Yabushita, Tadachika; Kokai, Satoshi; Ono, Takashi

    2017-03-23

    Postnatal growth is influenced by genetic and environmental factors. Nasal obstruction during growth alters the electromyographic activity of orofacial muscles. The facial primary motor area represents muscles of the tongue and jaw, which are essential in regulating orofacial motor functions, including chewing and jaw opening. This study aimed to evaluate the effect of chronic unilateral nasal obstruction during growth on the motor representations within the face primary motor cortex (M1). Seventy-two 6-day-old male Wistar rats were randomly divided into control (n = 36) and experimental (n = 36) groups. Rats in the experimental group underwent unilateral nasal obstruction after cauterization of the external nostril at 8 days of age. Intracortical microstimulation (ICMS) mapping was performed when the rats were 5, 7, 9, and 11 weeks old in control and experimental groups (n = 9 per group per time point). Repeated-measures multivariate analysis of variance was used for intergroup and intragroup statistical comparisons. In the control and experimental groups, the total number of positive ICMS sites for the genioglossus and anterior digastric muscles was significantly higher at 5, 7, and 9 weeks, but there was no significant difference between 9 and 11 weeks of age. Moreover, the total number of positive ICMS sites was significantly smaller in the experimental group than in the control at each age. It is possible that nasal obstruction induced the initial changes in orofacial motor behavior in response to the altered respiratory pattern, which eventually contributed to face-M1 neuroplasticity.

  10. Double-layered reconstruction of the nasal floor in complete cleft deformity of the primary palate using superfluous lip tissue.

    PubMed

    Park, Young-Wook; Kwon, Kwang-Jun; Kim, Min-Keun

    2015-12-01

    After cleft lip repair, many patients suffer from nasolabial fistulas, asymmetrical nasal floor, or an indistinct nostril sill, as well as intraoral wound dehiscence and subsequent scar contracture of surgical wounds leading to vestibular stenosis. For successful primary nasolabial repair of complete cleft deformity of the primary palate, cleft surgeons need special care in reconstructing the sound nasal floor. Especially when the cleft gap is wide or when any type of nasoalveolar molding therapy was not performed, three-dimensional reconstruction of the nasal floor is critical for a balanced nasal shape. In this study, the author describes an effective method for reconstructing a double-layered nasal floor using two mucosal flaps from both sides of the fissured upper lip. This is a report of six patients with unilateral or bilateral complete cleft of the primary palate with a detailed description of the surgical technique and a literature review.

  11. 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.

  12. 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

  13. Effect of nitrogen dioxide on human nasal epithelium

    SciTech Connect

    Carson, J.L.; Collier, A.M.; Hu, S.C.; Delvin, R.B. )

    1993-09-01

    The nasal epithelium of young adult white men in good health was evaluated by electron microscopy in a condition blind fashion relative to exposures of 2 ppm nitrogen dioxide (NO2) or clean air for 4 h. The exposure protocol involved two separate exposures of the same individuals to NO2 or clean air approximately 3 wk apart. We found qualitative and quantitative evidence that luminal border membranes of ciliated cells were ultrastructurally altered in six of seven samples of nasal epithelium obtained following NO2 exposures, although subsequent morphometric statistical analyses were not significant. This alteration was characterized by cilia containing excess matrix in which individual or, more commonly, multiple ciliary axonemes were embedded, and by vesiculations of luminal border ciliary membranes, a pattern less common in clean air-exposed control specimens. Although these patterns were not widespread, their morphology was consistent with findings of previous animal studies involving acute and chronic exposure to NO2. Our findings suggest that adverse effects on mucociliary function in normal humans due to acute exposure to low levels of NO2 are most likely minimal. However, in view of other reports of NO2 exposure in laboratory animals documenting ciliary injury, our observations support a view that similar patterns might appear more prominently with higher NO2 levels and/or more extended exposure intervals.

  14. 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.

  15. Geno- and cytotoxicity of salinomycin in human nasal mucosa and peripheral blood lymphocytes.

    PubMed

    Scherzad, Agmal; Hackenberg, Stephan; Schramm, Carolin; Froelich, Katrin; Ginzkey, Christian; Hagen, Rudolf; Kleinsasser, Norbert

    2015-06-01

    Salinomycin is usually applied in stock breading but has also been described as a promising agent against cancer stem cells (CSC). However, knowledge about the toxicity of this ionophor substance is incomplete. The aim of this study was to investigate cyto- and genotoxic effects of salinomycin in human non-malignant cells. Primary human nasal mucosa cells (monolayer and mini organ cultures) and peripheral blood lymphocytes from 10 individuals were used to study the cytotoxic effects of salinomycin (0.1-175 μM) by annexin-propidiumiodide- and MTT-test. The comet assay was performed to evaluate DNA damage. Additionally, the secretion of interleukin-8 was analyzed by ELISA. Flow cytometry and MTT assay revealed significant cytotoxic effects in nasal mucosa cells and lymphocytes at low salinomycin concentrations of 10-20 μM. No genotoxic effects could be observed. IL-8 secretion was elevated at 5 μM. Salinomycin-induced cytotoxic and pro-inflammatory effects were seen at concentrations relevant for anti-cancer treatment. Concurrent to the evaluation of salinomycin application in experimental oncology, adverse effects in non-malignant cells need to be monitored and reduced as much as possible. Further studies are also warranted to evaluate the toxic effects in a variety of human cell systems, e.g., liver, kidney and muscle cells.

  16. 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.

  17. Effects of cold dry air nasal stimulation on airway mucosal blood flow in humans.

    PubMed

    Le Merre, C; Isber, J; Chediak, A D; Wanner, A

    2003-10-01

    Several studies have demonstrated that nasal challenges can induce reflex responses in the respiratory system. Some authors have described bronchoconstriction and modification of the pattern of breathing following nasal challenges by irritants and cold air. We propose to determine the effect of nasal stimulation with cold dry air on airway mucosal blood flow (Qaw) in the proximal tracheal bronchial tree of healthy humans. Nine healthy subjects participated in the study. Baseline measurement Qaw, nasal airway resistance (NAR) and airway caliber by specific airways conductance (SGaw) were followed by nasal challenge with cold dry air. Qaw, NAR and Sgaw were determined after the challenge. In those subjects in which a significant decline in Qaw was recorded the protocol was repeated after pretreatment with nasal anesthesia using topical lidocaine. Cold dry air challenge produced a significant decrease in mean Qaw for the nine subjects and this response was abolished by pretreatment with nasal anesthesia using topical lidocaine. There was no significant change in Sgaw and NAR after the challenge and topical lidocaine anesthesia. Our data indicates that nasal stimulation with cold dry air leads to a reduction in Qaw and that this effect may be mediated by a nasal reflex.

  18. 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.

  19. Measurement of multiple microcirculatory parameters in human nasal mucosa using laser-Doppler velocimetry.

    PubMed

    Druce, H M; Kaliner, M A; Ramos, D; Bonner, R F

    1989-09-01

    LDV has been modified to measure four microcirculatory responses in human nasal mucosa. Resting nasal blood flow was measured in 115 observations in 23 nonatopic subjects and 111 observations in 21 atopic subjects with allergic nasal disease. Other parameters measured concurrently were the number density of moving red blood cells (RBC), mean RBC speed, and flow pulsatility. Challenges with aerosolized buffered saline or water had no significant effect on any parameter. By contrast, nasal application of alpha-adrenergic agonists, oxymetazoline and phenylephrine, produced significant dose-dependent reductions in flow without any significant change in RBC number density. These results suggest a selective alpha-agonist effect on resistance vessels but not on capacitance vessels. Topical cholinergic stimulation with methacholine selectively reduced the RBC number density without affecting other parameters. These modifications of LDV may prove useful in analyzing nasal responses to provocation and determining the sites of action of vasoactive agents on the microcirculation.

  20. Recommendations for the standardisation of oxytocin nasal administration and guidelines for its reporting in human research.

    PubMed

    Guastella, Adam J; Hickie, Ian B; McGuinness, Margaret M; Otis, Melissa; Woods, Elizabeth A; Disinger, Hannah M; Chan, Hak-Kim; Chen, Timothy F; Banati, Richard B

    2013-05-01

    A series of studies have reported on the salubrious effects of oxytocin nasal spray on social cognition and behavior in humans, across physiology (e.g., eye gaze, heart rate variability), social cognition (e.g., attention, memory, and appraisal), and behavior (e.g., trust, generosity). Findings suggest the potential of oxytocin nasal spray as a treatment for various psychopathologies, including autism and schizophrenia. There are, however, increasing reports of variability of response to oxytocin nasal spray between experiments and individuals. In this review, we provide a summary of factors that influence transmucosal nasal drug delivery, deposition, and their impact on bioavailability. These include variations in anatomy and resultant airflow dynamic, vascularisation, status of blood vessels, mode of spray application, gallenic formulation (including presence of uptake enhancers, control release formulation), and amount and method of administration. These key variables are generally poorly described and controlled in scientific reports, in spite of their potential to alter the course of treatment outcome studies. Based on this review, it should be of no surprise that differences emerge across individuals and experiments when nasal drug delivery methods are employed. We present recommendations for researchers to use when developing and administering the spray, and guidelines for reporting on peptide nasal spray studies in humans. We hope that these recommendations assist in establishing a scientific standard that can improve the rigor and subsequent reliability of reported effects of oxytocin nasal spray in humans.

  1. 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.

  2. Nasal Anatomy

    MedlinePlus

    ... ARS HOME ANATOMY Nasal Anatomy Sinus Anatomy Nasal Physiology Nasal Endoscopy Skull Base Anatomy Virtual Anatomy Disclosure ... ANATOMY > Nasal Anatomy Nasal Anatomy Sinus Anatomy Nasal Physiology Nasal Endoscopy Skull Base Anatomy Virtual Anatomy Disclosure ...

  3. Activation of histamine H3 receptors in human nasal mucosa inhibits sympathetic vasoconstriction.

    PubMed

    Varty, LoriAnn M; Gustafson, Eric; Laverty, Maureen; Hey, John A

    2004-01-19

    The peripheral histamine H3 receptor is a presynaptic heterologous receptor located on postganglionic sympathetic nerve fibers innervating sympathetic effector systems such as blood vessels and the heart. An extensive body of evidence shows that activation of the histamine H3 receptor attenuates sympathetic tone by presynaptic inhibition of noradrenaline release. It is proposed that this sympathoinhibitory action, in vivo, leads to reduced vasoconstriction, thereby eliciting a vasodilatory effect. In humans, the peripheral histamine H3 receptor has also been shown to exert a sympathoinhibitory function on specific peripheral autonomic effector systems. For example, human saphenous vein and heart possess functional presynaptic histamine H3 receptors on the sympathetic nerve terminals that upon activation decrease the sympathetic tone to these respective organs. The present studies were conducted to define the role of histamine H3 receptors on neurogenic sympathetic vasoconstrictor responses in human nasal turbinate mucosa. Contractility studies were conducted to evaluate the effect of histamine H3 receptor activation on sympathetic vasoconstriction in surgically isolated human nasal turbinate mucosa. We found that the histamine H3 receptor agonist, (R)-alpha-methylhistamine (30 and 300 nM), inhibited electrical field stimulation-induced (neurogenic) sympathetic vasoconstriction in a concentration-dependent fashion. Pretreatment with the selective histamine H3 receptor antagonist, clobenpropit (100 nM), blocked the sympathoinhibitory effect of (R)-alpha-methylhistamine on the neurogenic sympathetic vasoconstriction. In addition, analysis of Taqman mRNA expression studies showed a specific, high level of distribution of the histamine H3 receptor localized in the human nasal mucosa. Taken together, these studies indicate that histamine H3 receptors modulate vascular contractile responses in human nasal mucosa most likely by inhibiting noradrenaline release from

  4. 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

  5. Outcome of modified turn in flaps for the lining with primary cartilage support in nasal reconstruction.

    PubMed

    Bashir, Muhammad Mustehsan; Khan, Bilal Ahmad; Abbas, Muhammad; Khan, Farid Ahmad

    2013-03-01

    Turning in adjacent skin from the residual nose to line a full-thickness defect is still a controversial option. Text books continue to perpetuate that such flaps are poorly vascularized and may not survive if longer than 1.5 cm. The rationale of our study was to challenge the traditional thoughts about the turn-in flaps for the lining and describe our modified technique of raising these flaps so that well-vascularized thin tissue can be provided for the lining. The study was conducted at the Department of Plastic Surgery, KEMU, Lahore, from January 2007 to March 2011. Eighteen patients were included. They had posttraumatic full-thickness nasal defect of variable extent, involving the lower third of the nose. In the first stage of reconstruction, the epithelialized portion and 5-mm portion of normal adjoining skin were dermabraded. The residual skin of nasal dorsum, side walls, and alae was turned in to form inner lining of 2 nostrils. These flaps were based on healthy dermabraded skin to ensure adequate blood supply. Residual septal and conchal cartilages were used for primary support. Standard ipsilateral paramedian forehead flap with slight oblique design was used for resurfacing. Final assessment of airway patency and alar rim contour was made by the patient at 6 months as satisfactory, just satisfactory, and not satisfactory. There were 12 female and 6 male patients. There was necrosis of distal portion of the forehead flap in 1 case. Partial graft loss at the donor site with bone exposure was noted in another case. There was partial dehiscence and necrosis of turndown flap in 3cases. Mean flap size was 2.05 ± 0.28 cm. As regards airway patency, 12 patients were satisfied, 4 patients were just satisfied, and 2 patients were unsatisfied. When asked about alar rim contour, 3 patients said it to be satisfactory, 9 patients found it just satisfactory, and 6 patients declared it unsatisfactory. Nasal turndown flaps provide reliable tissue for the lining and allow

  6. Morphological interaction between the nasal septum and nasofacial skeleton during human ontogeny.

    PubMed

    Goergen, Matthew J; Holton, Nathan E; Grünheid, Thorsten

    2017-05-01

    The nasal septal cartilage is thought to be a key growth center that contributes to nasofacial skeletal development. Despite the developmental influence of the nasal septum however, humans often exhibit a high frequency of septal deviation suggesting discordance in the growth between the septum and surrounding nasofacial skeleton. While there are numerous etiological factors that contribute to septal deviation, the surrounding nasofacial skeleton may also act to constrain the septum, resulting in altered patterns of growth. That is, while the nasal septum has a direct morphogenetic influence on aspects of the nasofacial skeleton, other nasofacial skeletal components may restrict septal growth resulting in deviation. Detailing the developmental relationship between these structures is important not only for understanding the causal determinants of nasal septal deviation, but also for developing a broader understanding of the complex interaction between the facial skeleton and chondrocranium. We selected 66 non-syndromic subjects from the University of Minnesota Orthodontic Clinic who ranged from 7 to 18 years in age and had an existing pretreatment cone-beam computed tomography (CBCT) scan. Using CBCT data, we examined the developmental relationship between nasal septal deviation and the surrounding nasofacial skeleton. We measured septal deviation as a percentage of septal volume relative to a modeled non-deviated septum. We then collected a series of coordinate landmark data in the region immediately surrounding the nasal septum in the midsagittal plane representing the nasofacial skeleton. First, we examined ontogenetic changes in the magnitude of nasal septal deviation relative to chronological age and nasofacial size. Next, using Procrustes-based geometric morphometric techniques, we assessed the morphological relationship between nasal septal deviation and nasofacial skeletal shape. Our results indicate that variation in the magnitude of nasal septal

  7. 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).

  8. The nasal complex of Neanderthals: an entry portal to their place in human ancestry.

    PubMed

    Márquez, Samuel; Pagano, Anthony S; Delson, Eric; Lawson, William; Laitman, Jeffrey T

    2014-11-01

    Neanderthals are one of the most intensely studied groups of extinct humans, as aspects of their phylogeny and functional morphology remain controversial. They have long been described as cold adapted but recent analyses of their nasal anatomy suggest that traits formerly considered adaptations may be the result of genetic drift. This study performs quantitative and qualitative analysis of aspects of the nasal complex (NC) in Neanderthals and other later Pleistocene fossils from Europe and Africa. A geographically diverse sample of modern human crania was used to establish an anatomical baseline for populations inhabiting cold and tropical climates. Nasofrontal angle, piriform aperture dimensions, and relative maxillary sinus volume were analyzed along with qualitative features of the piriform aperture rim. Results indicate that Neanderthals and other later Pleistocene Homo possessed NC's that align them with tropical modern humans. Thus comparison of Neanderthal nasal morphology with that of modern humans from cold climates may not be appropriate as differences in overall craniofacial architecture may constrain the narrowing of the piriform apertures in Neanderthals. They retain primitively long, low crania, large maxillary sinuses, and large piriform aperture area similar to mid-Pleistocene Homo specimens such as Petralona 1 and Kabwe 1. Adaptation to cold climate may have necessitated other adaptations such as bony medial projections at the piriform aperture rim and, potentially, midfacial prognathism. Nasal complex components of the upper respiratory tract remain a critical but poorly understood area that may yet offer novel insight into one of the greatest continuing controversies in paleoanthropology.

  9. 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.

  10. Validation of human physiologically based pharmacokinetic model for vinyl acetate against human nasal dosimetry data.

    PubMed

    Hinderliter, P M; Thrall, K D; Corley, R A; Bloemen, L 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 13C1,13C2 vinyl acetate via inhalation. A probe inserted into the nasopharyngeal region sampled both 13C1,13C2 vinyl acetate and the major metabolite 13C1,13C2 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.

  11. 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.

  12. [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.

  13. Utility of human amniotic membrane allograft in re-epithelialization of the nasal tip

    PubMed Central

    Dennis, D'Antonio C.; Turnock, Adam R.; Sutton, Collin; Chastant, Bradley; Vanderlan, Wesley B.

    2016-01-01

    Variations in skin thickness and contours pose significant challenges to reconstruction of the lower third of the nose. Human amniotic membrane allograft offers a potential alternative to tissue transfer in reconstruction of the lower third of the nose. We reviewed the procedure and photographs of a healthy 56-year-old male with a 22 × 18 mm lower third nasal defect involving full thickness skin and subcutaneous tissue. Following preparation for grafting, dehydrated human amniotic membrane was fashioned to the dimensions of the defect and applied. No further surgical intervention was provided for 3 months. Complete re-epithelialization of the nasal and adjacent defects was achieved with minimal scar formation. Human amniotic membrane allograft provides an efficacious and cosmetically acceptable alternative to local and regional tissue transfer.

  14. Nasal nitric oxide screening for primary ciliary dyskinesia: systematic review and meta-analysis.

    PubMed

    Collins, Samuel A; Gove, Kerry; Walker, Woolf; Lucas, Jane S A

    2014-12-01

    Nasal nitric oxide (nNO) concentrations are low in patients with primary ciliary dyskinesia (PCD) providing a noninvasive screening test. We conducted a systematic review of the literature to examine the utility of nNO in screening for PCD, in particular 1) different respiratory manoeuvres during sampling (velum closure, tidal breathing, etc.), 2) accuracy in screening young/uncooperative children, 3) stationary versus portable analysers, and 4) nNO in "atypical" PCD. 96 papers were assessed according to modified PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria and 22 were included in this review. Meta-analysis of 11 studies comparing nNO during a velum closure breath hold gave a mean±SD nNO of 19.4±18.6 nL·min(-1) in PCD (n = 478) and 265.0±118.9 nL·min(-1) in healthy controls (n = 338). Weighted mean difference for PCD versus healthy controls was 231.1 nL·min(-1) (95% CI 193.3-268.9; n = 338) and 114.1 nL·min(-1) (95% CI 101.5-126.8; n = 415) for PCD versus cystic fibrosis. Five studies of nNO measurement during tidal breathing demonstrated that this is an acceptable manoeuvre in young children where velum closure is not possible, but the discriminatory value was reduced. Four small studies of portable NO analysers suggest these are reliable tools for screening for PCD. However, nNO must be interpreted alongside clinical suspicion. Future studies should focus on standardising sampling techniques and reporting.

  15. The effects of injection modes on instantaneous particle deposition in a realistic human nasal cavity.

    PubMed

    Wen, Jian; Gu, Xin; Wang, Mengmeng; Jian, Guanping; Wang, Simin; Zheng, Guoxi

    2017-03-01

    To understand the instantaneous particle deposition in nasal cavity, effects of two injection models on particle deposition characteristic were discussed in this paper. Based on a realistic human nasal cavity geometry obtained from CT scans, a comparison of deposition pattern in the nasal cavity between single injection and continuous injection was investigated through the Lagrangian approach. The instantaneous airflow field was simulated with the tidal volume of 159 and 318 mL by two sine wave curves at inlet. For the case of single injection, particles have finished deposition in the first half of inhalation, and a negative correlation between the tidal volumes and deposition can be observed when the particle diameter was larger than 10 µm. Moreover, particles were mainly deposited in the turbinate area that was beneficial for aerosol therapy. The inertial parameter was not suitable to predict the particle deposition in the case of single injection. With respect to continuous injection, a reduction in total deposition caused by the deceleration process of inhalation can be observed after 1.5 s. The deposition was closely associated with the time-varying flow field, and particles were mainly deposited in the anterior region and turbinate area. Besides, the particle deposition increased with the inertial parameter for continuous injection. The results indicated that the injection modes had an influence on both the total deposition and local deposition pattern in the nasal cavity. Copyright © 2016 John Wiley & Sons, Ltd.

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

    PubMed Central

    Calderon-Garciduenas, L; Osnaya-Brizuela, N; Ramirez-Martinez, L; Villarreal-Calderon, A

    1996-01-01

    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 induces SSBs in nasal epithelium, we studied 139 volunteers, including a control population 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

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

    PubMed

    Calderon-Garciduenas, L; Osnaya-Brizuela, N; Ramirez-Martinez, L; Villarreal-Calderon, A

    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 induces SSBs in nasal epithelium, we studied 139 volunteers, including a control population 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

  18. 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.

  19. 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

  20. 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.

  1. Tragal cartilage in the primary reconstruction of defects resulting from a nasal septal abscess.

    PubMed

    Schrader, M; Jahnke, K

    1995-12-01

    Immediate reconstruction of nasal septal sequestration following a septal abscess with autologous tragal cartilage graft is the method of choice in children and adolescents. On one hand autologous tissue is used, thus foreign body reaction with rejection or irregular resorption does not occur. On the other hand further defects in the posterior septal segment with additional damage to growth zones do not arise. Furthermore local tissue is saved, thus it will be available later, in case revision surgery will be necessary. But in contrast to costal cartilage tragal cartilage is easy to obtain in reconstruction of the nasal septum. No visible or functional defect arise at the donor site.

  2. Nasal polyps

    MedlinePlus

    ... get rid of nasal polyps. Nasal steroid sprays shrink polyps. They help clear blocked nasal passages and ... is stopped. Corticosteroid pills or liquid may also shrink polyps, and can reduce swelling and nasal congestion. ...

  3. 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 ...

  4. Effect of budesonide and azelastine on histamine signaling regulation in human nasal epithelial cells.

    PubMed

    Liu, Shao-Cheng; Lin, Chun-Shu; Chen, Shyi-Gen; Chu, Yueng-Hsiang; Lee, Fei-Peng; Lu, Hsuan-Hsuan; Wang, Hsing-Won

    2017-02-01

    Both glucocorticoids and H1-antihistamines are widely used on patients with airway diseases. However, their direct effects on airway epithelial cells are not fully explored. Therefore, we use the primary culture of human nasal epithelial cells (HNEpC) to delineate in vitro mucosal responses to above two drugs. HNEpC cells were cultured with/without budesonide and azelastine. The growth rate at each group was recorded and measured as population double time (PDT). The histamine1-receptor (H1R), muscarinic1-receptor (M1R) and M3R were measured using immunocytochemistry and western blotting after 7-days treatment. Then, we used histamine and methacholine to stimulate the mucus secretion from HNEpC and observed the MUC5AC expression in culture supernatants. Concentration-dependent treatment-induced inhibition of HNEpC growth rate was observed. Cells incubated with azelastine proliferated significantly slower than that with budesonide and the combined use of those drugs led to significant PDT prolong. The immunocytochemistry showed the H1R, M1R and M3R were obviously located in the cell membrane without apparent difference after treatment. However, western blotting showed that budesonide can significantly up-regulate the H1R, M1R and M3R level while azelastine had opposite effects. Histamine and methacholine stimulated MUC5AC secretion was greater in cells treated with budesonide but was lesser in those treated with azelastine, as compared to controls. Our data suggest that both budesonide and azelastine can significantly inhibit HNEpC proliferation, and therefore, be helpful in against airway remodeling. Long-term use of budesonide might amplify histamine signaling and result in airway hyperreactivity to stimulants by enhancing H1R, M1R and M3R expression while azelastine can oppose this effect. Therefore, combined use of those two drugs in patients with chronic inflammatory airway diseases may be an ideal option.

  5. Amoebae-resisting bacteria isolated from human nasal swabs by amoebal coculture.

    PubMed

    Greub, Gilbert; La Scola, Bernard; Raoult, Didier

    2004-03-01

    Amoebae feed on bacteria, and few bacteria can resist their microbicidal ability. Amoebal coculture could therefore be used to selectively grow these amoebae-resisting bacteria (ARB), which may be human pathogens. To isolate new ARB, we performed amoebal coculture from 444 nasal samples. We recovered 7 (1.6%) ARB from 444 nasal swabs, including 4 new species provisionally named Candidatus Roseomonas massiliae, C. Rhizobium massiliae, C. Chryseobacterium massiliae, and C. Amoebinatus massiliae. The remaining isolates were closely related to Methylobacterium extorquens, Bosea vestrii, and Achromobacter xylosoxidans. Thus, amoebal coculture allows the recovery of new bacterial species from heavily contaminated samples and might be a valuable approach for the recovery of as-yet unrecognized emerging pathogens from clinical specimens.

  6. Hyperresponsiveness in the human nasal airway: new targets for the treatment of allergic airway disease.

    PubMed Central

    Turner, P J; Foreman, J C

    1999-01-01

    Allergic rhinitis is a condition which affects over 15% of the population in the United Kingdom. The pathological process involves two stages: nasal inflammation, and the development of nasal airway hyperresponsiveness (AHR) to allergen and a number of other stimuli. This results in the amplification of any subsequent allergic reaction, contributing to the chronic allergic state. A number of different hypotheses have been proposed to explain the underlying mechanism of AHR, including a role for eosinophil-derived proteins, free radicals and neuropeptides. While there may be a number of independent pathways which can result in AHR, evidence obtained from both animal models and in vivo experiments in humans indicate that some mediators may interact with one another, resulting in AHR. Further research into these interactions may open new avenues for the pharmacological treatment of chronic allergic rhinitis, and possibly other allergic airway diseases. PMID:10704051

  7. Volume Expansion of Tissue Engineered Human Nasal Septal Cartilage

    PubMed Central

    Reuther, Marsha S; Briggs, Kristen K; Neuman, Monica K; Masuda, Koichi; Sah, Robert L; Watson, Deborah

    2014-01-01

    Importance Cartilaginous craniofacial defects range in size and autologous cartilaginous tissue is preferred for repair of these defects. Therefore, it is important to have the ability to produce large size cartilaginous constructs for repair of cartilaginous abnormalities. Objectives To produce autologous human septal neocartilage constructs substantially larger in size than previously produced constructs To demonstrate that volume expanded neocartilage constructs possess comparable histological and biochemical properties to standard size constructs To show that volume expanded neocartilage constructs retain similar biomechanical properties to standard size constructs Design Prospective, basic science Setting Laboratory Participants The study used remnant human septal specimens removed during routine surgery at the University of California, San Diego Medical Center or San Diego Veterans Affairs Medical Center. Cartilage from a total of 8 donors was collected. Main Outcomes Measured Human septal chondrocytes from 8 donors were used to create 12mm and 24mm neocartilage constructs. These were cultured for a total of 10 weeks. Photo documentation, histological, biochemical, and biomechanical properties were measured and compared. Results The 24mm diameter constructs were qualitatively similar to the 12mm constructs. They possessed adequate strength and durability to be manually manipulated. Histological analysis of the constructs demonstrated similar staining patterns in standard and volume expanded constructs. Proliferation, as measured by DNA content, was similar in 24mm and 12mm constructs. Additionally, glycosaminoglycan (GAG) and total collagen content did not significantly differ between the two construct sizes. Biomechanical analysis of the 24mm and 12mm constructs demonstrated comparable compressive and tensile properties. Conclusion and Relevance Volume expanded human septal neocartilage constructs are qualitatively and histologically similar to standard 12mm

  8. Evidence of connections between cerebrospinal fluid and nasal lymphatic vessels in humans, non-human primates and other mammalian species

    PubMed Central

    Johnston, Miles; Zakharov, Andrei; Papaiconomou, Christina; Salmasi, Giselle; Armstrong, Dianna

    2004-01-01

    Background The parenchyma of the brain does not contain lymphatics. Consequently, it has been assumed that arachnoid projections into the cranial venous system are responsible for cerebrospinal fluid (CSF) absorption. However, recent quantitative and qualitative evidence in sheep suggest that nasal lymphatics have the major role in CSF transport. Nonetheless, the applicability of this concept to other species, especially to humans has never been clarified. The purpose of this study was to compare the CSF and nasal lymph associations in human and non-human primates with those observed in other mammalian species. Methods Studies were performed in sheep, pigs, rabbits, rats, mice, monkeys and humans. Immediately after sacrifice (or up to 7 hours after death in humans), yellow Microfil was injected into the CSF compartment. The heads were cut in a sagittal plane. Results In the seven species examined, Microfil was observed primarily in the subarachnoid space around the olfactory bulbs and cribriform plate. The contrast agent followed the olfactory nerves and entered extensive lymphatic networks in the submucosa associated with the olfactory and respiratory epithelium. This is the first direct evidence of the association between the CSF and nasal lymph compartments in humans. Conclusions The fact that the pattern of Microfil distribution was similar in all species tested, suggested that CSF absorption into nasal lymphatics is a characteristic feature of all mammals including humans. It is tempting to speculate that some disorders of the CSF system (hydrocephalus and idiopathic intracranial hypertension for example) may relate either directly or indirectly to a lymphatic CSF absorption deficit. PMID:15679948

  9. Evidence of connections between cerebrospinal fluid and nasal lymphatic vessels in humans, non-human primates and other mammalian species.

    PubMed

    Johnston, Miles; Zakharov, Andrei; Papaiconomou, Christina; Salmasi, Giselle; Armstrong, Dianna

    2004-12-10

    BACKGROUND: The parenchyma of the brain does not contain lymphatics. Consequently, it has been assumed that arachnoid projections into the cranial venous system are responsible for cerebrospinal fluid (CSF) absorption. However, recent quantitative and qualitative evidence in sheep suggest that nasal lymphatics have the major role in CSF transport. Nonetheless, the applicability of this concept to other species, especially to humans has never been clarified. The purpose of this study was to compare the CSF and nasal lymph associations in human and non-human primates with those observed in other mammalian species. METHODS: Studies were performed in sheep, pigs, rabbits, rats, mice, monkeys and humans. Immediately after sacrifice (or up to 7 hours after death in humans), yellow Microfil was injected into the CSF compartment. The heads were cut in a sagittal plane. RESULTS: In the seven species examined, Microfil was observed primarily in the subarachnoid space around the olfactory bulbs and cribriform plate. The contrast agent followed the olfactory nerves and entered extensive lymphatic networks in the submucosa associated with the olfactory and respiratory epithelium. This is the first direct evidence of the association between the CSF and nasal lymph compartments in humans. CONCLUSIONS: The fact that the pattern of Microfil distribution was similar in all species tested, suggested that CSF absorption into nasal lymphatics is a characteristic feature of all mammals including humans. It is tempting to speculate that some disorders of the CSF system (hydrocephalus and idiopathic intracranial hypertension for example) may relate either directly or indirectly to a lymphatic CSF absorption deficit.

  10. [Investigation of nasal carriage of community-acquired methicillin resistant Staphylococcus aureus in primary and high school students].

    PubMed

    Ozgüven, Atalay; Tünger, Ozlem; Cetin, Ciğdem Banu; Dinç, Gönül

    2008-10-01

    The aim of this study was to evaluate the carriage rate and risk factors of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) among the students in Manisa, Turkey. A total of 2015 students (1012 from the last phase of high schools and 1003 from the first phase of primary schools) were included in the study. None of the students had nasal MRSA carriage. Methicillin-sensitive S. aureus (MSSA) colonization rate was 14.7% (296/2015). Nasal carriage of MSSA was significantly higher in the primary school students (17.8%) than the high school students (11.6%) (p < 0.001). MSSA carriage was also higher in students of higher socioeconomical status than the students of lower status (p < 0.05). A statistically significant relationship was not determined between the nasal carriage and the risk factors (history of hospitalisation or surgical operation in the previous one year, use of antibiotics or history of skin/soft tissue infection in the last 6 months, presence of children < 15-years-old in the family, presence of healthcare workers in the same house, living in a crowded house). Penicillin and erythromycin resistance was found in 93.6% and 14.2% of MSSA strains, respectively. No resistance was detected against ciprofloxacin, co-trimoxazole, linezolid and vancomycin. There was a statistically significant difference between erythromycin resistance and antibiotic use within the last six months and the number of family members (p < 0.05). In conclusion, current treatment regimens still seem to be affective and safe for the empirical treatment of community-acquired S. aureus infections. Although CA-MRSA infections seem not to be a serious threat in our region yet, it is essential to carry out prevalence studies in the different populations of the community.

  11. Flow modeling of actual human nasal cavity for various breathing conditions

    NASA Astrophysics Data System (ADS)

    Mokhtar, Nur Hazwani; Yaakob, Muhammad Syauki; Osman, Kahar; Kadir, Mohammed Rafiq Abdul; Abdullah, Wan Kamil Wan; Haron, Juhara

    2012-06-01

    Flow in the human nasal cavity varies when the body is under various physical activities. However, in order to visualize the flow pattern, traditional in-vivo technique may disturb the flow patterns. In this study, computational method was used to model the flow in the nasal cavity under various breathing conditions. Image from CT-Scan was used to mimic the actual cavity geometry. The image was computationally constructed and EFD. Lab was used to predict the flow behavior. Steady incompressible flow was considered for all case studies. The result shows that, for all breathing conditions, vortices were observed in the turbinate region which confirms the turbinate functions as a filter before the flow reaches the olfactory area. Larger vortices were detected when the flow rates were higher. In the olfactory region, the flow velocities were shown to be dramatically dropped to the ideal odorant uptake velocity range for all cases studied. This study had successfully produced visual description of air flow pattern in the nasal cavity.

  12. 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

  13. A Novel Approach for Full-Thickness Defect of the Nasal Alar Rim: Primary Closure of the Defect and Reduction of the Contralateral Normal Ala for Symmetry

    PubMed Central

    Choe, Yun Seon; Kim, Min-Woo

    2015-01-01

    In full-thickness defects of the nasal alar rim, to achieve projection and maintain airway patency, cartilage graft is frequently needed. However, cartilage graft presents a challenge in considerations such as appropriate donor site, skeletal shape and size, and healing of the donor area. To avoid these demerits, we tried primary closure of alar rim defects by also making the contralateral normal ala smaller. We treated two patients who had a full-thickness nasal alar defect after tumor excision. Cartilage graft was considered for the reconstruction. However, their alar rims were overly curved and their nostril openings were large. To utilize their nasal shape, we did primary closure of the defect rather than cartilage graft, and then downsized the contralateral nasal ala by means of wedge resection to make the alae symmetric. Both patients were satisfied with their aesthetic results, which showed a smaller nostril and nearly straight alar rims. Moreover, functionally, there was no discomfort during breathing in both patients. We propose our idea as one of the reconstruction options for nasal alar defects. It is a simple and easy-to-perform procedure, in addition to enhancing the nasal contour. This method would be useful for patients with a large nostril and an overly curved alar rim. PMID:26719646

  14. Analysis of the size variability of the human normal and cleft palate fetal nasal capsule by means of three-dimensional computer reconstruction of histologic preparations.

    PubMed

    Siegel, M I; Mooney, M P; Kimes, K R; Todhunter, J

    1987-07-01

    As part of an ongoing study of cleft palate fetal morphology, normal and dysmorphic development of the human fetal nasal capsule was studied in a cross-sectional sample of 29 human fetuses (20 "normal" and 9 cleft), ranging in age from 8 to 21 postmenstrual weeks. The specimens were celloidin embedded, sectioned at 20 microns, and every tenth section stained with hematoxylin and eosin. A computer reconstruction technique was applied to produce three-dimensional representations of the nasal capsule, nasal septal cartilage, and nasal airway. Qualitatively, the cleft palate nasal capsule exhibited gross abnormalities including cartilaginous nasal septum deformities, abnormal septal volume and hypertrophy, reduced nasal airway and capsule volumes, and abnormal spatial relationships between the nasal capsule components. These results suggest that the reduced nasal airways, noted clinically in cleft perinates, may be a function of an interaction of nasal capsule deficiency and nasal septum hypertrophy. However, when lengths and volumes were plotted against fetal postmenstrual age, producing fetal "growth" curves, no significant differences (p greater than 0.05) were noted for growth rates (slopes) or nasal capsule size between the normal and cleft palate fetal samples. Curvilinear regression analysis revealed that both normal and cleft palate nasal capsule and septum lengths changed in a sigmoidal fashion, with the steepest increases from 13 to 17 weeks. In contrast, nasal capsule, airway, and septum volumes changed curvilinearly, showing slow relative growth rates from 8 to 17 weeks, which increased sharply from 18 to 21 weeks. Results suggest that from 8 to 21 weeks prenatally, normal and cleft palate specimens exhibited a similar pattern of fetal nasal capsule development that was characterized by an initial anteroposterior elongation followed by circumferential (i.e., volumetric) growth.

  15. Pharmacological inhibition of DNA methyltransferase 1 promotes neuronal differentiation from rodent and human nasal olfactory stem/progenitor cell cultures.

    PubMed

    Franco, I; Ortiz-López, L; Roque-Ramírez, B; Ramírez-Rodríguez, G B; Lamas, M

    2017-05-01

    Nasal olfactory stem and neural progenitor cells (NOS/PCs) are considered possible tools for regenerative stem cell therapies in neurodegenerative diseases. Neurogenesis is a complex process regulated by extrinsic and intrinsic signals that include DNA-methylation and other chromatin modifications that could be experimentally manipulated in order to increase neuronal differentiation. The aim of the present study was the characterization of primary cultures and consecutive passages (P2-P10) of NOS/PCs isolated from male Swiss-Webster (mNOS/PCs) or healthy humans (hNOS/PCs). We evaluated and compared cellular morphology, proliferation rates and the expression pattern of pluripotency-associated markers and DNA methylation-associated gene expression in these cultures. Neuronal differentiation was induced by exposure to all-trans retinoic acid and forskolin for 7 days and evaluated by morphological analysis and immunofluorescence against neuronal markers MAP2, NSE and MAP1B. In response to the inductive cues mNOS/PCs expressed NSE (75.67%) and MAP2 (35.34%); whereas the majority of the hNOS/PCs were immunopositive to MAP1B. Treatment with procainamide, a specific inhibitor of DNA methyltransferase 1 (DNMT1), increases in the number of forskolin'/retinoic acid-induced mature neuronal marker-expressing mNOS/PCs cells and enhances neurite development in hNOS/PCs. Our results indicate that mice and human nasal olfactory stem/progenitors cells share pluripotency-related gene expression suggesting that their application for stem cell therapy is worth pursuing and that DNA methylation inhibitors could be efficient tools to enhance neuronal differentiation from these cells.

  16. Nasal Physiology

    MedlinePlus

    ... nasal mucosa can help adjust the humidity and temperature of the air before it reaches the lungs. ... area of the nasal mucosa helps regulate the temperature and humidity of inspired air. The nasal cycle ...

  17. 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.

  18. Neural net applied to anthropological material: a methodical study on the human nasal skeleton.

    PubMed

    Prescher, Andreas; Meyers, Anne; Gerf von Keyserlingk, Diedrich

    2005-07-01

    A new information processing method, an artificial neural net, was applied to characterise the variability of anthropological features of the human nasal skeleton. The aim was to find different types of nasal skeletons. A neural net with 15*15 nodes was trained by 17 standard anthropological parameters taken from 184 skulls of the Aachen collection. The trained neural net delivers its classification in a two-dimensional map. Different types of noses were locally separated within the map. Rare and frequent types may be distinguished after one passage of the complete collection through the net. Statistical descriptive analysis, hierarchical cluster analysis, and discriminant analysis were applied to the same data set. These parallel applications allowed comparison of the new approach to the more traditional ones. In general the classification by the neural net is in correspondence with cluster analysis and discriminant analysis. However, it goes beyond these classifications because of the possibility of differentiating the types in multi-dimensional dependencies. Furthermore, places in the map are kept blank for intermediate forms, which may be theoretically expected, but were not included in the training set. In conclusion, the application of a neural network is a suitable method for investigating large collections of biological material. The gained classification may be helpful in anatomy and anthropology as well as in forensic medicine. It may be used to characterise the peculiarity of a whole set as well as to find particular cases within the set.

  19. A preliminary 3D computed tomography study of the human maxillary sinus and nasal cavity.

    PubMed

    Butaric, Lauren N; McCarthy, Robert C; Broadfield, Douglas C

    2010-11-01

    Despite centuries of investigation, the function of the maxillary sinus (MS) and underlying patterns governing its form remain elusive. In this study, we articulate a methodology for collecting volumetric data for the MS and nasal cavity (NC) from computed tomography (CT) scans and report details for a small sample of 39 dried human crania of known ecogeographic provenience useful for assessing variation in MS size and shape. We use scaling analyses to preliminarily test the hypothesis that volumes of the nasal cavity (NCV) and maxillary sinus (MSV) are inversely correlated such that the NC covaries with size of the face, whereas the MS "fills in" the leftover space [proposed by Shea: Am J Phys Anthropol 47 (1977):289-300]. Against expectation, MSV is not significantly correlated with NCV or any cranial size variable. NCV, on the other hand, scales isometrically with facial size. The results of this pilot study suggest that NCV covaries with facial size, but that the MS does not simply fill in the leftover space in the face. The role, if any, of the MSs in midfacial function and architecture remains unclear. Larger sample sizes, additional environmental variables, and assessment of MS and NC shape are necessary to resolve this issue.

  20. 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

  1. Comparison of cadmium cytotoxicity in human versus rat nasal epithelial cells in vitro

    SciTech Connect

    Morgan, D.L.; Humphreys, J.E.; Bilotta, J.M.; Nixon, J.C.; Hatch, G.E.

    1990-01-01

    Quantitative extrapolation of toxicity data from animals to humans will allow more accurate assessments of human health risks. The overall objective of this investigation is to provide the tissue sensitivity data necessary to extrapolate quantitatively the toxic effects of inhaled particles from animals to humans. In the initial study, cadmium sulfate (CdSO4) toxicity for human and Fischer 344 rat nasal turbinate epithelial (NTE) cells was evaluated in vitro. The studies were unique in that both rat and human NTE cells were obtained from fresh, normal tissue. Methods were developed for isolating and culturing NTE cells from rat and human tissue using identical procedures, and for measuring the cellular nucleotides by HPLC. Changes in adenylate energy charge (EC) and nucleotide levels were used as toxicity endpoints. Cellular Cd levels were measured by graphite furnace atomic absorption spectrometry and expressed as microgram Cd/microgram DNA. Using these methods, the cellular Cd dose and the toxic effect in each cell type were measured and compared.

  2. 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...

  3. 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.

  4. Silver resistance in MRSA isolated from wound and nasal sources in humans and animals.

    PubMed

    Loh, Jia V; Percival, Steven L; Woods, Emma J; Williams, Nicola J; Cochrane, Christine A

    2009-02-01

    Methicillin-resistant Staphylococcus aureus (MRSA) colonises skin, nasal passages and dermal wounds. Methods used to manage wounds infected and colonised with MRSA often include the use of topical antiseptics such as ionic silver and iodine. The objectives of this study were to determine the prevalence of silver-resistance (sil) genes in MRSA and methicillin-resistant coagulase-negative staphylococci (MR-CNS) isolated from wounds and nasal cavities of humans and animals, and also to determine the susceptibility of sil-positive and sil-negative MRSA isolates to a silver-containing Hydrofiber (SCH) wound dressing, on planktonic silE-positive and silE-negative MRSA. Polymerase chain reaction was used to determine the presence of three silver-resistance (sil) genes, silE, silP and silS in 33 MRSA and 8 methicillin-resistant staphylococci (MR-CNS). SilP and silS genes were absent in all isolates tested; however, two MRSA strains were found to contain the silE gene, together with one isolate of MR-CNS. Phenotypic resistance of the silE-positive strains and their susceptibility to the SCH dressing was evaluated using the zone of inhibition test on Mueller Hinton agar, and confocal laser microscopy using a live/dead fluorescent stain. Results confirmed that the SCH dressing was effective in killing all MRSA strains with and without the silE gene. First, this study showed that the prevalence of sil genes was low in the isolates investigated; and secondly, that the presence of a silver-resistance gene (silE) in MRSA and MR-CNS did not afford protection to the organism in the presence of a SCH wound dressing. The use of topical antiseptics in chronic wound care should be considered before the use of antibiotics that can result in their overuse and the risk of further resistance.

  5. A Case Report of Primary Nasal Natural Killer (NK)/T-Cell Lymphoma in an African American Patient Presenting with Hemophagocytic Syndrome

    PubMed Central

    Tan, Bowei; Abdelmalek, Cherif; O’Donnell, James E.; Toltaku, Thomas; Chaudhry, Rashid; Wang, Jen C.; Gotlieb, Vladimir

    2017-01-01

    Patient: Male, 55 Final Diagnosis: Primary NK-T cell lymphoma • nasal type Symptoms: Fever • nasal bleeding • nasal mass • weight loss Medication: — Clinical Procedure: Chemotherapy×2 cycles • radiation therap Specialty: Oncology Objective: Rare disease Background: Extranodal natural killer/T-cell lymphoma, nasal type (ENKTCL) is generally an aggressive and rare non-Hodgkin lymphoma. It is most common in East Asians, Native Americans, and South Americans, but is rarely reported in blacks. Case Report: A 55-year-old African American male born in Grenada presented with a left nostril mass with facial swelling and biopsy subsequently confirmed a diagnosis of extranodal NK/T-cell lymphoma, nasal type (ENKTCL). Immunochemistry was positive for CD2, cytoplasmic CD3, CD7, CD 43, CD 56, granzyme B, and TIA-1. In situ hybridization was positive for Epstein-Barr virus encoded ribonucleic acid (EBERs). Bone marrow aspiration did not show lymphoma involvement. The patient had progressive neutropenia upon presentation, with further investigations showing hepatomegaly, hyperferritinemia, and hemophagocytosis in the bone marrow. We reached a diagnosis of hemophagocytic syndrome. He was treated with a high-dose combination chemotherapy and radiation therapy; the neutropenia improved significantly with steroids as treatment for immune activation in the setting of hemophagocytic syndrome. Conclusions: To the best of our knowledge, this is the only second report of extranodal NK/T-cell lymphoma, nasal type in a black patient, and it raises the awareness of early recognition of rare manifestations of NK/T-cell lymphoma such as hemophagocytic syndrome. PMID:28193996

  6. 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 ...

  7. Application of RPMI 2650 nasal cell model to a 3D printed apparatus for the testing of drug deposition and permeation of nasal products.

    PubMed

    Pozzoli, Michele; Ong, Hui Xin; Morgan, Lucy; Sukkar, Maria; Traini, Daniela; Young, Paul M; Sonvico, Fabio

    2016-10-01

    The aim of this study was to incorporate an optimized RPMI2650 nasal cell model into a 3D printed model of the nose to test deposition and permeation of drugs intended for use in the nose. The nasal cell model was optimized for barrier properties in terms of permeation marker and mucus production. RT-qPCR was used to determine the xenobiotic transporter gene expression of RPMI 2650 cells in comparison with primary nasal cells. After 14days in culture, the cells were shown to produce mucus, and to express TEER (define) values and sodium fluorescein permeability consistent with values reported for excised human nasal mucosa. In addition, good correlation was found between RPMI 2650 and primary nasal cell transporter expression values. The purpose-built 3D printed model of the nose takes the form of an expansion chamber with inserts for cells and an orifice for insertion of a spray drug delivery device. This model was validated against the FDA glass chamber with cascade impactors that is currently approved for studies of nasal products. No differences were found between the two apparatus. The apparatus including the nasal cell model was used to test a commercial nasal product containing budesonide (Rhinocort, AstraZeneca, Australia). Drug deposition and transport studies on RPMI 2650 were successfully performed. The new 3D printed apparatus that incorporates cells can be used as valid in vitro model to test nasal products in conditions that mimic the delivery from nasal devices in real life conditions.

  8. 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 ...

  9. 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.

  10. Reconstruction of nasal tip support in primary, open approach septorhinoplasty : A retrospective analysis between the tongue-in-groove technique and the columellar strut.

    PubMed

    Karaiskakis, Periklis; Bromba, Michael; Dietz, Andreas; Sand, Michael; Dacho, Andreas

    2016-09-01

    The reconstruction of the nasal tip support is one of the most essential issues in septorhinoplasty. A comparison of the results after using the tongue-in-groove technique and the columellar strut technique was the target of this study. Thirty-three patients who underwent a primary, open approach septorhinoplasty using the above-mentioned techniques were retrospectively analyzed. The gain in tip rotation postoperatively, the sensitivity and the rigidity of the nasal tip and the aesthetic outcome after surgery were examined and evaluated. Both techniques led to an increase in nasal tip rotation postoperatively. The gain in rotation was higher in patients, treated with the tongue-in-groove technique (p = 0.0052). The sensitivity of the tip region in the tongue-in-groove group of patients was significantly lower than that in the columellar strut group of patients (p = 0.0424). Both techniques led to high percentages of tip rigidity after surgery with satisfactory aesthetic results though. The tongue-in-groove technique and the columellar strut technique are both reliable techniques for reconstructing the nasal tip support and correcting a droopy tip. Although the tongue-in-groove technique might result in a more significant increase in tip rotation, it leads to less sensitivity in the tip region.

  11. A critical review of the influence of oxytocin nasal spray on social cognition in humans: evidence and future directions.

    PubMed

    Guastella, Adam J; Graustella, Adam J; MacLeod, Colin

    2012-03-01

    The past eight years of research has demonstrated that oxytocin nasal spray has a significant impact on human social cognition. The aim of this review is to provide critical comment on the literature using an information-processing framework. We provide a summary of fundamental assumptions of information-processing models and highlight an impressive range of consistent findings that demonstrate the impact of oxytocin nasal spray on social information processing. These findings include that oxytocin nasal spray improves the early conceptual detection of affect from social cues and improves the accurate appraisal of affect from social cues at elaborate and strategic levels of processing. There is some evidence that these effects may be particularly powerful for positive social cues. This review comments on inconsistent results that have been reported. We argue that such inconsistencies can, in part, be explained by variability across experiments in the degree to which potential extraneous confounds have been controlled, the different methods upon which studies assessed cognition, and the extent to which the focus of investigation has been on group-based outcomes. Finally, we argue that sound cognitive experimental methods can provide powerful tools to identify markers of response to oxytocin nasal spray that can be integrated into more complex circuitry models. The identification of robust markers has particular value in predicting behavioral and therapeutic response to intervention. This should now be a major focus for future research. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior.

  12. 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...

  13. 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...

  14. Human Nasal Myiasis Caused by Oestrus ovis in the Highlands of Cusco, Peru: Report of a Case and Review of the Literature.

    PubMed

    Hoyer, P; Williams, R R; Lopez, M; Cabada, M M

    2016-01-01

    Myiasis is the infestation by dipterous larvae. The larvae can infect intact or decaying tissue including the skin or epithelial surfaces of the orbits, nose, and genitourinary and gastrointestinal tracts. We report a case of primary obligatory nasal myiasis by Oestrus ovis in a 56-year-old man from Cusco in Peru. He presented with nasal pruritus, congestion, and sneezing white "cottony" material. The material was identified as O. ovis larvae. A literature review of publications reporting nasal myiasis caused by O. ovis is presented.

  15. Human Nasal Myiasis Caused by Oestrus ovis in the Highlands of Cusco, Peru: Report of a Case and Review of the Literature

    PubMed Central

    Lopez, M.

    2016-01-01

    Myiasis is the infestation by dipterous larvae. The larvae can infect intact or decaying tissue including the skin or epithelial surfaces of the orbits, nose, and genitourinary and gastrointestinal tracts. We report a case of primary obligatory nasal myiasis by Oestrus ovis in a 56-year-old man from Cusco in Peru. He presented with nasal pruritus, congestion, and sneezing white “cottony” material. The material was identified as O. ovis larvae. A literature review of publications reporting nasal myiasis caused by O. ovis is presented. PMID:28116184

  16. Enhancing effect of borneol and muscone on geniposide transport across the human nasal epithelial cell monolayer.

    PubMed

    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.

  17. 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.

  18. A low percentage of autologous serum can replace bovine serum to engineer human nasal cartilage.

    PubMed

    Wolf, F; Haug, M; Farhadi, J; Candrian, C; Martin, I; Barbero, A

    2008-02-05

    For the generation of cell-based therapeutic products, it would be preferable to avoid the use of animal-derived components. Our study thus aimed at investigating the possibility to replace foetal bovine serum (FBS) with autologous serum (AS) for the engineering of cartilage grafts using expanded human nasal chondrocytes (HNC). HNC isolated from 7 donors were expanded in medium containing 10% FBS or AS at different concentrations (2%, 5% and 10%) and cultured in pellets using serum-free medium or in Hyaff(R)-11 meshes using medium containing FBS or AS. Tissue forming capacity was assessed histologically (Safranin O), immunohistochemically (type II collagen) and biochemically (glycosaminoglycans -GAG- and DNA). Differences among experimental groups were assessed by Mann Whitney tests. HNC expanded under the different serum conditions proliferated at comparable rates and generated cartilaginous pellets with similar histological appearance and amounts of GAG. Tissues generated by HNC from different donors cultured in Hyaff(R)-11 had variable quality, but the accumulated GAG amounts were comparable among the different serum conditions. Staining intensity for collagen type II was consistent with GAG deposition. Among the different serum conditions tested, the use of 2% AS resulted in the lowest variability in the GAG contents of generated tissues. In conclusion, a low percentage of AS can replace FBS both during the expansion and differentiation of HNC and reduce the variability in the quality of the resulting engineered cartilage tissues.

  19. 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.

  20. Comparison of human nasal epithelial cells grown as explant outgrowth cultures or dissociated tissue cultures in vitro.

    PubMed

    Jiao, Jian; Meng, Na; Wang, Hong; Zhang, Luo

    2013-12-01

    The purpose of this study was to compare cell growth characteristics, ciliated cell differentiation, and function of human nasal epithelial cells established as explant outgrowth cultures or dissociated tissue cultures. Human nasal mucosa of the uncinate process was obtained by endoscopy and epithelial cell cultures were established by explant outgrowth or dissociated tissue culture methods. Epithelial cell growth characteristics were observed by inverted phase contrast microscopy. Ciliated cell differentiation was detected by β-tubulin IVand ZO-1 immunocytochemistry. Basal and ATP-stimulated ciliary beat frequency (CBF) was measured using a highspeed digital microscopic imaging system. Both the explant and dissociated tissue cultures established as monolayers with tight junctions and differentiated cell composition, with both types of cultures comprising ciliated and non-ciliated epithelial cells. Fibroblasts were also frequently found in explant cultures but rarely seen in dissociated tissue cultures. In both culture systems, the highest ciliated cell density appeared at 7th-10th culture day and declined with time, with the lifespan of ciliated cells ranging from 14 to 21 days. Overall, 10% of the cells in explant cultures and 20% of the cells in the dissociated tissue cultures were ciliated. These two cultures demonstrated similar ciliary beat frequency values at baseline (7.78 ± 1.99 Hz and 7.91 ± 2.52 Hz, respectively) and reacted equivalently following stimulation with 100 μM ATP. The results of this study indicate that both the explant outgrowth and dissociated tissue culture techniques are suitable for growing well-differentiated nasal ciliated and non-ciliated cells, which have growth characteristics and ciliary activity similar to those of nasal epithelial cells in vivo.

  1. 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.

  2. Nasal polyposis

    PubMed Central

    Brown, Gerald A.

    1969-01-01

    A review of 313 cases of nasal polyposis indicates that there is a high incidence of recurrence in this disease. Other nasal pathology affects a significant number of these patients. Simple surgical removal of the polypi by a transnasal route is the common mode of treatment. PMID:4187956

  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. Staphylococcus aureus enterotoxins induce IL-8 secretion by human nasal epithelial cells

    PubMed Central

    O'Brien, Garrett J; Riddell, Gareth; Elborn, J Stuart; Ennis, Madeleine; Skibinski, Grzegorz

    2006-01-01

    Background Staphylococcus aureus produces a set of proteins which act both as superantigens and toxins. Although their mode of action as superantigens is well understood, little is known about their effects on airway epithelial cells. Methods To investigate this problem, primary nasal epithelial cells derived from normal and asthmatic subjects were stimulated with staphylococcal enterotoxin A and B (SEA and SEB) and secreted (supernatants) and cell-associated (cell lysates) IL-8, TNF-α, RANTES and eotaxin were determined by specific ELISAs. Results Non-toxic concentrations of SEA and SEB (0.01 μg/ml and 1.0 μg/ml) induced IL-8 secretion after 24 h of culture. Pre-treatment of the cells with IFN-γ (50 IU/ml) resulted in a further increase of IL-8 secretion. In cells from healthy donors pretreated with IFN-γ, SEA at 1.0 μg/ml induced release of 1009 pg/ml IL-8 (733.0–1216 pg/ml, median (range)) while in cells from asthmatic donors the same treatment induced significantly higher IL-8 secretion – 1550 pg/ml (1168.0–2000.0 pg/ml p = 0.04). Normal cells pre-treated with IFN-γ and then cultured with SEB at 1.0 μg/ml released 904.6 pg/ml IL-8 (666.5–1169.0 pg/ml). Cells from asthmatics treated in the same way produced significantly higher amounts of IL-8 – 1665.0 pg/ml (1168.0–2000.0 pg/ml, p = 0.01). Blocking antibodies to MHC class II molecules added to cultures stimulated with SEA and SEB, reduced IL-8 secretion by about 40% in IFN-γ unstimulated cultures and 75% in IFN-γ stimulated cultures. No secretion of TNF-α, RANTES and eotaxin was noted. Conclusion Staphylococcal enterotoxins may have a role in the pathogenesis of asthma. PMID:16952309

  5. 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

  6. [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.

  7. 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

  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. Optical recordings from the human nasal mucosa in response to olfactory stimulation.

    PubMed

    Ishimaru, Tadashi; Reden, Jens; Krone, Franziska; Scheibe, Mandy

    2007-08-23

    Using the intrinsic optical signal the present study aimed to investigate changes in blood flow at the nasal epithelium in response to specific olfactory stimulation. Recording equipment included an endoscope, a CCD camera, and a light source of 617 nm. Two concentrations of the specific olfactory stimulant H(2)S (2.8 and 5.6 ppm), generated by a computer-controlled olfactometer, were used for olfactory stimulation. Eight healthy normosmic volunteers participated. Using 5.6 ppm H(2)S stimuli, responses were typically recorded from the olfactory cleft, middle turbinate, and middle meatus while responses were less pronounced for 2.8 ppm H(2)S stimuli. Response areas were significantly larger for the 5.6 ppm H(2)S stimuli. While further experiments are needed, recordings of the intrinsic optical signal may be used to obtain responses from the nasal cavity to specific olfactory stimuli.

  10. Lack of a primary physicochemical determinant in the direct transport of drugs to the brain after nasal administration in rats: potential involvement of transporters in the pathway.

    PubMed

    Lee, Kyeong-Ryoon; Maeng, Han-Joo; Chae, Jung-Byung; Chong, Saeho; Kim, Dae-Duk; Shim, Chang-Koo; Chung, Suk-Jae

    2010-01-01

    The objectives of this study were to evaluate the relative contribution of the direct pathway in overall brain transport for 17 model drugs with different physicochemical properties after nasal administrations and to identify factors that govern the fraction of the dose transported to the brain via the direct pathway (F(a, direct)). When the model drugs were nasally administered to rats, 5 of the 17 model drugs were delivered to a significant extent to the brain via the direct pathway. Multiple linear regression analyses showed that the correlation between various physicochemical properties and F(a, direct) was not statistically significant, indicative of a lack of primary physicochemical determinants in the direct transport pathway. Transporters such as rOAT3 and rOCT2 were expressed at significant levels in rat olfactory epithelia, and uptakes of standard substrates were significantly decreased in HEK293 cells expressing rOAT3 and rOCT2 in the presence of the five model drugs that were delivered to appreciable extents to the brain via the direct pathway. Therefore, these observations indicate that carrier-mediated transport may play a role in the brain delivery of drugs from the nose via the direct transport pathway.

  11. Effect of High, Medium, and Low Molecular Weight Hyaluronan on Inflammation and Oxidative Stress in an In Vitro Model of Human Nasal Epithelial Cells

    PubMed Central

    Albano, Giusy Daniela; Bonanno, Anna; Cavalieri, Luca; Ingrassia, Eleonora; Di Sano, Caterina; Siena, Liboria; Riccobono, Loredana; Gagliardo, Rosalia; Profita, Mirella

    2016-01-01

    IL-17A is involved in the activation of oxidative stress and inflammation in nasal epithelial cells. Hyaluronan (HA) in its high molecular weight form (HMW-HA) shows anti-inflammatory responses in contrast to low and medium molecular weight HA (LMW-HA and MMW-HA). The aim of this study was to investigate the pro- or anti-inflammatory biologic function of HA at different molecular weight in an in vitro model of nasal inflammation IL-17A mediated. We evaluated the ERK1/2 and IκBα phosphorylation, NF-κB signal pathway activation, ROS production, IL-8 and NOX-4 protein, and mRNA levels, in nasal epithelial cells RPMI 2650 stimulated with recombinant human (rh) IL-17A. Furthermore, the cells were treated with HMW-HA, MMW-HA, LMW-HA, and U0126. Our results showed that rhIL-17A increased the ERK1/2, IκBα phosphorylation and NF-κB signal pathway activation, ROS production, IL-8 and NOX-4 proteins, and mRNA levels. The addiction of HMW-HA or U0126 showed a significant downregulatory effect on inflammation due to the rhIL-17A stimulation in nasal epithelial cells. IL-17A is able to generate oxidative stress and inflammation via the activation of ERK1/2/NF-κB pathway in nasal epithelial cells. The HMW-HA might represent a coadjuvant of the classic anti-inflammatory/antioxidative treatment of nasal epithelial cells during IL-17A nasal inflammation. PMID:27212811

  12. Gene targeting in primary human trophoblasts

    PubMed Central

    Rosario, Fredrick J; Sadovsky, Yoel; Jansson, Thomas

    2012-01-01

    Studies in primary human trophoblasts provide critical insights into placental function in normal and complicated pregnancies. Mechanistic studies in these cells require experimental tools to modulate gene expression. Lipid-based methods to transfect primary trophoblasts are fairly simple to use and allow for the efficient delivery of nucleic acids, but potential toxic effects limit these methods. Viral vectors are versatile transfection tools of native trophoblastic or foreign cDNAs, providing high transfection efficiency, low toxicity and stable DNA integration into the trophoblast genome. RNA interference (RNAi), using small interfering RNA (siRNA) or microRNA, constitutes a powerful approach to silence trophoblast genes. However, off-target effects, such as regulation of unintended complementary transcripts, inflammatory responses and saturation of the endogenous RNAi machinery, are significant concerns. Strategies to minimize off-target effects include using multiple individual siRNAs, elimination of pro-inflammatory sequences in the siRNA construct and chemical modification of a nucleotide in the guide strand or of the ribose moiety. Tools for efficient gene targeting in primary human trophoblasts are currently available, albeit not yet extensively validated. These methods are critical for exploring the function of human trophoblast genes and may provide a foundation for the future application of gene therapy that targets placental trophoblasts. PMID:22831880

  13. Primary hypothyroidism-associated TSH-secreting pituitary adenoma/hyperplasia presenting as a bleeding nasal mass and extremely elevated TSH level.

    PubMed

    Ghannam, N N; Hammami, M M; Muttair, Z; Bakheet, S M

    1999-06-01

    A 41-year-old male with primary hypothyroidism and a huge TSH-secreting pituitary tumor presented with a bleeding nasal mass that was initially misdiagnosed as a paraganglioma. Other unique features of the case include lack of complaints related to hypothyroidism, an extremely elevated TSH level of 3474 mU/l, and a low prolactin level. The presence of primary hypothyroidism made differentiating TSH-secreting pituitary adenoma from secondary thyrotroph hyperplasia difficult. A low molar ratio of alpha-subunit to TSH on presentation, together with normalization of TSH level and a 50% reduction in the size of the tumor after 6 weeks of thyroxine replacement therapy, suggested the presence of thyrotroph hyperplasia. However, the lack of further decrease in the size of the tumor that was associated with increased metabolic activity on 18-FDG PET scan, intense uptake on octreotide scan, and an elevated alpha-subunit to TSH molar ratio despite the normalization of free T4 and TSH levels for 16 months suggested the coexistence of thyrotroph adenoma. Together, the findings support the view that thyrotroph adenoma/irreversible hyperplasia can result from long standing primary hypothyroidism.

  14. Oro-nasal fistula development and velopharyngeal insufficiency following primary cleft palate surgery--an audit of 148 children born between 1985 and 1997.

    PubMed

    Inman, D S; Thomas, P; Hodgkinson, P D; Reid, C A

    2005-12-01

    We present an audit of primary cleft palate surgery in our unit including rates of two important post-operative complications. Multidisciplinary audit clinics ran from March 1998 to April 2002 to follow up all local patients with a cleft lip or palate who had undergone primary palatal surgery in our unit. One hundred and forty eight patients were studied. Patient ages at follow-up ranged from 3 years and 10 months to 17 years and 4 months. Two surgeons performed the primary surgery. One hundred and twenty eight Wardill-Kilner and 20 Von Langenbeck repairs were performed. We found a 4.7% rate of oro-nasal fistula development requiring surgical closure, and a 26.4% rate of velopharyngeal insufficiency (VPI) requiring subsequent pharyngoplasty. We noted that the type of cleft involved affected the rate of VPI, 16% of patients with unilateral cleft lip and palate versus 29.2% of patients with a solitary cleft palate requiring secondary surgery. Outcome of surgery was determined by a 'Cleft Audit Protocol for Speech' (CAPS) speech therapy assessment at follow-up clinics. Only 14.9% of all patients assessed demonstrated any degree of hypernasality. Our results compare favourably with other recent studies including the Clinical Standards Advisory Group (CSAG) report into treatment of children with cleft lip and palate.

  15. Cytogenetic diversity in primary human tumors.

    PubMed

    Wolman, S R; Camuto, P M; Perle, M A

    1988-02-01

    Cytogenetic patterns from primary short-term culture of breast cancer, renal carcinoma, and tumors of the central nervous system are presented to illustrate the range of karyotypic diversity of human solid tumors as well as their biologic differences in culture systems that support their growth. These studies have illustrated several major issues. 1) Results vary with the tissue of origin: primary cultures from breast are almost uniformly diploid, while renal tumors are near-diploid, mosaic, and show clonal aberrations; and CNS tumors are heterogeneous: some diploid, some near-diploid and some highly aneuploid. 2) Results after short-term culture are selective, representing subpopulations from the heterogeneous cells that are detected on direct analysis of fresh tumors by cytogenetics or flow cytometry (FCM). It is not yet clear whether prognosis depends on the dominant population of the primary tumor or alternatively should be influenced by detection of small aneuploid subpopulations. 3) Evidence from all three tumor types supports the interpretation that cytogenetically normal diploid cells constitute part of some tumor populations, and may be better adapted to routine growth in culture than aneuploid subpopulations from the same primary tumors. These cells may also compose a major portion of the viable population of tumors in vivo and, therefore, could represent a useful model for studies of tumorigenesis and therapeutic regimens.

  16. Nasal dorsal augmentation with silicone implants.

    PubMed

    Erlich, Mark A; Parhiscar, Afshin

    2003-11-01

    Silicone rubber has been used safely and effectively for facial augmentation for nearly 5 decades in eastern Asia. We have used silicone rubber nasal implants in primary ethnic rhinoplasty and have found consistent and long-lasting results with low complication rates. Silicone dorsal nasal augmentation in primary rhinoplasty avoids donor site morbidity and implant resorption as seen with autogenous implants. Silicone nasal implants have a low extrusion and infection rate. In the appropriate patient with proper placement, silicone nasal implant is nearly the ideal implant material.

  17. [Localization and distribution of human olfactory mucosa in the nasal cavities].

    PubMed

    Escada, Pedro

    2013-01-01

    Introdução: A distribuição da mucosa olfactiva humana só pode ser determinada em estudos que avaliem a totalidade da região olfactiva. O objectivo deste trabalho é determinar a distribuição da mucosa olfactiva humana a partir do estudo histológico, por microscopia óptica, de peças anatómicas da região olfactiva obtidas do cadáver.Material e Métodos: Utilizaram-se peças anatómicas da região olfactiva colhidas durante a autópsia de cadáveres recentes. Em cada uma das peças foi determinada a distância entre a lâmina crivosa e o limite inferior da região olfactiva em três localizações diferentes da parede septal e da parede lateral.Resultados: das 230 peças anatómicas disponíveis, 217 foram excluídas por razões clínicas ou técnicas. Realizaram-se estudosmorfométricos em 13 peças num total de 156 medições. O limite inferior da mucosa olfactiva no septo nasal estava a 15,9 ± 3,2 mm, a 15,3 ± 3 mm e a 16 ± 2,8 mm nas porções anterior, média e posterior da região olfactiva. O limite inferior da mucosa olfactiva na parede turbinal estava a 15,3 ± 2,4 mm, a 14,8 ± 2,3 mm e a 12,3 ± 1,9 mm nas mesmas localizações. O valor mínimo observado foi de 12 mm.Conclusões: A mucosa olfactiva estende-se pelo corneto superior e médio e pelo septo nasal confrontante numa distância que nunca é inferior a 12 mm e que pode ultrapassar os 16 mm. O conhecimento da distribuição exacta da mucosa olfactiva nas fossas nasais pode ser útil para orientar a colheita em seres humanos, com propósitos diagnósticos ou terapêuticos.

  18. 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.

  19. 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...

  20. 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

  1. [Microbiocenosis of the human nasal mucous membrane in the conditions of industrial city].

    PubMed

    Voĭtovich, A V

    2013-12-01

    In this work we studied the effect of industrial pollution on the mechanisms involved in the adaptation of the nasal microbiocenosis of healthy residents of the industrial city to external influences. In the given biotop composition of the microbiota and its biological properties, as well as the specific indicators of rhinocytogram and expression of TLR-2 and TLR-4 cells of the mucous membranes have been studied. Accommodation in relatively polluted industrial areas of the city induces an increase in the population of coagulase positive staphylococci and improve their adhesion activity, as well as strengthens destructive processes in the epithelium. Analysis of resistance phenotypes of staphylococcus showed that around 30 % of the strains of coagulase negative staphylococci and about 20 % of the strains of coagulase positive staphylococci have phenotype mecA. Among coagulase negative staphylococci higher number of strains with multiple resistance to β- lactams, aminoglycosides, and antibiotics of MLS group have been revealed. To such changes in the components of microbiocenosis the cells of the mucous membrane of the nose react by increasing the numbers of TLR-2+ epithelial cells, increased expression of TLR-2 by epithelial cells and reduced expression of TLR-4 by neutrophils.

  2. 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.

  3. Immunoglobulins in Nasal Secretions of Healthy Humans: Structural Integrity of Secretory Immunoglobulin A1 (IgA1) and Occurrence of Neutralizing Antibodies to IgA1 Proteases of Nasal Bacteria

    PubMed Central

    Kirkeby, Line; Rasmussen, Trine Tang; Reinholdt, Jesper; Kilian, Mogens

    2000-01-01

    Certain bacteria, including overt pathogens as well as commensals, produce immunoglobulin A1 (IgA1) proteases. By cleaving IgA1, including secretory IgA1, in the hinge region, these enzymes may interfere with the barrier functions of mucosal IgA antibodies, as indicated by experiments in vitro. Previous studies have suggested that cleavage of IgA1 in nasal secretions may be associated with the development and perpetuation of atopic disease. To clarify the potential effect of IgA1 protease-producing bacteria in the nasal cavity, we have analyzed immunoglobulin isotypes in nasal secretions of 11 healthy humans, with a focus on IgA, and at the same time have characterized and quantified IgA1 protease-producing bacteria in the nasal flora of the subjects. Samples in the form of nasal wash were collected by using a washing liquid that contained lithium as an internal reference. Dilution factors and, subsequently, concentrations in undiluted secretions could thereby be calculated. IgA, mainly in the secretory form, was found by enzyme-linked immunosorbent assay to be the dominant isotype in all subjects, and the vast majority of IgA (median, 91%) was of the A1 subclass, corroborating results of previous analyses at the level of immunoglobulin-producing cells. Levels of serum-type immunoglobulins were low, except for four subjects in whom levels of IgG corresponded to 20 to 66% of total IgA. Cumulative levels of IgA, IgG, and IgM in undiluted secretions ranged from 260 to 2,494 (median, 777) μg ml−1. IgA1 protease-producing bacteria (Haemophilus influenzae, Streptococcus pneumoniae, or Streptococcus mitis biovar 1) were isolated from the nasal cavities of seven subjects at 2.1 × 103 to 7.2 × 106 CFU per ml of undiluted secretion, corresponding to 0.2 to 99.6% of the flora. Nevertheless, α-chain fragments characteristic of IgA1 protease activity were not detected in secretions from any subject by immunoblotting. Neutralizing antibodies to IgA1 proteases of autologous

  4. Human factors in primary care telemedicine encounters.

    PubMed

    Bulik, Robert J

    2008-01-01

    Traditional delivery of primary care takes place in a face-to-face transaction between provider and patient. In telemedicine, however, the transaction is 'filtered' by the distance and technology. The potential problem of filtered communication in a telemedicine encounter was examined from a human factors perspective. Patients with and without experience of telemedicine, and providers who had experience of telemedicine, were asked about patient-provider relationships in interviews and focus groups. Seven themes emerged: initial impressions, style of questions, field of view, physical interaction, social talk, control of encounter and ancillary services. This suggests that communication can be improved and better patient-provider relationships can be developed in a primary care telemedicine encounter if attention is paid to four areas of the interaction: verbal, non-verbal, relational and actions/transactional. The human factors dimension of telemedicine is an important element in delivery of health care at a distance - and is one of few factors over which the provider has direct control.

  5. Nasal mucosal biopsy

    MedlinePlus

    ... Results Mean Cancer Infections, such as tuberculosis Necrotizing granuloma , a type of tumor Nasal polyps Nasal tumors ... Granulomatosis with polyangiitis Juvenile angiofibroma Nasal polyps Necrotizing granuloma Tumor Review Date 4/11/2015 Updated by: ...

  6. Post-Nasal Drip

    MedlinePlus

    ... Find an ENT Doctor Near You Post-Nasal Drip Post-Nasal Drip Patient Health Information News media ... guaifenesin (Humibid®, Robitussin®) may also thin secretions. Nasal irrigations may alleviate thickened secretions. These can be performed ...

  7. 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"…

  8. Bilateral cleft lip nasal deformity

    PubMed Central

    Singh, Arun Kumar; Nandini, R.

    2009-01-01

    Bilateral cleft lip nose deformity is a multi-factorial and complex deformity which tends to aggravate with growth of the child, if not attended surgically. The goals of primary bilateral cleft lip nose surgery are, closure of the nasal floor and sill, lengthening of the columella, repositioning of the alar base, achieving nasal tip projection, repositioning of the lower lateral cartilages, and reorienting the nares from horizontal to oblique position. The multiplicity of procedures in the literature for correction of this deformity alludes to the fact that no single procedure is entirely effective. The timing for surgical intervention and its extent varies considerably. Early surgery on cartilage may adversely affect growth and development; at the same time, allowing the cartilage to grow in an abnormal position and contributing to aggravation of deformity. Some surgeons advocate correction of deformity at an early age. However, others like the cartilages to grow and mature before going in for surgery. With peer pressure also becoming an important consideration during the teens, the current trend is towards early intervention. There is no unanimity in the extent of nasal dissection to be done at the time of primary lip repair. While many perform limited nasal dissection for the fear of growth retardation, others opt for full cartilage correction at the time of primary surgery itself. The value of naso-alveolar moulding (NAM) too is not universally accepted and has now more opponents than proponents. Also most centres in the developing world have neither the personnel nor the facilities for the same. The secondary cleft nasal deformity is variable and is affected by the extent of the original abnormality, any prior surgeries performed and alteration due to nasal growth. This article reviews the currently popular methods for correction of nasal deformity associated with bilateral cleft lip, it's management both at the time of cleft lip repair and also secondarily

  9. Standardized cryopreservation of human primary cells.

    PubMed

    Ramos, Thomas V; Mathew, Aby J; Thompson, Maria L; Ehrhardt, Rolf O

    2014-09-02

    Cryopreservation is the use of low temperatures to preserve structurally intact living cells. The cells that survive the thermodynamic journey from the 37 °C incubator to the -196 °C liquid nitrogen storage tank are free from the influences of time. Thus, cryopreservation is a critical component of cell culture and cell manufacturing protocols. Successful cryopreservation of human cells requires that the cells be derived from patient samples that are collected in a standardized manner, and carefully handled from blood draw through cell isolation. Furthermore, proper equipment must be in place to ensure consistency, reproducibility, and sterility. In addition, the correct choice and amount of cryoprotectant agent must be added at the correct temperature, and a controlled rate of freezing (most commonly 1 °C/min) must be applied prior to a standardized method of cryogenic storage. This appendix describes how human primary cells can be frozen for long-term storage and thawed for growth in a tissue culture vessel.

  10. 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

  11. 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.

  12. Recent advances in primary palate and midface morphogenesis research.

    PubMed

    Diewert, V M; Wang, K Y

    1992-01-01

    During the sixth week of human development, the primary palate develops as facial prominences enlarge around the nasal pits to form the premaxillary region. Growth of craniofacial components changes facial morphology and affects the extent of contact between the facial prominences. Our recent studies have focused on developing methods to analyze growth of the primary palate and the craniofacial complex to define morphological phases of normal development and to determine alterations leading to cleft lip malformation. Analysis of human embryos in the Carnegie Embryology Collection and mouse embryos of cleft lip and noncleft strains showed that human and mouse embryos have similar phases of primary palate development: first, an epithelial seam, the nasal fin, forms; then a mesenchymal bridge develops through the nasal fin and enlarges rapidly. A robust mesenchymal bridge must form between the facial prominences before advancing midfacial growth patterns tend to separate the facial components as the medial nasal region narrows and elongates, the nasal pits narrow, and the primary choanae (posterior nares) open posterior to the primary palate. In mouse strains with cleft lip gene, maxillary growth, nasal fin formation, and mesenchymal replacement of the nasal fin were all delayed compared with noncleft strains of mice. Successful primary palate formation involves a sequence of local cellular events that are closely timed with spatial changes associated with craniofacial growth that must occur within a critical developmental period.

  13. [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.

  14. Pilot study to establish a nasal tip prediction method from unknown human skeletal remains for facial reconstruction and skull photo superimposition as applied to a Japanese male populations.

    PubMed

    Utsuno, Hajime; Kageyama, Toru; Uchida, Keiichi; Kibayashi, Kazuhiko; Sakurada, Koichi; Uemura, Koichi

    2016-02-01

    Skull-photo superimposition is a technique used to identify the relationship between the skull and a photograph of a target person: and facial reconstruction reproduces antemortem facial features from an unknown human skull, or identifies the facial features of unknown human skeletal remains. These techniques are based on soft tissue thickness and the relationships between soft tissue and the skull, i.e., the position of the ear and external acoustic meatus, pupil and orbit, nose and nasal aperture, and lips and teeth. However, the ear and nose region are relatively difficult to identify because of their structure, as the soft tissues of these regions are lined with cartilage. We attempted to establish a more accurate method to determine the position of the nasal tip from the skull. We measured the height of the maxilla and mid-lower facial region in 55 Japanese men and generated a regression equation from the collected data. We obtained a result that was 2.0±0.99mm (mean±SD) distant from the true nasal tip, when applied to a validation set consisting of another 12 Japanese men.

  15. 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.

  16. 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.

  17. 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.

  18. The ΔF508-CFTR mutation inhibits wild-type CFTR processing and function when co-expressed in human airway epithelia and in mouse nasal mucosa

    PubMed Central

    2012-01-01

    Background Rescue or correction of CFTR function in native epithelia is the ultimate goal of CF therapeutics development. Wild-type (WT) CFTR introduction and replacement is also of particular interest. Such therapies may be complicated by possible CFTR self-assembly into an oligomer or multimer. Results Surprisingly, functional CFTR assays in native airway epithelia showed that the most common CFTR mutant, ΔF508-CFTR (ΔF-CFTR), inhibits WT-CFTR when both forms are co-expressed. To examine more mechanistically, both forms of CFTR were transfected transiently in varying amounts into IB3-1 CF human airway epithelial cells and HEK-293 human embryonic kidney cells null for endogenous CFTR protein expression. Increasing amounts of ΔF-CFTR inhibited WT-CFTR protein processing and function in CF human airway epithelial cells but not in heterologous HEK-293 cells. Stably expressed ΔF-CFTR in clones of the non-CF human airway epithelial cell line, CALU-3, also showed reduction in cAMP-stimulated anion secretion and in WT-CFTR processing. An ultimate test of this dominant negative-like effect of ΔF-CFTR on WT-CFTR was the parallel study of two different CF mouse models: the ΔF-CFTR mouse and the bitransgenic CFTR mouse corrected in the gut but null in the lung and airways. WT/ΔF heterozygotes had an intermediate phenotype with regard to CFTR agonist responses in in vivo nasal potential difference (NPD) recordings and in Ussing chamber recordings of short-circuit current (ISC) in vitro on primary tracheal epithelial cells isolated from the same mice. In contrast, CFTR bitransgenic +/− heterozygotes had no difference in their responses versus +/+ wild-type mice. Conclusions Taken altogether, these data suggest that ΔF-CFTR and WT-CFTR co-assemble into an oligomeric macromolecular complex in native epithelia and share protein processing machinery and regulation at the level of the endoplasmic reticulum (ER). As a consequence, ΔF-CFTR slows WT-CFTR protein processing

  19. Exploring the role of intra-nasal oxytocin on the partner preference effect in humans.

    PubMed

    Liu, Jean C J; Guastella, Adam J; Dadds, Mark R

    2013-04-01

    Previous studies with prairie voles suggest that the hormone oxytocin is crucial for bond formation - indicated when a partner preference is formed towards the target vole. In this study, we conduct the first empirical test of whether oxytocin likewise promotes partner preferences in humans. Seventy-six undergraduate students received either oxytocin or placebo before being introduced to a male and female persona (via pre-recorded videoclips). One day later, participants were assessed for a partner preference towards the personae: across three situations, participants were asked to choose as company one of the personae they had been introduced to, or an opposite- or same-gendered person they had not been introduced to before; participants were additionally offered a choice to have no company. We found evidence suggesting oxytocin increases preference for persons introduced under the influence of oxytocin; however, this was not targeted at persons of the opposite-gender, and was found in only one aspect of social interaction (finding out more information about the person, but not in choice of company to work with or for a date). Taken together, our findings suggest that oxytocin might not promote human bond formation in ways analogous to prairie voles - that is, by inducing a partner preference effect.

  20. 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.

  1. 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...

  2. 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...

  3. 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...

  4. Influence of TASP-V, a novel neuropeptide Y (NPY) Y2 agonist, on nasal and bronchial responses evoked by histamine in anaesthetized pigs and in humans

    PubMed Central

    Malis, Didier-David; Grouzmann, Eric; Morel, Denis R; Mutter, Manfred; Lacroix, Jean-Silvain

    1999-01-01

    In nine anaesthetized pigs we have studied the influence of intranasal or intrabronchial pretreatment with TASP-V, a neuropeptide Y (NPY) Y2 agonist formed by the attachment of NPY 21-36 to a template-assembled synthetic peptide (TASP), on the functional responses to subsequent intranasal or intrabronchial histamine challenge. In a parallel study, subjective and objective nasal airway resistance (NAR) increase following intranasal histamine challenge was evaluated in 11 healthy volunteers after TASP-V or placebo pretreatment. In pigs, increase in sphenopalatine blood flow induced by histamine dihydrochloride nasal spray (0.25 mg kg−1 in 3 ml of saline) was significantly reduced by 65% (P<0.05) following intranasal pretreatment with 10 μg kg−1 of TASP-V. Bronchoconstriction induced by histamine dihydrochloride nebulization (0.5 mg kg−1 in 3 ml of saline) was significantly attenuated by 25 and 55% following aerosolized pretreatment with TASP-V analogue at 10 and 20 μg kg−1, respectively. In healthy volunteers, objective increase in NAR and reduction in nasal minimal cross section area (MCSA) induced by intranasal spray of histamine dihydrochloride (15 μg kg−1 in 200 μl of saline) were significantly attenuated by 50% following local pretreatment with 1.275 μg kg−1 of TASP-V when compared with saline. It is concluded that intranasal or intrabronchial pretreatment with TASP-V reduced nasal obstruction and bronchoconstriction evoked by histamine challenge in the pig. In healthy human volunteers, this agent attenuated NAR increase and MCSA reduction induced by intranasal application of histamine. PMID:10193779

  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. Deprojecting the nasal profile.

    PubMed

    Papel, I D; Mabrie, D C

    1999-02-01

    The nose is the most prominent aesthetic feature of the facial profile. Nasal length, tip rotation, and tip projection are integral aspects in analysis of the nasal profile. In most rhinoplasties the surgeon has the difficult task of increasing or maintaining tip projection of an underprojected or normally projected nasal tip. Less commonly, the rhinoplastic surgeon is presented with an overprojected nasal tip, and efforts are focused on deprojecting the nasal profile. In this article, the authors present a discussion of the overprojected tip, elucidating strategies of analysis, etiologies, and management of the nasal profile and give clinical examples.

  7. Nasal Injuries in Sports.

    PubMed

    Marston, Alexander P; O'Brien, Erin K; Hamilton, Grant S

    2017-04-01

    Nasal trauma is a common consequence of athletic competition. The nasal bones are the most commonly fractured facial bone and are particularly at risk during sports participation. Acute management of trauma to the nose includes thorough evaluation of all injuries and may require immediate management for repair of facial lacerations, epistaxis control, or septal hematoma drainage. Nasal fractures can often be addressed with closed reduction techniques; however, in the setting of complex nasal trauma, an open approach may be indicated. Using appropriate treatment techniques, posttraumatic nasal sequelae can be minimized; most patients report satisfactory long-term nasal form and function.

  8. Triamcinolone Nasal Spray

    MedlinePlus

    ... itchy nose and itchy, watery eyes caused by hay fever or other allergies. Triamcinolone nasal spray should not ... germs.Triamcinolone nasal spray controls the symptoms of hay fever and allergies but does not cure these conditions. ...

  9. Flunisolide Nasal Spray

    MedlinePlus

    ... sneezing, runny, stuffy, or itchy nose caused by hay fever or other allergies. Flunisolide nasal spray should not ... germs.Flunisolide nasal spray controls the symptoms of hay fever or allergies but does not cure these conditions. ...

  10. Saline nasal washes

    MedlinePlus

    ... a neti pot, squeeze bottle, or rubber nasal bulb at your drug store. You can also buy ... infection. Always clean the neti pot or nasal bulb with distilled, boiled, or filtered water after every ...

  11. Nasal corticosteroid sprays

    MedlinePlus

    ... or concerns about your symptoms Trouble using the medicine Alternative Names Steroid nasal sprays; Allergies - nasal corticosteroid sprays References American Academy of ... of Medicine, Division of Allergy, Immunology, and Rheumatology, Georgetown University ...

  12. Nasal septal hematoma

    MedlinePlus

    ... medlineplus.gov/ency/article/001292.htm Nasal septal hematoma To use the sharing features on this page, ... heal. References Chegar BE, Tatum SA III. Nasal fractures. In: Flint PW, Haughey BH, Lund VJ, et ...

  13. 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.

  14. 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…

  15. Specific Induction of TSLP by the Viral RNA Analogue Poly(I:C) in Primary Epithelial Cells Derived from Nasal Polyps

    PubMed Central

    van Egmond, Danielle; de Groot, Esther J.; Fokkens, Wytske J.; van Drunen, Cornelis M.

    2016-01-01

    Introduction Chronic rhinosinusitis with nasal polyposis is an inflammatory disease that, although not directly linked to allergy, often displays a Th2-skewed inflammation characterized by elevated local IgE and IL-5 levels. The nasal cavity is constantly exposed to bacteria and viruses that may trigger epithelial inflammatory responses. To gain more insight into mechanisms by which such a biased inflammation might arise, we have investigated the epithelial expression of the Th2 skewing mediators (TSLP, IL-25, and IL-33) in relationship to disease and microbial triggers. Methods Epithelial cells were obtained from polyp tissues of nasal polyposis patients and from inferior turbinates of non-diseased controls. Cells were exposed to various TLR-specific triggers to study the effect on mRNA and protein expression level of TSLP, IL-25, and IL-33 and the potential regulatory mechanisms through the expression profile the transcription factors ATF-3, DUSP-1, EGR-1, and NFKB-1. Results The TLR3 agonist and viral analogue poly(I:C) induced TSLP mRNA 13.0 ± 3.1 fold (p < 0.05) and protein expression by 12.1 ± 2.3-fold (p < 0.05) higher in epithelium isolated from nasal polyposis patients than in epithelium form healthy controls. This enhanced induction of TSLP may be a consequence of a down-regulated expression of DUSP-1 in polyp epithelium. Conclusion The TLR3 induced expression of TSLP introduces a mechanism by which the Th2-skewed tissue environment might arise in nasal polyps and invites a further evaluation of the potential contribution of current or past viral infections to polyposis pathogenesis. PMID:27050744

  16. 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

  17. Nasal Harmony in Aguaruna.

    ERIC Educational Resources Information Center

    Moon, Gui-Sun

    A discussion of the nasal harmony of Aguaruna, a language of the Jivaroan family in South America, approaches the subject from the viewpoint of generative phonology. This theory of phonology proposes an underlying nasal consonant, later deleted, that accounts for vowel nasalization. Complex rules that suppose a complex system of vowel and…

  18. Nasal septal hematoma.

    PubMed

    Ginsburg, C M

    1998-04-01

    Nasal septal hematoma is a rare but potentially serious complication of nasal trauma. Proper management consists of early recognition, prompt surgical evacuation of the hematoma, and antimicrobial therapy if a secondary nasal septal abscess is suspected. Clindamycin is recommended as initial therapy until the results of cultures and susceptibility studies are available.

  19. Nasal computed tomography.

    PubMed

    Kuehn, Ned F

    2006-05-01

    Chronic nasal disease is often a challenge to diagnose. Computed tomography greatly enhances the ability to diagnose chronic nasal disease in dogs and cats. Nasal computed tomography provides detailed information regarding the extent of disease, accurate discrimination of neoplastic versus nonneoplastic diseases, and identification of areas of the nose to examine rhinoscopically and suspicious regions to target for biopsy.

  20. 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.

  1. 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

  2. Perceiving nasal patency through mucosal cooling rather than air temperature or nasal resistance.

    PubMed

    Zhao, Kai; Blacker, Kara; Luo, Yuehao; Bryant, Bruce; Jiang, Jianbo

    2011-01-01

    Adequate perception of nasal airflow (i.e., nasal patency) is an important consideration for patients with nasal sinus diseases. The perception of a lack of nasal patency becomes the primary symptom that drives these patients to seek medical treatment. However, clinical assessment of nasal patency remains a challenge because we lack objective measurements that correlate well with what patients perceive. The current study examined factors that may influence perceived patency, including air temperature, humidity, mucosal cooling, nasal resistance, and trigeminal sensitivity. Forty-four healthy subjects rated nasal patency while sampling air from three facial exposure boxes that were ventilated with untreated room air, cold air, and dry air, respectively. In all conditions, air temperature and relative humidity inside each box were recorded with sensors connected to a computer. Nasal resistance and minimum airway cross-sectional area (MCA) were measured using rhinomanometry and acoustic rhinometry, respectively. General trigeminal sensitivity was assessed through lateralization thresholds to butanol. No significant correlation was found between perceived patency and nasal resistance or MCA. In contrast, air temperature, humidity, and butanol threshold combined significantly contributed to the ratings of patency, with mucosal cooling (heat loss) being the most heavily weighted predictor. Air humidity significantly influences perceived patency, suggesting that mucosal cooling rather than air temperature alone provides the trigeminal sensation that results in perception of patency. The dynamic cooling between the airstream and the mucosal wall may be quantified experimentally or computationally and could potentially lead to a new clinical evaluation tool.

  3. Staphylococcus aureus nasal carriage, virulence traits, antibiotic resistance mechanisms, and genetic lineages in healthy humans in Spain, with detection of CC398 and CC97 strains.

    PubMed

    Lozano, Carmen; Gómez-Sanz, Elena; Benito, Daniel; Aspiroz, Carmen; Zarazaga, Myriam; Torres, Carmen

    2011-08-01

    S. aureus nasal carriage was investigated in 278 healthy humans, determining the antibiotic resistance mechanisms, virulence traits, and genetic lineages of recovered isolates. Nasal samples were cultured in specific media for S. aureus and methicillin-resistant S. aureus (MRSA) recovery. S. aureus was detected in 53 of 278 nasal samples (19.1%): MRSA was found in one sample (0.4%) and methicillin-susceptible S. aureus (MSSA) in the remaining 52 samples. The MRSA isolate was typed as ST1649-t701-agrI-SCCmec-IVc and only exhibited resistance to beta-lactams. A high diversity of spa types (n=37) was identified among the 52 MSSA, identifying 5 new spa-types. Multi-locus sequence typing (MLST) typing was performed in 30 selected MSSA, detecting 16 different sequence types, 2 of them being new. MSSA strains presented agr types I (30.2%), II (30.2%), III (34%), and IV (5.6%). Eleven strains showed erythromycin resistance and harbored different combinations of erm(A), erm(B), erm(C), erm(T), and msr(A) genes. Two strains exhibited ciprofloxacin resistance, and one of them presented amino acid changes in GyrA and GrlA proteins. The presence of 28 genes encoding staphylococcal toxins was investigated by PCR in all 53 S. aureus isolates. The toxic shock syndrome toxin 1 (TSST-1) gene was detected in 15 MSSA isolates (11 of them typed within the clonal complex CC30) and the gene of exfoliative toxin A in 2 strains. Different combinations of enterotoxin genes were identified among S. aureus strains. None of the S. aureus isolates harbored the Panton-Valentine leukocidin gene. Two MSSA presented the sequence-type ST398 [harboring erm(T) gene], and 2 additional isolates were typed as ST97. Interestingly, MSSA CC398 and CC97 isolates were detected. These clonal complexes are associated with food-producing animals.

  4. Interhemispheric Connections between the Primary Visual Cortical Areas via the Anterior Commissure in Human Callosal Agenesis.

    PubMed

    van Meer, Nathalie; Houtman, Anne C; Van Schuerbeek, Peter; Vanderhasselt, Tim; Milleret, Chantal; Ten Tusscher, Marcel P

    2016-01-01

    Aim: In humans, images in the median plane of the head either fall on both nasal hemi-retinas or on both temporal hemi-retinas. Interhemispheric connections allow cortical cells to have receptive fields on opposite sides. The major interhemispheric connection, the corpus callosum, is implicated in central stereopsis and disparity detection in front of the fixation plane. Yet individuals with agenesis of the corpus callosum may show normal stereopsis and disparity vergence. We set out to study a possible interhemispheric connection between primary visual cortical areas via the anterior commissure to explain this inconsistency because of the major role of these cortical areas in elaborating 3D visual perception. Methods: MRI, DTI and tractography of the brain of a 53-year old man with complete callosal agenesis and normal binocular single vision was undertaken. Tractography seed points were placed in both the right and the left V1 and V2. Nine individuals with both an intact corpus callosum and normal binocularity served as controls. Results: Interhemispheric tracts through the anterior commissure linking both V1 and V2 visual cortical areas bilaterally were indeed shown in the subject with callosal agenesis. All other individuals showed interhemispheric visual connections through the corpus callosum only. Conclusion: Callosal agenesis may result in anomalous interhemispheric connections of the primary visual areas via the anterior commissure. It is proposed here that these connections form as alternative to the normal callosal pathway and may participate in binocularity.

  5. Interhemispheric Connections between the Primary Visual Cortical Areas via the Anterior Commissure in Human Callosal Agenesis

    PubMed Central

    van Meer, Nathalie; Houtman, Anne C.; Van Schuerbeek, Peter; Vanderhasselt, Tim; Milleret, Chantal; ten Tusscher, Marcel P.

    2016-01-01

    Aim: In humans, images in the median plane of the head either fall on both nasal hemi-retinas or on both temporal hemi-retinas. Interhemispheric connections allow cortical cells to have receptive fields on opposite sides. The major interhemispheric connection, the corpus callosum, is implicated in central stereopsis and disparity detection in front of the fixation plane. Yet individuals with agenesis of the corpus callosum may show normal stereopsis and disparity vergence. We set out to study a possible interhemispheric connection between primary visual cortical areas via the anterior commissure to explain this inconsistency because of the major role of these cortical areas in elaborating 3D visual perception. Methods: MRI, DTI and tractography of the brain of a 53-year old man with complete callosal agenesis and normal binocular single vision was undertaken. Tractography seed points were placed in both the right and the left V1 and V2. Nine individuals with both an intact corpus callosum and normal binocularity served as controls. Results: Interhemispheric tracts through the anterior commissure linking both V1 and V2 visual cortical areas bilaterally were indeed shown in the subject with callosal agenesis. All other individuals showed interhemispheric visual connections through the corpus callosum only. Conclusion: Callosal agenesis may result in anomalous interhemispheric connections of the primary visual areas via the anterior commissure. It is proposed here that these connections form as alternative to the normal callosal pathway and may participate in binocularity. PMID:28082873

  6. 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 Central

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

    2001-01-01

    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

  7. Low prevalence of oral and nasal human papillomavirus in employees performing CO2-laser evaporation of genital warts or loop electrode excision procedure of cervical dysplasia.

    PubMed

    Kofoed, Kristian; Norrbom, Christina; Forslund, Ola; Møller, Charlotte; Frøding, Ligita P; Pedersen, Anders Elm; Markauskas, Algirdas; Blomberg, Maria; Baumgartner-Nielsen, Jane; Madsen, Jakob Torp; Strauss, Gitte; Madsen, Klaus G; Sand, Carsten

    2015-02-01

    Risk of human papillomavirus (HPV) transmission during laser vaporisation of genital warts or loop electrode excision procedure is controversial. An oral rinse, a nasal swabs, history of HPV related diseases and data on HPV exposure were collected from 287 employees at departments of dermato-venerology and gynaecology in Denmark. A mucosal HPV type was found among 5.8% of employees with experience of laser treatment of genital warts as compared to 1.7% of those with no experience (p = 0.12). HPV prevalence was not higher in employees participating in electrosurgical treatment or cryotherapy of genital warts, or loop electrode excision procedure compared with those who did not. HPV 6 or 11 were not detected in any samples. Hand warts after the age of 24 years was more common among dermatology than among non-dermatology personnel (18% vs. 8.0%, p = 0.03). Mucosal HPV types are infrequent in the oral and nasal cavity of health care personnel, however, employees at departments of dermato-venereology are at risk of acquiring hand warts.

  8. Phenotype and function of nasal dendritic cells

    PubMed Central

    Lee, Haekyung; Ruane, Darren; Law, Kenneth; Ho, Yan; Garg, Aakash; Rahman, Adeeb; Esterházy, Daria; Cheong, Cheolho; Goljo, Erden; Sikora, Andrew G.; Mucida, Daniel; Chen, Benjamin; Govindraj, Satish; Breton, Gaëlle; Mehandru, Saurabh

    2015-01-01

    Intranasal vaccination generates immunity across local, regional and distant sites. However, nasal dendritic cells (DC), pivotal for the induction of intranasal vaccine- induced immune responses, have not been studied in detail. Here, using a variety of parameters, we define nasal DCs in mice and humans. Distinct subsets of “classical” DCs, dependent on the transcription factor zbtb46 were identified in the murine nose. The murine nasal DCs were FLT3 ligand-responsive and displayed unique phenotypic and functional characteristics including the ability to present antigen, induce an allogeneic T cell response and migrate in response to LPS or live bacterial pathogens. Importantly, in a cohort of human volunteers, BDCA-1+ DCs were observed to be the dominant nasal DC population at steady state. During chronic inflammation, the frequency of both BDCA-1+ and BDCA-3hi DCs was reduced in the nasal tissue, associating the loss of these immune sentinels with chronic nasal inflammation. The present study is the first detailed description of the phenotypic, ontogenetic and functional properties of nasal DCs and will inform the design of preventative immunization strategies as well as therapeutic modalities against chronic rhinosinusitis. PMID:25669151

  9. Proteomic Analysis of Nasal Epithelial Cells from Cystic Fibrosis Patients

    PubMed Central

    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. PMID:25268127

  10. 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.

  11. Management of the middle nasal third in revision rhinoplasty.

    PubMed

    Sykes, Jonathan M

    2008-08-01

    The middle nasal third is often the source of both aesthetic and functional problems with primary rhinoplasty. Weakness of the middle nasal vault can occur from overresection of the upper lateral cartilages or cartilaginous nasal septum, malposition of the upper lateral cartilages, or from secondary scarring from the primary rhinoplasty. These functional and aesthetic problems can be avoided by maintaining an adequate infrastructure to the middle nasal vault. If secondary problems occur in the middle nasal third, precise anatomic reconstruction can be performed in the form of cartilage grafting and/or suture reconstitution. This reconstruction requires an in-depth knowledge of the functional nasal anatomy and the ability to re-create the infrastructure so that it withstands the forces of scarring and wound contraction. This article outlines the anatomy of the middle third of the nose, the conditions that cause secondary middle-third problems, and the surgical management of these deformities.

  12. 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.

  13. [Nasal fractures in adults].

    PubMed

    Sjöstedt, Sannia; Larsen, Christian Grønhøj; Bilde, Anders; von Buchwald, Christian

    2016-03-07

    The risk of complications warrants treatment of most dislocated nasal fractures. Other injuries including other facial fractures and septal haematoma must be treated if present at the initial presentation. The usual treatment for a simple nasal fracture is closed reduction in local anaesthesia after five to seven days. Complicated cases require open reduction in general anaesthesia. Later revision of the deviated nose may become necessary in patients suffering from complications such as persistent nasal stenosis and/or deformity.

  14. 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.

  15. The supernumerary nasal tooth.

    PubMed

    Kirmeier, R; Truschnegg, A; Payer, M; Malyk, J; Daghighi, S; Jakse, N

    2009-11-01

    Teeth exceeding the normal dental complement that have erupted into the nasal cavity are a rare pathological entity. This case report describes a female patient with recurrent complaints and fetid discharge from the left nasal cavity. The suspected clinical diagnosis of a supernumerary nasal tooth was confirmed by computed tomography. After endoscopic removal, the tooth was examined using X-ray microtomography and thin-section preparations; these findings are presented for the first time. A literature search identified 25 supernumerary nasal teeth in 23 patients.

  16. 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…

  17. Efficient Gene Editing in Primary Human T Cells.

    PubMed

    Chen, Yvonne Y

    2015-11-01

    Recent advances in T-cell therapy for cancer, viral infections, and autoimmune diseases highlight the broad therapeutic potential of T-cell engineering. However, site-specific genetic manipulation in primary human T cells remains challenging. Two recent studies describe efficient genome editing in T cells using CRISPR and TALEN approaches.

  18. Nasality in Taiwanese

    ERIC Educational Resources Information Center

    Pan, Ho-hsien

    2004-01-01

    This study used perceptual and articulatory data to investigate a language specific phonemic inventory, and allophonic rules for homorganic initial voiced stops versus homorganic nasal stops, and oral versus nasal vowels in Taiwanese. Four experiments were conducted: concept formation, gating, and two airflow studies. Results of a first nasal…

  19. Lining in nasal reconstruction.

    PubMed

    Haack, Sebastian; Fischer, Helmut; Gubisch, Wolfgang

    2014-06-01

    Restoring nasal lining is one of the essential parts during reconstruction of full-thickness defects of the nose. Without a sufficient nasal lining the whole reconstruction will fail. Nasal lining has to sufficiently cover the shaping subsurface framework. But in addition, lining must not compromise or even block nasal ventilation. This article demonstrates different possibilities of lining reconstruction. The use of composite grafts for small rim defects is described. The limits and technical components for application of skin grafts are discussed. Then the advantages and limitations of endonasal, perinasal, and hingeover flaps are demonstrated. Strategies to restore lining with one or two forehead flaps are presented. Finally, the possibilities and technical aspects to reconstruct nasal lining with a forearm flap are demonstrated. Technical details are explained by intraoperative pictures. Clinical cases are shown to illustrate the different approaches and should help to understand the process of decision making. It is concluded that although the lining cannot be seen after reconstruction of the cover it remains one of the key components for nasal reconstruction. When dealing with full-thickness nasal defects, there is no way to avoid learning how to restore nasal lining.

  20. 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.

  1. [Nasal allergenic provocation test].

    PubMed

    Becerril Angeles, M H; Pérez López, A; Azuara Pliego, E

    2000-01-01

    This is a method to evaluate both specific sensitivity to allergens in the nasal mucosa, IgE-mediated hypersensitivity, and antiinflammatory and antiallergic drugs efficacy, whose objectives are for research in diagnosis and treatment. The method is based in allergen extracts delivery in the nasal mucosa and the post-challenge measurement of rhinitis symptoms, vasoactive mediators release quantification and nasal obstruction degree evaluated by rhinomanometry. Nasal allergen challenge is a procedure of diagnostic and therapeutic evaluation usefulness, that must be performed in selected patients, in adequate facilities, by experts physicians, with standardised allergen dosages, in an specific nasal area, with objective measurements (rhinomanometry, mediators and secretions of the allergic response) and symptoms scoring that allow get reliable results in patients with allergic rhinitis under study.

  2. Prevalence of Staphylococcus aureus Nasal Carriage in Human Immunodeficiency Virus-Infected and Uninfected Children in Botswana: Prevalence and Risk Factors.

    PubMed

    Reid, Michael J A; Fischer, Rebecca S B; Mannathoko, Naledi; Muthoga, Charles; McHugh, Erin; Essigmann, Heather; Brown, Eric L; Steenhoff, Andrew P

    2017-02-06

    Staphylococcus aureus is an important cause of morbidity and mortality in children in sub-Saharan Africa (SSA). A major risk factor for staphylococcal infection is S. aureus colonization of the anterior nares. We sought to define risk factors for S. aureus carriage and characterize antimicrobial resistance patterns in children in Botswana. A cross-sectional study was conducted at two clinical sites in southern Botswana. Patients under 18 years of age underwent two nasal swabs and brief interviews, 4 weeks apart. Standard microbiological techniques were used. For persistent carriers, S. aureus was isolated from swabs at both time points, and for intermittent carriers, S. aureus was isolated from only one swab. Poisson regression with robust variance estimator was used to compare prevalence of carriage and the resistance phenotypes. Among 56 enrollees, prevalence of S. aureus colonization was 55% (N = 31), of whom 42% (N = 13) were persistent carriers. Of human immunodeficiency virus-infected children, 64% (N = 9) were carriers. Risk factors for nasal carriage included a history of tuberculosis (prevalence ratio [PR] = 1.60; 95% confidence interval [CI] = 1.02, 2.51; P = 0.040) and closer proximity to health care (PR = 0.89; 95% CI = 0.80, 0.99; P = 0.048). Prior pneumonia was more common among persistent rather than intermittent carriers (PR = 2.64; 95% CI = 1.64, 4.23; P < 0.001). Methicillin-resistant S. aureus (MRSA) prevalence was 13%. Of isolates tested, 16% were resistant to three or more drugs (N = 7/44). In summary, children in southern Botswana are frequently colonized with S. aureus Antibiotic resistance, especially MRSA, is also widespread. Antibiotic recommendations for treatment of staphylococcal infections in SSA should take cognizance of these resistance patterns.

  3. Forkhead Box C1 Regulates Human Primary Keratinocyte Terminal Differentiation

    PubMed Central

    Deng, Liehua; Yang, Hengwen; Zhu, Leqing; Wang, Xiao; Edwards, Michael G.; Richers, Brittany; Leung, Donald Y. M.

    2016-01-01

    The epidermis serves as a critical protective barrier between the internal and external environment of the human body. Its remarkable barrier function is established through the keratinocyte (KC) terminal differentiation program. The transcription factors specifically regulating terminal differentiation remain largely unknown. Using a RNA-sequencing (RNA-seq) profiling approach, we found that forkhead box c 1 (FOXC1) was significantly up-regulated in human normal primary KC during the course of differentiation. This observation was validated in human normal primary KC from several different donors and human skin biopsies. Silencing FOXC1 in human normal primary KC undergoing differentiation led to significant down-regulation of late terminal differentiation genes markers including epidermal differentiation complex genes, keratinization genes, sphingolipid/ceramide metabolic process genes and epidermal specific cell-cell adhesion genes. We further demonstrated that FOXC1 works down-stream of ZNF750 and KLF4, and upstream of GRHL3. Thus, this study defines FOXC1 as a regulator specific for KC terminal differentiation and establishes its potential position in the genetic regulatory network. PMID:27907090

  4. 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

  5. Dose-Response Functions for the Olfactory, Nasal Trigeminal, and Ocular Trigeminal Detectability of Airborne Chemicals by Humans.

    PubMed

    Cometto-Muñiz, J Enrique; Abraham, Michael H

    2016-01-01

    We gathered from the literature 47 odor and 37 trigeminal (nasal and ocular) chemesthetic psychometric (i.e., detectability or dose-response) functions from a group of 41 chemicals. Vapors delivered were quantified by analytical methods. All functions were very well fitted by the sigmoid (logistic) equation: y = 1 / (1 + e({-(x-C)/D})), where parameter C quantifies the detection threshold concentration and parameter D the steepness of the function. Odor and chemesthetic functions showed no concentration overlap: olfactory functions grew along the parts per billion (ppb by volume) range or lower, whereas trigeminal functions grew along the part per million (ppm by volume) range. Although, on average, odor detectability rose from chance detection to perfect detection within 2 orders of magnitude in concentration, chemesthetic detectability did it within one. For 16 compounds having at least 1 odor and 1 chemesthetic function, the average gap between the 2 functions was 4.6 orders of magnitude in concentration. A quantitative structure-activity relationship (QSAR) using 5 chemical descriptors that had previously described stand-alone odor and chemesthetic threshold values, also holds promise to describe, and eventually predict, olfactory and chemesthetic detectability functions, albeit functions from additional compounds are needed to strengthen the QSAR.

  6. 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…

  7. 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…

  8. 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 ...

  9. 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.

  10. 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

  11. 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

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

    PubMed

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

    1998-07-01

    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.

  13. 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.

  14. Antigen-specific modulation of experimental myasthenia gravis: nasal tolerization with recombinant fragments of the human acetylcholine receptor alpha-subunit.

    PubMed

    Barchan, D; Souroujon, M C; Im, S H; Antozzi, C; Fuchs, S

    1999-07-06

    Myasthenia gravis (MG) and experimental autoimmune myasthenia gravis (EAMG) are antibody-mediated autoimmune diseases in which the nicotinic acetylcholine receptor (AcChoR) is the major autoantigen. The immune response in these diseases is heterogeneous and is directed to a wide variety of T and B cell epitopes of AcChoR. Candidate molecules for specific immunotherapy of MG should, therefore, have a broad specificity. We used recombinant fragments of the human AcChoR, encompassing the extracellular domain of the alpha-subunit, or shorter fragments derived from it, in experiments to modulate EAMG. We have demonstrated that intranasal administration of these recombinant fragments, which represent a major portion of epitopes involved in MG, prevents the induction of EAMG in rats and immunosuppresses an ongoing disease, as assessed by clinical symptoms, weight loss, and muscle AcChoR content. These effects on EAMG were accompanied by a marked reduction in the proliferative T-cell response and IL-2 production in response to AcChoR, in reduced anti-self AcChoR antibody titers and in an isotype switch of AcChoR-specific antibodies, from IgG2 to IgG1. We conclude that nasal tolerance induced by appropriate recombinant fragments of human AcChoR is effective in suppressing EAMG and might possibly be considered as a therapeutic modality for MG.

  15. Antigen-specific modulation of experimental myasthenia gravis: Nasal tolerization with recombinant fragments of the human acetylcholine receptor α-subunit

    PubMed Central

    Barchan, Dora; Souroujon, Miriam C.; Im, Sin-Hyeog; Antozzi, Carlo; Fuchs, Sara

    1999-01-01

    Myasthenia gravis (MG) and experimental autoimmune myasthenia gravis (EAMG) are antibody-mediated autoimmune diseases in which the nicotinic acetylcholine receptor (AcChoR) is the major autoantigen. The immune response in these diseases is heterogeneous and is directed to a wide variety of T and B cell epitopes of AcChoR. Candidate molecules for specific immunotherapy of MG should, therefore, have a broad specificity. We used recombinant fragments of the human AcChoR, encompassing the extracellular domain of the α-subunit, or shorter fragments derived from it, in experiments to modulate EAMG. We have demonstrated that intranasal administration of these recombinant fragments, which represent a major portion of epitopes involved in MG, prevents the induction of EAMG in rats and immunosuppresses an ongoing disease, as assessed by clinical symptoms, weight loss, and muscle AcChoR content. These effects on EAMG were accompanied by a marked reduction in the proliferative T-cell response and IL-2 production in response to AcChoR, in reduced anti-self AcChoR antibody titers and in an isotype switch of AcChoR-specific antibodies, from IgG2 to IgG1. We conclude that nasal tolerance induced by appropriate recombinant fragments of human AcChoR is effective in suppressing EAMG and might possibly be considered as a therapeutic modality for MG. PMID:10393952

  16. 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.

  17. Primary pulmonary hypertension, Castleman's disease and human herpesvirus-8.

    PubMed

    Bull, T M; Cool, C D; Serls, A E; Rai, P R; Parr, J; Neid, J M; Geraci, M W; Campbell, T B; Voelkel, N F; Badesch, D B

    2003-09-01

    Primary pulmonary hypertension (PPH) and Castleman's disease (CD) are rare conditions infrequently encountered in clinical practice. In this paper, two patients diagnosed with both of these diseases are reported. The authors speculate that rather than being a chance occurrence, these conditions are linked by a common angio-proliferative mechanism. Therefore, an association between infection with the human herpesvirus-8 and the diseases of PPH and CD was sought. Evidence of human herpesvirus-8 infection was found in the lung tissue and, specifically, in the plexiform lesions from one of the patients.

  18. Vascular Endothelial Growth Factor Drives Autocrine Epithelial Cell Proliferation and Survival in Chronic Rhinosinusitis with Nasal Polyposis

    PubMed Central

    Lee, Hyun Sil; Myers, Allen; Kim, Jean

    2009-01-01

    Rationale: The pathogenesis of nasal polyps in chronic rhinosinusitis is poorly understood. Objectives: These studies seek to implicate a functional role for vascular endothelial growth factor (VEGF) in perpetuating primary nasal epithelial cell overgrowth, a key feature of hyperplastic polyps. Methods: Comparison of VEGF and receptor expression was assessed by ELISA of nasal lavage, immunohistochemistry of sinus tissue, flow cytometry of nasal epithelial cells, and ELISA of supernatants. VEGF-dependent cell growth and apoptosis were assessed with blocking antibodies to VEGF, their receptors, or small interfering RNA knockdown of neuropilin-1 by cell proliferation assays and flow cytometric binding of annexin V. Measurements and Main Results: VEGF protein was sevenfold higher in nasal lavage from patients with polyposis compared with control subjects (P < 0.001). We also report elevated expression of VEGF (P < 0.012), receptors VEGFR2 and phospho-VEGFR2 (both P < 0.04), and identification of VEGF coreceptor neuropilin-1 in these tissues. Nasal epithelial cells from patients with polyps demonstrated faster growth rates (P < 0.005). Exposure of cells to blocking antibodies against VEGF resulted in inhibition of cell growth (P < 0.05). VEGF receptor blockade required blockade of neuropilin-1 (P < 0.05) and resulted in increased apoptosis (P < 0.001) and inhibition of autocrine epithelial VEGF production (P < 0.05). Conclusions: These data demonstrate that VEGF is a novel biomarker for chronic rhinosinusitis with hyperplastic sinonasal polyposis that functions in an autocrine feed-forward manner to promote nasal epithelial cell growth and to inhibit apoptosis. These findings implicate a previously unrecognized and novel role of VEGF functioning through neuropilin-1 on nonneoplastic primary human airway epithelial cells, to amplify cell growth, contributing to exuberant hyperplastic polyposis. PMID:19762561

  19. Cobalt ions induce chemokine secretion in primary human osteoblasts.

    PubMed

    Queally, J M; Devitt, B M; Butler, J S; Malizia, A P; Murray, D; Doran, P P; O'Byrne, J M

    2009-07-01

    Chemokines are major regulators of the inflammatory response and have been shown to play an important role in periprosthetic osteolysis. Titanium particles have previously been shown to induce IL-8 and MCP-1 secretion in osteoblasts. These chemokines result in the chemotaxis and activation of neutrophils and macrophages, respectively. Despite a resurgence in the use of cobalt-chromium-molybdenum alloys in metal-on-metal arthroplasty, cobalt and chromium ion toxicity in the periprosthetic area has been insufficiently studied. In this study we investigate the in vitro effect of cobalt ions on primary human osteoblast activity. We demonstrate that cobalt ions rapidly induce the protein secretion of IL-8 and MCP-1 in primary human osteoblasts. This elevated chemokine secretion is preceded by an increase in the transcription of the corresponding chemokine gene. Using a Transwell migration chemotaxis assay we also demonstrate that the chemokines secreted are capable of inducing neutrophil and macrophage migration. Furthermore, cobalt ions significantly inhibit osteoblast function as demonstrated by reduced alkaline phosphatase activity and calcium deposition. In aggregate these data demonstrate that cobalt ions can activate transcription of the chemokine genes IL-8 and MCP-1 in primary human osteoblasts. Cobalt ions are not benign and may play an important role in the pathogenesis of osteolysis by suppressing osteoblast function and stimulating the production and secretion of chemokines that attract inflammatory and osteoclastic cells to the periprosthetic area.

  20. Nasal septal trauma in children.

    PubMed

    Olsen, K D; Carpenter, R J; Kern, E B

    1979-07-01

    If the septal component of a nasal injury is adequately managed, usually the entire nasal injury will be well managed. Major or minor nasal trauma can cause cartilage fracture, deviation, dislocation, hematoma, or abscess formation, and the various associated sequelae, some of them life-threatening. A negative x-ray report should never be used as a substitute for a complete intranasal examination in any child with nasal trauma. Any nasal abnormality should be referred for immediate evaluation and treatment.

  1. Budesonide Nasal Spray

    MedlinePlus

    ... sneezing, runny, stuffy, or itchy nose caused by hay fever or other allergies (caused by an allergy to ... germs.Budesonide nasal spray controls the symptoms of hay fever or allergies but does not cure these conditions. ...

  2. Fluticasone Nasal Spray

    MedlinePlus

    ... itchy nose and itchy, watery eyes caused by hay fever or other allergies (caused by an allergy to ... germs.Fluticasone nasal spray controls the symptoms of hay fever or allergies but does not cure these conditions. ...

  3. Mometasone Nasal Spray

    MedlinePlus

    ... sneezing, runny, stuffy, or itchy nose caused by hay fever or other allergies. It is also used to ... using mometasone nasal spray to prevent or relieve hay fever or allergy symptoms, it is usually sprayed in ...

  4. Beclomethasone Nasal Spray

    MedlinePlus

    ... runny, stuffy, or itchy nose (rhinitis) caused by hay fever, other allergies, or vasomotor (nonallergic) rhinitis. It is ... germs.Beclomethasone nasal spray controls the symptoms of hay fever or allergies but does not cure these conditions. ...

  5. Nasal Wash Treatment

    MedlinePlus

    ... months or if it becomes discolored. Cleaning the Bulb Syringe (dropper, syringe or nasal spray bottle) After ... may be several times a day), fill the bulb syringe with water (described above), swish the water ...

  6. 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

  7. 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 ...

  8. Chapter 6: Nasal polyps.

    PubMed

    Settipane, Russell A; Peters, Anju T; Chiu, Alexander G

    2013-01-01

    Nasal polyps occur in 1-4% of the population, usually occurring in the setting of an underlying local or systemic disease. The most common associated condition is chronic rhinosinusitis (CRS). A high prevalence of nasal polyps is also seen in allergic fungal rhinosinusitis, aspirin-exacerbated respiratory disease, Churg-Strauss syndrome, and cystic fibrosis. In the setting of CRS, nasal polyps are not likely to be cured by either medical or surgical therapy; however, control is generally attainable. The best medical evidence supports the use of intranasal corticosteroids for maintenance therapy and short courses of oral corticosteroids for exacerbations. The evidence for short- and long-term antibiotics is much less robust. For patients with symptomatic nasal polyposis nonresponsive to medical therapies, functional endoscopic sinus surgery provides an adjunctive therapeutic option.

  9. How Are Nasal Cavity and Paranasal Sinus Cancers Staged?

    MedlinePlus

    ... nasal cavity or ethmoid sinuses. T categories for maxillary sinus cancer TX: Primary (main) tumor cannot be ... the nose from the brain), and/or the maxillary sinus. T4a: Tumor has grown into other structures ...

  10. Pathophysiology of nasal congestion

    PubMed Central

    Naclerio, Robert M; Bachert, Claus; Baraniuk, James N

    2010-01-01

    Nasal congestion is a common symptom in rhinitis (both allergic and nonallergic), rhinosinusitis and nasal polyposis. Congestion can also be caused by physical obstruction of nasal passages and/or modulation of sensory perception. Mucosal inflammation underlies many of the specific and interrelated factors that contribute to nasal congestion, as well as other symptoms of both allergic rhinitis and rhinosinusitis. A wide range of biologically active agents (eg, histamine, tumor necrosis factor-α, interleukins, cell adhesion molecules) and cell types contribute to inflammation, which can manifest as venous engorgement, increased nasal secretions and tissue swelling/edema, ultimately leading to impaired airflow and the sensation of nasal congestion. Inflammation-induced changes in the properties of sensory afferents (eg, expression of peptides and receptors) that innervate the nose can also contribute to altered sensory perception, which may result in a subjective feeling of congestion. Increased understanding of the mechanisms underlying inflammation can facilitate improved treatment selection and the development of new therapies for congestion. PMID:20463823

  11. Titanium Mesh Nasal Repair without Nasal Lining.

    PubMed

    Zenga, Joseph; Kao, Katherine; Chen, Collin; Gross, Jennifer; Hahn, Samuel; Chi, John J; Branham, Gregory H

    2017-02-01

    The objective of this study was to describe outcomes for patients who underwent titanium mesh reconstruction of full-thickness nasal defects without internal lining repair. This is a retrospective cohort study. Patients with through-and-through nasal defects were identified at a single academic institution between 2008 and 2016. Nasal reconstruction was performed with either titanium mesh and external skin reconstruction without repair of the intranasal lining or traditional three-layer closure. Five patients underwent titanium mesh reconstruction and 11 underwent traditional three-layer repair. Median follow-up was 11 months (range, 2-66 months). The only significant difference between groups was older age in patients undergoing titanium reconstruction (mean, 81 vs. 63 years; difference of 18; 95% confidence interval [CI], 4-32 years). Defect extent including overall size and structures removed was similar between groups (p > 0.05). Paramedian forehead flap was the most common external reconstruction in both groups (100% for titanium mesh and 73% for three-layer closure). Time under anesthesia was significantly shorter for titanium mesh reconstruction (median, 119 vs. 314 minutes; difference of 195; 95% CI, 45-237). Estimated blood loss and length of hospital stay were similar between groups (p > 0.05). Complication rates were substantial although not significantly different, 40 and 36% in titanium and three-layer reconstruction, respectively (p > 0.05). All patients with complications after titanium reconstruction had prior or postoperative radiotherapy. Titanium mesh reconstruction of through-and-through nasal defects can successfully be performed without reconstruction of the intranasal lining, significantly decreasing operative times. This reconstructive technique may not be suitable for patients who undergo radiotherapy.

  12. 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....

  13. 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....

  14. 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....

  15. 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....

  16. 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....

  17. 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....

  18. A rapid and sensitive HPLC-APCI-MS/MS method determination of fluticasone in human plasma: application for a bioequivalency study in nasal spray formulations.

    PubMed

    Byrro, Ricardo Martins Duarte; César, Isabela Costa; de Santana e Silva Cardoso, Fabiana Fernandes; Mundim, Iram Moreira; Teixeira, Leonardo de Souza; Bonfim, Ricardo Rodrigues; Gomes, Sandro Antônio; Pianetti, Gerson Antônio

    2012-03-05

    A sensitive method for the determination of fluticasone in plasma was developed using high performance liquid chromatography with tandem mass spectrometric detection, whereas beclomethasone was used as internal standard. The analytes were extracted with a simple liquid-liquid extraction from the plasma samples and separated on an ACE C(18) 50 × 4.6 mm i.d.; 5 μm particle size column with a mobile phase consisting of acetonitrile - 0.01% formic acid (48:52, v/v) at a flow rate of 1 ml/min. Detection was achieved by an Applied Biosystems API 5000 mass spectrometer (LC-MS/MS) set at unit resolution in the multiple reaction monitoring mode. Atmospheric pressure chemical ionization (APCI) was used for ion production. The mean recovery for fluticasone propionate was 85%, with a lower limit of quantification set at 2 pg/mL. The validated analytical method was applied to a bioequivalence study of fluticasone propionate administered by nasal spray formulations in human volunteers.

  19. Axonal Degeneration in Dental Pulp Precedes Human Primary Teeth Exfoliation.

    PubMed

    Suzuki, K; Lovera, M; Schmachtenberg, O; Couve, E

    2015-10-01

    The dental pulp in human primary teeth is densely innervated by a plethora of nerve endings at the coronal pulp-dentin interface. This study analyzed how the physiological root resorption (PRR) process affects dental pulp innervation before exfoliation of primary teeth. Forty-four primary canine teeth, classified into 3 defined PRR stages (early, middle, and advanced) were fixed and demineralized. Longitudinal cryosections of each tooth were stained for immunohistochemical and quantitative analysis of dental pulp nerve fibers and associated components with confocal and electron microscopy. During PRR, axonal degeneration was prominent and progressive in a Wallerian-like scheme, comprising nerve fiber bundles and nerve endings within the coronal and root pulp. Neurofilament fragmentation increased significantly during PRR progression and was accompanied by myelin degradation and a progressive loss of myelinated axons. Myelin sheath degradation involved activation of autophagic activity by Schwann cells to remove myelin debris. These cells expressed a sequence of responses comprising dedifferentiation, proliferative activity, GAP-43 overexpression, and Büngner band formation. During the advanced PRR stage, increased immune cell recruitment within the dental pulp and major histocompatibility complex (MHC) class II upregulation by Schwann cells characterized an inflammatory condition associated with the denervation process in preexfoliative primary teeth. The ensuing loss of dental pulp axons is likely to be responsible for the progressive reduction of sensory function of the dental pulp during preexfoliative stages.

  20. Pulpotomies with Portland cement in human primary molars.

    PubMed

    Conti, Taísa Regina; Sakai, Vivien Thiemy; Fornetti, Ana Paula Camolese; Moretti, Ana Beatriz Silveira; Oliveira, Thais Marchini; Lourenço Neto, Natalino; Machado, Maria Aparecida Andrade Moreira; Abdo, Ruy Cesar Camargo

    2009-01-01

    Two clinical cases in which Portland cement (PC) was applied as a medicament after pulpotomy of mandibular primary molars in children are presented. Pulpotomy using PC was carried out in two mandibular first molars and one mandibular second molar, which were further followed-up. At the 3, 6 and 12-month follow-up appointments, clinical and radiographic examinations of the pulpotomized teeth and their periradicular area revealed that the treatments were successful in maintaining the teeth asymptomatic and preserving pulpal vitality. Additionally, the formation of a dentin bridge immediately below the PC could be observed in the three molars treated. PC may be considered as an effective alternative for primary molar pulpotomies, at least in a short-term period. Randomized clinical trials with human teeth are required in order to determine the suitability of PC before unlimited clinical use can be recommended.

  1. In vitro methods to culture primary human breast epithelial cells.

    PubMed

    Raouf, Afshin; Sun, Yu Jia

    2013-01-01

    Current evidence suggests that much like leukemia, breast tumors are maintained by a small subpopulation of tumor cells that have stem cell properties. These cancer stem cells are envisaged to be responsible for tumor formation and relapse. Therefore, knowledge about their nature will provide a platform to develop therapies to eliminate these breast cancer stem cells. This concept highlights the need to understand the mechanisms that regulate the normal functions of the breast stem cells and their immediate progeny as alterations to these same mechanisms can cause these primitive cells to act as cancer stem cells. The study of the primitive cell functions relies on the ability to isolate them from primary sources of breast tissue. This chapter describes processing of discarded tissue from reduction mammoplasty samples as sources of normal primary human breast epithelial cells and describes cell culture systems to grow single-cell suspensions prepared from these reduction samples in vitro.

  2. Chondrosarcoma of the nasal septum

    PubMed Central

    Bahgat, Mohammed; Bahgat, Yassin; Bahgat, Ahmed; Elwany, Yasmine

    2012-01-01

    Chondrosarcoma of the nasal septum is a rare malignancy. When it occurs, early diagnosis is difficult because patients generally present with common, non-specific sinonasal complaints. This is the report of a 62-year-old woman who presented with a 1-month history of nasal obstruction, headache and anosmia. Nasal endoscopy showed a nasal mass obstructing both nasal cavities not separable from the septum. A wedge biopsy of the nasal mass was taken. Histopathology was suggestive of chondrosarcoma. The tumour was removed by an endoscopic approach. The clinical presentation, diagnosis and treatment of this case as well as a review of the literature are discussed. PMID:22669930

  3. Primary Care of the Human Immunodeficiency Virus Patient.

    PubMed

    Buckhold, Fred R

    2015-09-01

    Human immunodeficiency virus (HIV) is a disease that affects 1 million patients in the United States. Many excellent drug regimens exist that effectively suppress the viral load and improve immune function, but there are consequences of long-term antiviral therapy. In addition, patients with HIV tend to have much higher rates of chronic disease, substance abuse, and cancer. Thus, while expert care in the treatment of HIV remains critical, the skill set of a primary care provider in the prevention, detection, and management of acute and chronic illness is vital to the care of the HIV patient.

  4. Hemiconvulsion-hemiplegia syndrome and primary human herpesvirus 7 infection.

    PubMed

    Kawada, Jun-Ichi; Kimura, Hiroshi; Yoshikawa, Tetsushi; Ihira, Masaru; Okumura, Akihisa; Morishima, Tsuneo; Hayakawa, Fumio

    2004-09-01

    We report a case of hemiconvulsion-hemiplegia (HH) syndrome. An 18-month-old female infant had a hemiconvulsion followed by left hemiplegia. Magnetic resonance imaging immediately after the onset of hemiplegia showed high intensity in the right hemisphere in diffusion-weighted images (DWI), while T1- and T2-weighted images were normal. Single photon emission computed tomography showed hypoperfusion of the right hemisphere in the acute phase. Virological analyses proved primary human herpesvirus 7 (HHV-7) infection. DWI are useful for the early evaluation of HH syndrome. Vascular disorders due to HHV-7 infection may have been related to the development of HH syndrome in this patient.

  5. Functional Effects of Toll-Like Receptor (TLR)3, 7, 9, RIG-I and MDA-5 Stimulation in Nasal Epithelial Cells

    PubMed Central

    Tengroth, Lotta; Millrud, Camilla Rydberg; Kvarnhammar, Anne Månsson; Kumlien Georén, Susanna; Latif, Leith; Cardell, Lars-Olaf

    2014-01-01

    Background The human nasal epithelium is an important physical barrier, and a part of the innate immune defense that protect against pathogens. The epithelial cells recognize microbial components by pattern-recognition receptors (PRRs), and thereby trigger an immune response. Even though TLR3, TLR7, TLR9, RIG-I and MDA-5 are all known to respond to viral stimulation, their potential role in chronic airway inflammation triggered by local cytokine release remains to be established. Methods mRNA and corresponding protein expression of TLR3, TLR7, TLR9, RIG-I and MDA-5 were analyzed in nasal biopsies and various upper airway epithelial cell lines using real-time reverse transcription PCR, immunohistochemistry and flow cytometry. Ligand induced, cytokine release, was evaluated with ELISA. Results Nasal biopsies were found to express TLR3, TLR7, TLR9, RIG-I and MDA-5, with the most abundant expression in the surface epithelium. These receptors were verified in primary human nasal epithelial cell (HNEC) as well as in the airway epithelial cell lines Detroit-562 and FaDu. Poly(I:C) (TLR3) and R-837 (TLR7) stimulation increased secretion of IL-6 and GM-CSF from the nasal mucosa and the epithelial cell lines. CpG (TLR9) stimulation caused release of IL-8 in the nasal mucosa and in FaDu. Poly(I:C)/LyoVec (RIG-I/MDA-5) stimulation activated the secretion of IFN-β in the nasal mucosa. A corresponding release was also detected from HNEC and Detroit-562. Conclusion The nasal epithelium has the ability to recognize viral intrusion through TLR and RLR receptors, and the subsequent response might have a role in exacerbation of inflammatory diseases like allergic rhinitis and chronic rhinosinusitis. PMID:24886842

  6. 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.

  7. 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.

  8. 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

  9. Nasalance in Cochlear Implantees

    PubMed Central

    Sreedevi, N; Lepcha, Anjali; Mathew, John

    2015-01-01

    Objectives Speech intelligibility is severely affected in children with congenital profound hearing loss. Hypernasality is a problem commonly encountered in their speech. Auditory information received from cochlear implants is expected to be far superior to that from hearing aids. Our study aimed at comparing the percentages of nasality in the speech of the cochlear implantees with hearing aid users and also with children with normal hearing. Methods Three groups of subjects took part in the study. Groups I and II comprised 12 children each, in the age range of 4-10 years, with prelingual bilateral profound hearing loss, using multichannel cochlear implants and digital hearing aids respectively. Both groups had received at least one year of speech therapy intervention since cochlear implant surgery and hearing aid fitting respectively. The third group consisted of age-matched and sex-matched children with normal hearing. The subjects were asked to say a sentence which consisted of only oral sounds and no nasal sounds ("Buy baby a bib"). The nasalance score as a percentage was calculated. Results Statistical analysis revealed that the children using hearing aids showed a high percentage of nasalance in their speech. The cochlear implantees showed a lower percentage of nasalance compared to children using hearing aids, but did not match with their normal hearing peers. Conclusion The quality of speech of the cochlear implantees was superior to that of the hearing aid users, but did not match with the normal controls. The study suggests that acoustic variables still exist after cochlear implantation in children, with hearing impairments at deviant levels, which needs attention. Further research needs to be carried out to explore the effect of the age at implantation as a variable in reducing nasality in the speech and attaining normative values in cochlear implantees, and also between unilateral versus bilateral implantees. PMID:26330912

  10. Nasal spray flu vaccine (image)

    MedlinePlus

    The flu vaccine can also be administered as a nasal spray instead of the usual injection method. It can be ... the recombinant influenza vaccine (RIV). The nasal spray flu vaccine (live attenuated influenza vaccine or LAIV) should not ...

  11. Nasal reconstruction after epithelioma.

    PubMed

    Rodríguez-Camps, S

    2001-01-01

    In this paper we present our procedure for the treatment, histopathological diagnosis, and resection of skin cancer in the nasal pyramid and its subsequent reconstruction. Because we are dealing with the most important anatomical feature of the face our goal is an aesthetic reconstruction [2,4] according to the anatomical subunits criterion of Burget [3]. First, a histopathological diagnosis is made to determine the nature of the tumor. Then, we proceed with the resection according to the Mohs Micrographic Surgery [1,5,7]. Then we begin with the first step of the nasal reconstruction.

  12. Large rhinolith causing nasal obstruction

    PubMed Central

    Dincer Kose, Onur; Kose, Taha Emre; Erdem, Mehmet Ali; Cankaya, Abdulkadir Burak

    2015-01-01

    Rhinoliths are calcified masses located in the nasal cavity and may cause symptoms such as nasal obstruction, fetid odour and facial pain. They are usually diagnosed incidentally on radiographic examinations or depending on the symptoms. In this paper we report a 27-year-old Caucasian woman with a calcified mass in the right nasal cavity causing nasal obstruction, anosmia and facial pain. The calcified mass was removed by endonasal approach. PMID:25759270

  13. 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…

  14. Involvement of B2 receptor in bradykinin-induced proliferation and proinflammatory effects in human nasal mucosa-derived fibroblasts isolated from chronic rhinosinusitis patients.

    PubMed

    Tsai, Yih-Jeng; Hao, Sheng-Po; Chen, Chih-Li; Lin, Brian J; Wu, Wen-Bin

    2015-01-01

    Chronic rhinosinusitis (CRS) is a chronic inflammatory disease of the sinonasal mucosa either accompanied by polyp formation (CRSwNP) or without polyps (CRSsNP). CRSsNP accounts for the majority of CRS cases and is characterized by fibrosis and neutrophilic inflammation. However, the pathogenesis of CRS, especially CRSsNP, remains unclear. Immunohistochemistry of CRSsNP specimens in the present study showed that the submucosa, perivascular areas, and the mucous glands were abundant in fibroblasts. Therefore, we investigated the effects bradykinin (BK), an autacoid known to participate in inflammation, on human CRSsNP nasal mucosa-derived fibroblasts (NMDFs). BK increased CXCL1 and -8 secretion and mRNA expression with EC50 ranging from 0.15~0.35 μM. Moreover, BK enhanced cell proliferation and upregulated the expressions of proinflammatory molecules, including cell adhesion molecules (CAMs) and cyclooxygenase (COX)-1 and -2. These functionally caused an increase in monocyte adhesion to fibroblast monolayer. Using pharmacological intervention and BKR siRNA knockdown, we demonstrated that the BK-induced CXCL chemokine release, cell proliferation and COX and CAM expressions were mainly through the B2 receptor (B2R). Accordingly, the B2R was preferentially expressed in the NMDFs than B1R. The B2R was highly expressed in the CRSsNP than the control specimens, while the B1R and kininogen (KNG)/BK expression slightly increased in the CRSsNP mucosa. Collectively, we report here for the first time that fibroblasts, KNG/BK, and BKRs are overexpressed in CRSsNP mucosa and BK upregulates chemokine expression, proliferation, and proinflammatory molecule expression in NMDFs via B2R activation, which lead to a functional increase in monocyte-fibroblast interaction. Our findings reveal a critical role of fibroblast, KNG/BK, and BKRs in the development of CRSsNP.

  15. 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.

  16. Airflow, gas deposition, and lesion distribution in the nasal passages.

    PubMed Central

    Morgan, K T; Monticello, T M

    1990-01-01

    The nasal passages of laboratory animals and man are complex, and lesions induced in the delicate nasal lining by inhaled air pollutants vary considerably in location and nature. The distribution of nasal lesions is generally a consequence of regional deposition of the inhaled material, local tissue susceptibility, or a combination of these factors. Nasal uptake and regional deposition are are influenced by numerous factors including the physical and chemical properties of the inhaled material, such as water solubility and reactivity; airborne concentration and length of exposure; the presence of other air contaminants such as particulate matter; nasal metabolism, and blood and mucus flow. For certain highly water-soluble or reactive gases, nasal airflow patterns play a major role in determining lesion distribution. Studies of nasal airflow in rats and monkeys, using casting and molding techniques combined with a water-dye model, indicate that nasal airflow patterns are responsible for characteristic differences in the distribution of nasal lesions induced by formaldehyde in these species. Local tissue susceptibility is also a complex issue that may be a consequence of many factors, including physiologic and metabolic characteristics of the diverse cell populations that comprise each of the major epithelial types lining the airways. Identification of the principal factors that influence the distribution and nature of nasal lesions is important when attempting the difficult process of determining potential human risks using data derived from laboratory animals. Toxicologic pathologists can contribute to this process by carefully identifying the site and nature of nasal lesions induced by inhaled materials. Images FIGURE 4. FIGURE 6. FIGURE 7. PMID:2200663

  17. Secretome profiling of primary human skeletal muscle cells.

    PubMed

    Hartwig, Sonja; Raschke, Silja; Knebel, Birgit; Scheler, Mika; Irmler, Martin; Passlack, Waltraud; Muller, Stefan; Hanisch, Franz-Georg; Franz, Thomas; Li, Xinping; Dicken, Hans-Dieter; Eckardt, Kristin; Beckers, Johannes; de Angelis, Martin Hrabe; Weigert, Cora; Häring, Hans-Ulrich; Al-Hasani, Hadi; Ouwens, D Margriet; Eckel, Jürgen; Kotzka, Jorg; Lehr, Stefan

    2014-05-01

    The skeletal muscle is a metabolically active tissue that secretes various proteins. These so-called myokines have been proposed to affect muscle physiology and to exert systemic effects on other tissues and organs. Yet, changes in the secretory profile may participate in the pathophysiology of metabolic diseases. The present study aimed at characterizing the secretome of differentiated primary human skeletal muscle cells (hSkMC) derived from healthy, adult donors combining three different mass spectrometry based non-targeted approaches as well as one antibody based method. This led to the identification of 548 non-redundant proteins in conditioned media from hSkmc. For 501 proteins, significant mRNA expression could be demonstrated. Applying stringent consecutive filtering using SignalP, SecretomeP and ER_retention signal databases, 305 proteins were assigned as potential myokines of which 12 proteins containing a secretory signal peptide were not previously described. This comprehensive profiling study of the human skeletal muscle secretome expands our knowledge of the composition of the human myokinome and may contribute to our understanding of the role of myokines in multiple biological processes. This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge.

  18. Laterality of human primary gustatory cortex studied by MEG.

    PubMed

    Onoda, Keiko; Kobayakawa, Tatsu; Ikeda, Minoru; Saito, Sachiko; Kida, Akinori

    2005-10-01

    We examined the laterality of the human gustatory neural pathway by measuring gustatory-evoked magnetic fields (GEMfs) and demonstrating the activation of the human primary gustatory cortex (PGC). In patients whose chorda tympani nerve had been severed unilaterally on the right side, we stimulated the normal side (i.e., left side) of the chorda tympani nerve with NaCl solution using a device developed for measuring GEMfs. We used the whole-head magnetoencephalography system for recording GEMfs and analyzed the frequency and latency of PGC activation in each hemisphere. "The transitional cortex between the insula and the parietal operculum" was identified as PGC with the base of the central sulcus in this experiment. Significant difference was found in frequencies among bilateral, only-ipsilateral, and only-contralateral responses by the Friedman test (P < 0.05), and more frequent bilateral responses were observed than only-ipsilateral (P < 0.05) or only-contralateral responses (P < 0.01) by the multiple comparison tests. In the bilateral responses, the averaged activation latencies of the transitional cortex between the insula and the parietal operculum were not significantly different in both hemispheres. These results suggest that unilateral gustatory stimulation will activate the transitional cortex between the insula and the parietal operculum bilaterally in humans.

  19. Routine nasal packing follwoing nasal surgery-Is it necessary?

    PubMed

    Basha, S I; Gupta, D; Kaluskar, S K

    2005-01-01

    The practice of routine nasal packing after nasal surgery is usually customary and not evidence based. Post operative complications, while uncoumon, are sometimes pack related. A retrospective analysis of 110 patients who underwent a variety of nasal operations was performed to determine the incidence of complications when nasal packs were not routinely inserted 9 cases (8.2%) [6 out of these were revision surgeries] needed nasal packing for haemostasis at the end of surgery. 4 cases (3.6%) required to be packed in the immediate post operative period. One patient who required nasal packing developed a unilateral adhesion. No patient developed septal hematoma. The need for routine nasal packing is not supported. Packing should be indicated where there continuous bleeding at.

  20. Cromolyn Sodium Nasal Solution

    MedlinePlus

    Cromolyn comes as a solution to use with a special nasal applicator. It usually is inhaled three to six times a day to prevent allergy ... first time, read the instructions provided with the solution. Ask your doctor, pharmacist, or respiratory therapist to ...

  1. Ciclesonide Nasal Spray

    MedlinePlus

    ... Wash the dust cap and applicator with warm water. Dry and replace the applicator and press down and release the pump one time or until you see a fine spray. Replace the dust cap. Do not use pins or other sharp objects in the tiny spray hole on the nasal applicator to remove the blockage. ...

  2. Oxymetazoline Nasal Spray

    MedlinePlus

    ... Rinse the tip of the dispenser with hot water or wipe it clean after you use it.Follow the directions for using the nasal spray that appear on the package label. If you are using a product that comes in a pump dispenser, press down on the rim several times ...

  3. 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.

  4. Dopamine Receptor Activation Increases HIV Entry into Primary Human Macrophages

    PubMed Central

    Gaskill, Peter J.; Yano, Hideaki H.; Kalpana, Ganjam V.; Javitch, Jonathan A.; Berman, Joan W.

    2014-01-01

    Macrophages are the primary cell type infected with HIV in the central nervous system, and infection of these cells is a major component in the development of neuropathogenesis and HIV-associated neurocognitive disorders. Within the brains of drug abusers, macrophages are exposed to increased levels of dopamine, a neurotransmitter that mediates the addictive and reinforcing effects of drugs of abuse such as cocaine and methamphetamine. In this study we examined the effects of dopamine on HIV entry into primary human macrophages. Exposure to dopamine during infection increased the entry of R5 tropic HIV into macrophages, irrespective of the concentration of the viral inoculum. The entry pathway affected was CCR5 dependent, as antagonizing CCR5 with the small molecule inhibitor TAK779 completely blocked entry. The effect was dose-dependent and had a steep threshold, only occurring above 108 M dopamine. The dopamine-mediated increase in entry required dopamine receptor activation, as it was abrogated by the pan-dopamine receptor antagonist flupenthixol, and could be mediated through both subtypes of dopamine receptors. These findings indicate that the effects of dopamine on macrophages may have a significant impact on HIV pathogenesis. They also suggest that drug-induced increases in CNS dopamine may be a common mechanism by which drugs of abuse with distinct modes of action exacerbate neuroinflammation and contribute to HIV-associated neurocognitive disorders in infected drug abusers. PMID:25268786

  5. 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.

  6. Immune globulin subcutaneous (human) 20%: in primary immunodeficiency disorders.

    PubMed

    McCormack, Paul L

    2012-05-28

    Immune globulin subcutaneous 20% is a new high-concentration (200 g/L) solution of highly purified human IgG (≥98%) indicated in the EU and the US for antibody replacement therapy in patients with primary immunodeficiency with antibody deficiency, and in the EU for replacement therapy in humoral immunodeficiency secondary to myeloma or chronic lymphocytic leukaemia. Immune globulin subcutaneous 20% is formulated with L-proline, which imparts long-term stability at room temperature and a relatively low viscosity. In two pivotal phase III trials in stably treated patients with primary immunodeficiency, immune globulin subcutaneous 20% at weekly subcutaneous dosages either equivalent to each patient's previous intravenous or subcutaneous replacement therapy, or providing equivalent systemic exposure to previous intravenous therapy, produced mean serum IgG trough levels equal to or greater than pre-study levels. In each trial, there were no serious bacterial infections during treatment throughout the 28-week or 12-month efficacy periods. The rates of infectious episodes, days missed from work/school, days hospitalized or days with antibiotics were low. Immune globulin subcutaneous 20% was generally well tolerated. A high proportion of patients experienced local infusion-site reactions, but infusion-related systemic adverse events were relatively infrequent. Most adverse events were of mild or moderate intensity and did not interfere with therapy.

  7. Protein kinase C regulates the flow rate-dependent decline in human nasal ciliary beat frequency in vitro.

    PubMed

    Mwimbi, X K; Muimo, R; Green, M; Mehta, A

    2000-01-01

    Cilia provide the driving force for mucociliary clearance, the process that removes mucus from the airways. Protein kinase C (PKC) plays a poorly understood regulatory role in phosphorylation-based signal transduction cascades, including the control of human mucociliary clearance, especially with respect to ciliary beat frequency (CBF). Ciliary studies minimize the importance of fluid flow, because it is generally accepted that flow increases CBF. Here, we studied postflow events by measuring CBF in vitro in volunteers. Rose chamber-loaded cells were pulsed for 5 minutes at 30 mL/h in medium-199 +/- PKC modulators at 20 degrees C. The 5-minute pulse precipitated a fall in CBF noted within 1 minute after flow (acute dip response [ADR] to 84 +/- 2% of preflow baseline). Thereafter, CBF rose to 8% below baseline for 30 minutes [postrecovery plateau at 92 +/- 3%]. Preincubation with 1 microM of phorbol 12-myristate 13-acetate (PMA), a PKC-activating phorbol ester attenuated the ADR (c. 95%) and restored the postrecovery plateau almost to baseline levels (98 +/- 0.7%; p > 0.10 compared with baseline CBF). With respect to the ADR, the PMA protective effect was lost in the presence of the selective PKC inhibitor myristoylated epidermal growth factor peptide 651d-658 (Myr-PKCI; 10 microM). Myr-PKCI alone changed the ADR pattern such that the CBF remained at 15% below preflow baseline. We conclude that CBF fall and recovery after a fluid pulse is regulated by PKC activity either directly or indirectly.

  8. 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

  9. 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

  10. Proliferative Effects of Histamine on Primary Human Pterygium Fibroblasts

    PubMed Central

    Fu, Qiuli; Zhang, Lifang; Yin, Houfa; Jin, Xiuming; Tang, Qiaomei; Lyu, Danni

    2016-01-01

    Purpose. It has been confirmed that inflammatory cytokines are involved in the progression of pterygium. Histamine can enhance proliferation and migration of many cells. Therefore, we intend to investigate the proliferative and migratory effects of histamine on primary culture of human pterygium fibroblasts (HPFs). Methods. Pterygium and conjunctiva samples were obtained from surgery, and toluidine blue staining was used to identify mast cells. 3-[4, 5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) was performed to evaluate the proliferative rate of HPFs and human conjunctival fibroblasts (HCFs); ki67 expression was also measured by immunofluorescence analysis. Histamine receptor-1 (H1R) antagonist (Diphenhydramine Hydrochloride) and histamine receptor-2 (H2R) antagonist (Nizatidine) were added to figure out which receptor was involved. Wound healing model was used to evaluate the migratory ability of HPFs. Results. The numbers of total mast cells and degranulated mast cells were both higher in pterygium than in conjunctiva. Histamine had a proliferative effect on both HPFs and HCFs, the effective concentration (10 μmol/L) on HPFs was lower than on HCFs (100 μmol/L), and the effect could be blocked by H1R antagonist. Histamine showed no migratory effect on HPFs. Conclusion. Histamine may play an important role in the proliferation of HPFs and act through H1R. PMID:27872516

  11. 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.

  12. 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.

  13. 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

  14. Helicobacter hepaticus Induces an Inflammatory Response in Primary Human Hepatocytes

    PubMed Central

    Kleine, Moritz; Worbs, Tim; Schrem, Harald; Vondran, Florian W. R.; Kaltenborn, Alexander; Klempnauer, Jürgen; Förster, Reinhold; Josenhans, Christine; Suerbaum, Sebastian; Bektas, Hüseyin

    2014-01-01

    Helicobacter hepaticus can lead to chronic hepatitis and hepatocellular carcinoma in certain strains of mice. Until now the pathogenic role of Helicobacter species on human liver tissue is still not clarified though Helicobacter species identification in human liver cancer was successful in case controlled studies. Therefore we established an in vitro model to investigate the interaction of primary human hepatocytes (PHH) with Helicobacter hepaticus. Successful co-culturing of PHH with Helicobacter hepaticus was confirmed by visualization of motile bacteria by two-photon-microscopy. Isolated human monocytes were stimulated with PHH conditioned media. Changes in mRNA expression of acute phase cytokines and proteins in PHH and stimulated monocytes were determined by Real-time PCR. Furthermore, cytokines and proteins were analyzed in PHH culture supernatants by ELISA. Co-cultivation with Helicobacter hepaticus induced mRNA expression of Interleukin-1 beta (IL-1β), Tumor necrosis factor-alpha, Interleukin-8 (IL-8) and Monocyte chemotactic protein-1 (MCP-1) in PHH (p<0.05) resulting in a corresponding increase of IL-8 and MCP-1 concentrations in PHH supernatants (p<0.05). IL-8 and IL-1β mRNA expression was induced in monocytes stimulated with Helicobacter hepaticus infected PHH conditioned media (p<0.05). An increase of Cyclooxygenase-2 mRNA expression was observed, with a concomitant increase of prostaglandin E2 concentration in PHH supernatants at 24 and 48 h (p<0.05). In contrast, at day 7 of co-culture, no persistent elevation of cytokine mRNA could be detected. High expression of intercellular adhesion molecule-1 on PHH cell membranes after co-culture was shown by two-photon-microscopy and confirmed by flow-cytomety. Finally, expression of Cytochrome P450 3A4 and albumin mRNA were downregulated, indicating an impairment of hepatocyte synthesis function by Helicobacter hepaticus presence. This is the first in vitro model demonstrating a pathogenic effect of a

  15. Nasal neuron PET imaging quantifies neuron generation and degeneration

    PubMed Central

    Van de Bittner, Genevieve C.; Riley, Misha M.; Cao, Luxiang; Herrick, Scott P.; Ricq, Emily L.; O’Neill, Michael J.; Ahmed, Zeshan; Murray, Tracey K.; Smith, Jaclyn E.; Wang, Changning; Schroeder, Frederick A.; Albers, Mark W.; Hooker, Jacob M.

    2017-01-01

    Olfactory dysfunction is broadly associated with neurodevelopmental and neurodegenerative diseases and predicts increased mortality rates in healthy individuals. Conventional measurements of olfactory health assess odor processing pathways within the brain and provide a limited understanding of primary odor detection. Quantification of the olfactory sensory neurons (OSNs), which detect odors within the nasal cavity, would provide insight into the etiology of olfactory dysfunction associated with disease and mortality. Notably, OSNs are continually replenished by adult neurogenesis in mammals, including humans, so OSN measurements are primed to provide specialized insights into neurological disease. Here, we have evaluated a PET radiotracer, [11C]GV1-57, that specifically binds mature OSNs and quantifies the mature OSN population in vivo. [11C]GV1-57 monitored native OSN population dynamics in rodents, detecting OSN generation during postnatal development and aging-associated neurodegeneration. [11C]GV1-57 additionally measured rates of neuron regeneration after acute injury and early-stage OSN deficits in a rodent tauopathy model of neurodegenerative disease. Preliminary assessment in nonhuman primates suggested maintained uptake and saturable binding of [18F]GV1-57 in primate nasal epithelium, supporting its translational potential. Future applications for GV1-57 include monitoring additional diseases or conditions associated with olfactory dysregulation, including cognitive decline, as well as monitoring effects of neuroregenerative or neuroprotective therapeutics. PMID:28112682

  16. Nasal neuron PET imaging quantifies neuron generation and degeneration.

    PubMed

    Van de Bittner, Genevieve C; Riley, Misha M; Cao, Luxiang; Ehses, Janina; Herrick, Scott P; Ricq, Emily L; Wey, Hsiao-Ying; O'Neill, Michael J; Ahmed, Zeshan; Murray, Tracey K; Smith, Jaclyn E; Wang, Changning; Schroeder, Frederick A; Albers, Mark W; Hooker, Jacob M

    2017-02-01

    Olfactory dysfunction is broadly associated with neurodevelopmental and neurodegenerative diseases and predicts increased mortality rates in healthy individuals. Conventional measurements of olfactory health assess odor processing pathways within the brain and provide a limited understanding of primary odor detection. Quantification of the olfactory sensory neurons (OSNs), which detect odors within the nasal cavity, would provide insight into the etiology of olfactory dysfunction associated with disease and mortality. Notably, OSNs are continually replenished by adult neurogenesis in mammals, including humans, so OSN measurements are primed to provide specialized insights into neurological disease. Here, we have evaluated a PET radiotracer, [11C]GV1-57, that specifically binds mature OSNs and quantifies the mature OSN population in vivo. [11C]GV1-57 monitored native OSN population dynamics in rodents, detecting OSN generation during postnatal development and aging-associated neurodegeneration. [11C]GV1-57 additionally measured rates of neuron regeneration after acute injury and early-stage OSN deficits in a rodent tauopathy model of neurodegenerative disease. Preliminary assessment in nonhuman primates suggested maintained uptake and saturable binding of [18F]GV1-57 in primate nasal epithelium, supporting its translational potential. Future applications for GV1-57 include monitoring additional diseases or conditions associated with olfactory dysregulation, including cognitive decline, as well as monitoring effects of neuroregenerative or neuroprotective therapeutics.

  17. Nasal bots...a fascinating world!

    PubMed

    Angulo-Valadez, Carlos E; Scholl, Philip J; Cepeda-Palacios, Ramón; Jacquiet, Philippe; Dorchies, Philippe

    2010-11-24

    Larvae causing obligatory myiasis are numerous and they may affect cutaneous and subcutaneous tissues, wounds, nasopharyngeal cavities (nasal bots), internal organs and the digestive tract (bots) of domestic and wild animals and humans as well. Nasal bots belong to the Family Oestridae, Subfamily Oestrinae, which includes several important genera: Oestrus, Kirkioestrus, and Gedoelstia infecting Artiodactyla (except Cervidae) in Africa and Eurasia, Cephenemyia and Pharyngomyia infecting Cervidae, Rhinoestrus infecting horses, Cephalopina infecting camels, Pharyngobolus infecting African elephants, and Tracheomyia infecting Australian kangaroos. Nasal bots are widespread in Mediterranean and tropical areas and in affected animals they induce sneezing and nasal discharge which may become caked with dust making breathing very difficult. The aforementioned species of larvae are host-specific but sometimes the may be deposited in human eyes inducing a painful opthalmomyiasis of short duration. The first fascinating trait of these parasites is the very efficient morphological and biological adaptations to parasitism they show either as larvae or as adults, in order to facilitate their survival and search for a suitable host. Nasal bots have reached different degrees of complexity in their life cycles. Indeed, while for some species (e.g., Oestrus ovis, Rhinoestrus usbekistanicus) larvae are injected by flies directly into nostrils and develop in the sinuses before being ejected for external pupation, some other species migrate from eyes to blood before returning to nasal cavities either through the ethmoid bone (Gedoelstia hässleri) or via lungs and bronchi (Gedoelstia cristata). Moreover, larvae are very well-adapted to their environment being able to undergo through hypobiosis either inside or outside the host, according to the climatic environmental conditions and seasonality. The second fascinating trait of nasal bots is related to host behavioural and immune

  18. 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

  19. 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.

  20. 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.

  1. 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. PMID:27600213

  2. Some acoustic features of nasal and nasalized vowels: a target for vowel nasalization.

    PubMed

    Feng, G; Castelli, E

    1996-06-01

    In order to characterize acoustic properties of nasal and nasalized vowels, these sounds will be considered as a dynamic trend from an oral configuration toward an [n]-like configuration. The latter can be viewed as a target for vowel nasalization. This target corresponds to the pharyngonasal tract and it can be modeled, with some simplifications, by a single tract without any parallel paths. Thus the first two resonance frequencies (at about 300 and 1000 Hz) characterize this target well. A series of measurements has been carried out in order to describe the acoustic characteristics of the target. Measured transfer functions confirm the resonator nature of the low-frequency peak. The introduction of such a target allows the conception of the nasal vowels as a trend beginning with a simple configuration, which is terminated in the same manner, so allowing the complex nasal phenomena to be bounded. A complete study of pole-zero evolutions for the nasalization of the 11 French vowels is presented. It allows the proposition of a common strategy for the nasalization of all vowels, so a true nasal vowel can be placed in this nasalization frame. The measured transfer functions for several French nasal vowels are also given.

  3. Human immunoglobulin 10 % with recombinant human hyaluronidase: replacement therapy in patients with primary immunodeficiency disorders.

    PubMed

    Sanford, Mark

    2014-08-01

    Human immunoglobulin is an established replacement therapy for patients with primary immunodeficiency disorders (PIDs). Recombinant human hyaluronidase (rHuPH20) is a spreading factor that temporarily digests hyaluronan in the skin interstitium enabling large volumes of fluid or drug solutions to be infused and absorbed subcutaneously. HyQvia® (IGHy) is a new combination product whereby rHuPH20 is injected subcutaneously, followed by human immunoglobulin 10 % infused through the same needle. Thus, IGHy can be administered at a reduced frequency compared with non-facilitated subcutaneous injection of human immunoglobulin, and with a lower frequency of infusion reactions than with intravenous administration. Home-based administration of IGHy is also feasible for adequately trained patients. IGHy was compared with intravenous human immunoglobulin 10 % in a non-randomized, open-label, phase 3 study in patients aged ≥2 years with PIDs who were receiving human immunoglobulin replacement therapy (n = 87). In this study, trough IgG concentrations, acute serious bacterial infection rates (primary endpoint) and occurrences of adverse events during the IGHy treatment period were generally similar to those observed during an intravenous treatment period. IGHy was associated with a numerically lower rate of systemic adverse events and a numerically higher rate of localized adverse events than those observed with intravenous treatment. Compared with intravenous administration, IGHy was administered at a significantly higher maximum flow rate and at a similar frequency. Most patients preferred IGHy over intravenous administration. IGHy offers a new method for subcutaneous delivery of human immunoglobulin replacement therapy in patients with PIDs.

  4. Harpagoside suppresses IL-6 expression in primary human osteoarthritis chondrocytes.

    PubMed

    Haseeb, Abdul; Ansari, Mohammad Yunus; Haqqi, Tariq M

    2017-02-01

    There is growing evidence in support of the involvement of inflammatory response in the pathogenesis of osteoarthritis (OA). Harpagoside, one of the bioactive components of Harpagophytum procumbens (Hp), has been shown to possess anti-inflammatory properties. Here we used an in vitro model of inflammation in OA to investigate the potential of harpagoside to suppress the production of inflammatory cytokines/chemokines such as IL-6 and matrix degrading proteases. We further investigated the likely targets of harpagoside in primary human OA chondrocytes. OA chondrocytes were pre-treated with harpagoside before stimulation with IL-1β. mRNA expression profile of 92 cytokines/chemokines was determined using TaqMan Human Chemokine PCR Array. Expression levels of selected mRNAs were confirmed using TaqMan assays. Protein levels of IL-6 and MMP-13 were assayed by ELISA and immunoblotting. Total protein levels and phosphorylation of signaling proteins were determined by immunoblotting. Cellular localization of IL-6 and c-Fos was performed by immunofluorescence and confocal microscopy. DNA binding activity of c-FOS/AP-1 was determined by ELISA. Harpagoside significantly altered the global chemokine expression profile in IL-1β-stimulated OA chondrocytes. Expression of IL-6 was highly induced by IL-1β, which was significantly inhibited by pre-treatment of OA chondrocytes with harpagoside. Harpagoside did not inhibit the IL-1β-induced activation of NF-κB and C/EBPβ transcription factors but suppressed the IL-1β-triggered induction, phosphorylation, and DNA binding activity of c-FOS, one of the main components of AP-1 transcription factors. Further, harpagoside significantly inhibited the expression of MMP-13 in OA chondrocytes under pathological conditions. siRNA-mediated knockdown of IL-6 resulted in suppressed expression and secretion of MMP-13 directly linking the role of IL-6 with MMP-13 expression. Taken together, the present study suggests that harpagoside exerts a

  5. 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

  6. Comparison between Perceptual Assessments of Nasality and Nasalance Scores

    ERIC Educational Resources Information Center

    Brunnegard, Karin; Lohmander, Anette; van Doorn, Jan

    2012-01-01

    Background: There are different reports of the usefulness of the Nasometer[TM] as a complement to listening, often as correlation calculations between listening and nasalance measurements. Differences between findings have been attributed to listener experience and types of speech stimuli. Aims: To compare nasalance scores from the Nasometer with…

  7. Objective Measure of Nasal Air Emission Using Nasal Accelerometry

    PubMed Central

    Cler, Meredith J.; Lien, Yu-An S.; Braden, Maia N.; Mittelman, Talia; Downing, Kerri

    2016-01-01

    Purpose This article describes the development and initial validation of an objective measure of nasal air emission (NAE) using nasal accelerometry. Method Nasal acceleration and nasal airflow signals were simultaneously recorded while an expert speech language pathologist modeled NAEs at a variety of severity levels. In addition, microphone and nasal accelerometer signals were collected during the production of /pɑpɑpɑpɑ/ speech utterances by 25 children with and without cleft palate. Fourteen inexperienced raters listened to the microphone signals from the pediatric speakers and rated the samples for the severity of NAE using direct magnitude estimation. Mean listener ratings were compared to a novel quantitative measurement of NAE derived from the nasal acceleration signals. Results Correlation between the nasal acceleration energy measure and the measured nasal airflow was high (r = .87). Correlation between the measure and auditory-perceptual ratings was moderate (r = .49). Conclusion The measure presented here is quantitative and noninvasive, and the required hardware is inexpensive ($150). Future studies will include speakers with a wider range of NAE severity and etiology, including cleft palate, hearing impairment, or dysarthria. Further development will also involve validation of the measure against airflow measures across subjects. PMID:27618145

  8. Comparative pathology of the nasal mucosa in laboratory animals exposed to inhaled irritants.

    PubMed Central

    Harkema, J R

    1990-01-01

    The nasal cavity is susceptible to chemically induced injury as a result of exposure to inhaled irritants. Some responses of the nasal mucosa to inhaled toxicants are species specific. These species-related differences in response may be due to variations in structural, physiologic, and biochemical factors, such as gross nasal cavity structure, distribution of luminal epithelial cell populations along the nasal airway, intranasal airflow patterns, nasal mucociliary apparatus, and nasal xenobiotic metabolism among animal species. This paper reviews the comparative anatomy and irritant-induced pathology of the nasal cavity in laboratory animals. The toxicologist, pathologist, and environmental risk assessor must have a good working knowledge of the similarities and differences in normal nasal structure and response to injury among species before they can select animal models for nasal toxicity studies, recognize toxicant-induced lesions in the nasal airway, and extrapolate experimental results to estimate the possible effects of an inhaled toxicant on the human nasal airway. Images PLATE 1. PLATE 2. A PLATE 2. B PLATE 3. PMID:2116960

  9. 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…

  10. 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.

  11. 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

    2009-04-09

    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

  12. How Reliable Are Sino-Nasal Cell Lines for Studying the Pathophysiology of Chronic Rhinosinusitis?

    PubMed Central

    Suwara, Monika I.; Borthwick, Lee A.; Wilson, Janet A.; Mann, Derek A.; Fisher, Andrew J.

    2015-01-01

    Background: Well-characterized cell lines represent useful scientific tools to study the pathophysiology of human disease. Chronic rhinosinusitis (CRS) is a very common condition, though the number of CRS cell lines is limited, as are data showing how closely they resemble primary cells. Methodology: Searches for available human cell lines were performed using the American Type Culture Collection (ATCC) and European Collection of Cell Cultures (ECACC). Identified cells were cultured and characterized with tinctorial and immunohistochemical staining and ELISA to assess their response to common, disease-relevant inflammatory stimuli. Carefully phenotyped CRS patients were recruited with informed consent. Primary nasal epithelial cell (PNEC) brushings were harvested, cultured, and compared to the available cell lines. Results: Searches identified 1 relevant CRS sino-nasal cell line, RPMI 2650. Cultured PNECs showed strong expression of epithelial markers while being negative for mesenchymal markers. However, RPMI 2650 cells show an atypical mixed epithelial/mesenchymal phenotype. When stimulated by pro-inflammatory ligands, PNECs responded in a dose-dependent manner, whereas RPMI 2650 cells showed limited response. Conclusions: The number and availability of cell lines to study the pathophysiology of CRS greatly underrepresent the disease burden. Additionally, the sole commercially available cell line appears to have a different phenotype and behavior to primary patient-derived cells. The development of further reproducible cell lines would be beneficial in our understanding of CRS. PMID:25539661

  13. 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.

  14. 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.…

  15. 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

  16. 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.

  17. Mouse Orthotopic Xenographs of Human Prostate Primary Tumors

    DTIC Science & Technology

    2006-11-01

    prostatic hyperplasia (BPH) and 4 from cancer) were isolated from multiple samples of 4 radical prostatectomy surgical specimens, two of which belonged...pellet (12.5 mg, 90 day- release) was implanted subcutaneously in all mice. 5 PI: Loda, Massimo b) Eight primary cell cultures (4 from benign

  18. Primary cell culture of human adenocarcinomas--practical considerations.

    PubMed

    Lerescu, Lucian; Tucureanu, Cătălin; Caraş, Iuliana; Neagu, Stefan; Melinceanu, Laura; Sălăgeanu, Aurora

    2008-01-01

    Cell culture is one of the major tools for oncology research, being an excellent system in which to study the biochemistry and molecular biology associated with individual cancer types and to understand cancer cell physiology. Progress in understanding the biology of any type of carcinoma has been impeded by the inability to culture adequately malignant cells from most epithelial tissues. The ultimate in vitro tumor model would completely reflect the in vivo tumor microenvironment in function and mechanism. Unfortunately, such a model does not currently exist. Homogeneous cell lines that can be continuously propagated on plastic surfaces have been extensively used as a surrogate for tumor environment; however they are very different from the in vivo tumor cells. Model systems involving primary culture represent the situation most closely related to the original tissue although they have a number of disadvantages over cell lines, such as the limited ability to repeat studies with a well characterized culture system that can be used in multiple laboratories. The primary culture may contain many types of stromal and infiltrating cell types potentially complicating the interpretation of data. Yet, their properties better reflect the cellular interactions present in intact tissue. The present article reviews the critical steps in obtaining, routine maintenance and cryopreservation of primary tumor cell cultures, based on information from literature and personal experience on the subject. The article also includes an updated protocol for primary tumor cell isolation and culture.

  19. The Relationship between Nasalance and Nasality in Children with Cleft Palate.

    ERIC Educational Resources Information Center

    Watterson, Thomas; And Others

    1993-01-01

    This study correlated measures of nasalance computed by the Nasometer with listener judgments of nasality of speech passages spoken by 25 children with craniofacial disorders. Results showed a significant correlation between nasalance and nasality only when nasal consonants were not included in the passage spoken. (Author/DB)

  20. Collagen V nasal tolerance in experimental model of systemic sclerosis.

    PubMed

    Velosa, Ana Paula Pereira; Teodoro, Walcy Rosolia; de Oliveira, Cristiane Carla; Dos Santos Filho, Antonio; Moutinho, Rodnei Francisco; Santos, Angela Gomes; Vendramini, Margarete Borges Galhardo; Bueno, Cleonice; Parra, Edwin Roger; Capelozzi, Vera Luiza; Yoshinari, Natalino Hajime

    2007-07-01

    Our aim was to study skin remodeling and autoantibody production in an experimental model of scleroderma (SSc), following nasal tolerance with human type V collagen (Col V). Female New Zealand rabbits (n = 12) were immunized with two doses of 1 mg/ml of Col V in complete Freund's adjuvant and additional two boosters in incomplete Freund's adjuvant to induce SSc. After 150 days, half of these immunized rabbits were submitted to type V collagen-induced tolerance receiving a daily nasal administration of 25 mug of Col V. Control animals (n = 6) were only submitted to type V collagen-induced tolerance. Serial skin biopsies were performed on days 0, 150 and 210, and stained with H&E, Masson's trichrome and Picrosirius for morphological and morphometric analysis. Types I, III and V collagen were identified by immunofluorescence. The animals' serum samples were collected to determine anti types I, III, IV and V collagen and antinuclear antibodies (ANA). Skin biopsies from immunized animals confirmed SSc morphology as previously described, such as progressive decrease of papillary dermis, appendages atrophy, increased type I, III and V collagen deposition. Rabbits with Col V-induced nasal tolerance showed reduction of skin involvement, with significant decrease of collagen amount. Humoral immune response did not change with nasal tolerance. Collagen V nasal tolerance promotes regression of skin remodeling process in an experimental model of SSc. We suggest that nasal tolerance with type V collagen can be a promising therapeutic option to treat scleroderma patients.

  1. Nasal Acai Polysaccharides Potentiate Innate Immunity to Protect against Pulmonary Francisella tularensis and Burkholderia pseudomallei Infections

    PubMed Central

    Skyberg, Jerod A.; Rollins, MaryClare F.; Holderness, Jeff S.; Marlenee, Nicole L.; Schepetkin, Igor A.; Goodyear, Andrew; Dow, Steven W.; Jutila, Mark A.; Pascual, David W.

    2012-01-01

    Pulmonary Francisella tularensis and Burkholderia pseudomallei infections are highly lethal in untreated patients, and current antibiotic regimens are not always effective. Activating the innate immune system provides an alternative means of treating infection and can also complement antibiotic therapies. Several natural agonists were screened for their ability to enhance host resistance to infection, and polysaccharides derived from the Acai berry (Acai PS) were found to have potent abilities as an immunotherapeutic to treat F. tularensis and B. pseudomallei infections. In vitro, Acai PS impaired replication of Francisella in primary human macrophages co-cultured with autologous NK cells via augmentation of NK cell IFN-γ. Furthermore, Acai PS administered nasally before or after infection protected mice against type A F. tularensis aerosol challenge with survival rates up to 80%, and protection was still observed, albeit reduced, when mice were treated two days post-infection. Nasal Acai PS administration augmented intracellular expression of IFN-γ by NK cells in the lungs of F. tularensis-infected mice, and neutralization of IFN-γ ablated the protective effect of Acai PS. Likewise, nasal Acai PS treatment conferred protection against pulmonary infection with B. pseudomallei strain 1026b. Acai PS dramatically reduced the replication of B. pseudomallei in the lung and blocked bacterial dissemination to the spleen and liver. Nasal administration of Acai PS enhanced IFN-γ responses by NK and γδ T cells in the lungs, while neutralization of IFN-γ totally abrogated the protective effect of Acai PS against pulmonary B. pseudomallei infection. Collectively, these results demonstrate Acai PS is a potent innate immune agonist that can resolve F. tularensis and B. pseudomallei infections, suggesting this innate immune agonist has broad-spectrum activity against virulent intracellular pathogens. PMID:22438809

  2. 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.

  3. 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.

  4. 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 (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS...

  5. 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 (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS...

  6. 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 (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS...

  7. 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 (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS...

  8. 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...

  9. Nasal septal and craniofacial form in European- and African-derived populations.

    PubMed

    Holton, Nathan E; Yokley, Todd R; Figueroa, Aaron

    2012-09-01

    As a component of the chondrocranium, the nasal septum influences the anteroposterior dimensions of the facial skeleton. The role of the septum as a facial growth center, however, has been studied primarily in long-snouted mammals, and its precise influence on human facial growth is not as well understood. Whereas the nasal septum may be important in the anterior growth of the human facial skeleton early in ontogeny, the high incidence of nasal septal deviation in humans suggests the septum's influence on human facial length is limited to the early phases of facial growth. Nevertheless, the nasal septum follows a growth trajectory similar to the facial skeleton and, as such, its prolonged period of growth may influence other aspects of facial development. Using computed tomography scans of living human subjects (n = 70), the goal of the present study is to assess the morphological relationship between the nasal septum and facial skeleton in European- and African-derived populations, which have been shown to exhibit early developmental differences in the nasal septal-premaxillary complex. First we assessed whether there is population variation in the size of the nasal septum in European- and African-derived samples. This included an evaluation of septal deviation and the spatial constraints that influence variation in this condition. Next, we assessed the relationship between nasal septal size and craniofacial shape using multivariate regression techniques. Our results indicate that there is significant population variation in septal size and magnitude of septal deviation, both of which are greater in the European-derived sample. While septal deviation suggests a disjunction between the nasal septum and other components of the facial skeleton, we nevertheless found a significant relationship between the size of the nasal septum and craniofacial shape, which appears to largely be a response to the need to accommodate variation in nasal septal size.

  10. Preliminary studies on nasal decongestant activity from the seed of the shea butter tree, Butyrospermum parkii.

    PubMed

    Tella, A

    1979-05-01

    1 The seed of Butyrospermum parkii yields shea butter which according to local traditional healers relieves inflammation of the nostrils. 2 Since there is as yet no absolutely satisfactory nasal decongestant in clinical use, it was decided to investigate the effects of shea butter in nasal congestion. The substance was prepared in the laboratory. 3 The human subjects used were those suffering from rhinitis with moderate to severe nasal congestion. They were divided into the test group which received shea butter, the control group which was treated with xylometazoline and the 'placebo' group which received white petroleum jelly B.P. 4 The results showed that nasal congestion was relieved more satisfactorily in the test group than in the other two groups. 5 It is concluded that shea butter may prove more efficacious in nasal congestion than conventional nasal drops.

  11. Tetrachromacy of human vision: spectral channels and primary colors

    NASA Astrophysics Data System (ADS)

    Gavrik, Vitali V.

    2002-06-01

    Full-color imaging requires four channels as, in contrast to a colorimeter, can add no primary to matched scene colors themselves. An ideal imaging channel should have the same spectral sensitivity of scene recording as a retinal receptor and evoke the same primary color sensation. The alternating matching functions of a triad of real primaries are inconsistent with the three cones but explicable of two pairs of independent opponent receptors with their alternating blue-yellow and green-red chromatic axes in the color space. Much other controversy of trichromatic approach can also be explained with the recently proposed intra- receptor processes in the photopic rod and cone, respectively. Each of their four primary sensations, unmixed around 465, 495, 575, and 650 nm, is evoked within a different spectral region. The current trichromatic photographic systems have been found separately to approximate the blue and red receptors, as well as their spectral opponency against the respective yellow and blue- green receptors simulated with a single middle-wave imaging channel. The channel sensitivities are delimited by the neutral points of rod and cone and cannot simulate the necessary overlap of non-opponent channels for properly to render some mixed colors. The yellow and cyan positive dyes closely control the brightness of blue and red sensations, respectively. Those red and blue respectively to control the yellow and blue-green sensations on brightness scales are replaced by magenta dye, controlling them together. Accurate rendering of natural saturation metameric colors, problematic blue-green, purple-red, and low-illumination colors requires to replace the hybrid 'green' channel with the blue-green and yellow channels.

  12. Critical factors in assessing risk from exposure to nasal carcinogens.

    PubMed

    Bogdanffy, M S; Mathison, B H; Kuykendall, J R; Harman, A E

    1997-10-31

    Anatomical, physiological, biochemical and molecular factors that contribute to chemical-induced nasal carcinogenesis are either largely divergent between test species and humans, or we know very little of them. These factors, let alone the uncertainty associated with our knowledge gap, present a risk assessor with the formidable task of making judgments about risks to human health from exposure to chemicals that have been identified in rodent studies to be nasal carcinogens. This paper summarizes some of the critical attributes of the hazard identification and dose-response aspects of risk assessments for nasal carcinogens that must be accounted for by risk assessors in order to make informed decisions. Data on two example compounds, dimethyl sulfate and hexamethylphosphoramide, are discussed to illustrate the diversity of information that can be used to develop informed hypotheses about mode of action and decisions on appropriate dosimeters for interspecies extrapolation. Default approaches to interspecies dosimetry extrapolation are described briefly and are followed by a discussion of a generalized physiologically based pharmacokinetic model that, unlike default approaches, is flexible and capable of incorporating many of the critical species-specific factors. Recent advancements in interspecies nasal dosimetry modeling are remarkable. However, it is concluded that without the development of research programs aimed at understanding carcinogenic susceptibility factors in human and rodent nasal tissues, development of plausible modes of action will lag behind the advancements made in dosimetry modeling.

  13. Complications of Nasal Bone Fractures.

    PubMed

    Hwang, Kun; Yeom, Seung Han; Hwang, Suk Hyun

    2017-01-27

    The aim of this study was to perform a systematic review of the treatment of nasal bone fractures. The search terms ("nasal bone fracture" AND complication) and ("nasal bone fracture" AND [anosmia OR olfaction OR olfactory nerve OR smell]) and (anosmia AND ["nasal preparation" OR "nasal antiseptics"]) were used to search PubMed and SCOPUS. Of the 500 titles, 40 full papers were reviewed. One paper was excluded, and 3 mined papers were added. Ultimately, 12 papers were analyzed. The overall deformity rate was 10.4% ± 4.8%. No significant differences were found between patients who underwent closed reduction (14.7% ± 7.3%) and those who underwent open reduction (9.4% ± 4.4%), between those who underwent local anesthesia (5.8% ± 4.5%), and those who underwent general anesthesia (8.8% ± 3.8%), or between those who received timely treatment (5.7%) and those whose treatment was delayed (9.0%). Septal deviation occurred in 10.0% of patients as a sequela of nasal bone fracture. The nasal obstruction rate was 10.5% ± 5.3%. Fewer patients of nasal obstruction occurred in the open reduction patients (6.9% ± 4.4%) than in the closed reduction patients (15.2%). One patient of epiphora and 1 patient of diplopia were reportedAmong the 77 patients with nasal bone fractures, 29 (37.7% ± 11.3%) complained of olfactory disturbances. No significant associations were found between the type of fracture and the presence of olfactory disturbances. It is recommended for providers to explain to patients that approximately one-tenth of nasal bone fractures exhibit deformity, septal deviation, or nasal obstruction after surgery. Surgeons should take considerable care to avoid the olfactory mucosa during reduction surgery.

  14. Cleft Nasal Deformity and Rhinoplasty

    PubMed Central

    Kaufman, Yoav; Buchanan, Edward P.; Wolfswinkel, Erik M.; Weathers, William M.; Stal, Samuel

    2012-01-01

    The cleft nasal deformity is a complex challenge in plastic surgery involving the skin, cartilage, mucosa, and skeletal platform. Ever since Blair and Brown first described the intricacies of the cleft pathology in 1931, the appropriate approach has been extensively debated in the literature with respect to timing, technique, and extent of surgical intervention. In this article, the authors review the literature and summarize the various modalities for achieving a successful rhinoplasty in the patient with a cleft nasal deformity. PMID:24179452

  15. 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.

  16. Appraisal of the Need for Human Capital Development for Standards-Based Curriculum in Primary Schools

    ERIC Educational Resources Information Center

    Enemuo, J. Obiageli; Onwuka, Lilian N.

    2011-01-01

    This study sought to identify primary school teachers' perception on the need for human capital development for standards-based curriculum in primary schools in Anambra State. Simple random sampling was used to draw a sample of 630 teachers. Four research questions were used for the study and a 41-item questionnaire was used to collect data. Data…

  17. Human intestinal parasites in primary school children in Kampala, Uganda.

    PubMed

    Kabatereine, N B; Kemijumbi, J; Kazibwe, F; Onapa, A W

    1997-05-01

    A cross sectional survey on intestinal parasite infections was carried out in 5,313 pupils between the ages of ten and fifteen years in 98 primary schools in Kampala. The aim was to identify the types and distribution of intestinal parasites and to estimate the prevalence in school children. Trichuris trichiura (28%), Ascaris lumbricoides (17%) and hookworms (12.9%) were common infections among the children. Other less commonly found parasites were S.mansoni, Strongyloides stercolaris, Taenia sp, Enterobius vermicularis, Giardia lamblia, Entamoeba coli and E. histolytica. Refuse dumps are probably a significant source of transmission of intestinal helminthic infections in Kampala.

  18. 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.

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

    PubMed

    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

    2015-12-03

    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.

  20. Human Resource Architectures for New Teachers in Flemish Primary Education

    ERIC Educational Resources Information Center

    Vekeman, Eva; Devos, Geert; Valcke, Martin

    2016-01-01

    Since research shows that the quality of a school's teaching force is related to its personnel practices, there is a growing interest in human resource management (HRM) in education. Existing research has generated insights into the differences, constraints and effects of single and isolated HR practices. Yet, little research is available…

  1. 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.

  2. 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

    2015-07-14

    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.

  3. 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

  4. 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.

  5. Immune Modulation in Primary Vaccinia virus Zoonotic Human Infections

    PubMed Central

    Gomes, Juliana Assis Silva; de Araújo, Fernanda Fortes; Trindade, Giliane de Souza; Quinan, Bárbara Resende; Drumond, Betânia Paiva; Ferreira, Jaqueline Maria Siqueira; Mota, Bruno Eduardo Fernandes; Nogueira, Maurício Lacerda; Kroon, Erna Geessien; Abrahão, Jônatas Santos; Côrrea-Oliveira, Rodrigo; da Fonseca, Flávio Guimarães

    2012-01-01

    In 2010, the WHO celebrated the 30th anniversary of the smallpox eradication. Ironically, infections caused by viruses related to smallpox are being increasingly reported worldwide, including Monkeypox, Cowpox, and Vaccinia virus (VACV). Little is known about the human immunological responses elicited during acute infections caused by orthopoxviruses. We have followed VACV zoonotic outbreaks taking place in Brazil and analyzed cellular immune responses in patients acutely infected by VACV. Results indicated that these patients show a biased immune modulation when compared to noninfected controls. Amounts of B cells are low and less activated in infected patients. Although present, T CD4+ cells are also less activated when compared to noninfected individuals, and so are monocytes/macrophages. Similar results were obtained when Balb/C mice were experimentally infected with a VACV sample isolated during the zoonotic outbreaks. Taking together, the data suggest that zoonotic VACVs modulate specific immune cell compartments during an acute infection in humans. PMID:22229039

  6. 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...

  7. Nasal and cutaneous aspergillosis in a goat.

    PubMed

    do Carmo, P M S; Portela, R A; de Oliveira-Filho, J C; Dantas, A F M; Simões, S V D; Garino, F; Riet-Correa, F

    2014-01-01

    Nasal and cutaneous aspergillosis is reported in an adult goat. The clinical signs were severe respiratory distress due to partial nasal obstruction, bilateral mucopurulent nasal discharge, skin nodules on the ears and dorsal nasal region and focal depigmentation of the ventral commissure of the right nostril. At necropsy examination, sagittal sectioning of the head revealed a yellow irregular mass extending from the nasal vestibule to the frontal portion of the nasal cavity. Microscopically, there was pyogranulomatous rhinitis and dermatitis, with numerous intralesional periodic acid-Schiff-positive fungal hyphae morphologically suggestive of Aspergillus spp. Aspergillus niger was isolated by microbiological examination.

  8. 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

  9. Micropatterned coculture of primary human hepatocytes and supportive cells for the study of hepatotropic pathogens.

    PubMed

    March, Sandra; Ramanan, Vyas; Trehan, Kartik; Ng, Shengyong; Galstian, Ani; Gural, Nil; Scull, Margaret A; Shlomai, Amir; Mota, Maria M; Fleming, Heather E; Khetani, Salman R; Rice, Charles M; Bhatia, Sangeeta N

    2015-12-01

    The development of therapies and vaccines for human hepatropic pathogens requires robust model systems that enable the study of host-pathogen interactions. However, in vitro liver models of infection typically use either hepatoma cell lines that exhibit aberrant physiology or primary human hepatocytes in culture conditions in which they rapidly lose their hepatic phenotype. To achieve stable and robust in vitro primary human hepatocyte models, we developed micropatterned cocultures (MPCCs), which consist of primary human hepatocytes organized into 2D islands that are surrounded by supportive fibroblast cells. By using this system, which can be established over a period of days, and maintained over multiple weeks, we demonstrate how to recapitulate in vitro hepatic life cycles for the hepatitis B and C viruses and the Plasmodium pathogens P. falciparum and P. vivax. The MPCC platform can be used to uncover aspects of host-pathogen interactions, and it has the potential to be used for drug and vaccine development.

  10. Primary function analysis of human mental retardation related gene CRBN.

    PubMed

    Xin, Wang; Xiaohua, Ni; Peilin, Chen; Xin, Chen; Yaqiong, Sun; Qihan, Wu

    2008-06-01

    The mutation of human cereblon gene (CRBN) is revealed to be related with mild mental retardation. Since the molecular characteristics of CRBN have not been well presented, we investigated the general properties of CRBN. We analyzed its gene structure and protein homologues. The CRBN protein might belong to a family of adenosine triphosphate (ATP)-dependent Lon protease. We also found that CRBN was widely expressed in different tissues, and the expression level in testis is significantly higher than other tissues. This may suggested it could play some important roles in several other tissues besides brain. Transient transfection experiment in AD 293 cell lines suggested that both CRBN and CRBN mutant (nucleotide position 1,274(C > T)) are located in the whole cells. This may suggest new functions of CRBN in cell nucleolus besides its mitochondria protease activity in cytoplasm.

  11. 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

  12. 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.

  13. The primary inhibitor of plasmin in human plasma.

    PubMed Central

    Müllertz, S; Clemmensen, I

    1976-01-01

    A complex between plasmin and an inhibitor was isolated by affinity chromatography from urokinase-activated human plasma. The complex did not react with antibodies against any of the known proteinase inhibitors in plasma. A rabbit antiserum against the complex was produced. It contained antibodies agianst plasminogen+plasmin and an alpha2 protein. By crossed immunoelectrophoresis the alpha2 protein was shown to form a complex with plasmin, when generated by urokinase in plasma, and with purified plasmin. The alpha2 protein was eluted by Sephadex G-200 gel filtration with KD approx. 0.35, different from the other inhibitors of plasmin in plasma, and corresponding to an apparent relative molecular mass (Mr) of about 75000. By sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, the Mr of the complex was found to be approx. 130000. After reduction of the complex two main bands of protein were observed, with Mr, about 72000 and 66000, probably representing an acyl-enzyme complex of plasmin-light chain and inhibitor-heavy chain, and a plasmin-heavy chain. A weak band with Mr 9000 was possibly an inhibitor-light chain. The inhibitor was partially purified and used to titrate purified plasmin of known active-site concentration. The inhibitor bound plasmin rapidly and strongly. Assuming an equimolar combining ratio, the concentration of active inhibitor in normal human plasma was estimated to be 1.1 mumol/1. A fraction about 0.3 of the antigenic inhibitor protein appeared to be functionally inactive. In plasma, plasmin is primarily bound to the inhibitor. Only after its saturation does lysis of fibrinogen and fibrin occur and a complex between plasmin and alpha2 macroglobulin appear. Images PLATE 1 PLATE 2 PLATE 3 PLATE 4 PMID:137718

  14. Gene expression analysis of primary normal human hepatocytes infected with human hepatitis B virus

    PubMed Central

    Ryu, Hyun Mi; Park, Sung Gyoo; Yea, Sung Su; Jang, Won Hee; Yang, Young-Il; Jung, Guhung

    2006-01-01

    AIM: To find the relationship between hepatitis B virus (HBV) and hepatocytes during the initial state of infection by cDNA microarray. METHODS: Primary normal human hepatocytes (PNHHs) were isolated and infected with HBV. From the PNHHs, RNA was isolated and inverted into complement DNA (cDNA) with Cy3- or Cy5- labeled dUTP for microarray analysis. The labeled cDNA was hybridized with microarray chip, including 4224 cDNAs. From the image of the microarray, expression profiles were produced and some of them were confirmed by RT-PCR, immunoblot analysis, and NF-κB luciferase reporter assay. RESULTS: From the cDNA microarray, we obtained 98 differentially regulated genes. Of the 98 genes, 53 were up regulated and 45 down regulated. Interestingly, in the up regulated genes, we found the TNF signaling pathway-related genes: LT-α, TRAF2, and NIK. By using RT-PCR, we confirmed the up-regulation of these genes in HepG2, Huh7, and Chang liver cells, which were transfected with pHBV1.2×, a plasmid encoding all HBV messages. Moreover, these three genes participated in HBV-mediated NF-κB activation. CONCLUSION: During the initial state of HBV infection, hepatocytes facilitate the activation of NF-κB through up regulation of LT-α, TRAF2, and NIK. PMID:16937494

  15. HIV-1 increases TLR responses in human primary astrocytes

    PubMed Central

    Serramía, M Jesús; Muñoz-Fernández, M Ángeles; Álvarez, Susana

    2015-01-01

    Astrocytes are the major glial cell within the central nervous system and have a number of important physiological properties related to brain homeostasis. They provide trophic support to neurons and are immune cells with key roles during states-of-inflammation. The potential for production of proinflammatory cytokines and its consequences has been studied in the context of HIV-1 infection of normal human astrocytes (NHA). NHA express TLR3, TLR4, and TLR5. TLR3 ligation induced the strongest proinflammatory polarizing response, characterized by generation of high levels of TNF-α, IL-6, and IL-8. HIV-1 increased the transient production of key inflammatory mediators, and exposure to LPS of HIV-1-infected cells increased significantly the cytokine secretion. We confirmed that it is necessary viral gene expression from the moment of pretreatment with antiretrovirals inhibited totally HIV-1-induced TLR response. The higher response to LPS from HIV-1-infected cells did not correlate with TLR4 or MyD88 increased expression. LPS responsiveness of infected cells parallels MHC class II expression, but not CD14. HIV-1-infected NHA present increased sensitivity to the proinflammatory effects of LPS. If this phenomenon occurs in vivo, it will contribute to the immunopathogenesis of this disease and may ultimately offer novel targets for immunomodulatory therapy. PMID:26671458

  16. 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

  17. Determination of growth hormone releasing peptides metabolites in human urine after nasal administration of GHRP-1, GHRP-2, GHRP-6, Hexarelin, and Ipamorelin.

    PubMed

    Semenistaya, Ekaterina; Zvereva, Irina; Thomas, Andreas; Thevis, Mario; Krotov, Grigory; Rodchenkov, Grigory

    2015-10-01

    Growth hormone releasing peptides (GHRPs) stimulate secretion of endogenous growth hormone and are listed on the World Anti-Doping Agency (WADA) Prohibited List. To develop an effective method for GHRPs anti-doping control we have investigated metabolites of GHRP-1, GHRP-2, GHRP-6, Hexarelin, and Ipamorelin in urine after nasal administration. Each compound was administrated to one volunteer. Samples were collected for 2 days after administration, processed by solid-phase extraction on weak cation exchange cartridges and analyzed by means of nano-liquid chromatography - high resolution mass spectrometry. Six metabolites of GHRP-1 were identified. GHRP-1 in the parent form was not detected. GHRP-1 (2-4) free acid was detected in urine up to 27 h. GHRP-2, GHRP-2 free acid and GHRP-2 (1-3) free acid were detected in urine up to 47 h after administration. GHRP-6 was mostly excreted unchanged and detected in urine 23 h after administration, its metabolites were detectable for 12 h only. Hexarelin and Ipamorelin metabolized intensively and were excreted as a set of parent compounds with metabolites. Hexarelin (1-3) free acid and Ipamorelin (1-4) free acid were detected in urine samples after complete withdrawal of parent substances. GHRPs and their most prominent metabolites were included into routine ultra-pressure liquid chromatography-tandem mass spectrometry procedure. The method was fully validated, calibration curves of targeted analytes were obtained and excretion curves of GHRPs and their metabolites were plotted. Our results confirm that the detection window after GHRPs administration depends on individual metabolism, drug preparation form and the way of administration.

  18. Effects of Nasal Port Area on Perception of Nasality and Measures of Nasalance Based on Computational Modeling

    PubMed Central

    Bunton, Kate

    2015-01-01

    Objective The purpose of this study was to extend previously published modeling work examining the relation between nasal port opening, measures of nasalance, and perceptual ratings of nasality by experienced listeners for three simulated English corner vowels, /i/, /u/, and /ɑ/. Design Samples were generated using a computational model that allowed for exact control of nasal port size and direct measures of nasalance. Perceptual ratings were obtained using a paired stimulus presentation. Participants Four experienced listeners. Main Outcome Measures Nasalance and perceptual ratings of nasality. Results Findings indicate that perceptual ratings of nasality and nasalance increased for samples generated with nasal port areas up to and including 0.16 cm2 but plateaued in samples generated with larger nasal port areas. No vowel differences were noted for perceptual ratings. Conclusions This work extends previously published work by including nasal port areas representative of those reported in the literature for clinical populations, however, continued work using samples with varied phonetic context, and varying suprasegmental and temporal characteristics are needed. PMID:24437587

  19. 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.

  20. Nasal mucociliary clearance after radiation therapy.

    PubMed

    Stringer, S P; Stiles, W; Slattery, W H; Krumerman, J; Parsons, J T; Mendenhall, W M; Cassisi, N J

    1995-04-01

    Irradiation has been demonstrated to cause decreased mucociliary clearance in animal models. We sought to verify this effect clinically by using the saccharin transport test to evaluate nasal mucociliary clearance in 9 patients previously treated with radiation therapy to the nasal cavity. The patients also completed a questionnaire examining the prevalence of nasal symptoms before and after radiation therapy. Patients who received radiation therapy had no clearance of saccharin from the nasal cavity at a minimum of 20 minutes. The controls had a median clearance time of 5 minutes. The patients noted a higher prevalence of nasal congestion, drainage, and facial pain after radiation therapy. This study demonstrates that radiation therapy to the nasal cavity causes a decrease in nasal mucociliary clearance. This alteration should be considered when selecting therapy for malignancies in the nasal area.

  1. Maturation and demise of human primary monocytes by carbon nanotubes

    NASA Astrophysics Data System (ADS)

    De Nicola, Milena; Mirabile Gattia, Daniele; Traversa, Enrico; Ghibelli, Lina

    2013-06-01

    The possibility of exploiting carbon nanotubes (CNT) in biomedical practices requires thorough analysis of the chemical or bulk effects they may exert on the immune system, the complex network that recognizes and eliminates foreign particles. In particular, the phagocytosing ability of cells belonging to the monocyte/macrophage lineage may render these immune cells an ideal toxicological target of pristine CNT, which may form aggregates of size exceeding monocyte/macrophage phagocytosing plasticity. To shed light on this issue, we analyzed the effects that pristine multi-walled CNT (MWCNT) without metal or biological impurities exert on survival and activation of freshly explanted human peripheral blood monocytes, analyzing in parallel the non-phagocytosing lymphocytes, and using graphite as control carbon material. MWCNT (diameter 10-50 nm, length up to 10 μm) exert two different toxic effects on mononuclear leukocytes: a minor apoptogenic effect (on lymphocytes > monocytes), and a major, apoptosis-independent effect that exclusively and deeply affect monocyte homeostasis. Analysis of monocyte number, adhesion, redox equilibrium, and the differentiation markers CD14 and CD11b reveals that MWCNT cause the selective disappearance of phagocytosis-competent monocytes by mechanisms related to the presence of large nanoparticle aggregates, suggesting phenomena of bulk toxicity possibly consisting of frustrated phagocytosis. At the same time, MWCNT stimulate adhesion of the phagocytosis-incompetent monocytes, and their differentiation toward a peculiar maturation asset. These observations point out novel mechanisms of CNT toxicity, renewing concerns that they may impair the innate immune system deranging the inflammatory responses.

  2. 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.

  3. Molecular identity and prevalence of Cryptococcus spp. nasal carriage in asymptomatic feral cats in Italy.

    PubMed

    Danesi, Patrizia; Furnari, Carmelo; Granato, Anna; Schivo, Alice; Otranto, Domenico; Capelli, Gioia; Cafarchia, Claudia

    2014-10-01

    Cryptococcosis is a life-threatening fungal disease that infects humans and animals worldwide. Inhalation of fungal particles from an environmental source can cause primary infection of the respiratory system. As animals can be considered a sentinel for human diseases, the aim of this study was to determine the prevalence and molecular identity of Cryptococcus spp. in the nasal cavity of feral cats. Cats from 162 urban and rural feral cat colonies were sampled over 3 years. Of 766 cats from which nasal swabs were obtained, Cryptococcus spp. were recovered from 95 (12.6%), including 37 C. magnus (4.8%), 16 C. albidus (2.0%), 15 C. carnescens (1.9%), 12 C. neoformans (1.6%), as well as C. oeirensis (n = 3), C. victoriae (n = 3), C. albidosimilis (n = 2), Filobasidium globisporum (n = 2), C. adeliensis (n = 1), C. flavescens (n = 1), C. dimnae (n = 1), C. saitoi (n = 1), and C. wieringae (n = 1) with prevalence <1%. Thirteen Cryptococcus species were identified by polymerase chain reaction and sequencing of internal transcribed spacer amplicons. Statistical analysis did not identify any predisposing factors that contributed to nasal colonization (eg, sex, age, season, or habitat). Results suggest that asymptomatic feral cats may carry C. neoformans and other Cryptococcus species in their sinonasal cavity. Genotyping of the specific cryptococcal isolates provides a better understanding of the epidemiology of these yeasts.

  4. Persistent gene expression in mouse nasal epithelia following feline immunodeficiency virus-based vector gene transfer.

    PubMed

    Sinn, Patrick L; Burnight, Erin R; Hickey, Melissa A; Blissard, Gary W; McCray, Paul B

    2005-10-01

    Gene transfer development for treatment or prevention of cystic fibrosis lung disease has been limited by the inability of vectors to efficiently and persistently transduce airway epithelia. Influenza A is an enveloped virus with natural lung tropism; however, pseudotyping feline immunodeficiency virus (FIV)-based lentiviral vector with the hemagglutinin envelope protein proved unsuccessful. Conversely, pseudotyping FIV with the envelope protein from influenza D (Thogoto virus GP75) resulted in titers of 10(6) transducing units (TU)/ml and conferred apical entry into well-differentiated human airway epithelial cells. Baculovirus GP64 envelope glycoproteins share sequence identity with influenza D GP75 envelope glycoproteins. Pseudotyping FIV with GP64 from three species of baculovirus resulted in titers of 10(7) to 10(9) TU/ml. Of note, GP64 from Autographa californica multicapsid nucleopolyhedrovirus resulted in high-titer FIV preparations (approximately 10(9) TU/ml) and conferred apical entry into polarized primary cultures of human airway epithelia. Using a luciferase reporter gene and bioluminescence imaging, we observed persistent gene expression from in vivo gene transfer in the mouse nose with A. californica GP64-pseudotyped FIV (AcGP64-FIV). Longitudinal bioluminescence analysis documented persistent expression in nasal epithelia for approximately 1 year without significant decline. According to histological analysis using a LacZ reporter gene, olfactory and respiratory epithelial cells were transduced. In addition, methylcellulose-formulated AcGP64-FIV transduced mouse nasal epithelia with much greater efficiency than similarly formulated vesicular stomatitis virus glycoprotein-pseudotyped FIV. These data suggest that AcGP64-FIV efficiently transduces and persistently expresses a transgene in nasal epithelia in the absence of agents that disrupt the cellular tight junction integrity.

  5. Quilting sutures for nasal septum.

    PubMed

    Hari, C; Marnane, C; Wormald, P J

    2008-05-01

    Suturing of the nasal septum after septal surgery is a commonly performed procedure designed to prevent complications such as septal haematoma and bleeding. It is also useful for closing any inadvertent tears of the septal mucosa and providing additional support for the cartilage pieces retained in septoplasty. In addition, the suture can be placed through the middle turbinates, stabilising them during the healing process. Placing knots for interrupted sutures in the posterior and middle part of the nasal septum can be technically difficult. We describe a continuous suturing technique for approximating the mucosal flaps following septal surgery.

  6. Nasal septal cyst--a case report.

    PubMed

    Chiang, C H; Juan, K H; Kuo, W R; Tai, C F; Wu, J R

    1996-04-01

    The usual complications of submucous resection of the nasal septum (SMR) are septal hematoma, infection, hemorrhage, septal perforation, and nasal deformity. We present a case of nasal septal cyst which may be a rare complication of SMR. Entrapment of free nasal mucosal remnants or inward folding of incised septal mucosa is thought to be the cause. The patient underwent deroofment of the left cystic wall by lateral rhinotomy. There was no recurrence after one year.

  7. [A patient with both cocaine-induced nasal septum destruction and antibodies against anti-neutrophil cytoplasmic antibodies (ANCA); potential confusion with Wegener's disease].

    PubMed

    Scheenstra, R J; van Buren, M; Koopman, J P

    2007-10-27

    A 37-year-old male cocaine user presented with continual, sanguinolent nasal obstruction and persistant pain following a nasal operation one year ago. Examination showed crustae, granulations and exposed septal cartilage in the right nasal passage in addition to a considerable septal deviation to the left. No other physical abnormalities were found. A biopsy of the nasal mucosa showed acute necrotic inflammation. The serological examination revealed markedly elevated anti-neutrophil cytoplasmic antibodies (ANCA) titres with positive reactions against proteinase-3, indicating Wegener's disease. Additional testing also showed a positive ANCA reaction for human neutrophil elastase, which made cocaine use a more plausible cause for the nasal abnormalities than Wegener's disease. Treatment consisted of nasal flushing with saline and, for a short period, a nasal tampon with hydrocortisone-oxytetracycline-polymyxin B ointment. However, the patient did, ultimately, develop a septal perforation. Cocaine-induced nasal abnormalities can imitate symptoms that may fit Wegener's disease, including relevant serological ANCA findings.

  8. Extramedullary plasmacytoma of the nasal sinus cavities.

    PubMed

    Lomeo, Paul E; McDonald, John E; Finneman, Judith; Shoreline

    2007-01-01

    This is case report of extramedullary plasmacytoma occurring in the nasal cavity. These are unusual tumors especially in the nasal area. Patients present mainly with nasal symptoms on the same side of the tumors. The treatment consists of surgery resection, or, radiation, or both. There is a fifty percent survival rate in five years.

  9. 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.

  10. 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.

  11. 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

  12. Nasal intubation: A comprehensive review

    PubMed Central

    Chauhan, Varun; Acharya, Gaurav

    2016-01-01

    Nasal intubation technique was first described in 1902 by Kuhn. The others pioneering the nasal intubation techniques were Macewen, Rosenberg, Meltzer and Auer, and Elsberg. It is the most common method used for giving anesthesia in oral surgeries as it provides a good field for surgeons to operate. The anatomy behind nasal intubation is necessary to know as it gives an idea about the pathway of the endotracheal tube and complications encountered during nasotracheal intubation. Various techniques can be used to intubate the patient by nasal route and all of them have their own associated complications which are discussed in this article. Various complications may arise while doing nasotracheal intubation but a thorough knowledge of the anatomy and physics behind the procedure can help reduce such complications and manage appropriately. It is important for an anesthesiologist to be well versed with the basics of nasotracheal intubation and advances in the techniques. A thorough knowledge of the anatomy and the advent of newer devices have abolished the negative effect of blindness of the procedure. PMID:27994382

  13. 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

  14. Low nasal bridge

    MedlinePlus

    ... al, eds. Cummings Otolaryngology . 6th ed. Philadelphia, PA: Elsevier Saunders; 2015:chap 35. Jones KL, Jones MC, ... Patterns of Human Malformation . 7th ed. Philadelphia, PA: Elsevier Saunders; 2013:chap K. Schmitz MR, Rush JK, ...

  15. 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.

  16. Nasal septal and premaxillary developmental integration: implications for facial reduction in Homo.

    PubMed

    Holton, Nathan E; Franciscus, Robert G; Marshall, Steven D; Southard, Thomas E; Nieves, Mary Ann

    2011-01-01

    The influence of the chondrocranium in craniofacial development and its role in the reduction of facial size and projection in the genus Homo is incompletely understood. As one component of the chondrocranium, the nasal septum has been argued to play a significant role in human midfacial growth, particularly with respect to its interaction with the premaxilla during prenatal and early postnatal development. Thus, understanding the precise role of nasal septal growth on the facial skeleton is potentially informative with respect to the evolutionary change in craniofacial form. In this study, we assessed the integrative effects of the nasal septum and premaxilla by experimentally reducing facial length in Sus scrofa via circummaxillary suture fixation. Following from the nasal septal-traction model, we tested the following hypotheses: (1) facial growth restriction produces no change in nasal septum length; and (2) restriction of facial length produces compensatory premaxillary growth due to continued nasal septal growth. With respect to hypothesis 1, we found no significant differences in septum length (using the vomer as a proxy) in our experimental (n = 10), control (n = 9) and surgical sham (n = 9) trial groups. With respect to hypothesis 2, the experimental group exhibited a significant increase in premaxilla length. Our hypotheses were further supported by multivariate geometric morphometric analysis and support an integrative relationship between the nasal septum and premaxilla. Thus, continued assessment of the growth and integration of the nasal septum and premaxilla is potentially informative regarding the complex developmental mechanisms that underlie facial reduction in genus Homo evolution.

  17. Ovarian carcinoma presenting as cutaneous nasal metastasis*

    PubMed Central

    António, Ana Marta; Alves, João Vitor; Goulão, João; Bártolo, Elvira

    2016-01-01

    Metastatic ovarian cancer uncommonly presents with skin metastasis. When present, skin metastases of ovarian cancer are usually localized in the vicinity of the primary tumor. We report a case of a 58-year-old woman with a rapid growing erythematous, well-defined nodule localized on the left nasal ala. A skin biopsy was performed and histopathological and immunohistochemical findings were compatible with a cutaneous metastasis of adenocarcinoma. A systematic investigation revealed a bilateral ovarian cystadenocarcinoma associated with visceral dissemination, likely associated with nose cutaneous metastasis. We report a very uncommon case because of the presentation of ovarian carcinoma as cutaneous metastasis. To our knowledge, this atypical localization on the nose has not been described yet in the literature. PMID:28300910

  18. Reconstituting development of pancreatic intraepithelial neoplasia from primary human pancreas duct cells

    PubMed Central

    Lee, Jonghyeob; Snyder, Emily R.; Liu, Yinghua; Gu, Xueying; Wang, Jing; Flowers, Brittany M.; Kim, Yoo Jung; Park, Sangbin; Szot, Gregory L.; Hruban, Ralph H.; Longacre, Teri A.; Kim, Seung K.

    2017-01-01

    Development of systems that reconstitute hallmark features of human pancreatic intraepithelial neoplasia (PanINs), the precursor to pancreatic ductal adenocarcinoma, could generate new strategies for early diagnosis and intervention. However, human cell-based PanIN models with defined mutations are unavailable. Here, we report that genetic modification of primary human pancreatic cells leads to development of lesions resembling native human PanINs. Primary human pancreas duct cells harbouring oncogenic KRAS and induced mutations in CDKN2A, SMAD4 and TP53 expand in vitro as epithelial spheres. After pancreatic transplantation, mutant clones form lesions histologically similar to native PanINs, including prominent stromal responses. Gene expression profiling reveals molecular similarities of mutant clones with native PanINs, and identifies potential PanIN biomarker candidates including Neuromedin U, a circulating peptide hormone. Prospective reconstitution of human PanIN development from primary cells provides experimental opportunities to investigate pancreas cancer development, progression and early-stage detection. PMID:28272465

  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. Human embryonic stem cells in culture possess primary cilia with hedgehog signaling machinery.

    PubMed

    Kiprilov, Enko N; Awan, Aashir; Desprat, Romain; Velho, Michelle; Clement, Christian A; Byskov, Anne Grete; Andersen, Claus Y; Satir, Peter; Bouhassira, Eric E; Christensen, Søren T; Hirsch, Rhoda Elison

    2008-03-10

    Human embryonic stem cells (hESCs) are potential therapeutic tools and models of human development. With a growing interest in primary cilia in signal transduction pathways that are crucial for embryological development and tissue differentiation and interest in mechanisms regulating human hESC differentiation, demonstrating the existence of primary cilia and the localization of signaling components in undifferentiated hESCs establishes a mechanistic basis for the regulation of hESC differentiation. Using electron microscopy (EM), immunofluorescence, and confocal microscopies, we show that primary cilia are present in three undifferentiated hESC lines. EM reveals the characteristic 9 + 0 axoneme. The number and length of cilia increase after serum starvation. Important components of the hedgehog (Hh) pathway, including smoothened, patched 1 (Ptc1), and Gli1 and 2, are present in the cilia. Stimulation of the pathway results in the concerted movement of Ptc1 out of, and smoothened into, the primary cilium as well as up-regulation of GLI1 and PTC1. These findings show that hESCs contain primary cilia associated with working Hh machinery.

  1. A simple nasal anemometer for clinical purposes.

    PubMed

    Hutters, B; Brøndsted, K

    1992-01-01

    There is a need for clinical methods which give more direct information about the behaviour of the velopharyngeal mechanism in natural speech than do the examination methods normally applied to patients suffering from velopharyngeal insufficiency. One possibility is the recording of nasal airflow in order to detect nasal emission of air. The purpose of the present study is to examine the qualities and the characteristics of a simple and cheap nasal anemometer. As this type of flowmeter is considered less reliable than most other flowmeters, its limitations must be clearly understood and accounted for in drawing conclusions. Therefore, nasal airflow in speech obtained with this flowmeter is discussed in relation to nasal airflow obtained by the more reliable pneumotachograph and in relation to nasal airflow data found in the literature. The tests made here suggest that, at least for the type of speech material and measurements used in the present study, reliable nasal airflow data can be obtained by the anemometer.

  2. 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

  3. African and Asian Zika virus strains differentially induce early antiviral responses in primary human astrocytes.

    PubMed

    Hamel, Rodolphe; Ferraris, Pauline; Wichit, Sineewanlaya; Diop, Fodé; Talignani, Loïc; Pompon, Julien; Garcia, Déborah; Liégeois, Florian; Sall, Amadou A; Yssel, Hans; Missé, Dorothée

    2017-04-01

    ZIKA virus (ZIKV) is a newly emerging arbovirus. Since its discovery 60years ago in Uganda, it has spread throughout the Pacific, Latin America and the Caribbean, emphasizing the capacity of ZIKV to spread to non-endemic regions worldwide. Although infection with ZIKV often leads to mild disease, its recent emergence in the Americas has coincided with an increase in adults developing Guillain-Barré syndrome and neurological complications in new-borns, such as congenital microcephaly. Many questions remain unanswered regarding the complications caused by different primary isolates of ZIKV. Here, we report the permissiveness of primary human astrocytes for two clinically relevant, Asian and African ZIKV strains and show that both isolates strongly induce antiviral immune responses in these cells albeit with markedly different kinetics. This study describes for the first time the specific antiviral gene expression in infected primary human astrocytes, the major glial cells within the central nervous system.

  4. Recombinant Adeno-Associated Virus Serotype 6 Efficiently Transduces Primary Human Melanocytes

    PubMed Central

    Verdon, Daniel; Chen, Jennifer; Taylor, John A.; Dunbar, P. Rod

    2013-01-01

    The study of melanocyte biology is important to understand their role in health and disease. However, current methods of gene transfer into melanocytes are limited by safety or efficacy. Recombinant adeno-associated virus (rAAV) has been extensively investigated as a gene therapy vector, is safe and is associated with persistent transgene expression without genome integration. There are twelve serotypes and many capsid variants of rAAV. However, a comparative study to determine which rAAV is most efficient at transducing primary human melanocytes has not been conducted. We therefore sought to determine the optimum rAAV variant for use in the in vitro transduction of primary human melanocytes, which could also be informative to future in vivo studies. We have screened eight variants of rAAV for their ability to transduce primary human melanocytes and identified rAAV6 as the optimal serotype, transducing 7–78% of cells. No increase in transduction was seen with rAAV6 tyrosine capsid mutants. The number of cells expressing the transgene peaked at 6–12 days post-infection, and transduced cells were still detectable at day 28. Therefore rAAV6 should be considered as a non-integrating vector for the transduction of primary human melanocytes. PMID:23646140

  5. 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…

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. The Effect of Nasal Obstruction after Different Nasal Surgeries Using Acoustic Rhinometry and Nasal Obstruction Symptom Evaluation Scale

    PubMed Central

    Kahraman, Erkan; Cil, Yakup; Incesulu, Armagan

    2016-01-01

    BACKGROUND The efficiency of nasal surgeries can be determined by objective or subjective methods. We have assessed the effect of nasal obstruction after different nasal surgeries using Acoustic Rhinometry (AR) and Nasal Obstruction Symptom Evaluation (NOSE) Scale. METHODS Between May 2011 and May 2012, 40 young adult patients and 10 healthy volunteers as control group who referred to Otorhinolaryngology Clinic in Eskisehir Military Hospital due to nasal obstruction were enrolled. Depending on operation, patients were divided into four equal groups. Group 1: Septoplasty, Group 2: Septoplasty with sprader graft, Group 3: Septorinoplasty and Group 4: Septorhinoplasty with spreader graft. The patients completed NOSE scale, 1 week before and 1 month after the surgery and AR measurements. RESULTS There were a significant improvement in mean NOSE scores of patients and statistical difference was found between pre and post-operational values for each group. There was a statistically significant change of the mean minimal cross section areas (MCA) of the deviated side of nasal passages measured by AR between pre and postoperative period. CONCLUSION In patients with nasal obstruction, functional nasal surgeries which were performed after appropriate medical examination and with right operation methods had a positive impact on quality of life and patient satisfaction. We observed that nasal findings were correlated with NOSE scores and MCA values. So, we suggest that NOSE scale and AR to be used for evaluation of the efficiency of functional nasal surgeries. PMID:27853686

  11. CYP2E1-dependent hepatotoxicity and oxidative damage after ethanol administration in human primary hepatocytes

    PubMed Central

    Liu, Lie-Gang; Yan, Hong; Yao, Ping; Zhang, Wen; Zou, Li-Jun; Song, Fang-Fang; Li, Ke; Sun, Xiu-Fa

    2005-01-01

    AIM: To observe the relationship between ethanol-induced oxidative damage in human primary cultured hepatocytes and cytochrome P450 2E1 (CYP2E1) activity, in order to address if inhibition of CYP2E1 could attenuate ethanol-induced cellular damage. METHODS: The dose-dependent (25-100 mmol/L) and time-dependent (0-24 h) exposures of primary human cultured hepatocytes to ethanol were carried out. CYP2E1 activity and protein expression were detected by spectrophotometer and Western blot analysis respectively. Hepatotoxicity was investigated by determination of lactate dehydrogenase (LDH) and aspartate transaminase (AST) level in hepatocyte culture supernatants, as well as the intracellular formation of malondialdehyde (MDA). RESULTS: A dose-and time-dependent response between ethanol exposure and CYP2E1 activity in human hepatocytes was demonstrated. Moreover, there was a time-dependent increase of CYP2E1 protein after 100 mmol/L ethanol exposure. Meanwhile, ethanol exposure of hepatocytes caused a time-dependent increase of cellular MDA level, LDH, and AST activities in supernatants. Furthermore, the inhibitor of CYP2E1, diallyl sulfide (DAS) could partly attenuate the increases of MDA, LDH, and AST in human hepatocytes. CONCLUSION: A positive relationship between ethanol-induced oxidative damage in human primary cultured hepatocytes and CYP2E1 activity was exhibited, and the inhibition of CYP2E1 could partly attenuate ethanol-induced oxidative damage. PMID:16052683

  12. 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

  13. 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.

  14. Porcine Nasal Epithelial Cultures for Studies of Cystic Fibrosis Sinusitis

    PubMed Central

    Dean, Nichole; Ranganath, Neel K.; Jones, Brandon; Zhang, Shaoyan; Skinner, Daniel; Rowe, Steven M.; Sorscher, Eric J.; Woodworth, Bradford A.

    2014-01-01

    Background Transgenic cystic fibrosis (CF) murine models do not develop spontaneous lung or sinus disease, two major causes of morbidity in human CF patients. Because of these limitations, transgenic CFTR−/− pigs have been developed and are currently being characterized. These CF animal models have phenotypes closely resembling that of human CF subjects. The objectives of the current study were to develop primary porcine nasal epithelial (PNE) cultures and evaluate their usefulness as a means to investigate sinonasal transepithelial transport and CFTR function. Methods PNE derived from the septum or turbinates of CFTR+/+ and CFTR−/− pigs were cultured at an air-liquid interface to confluence and full differentiation. Epithelial monolayers were mounted in Ussing chambers to investigate pharmacologic manipulation of ion transport. Ciliary beat frequency (CBF) and scanning electron microscopy of monolayers were used to indicate degree of ciliation and cell differentiation. Results Stimulation of CFTR-mediated anion transport(ΔIsc in μA/cm2) was significantly greater in epithelia derived from the septum when compared to turbinates(33.04+/−1.17 vs. 18.9+/−0.73;p<0.05). cAMP-activated Cl− secretion was absent in CFTR−/− and present in CFTR+/+ epithelia. Calcium-activated Cl− (CaCC) secretion was increased in CF, however, overall Cl− transport through CaCCs was very low. Degree of ciliation (90%) and CBF were similar between groups. Discussion Septal PNE exhibit a robust ion transport phenotype and indicate CFTR−/− sinus disease could be attributable to diminished alternative pathways for Cl− transport. Overall, PNE have similarities to human respiratory epithelia not demonstrated in murine cells and represent useful in vitro models for studying CF sinus disease. PMID:24733748

  15. Apoptosis in pulp elimination during physiological root resorption in human primary teeth.

    PubMed

    Rodrigues, Luciana Villela; Vasconcelos, Anilton César; Campos, Pedro Alves; Brant, Juliana Massote Caldeira

    2009-01-01

    Pulp samples of 50 healthy human teeth with indication for extraction were examined to evaluate the role of apoptosis in pulp elimination during physiological root resorption. Two groups were formed: a test group (n=30) composed of pulp samples of primary teeth with physiological root resorption and a control group (n=20) composed of pulp samples of permanent maxillary third molars. Morphological evidence of apoptosis as well as in situ detection of cellular DNA fragmentation by TUNEL assay and detection of internucleosomal pattern of fragmentation of the genomic DNA by electrophoresis were observed. The apoptotic index of the primary tooth group was significantly higher than that of the permanent tooth group (51.01 +/- 0.52 versus 25.32 +/- 0.68) (p<0.001). TUNEL reaction showed intense and diffuse labeling in the pulp samples of primary teeth, which were discrete in the controls. Intense DNA internucleosomal fragmentation, a specific pattern for apoptosis, was observed in primary tooth pulps DNA by electrophoresis, in the permanent tooth pulps this pattern fragmentation of the genomic DNA for apoptosis were not present. These results seem to indicate a role of apoptosis in pulp elimination during the physiological root resorption of human primary teeth.

  16. Nasal septal haematoma in Nigeria.

    PubMed

    Chukuezi, A B

    1992-05-01

    A prospective study of 46 consecutive patients with nasal septal haematoma admitted at the General Hospital, Owerri, Nigeria over a five year period is presented. The disease was commoner in males than females. The majority of the cases (65.6 per cent) were of unknown cause and were therefore grouped as spontaneous haematoma while 30.4 per cent were due to trauma. Trauma was more common in patients below the age of 15 years while spontaneous haematoma was common in patients above that age. All the patients with septal haematoma represented 0.2 per cent of total attendances to the ENT clinic over the period. Most of the patients presented with severe and threatening symptoms necessitating intense aggressive management. All the patients were managed by surgical incision and drainage, four had marked nasal abnormalities. Three patients died from a brain abscess as a complication of infected haematoma.

  17. 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

  18. Contrastive and contextual vowel nasalization in Ottawa

    NASA Astrophysics Data System (ADS)

    Klopfenstein, Marie

    2005-09-01

    Ottawa is a Central Algonquian language that possesses the recent innovation of contrastive vowel nasalization. Most phonetic studies done to date on contrastive vowel nasalization have investigated Indo-European languages; therefore, a study of Ottawa could prove to be a valuable addition to the literature. To this end, a percentage of nasalization (nasal airflow/oral + nasal airflow) was measured during target vowels produced by native Ottawa speakers using a Nasometer 6200-3. Nasalized vowels in the target word set were either contrastively or contextually nasalized: candidates for contextual nasalization were either regressive or perserverative in word-initial and word-final syllables. Subjects were asked to read words containing target vowels in a carrier sentence. Mean, minimum, and maximum nasalance were obtained for each target vowel across its full duration. Target vowels were compared across context (regressive or perseverative and word-initial or word-final). In addition, contexts were compared to determine whether a significant difference existed between contrastive and contextual nasalization. Results for Ottawa will be compared with results for vowels in similar contexts in other languages including Hindi, Breton, Bengali, and French.

  19. 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

  20. 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

  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. 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

  3. Severe Thrombocytopenia and Acute Cytomegalovirus Colitis during Primary Human Immunodeficiency Virus Infection

    PubMed Central

    Furuhata, Masanori; Yanagisawa, Naoki; Nishiki, Shingo; Sasaki, Shugo; Suganuma, Akihiko; Imamura, Akifumi; Ajisawa, Atsushi

    2016-01-01

    We herein report the case of a 25-year-old man who was referred to our hospital due to acute cytomegalovirus (CMV) colitis. The initial blood tests showed that the patient had concurrent primary human immunodeficiency virus (HIV) infection and severe thrombocytopenia. Raltegravir-based antiretroviral therapy (ART) was initiated without the use of ganciclovir or corticosteroids and resulted in a rapid clinical improvement. Platelet transfusions were only necessary for a short period, and subsequent colonoscopy revealed a completely healed ulcer. This case implies that ART alone could be effective for treating severe thrombocytopenia during primary HIV and CMV coinfection. PMID:27980271

  4. 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

  5. Retroviral-mediated gene transfer and expression of human phenylalanine hydroxylase in primary mouse hepatocytes.

    PubMed Central

    Peng, H; Armentano, D; MacKenzie-Graham, L; Shen, R F; Darlington, G; Ledley, F D; Woo, S L

    1988-01-01

    Genetic therapy for phenylketonuria (severe phenylalanine hydroxylase deficiency) may require introduction of a normal phenylalanine hydroxylase gene into hepatic cells of patients. We 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 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 form the retroviral and internal promoters. These results demonstrate that the transcriptional regulatory elements of the alpha 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. Images PMID:3186716

  6. Establishment of a Novel Primary Human Skeletal Myoblast Cellular Model for Chikungunya Virus Infection and Pathogenesis.

    PubMed

    Hussain, Khairunnisa' Mohamed; Lee, Regina Ching Hua; Ng, Mary Mah-Lee; Chu, Justin Jang Hann

    2016-02-19

    Chikungunya virus (CHIKV) is a re-emerging arbovirus known to cause chronic myalgia and arthralgia and is now considered endemic in countries across Asia and Africa. The tissue tropism of CHIKV infection in humans remains, however, ill-defined. Due to the fact that myositis is commonly observed in most patients infected with CHIKV, we sought to develop a clinically relevant cellular model to better understand the pathogenesis of CHIKV infection. In this study, primary human skeletal muscle myoblasts (HSMM) were established as a novel human primary cell line that is highly permissive to CHIKV infection, with maximal amounts of infectious virions observed at 16 hours post infection. Genome-wide microarray profiling analyses were subsequently performed to identify and map genes that are differentially expressed upon CHIKV infection. Infection of HSMM cells with CHIKV resulted in altered expressions of host genes involved in skeletal- and muscular-associated disorders, innate immune responses, cellular growth and death, host metabolism and virus replication. Together, this study has shown the establishment of a clinically relevant primary human cell model that paves the way for the further analysis of host factors and their involvement in the various stages of CHIKV replication cycle and viral pathogenesis.

  7. Establishment of a Novel Primary Human Skeletal Myoblast Cellular Model for Chikungunya Virus Infection and Pathogenesis

    PubMed Central

    Hussain, Khairunnisa’ Mohamed; Lee, Regina Ching Hua; Ng, Mary Mah-Lee; Chu, Justin Jang Hann

    2016-01-01

    Chikungunya virus (CHIKV) is a re-emerging arbovirus known to cause chronic myalgia and arthralgia and is now considered endemic in countries across Asia and Africa. The tissue tropism of CHIKV infection in humans remains, however, ill-defined. Due to the fact that myositis is commonly observed in most patients infected with CHIKV, we sought to develop a clinically relevant cellular model to better understand the pathogenesis of CHIKV infection. In this study, primary human skeletal muscle myoblasts (HSMM) were established as a novel human primary cell line that is highly permissive to CHIKV infection, with maximal amounts of infectious virions observed at 16 hours post infection. Genome-wide microarray profiling analyses were subsequently performed to identify and map genes that are differentially expressed upon CHIKV infection. Infection of HSMM cells with CHIKV resulted in altered expressions of host genes involved in skeletal- and muscular-associated disorders, innate immune responses, cellular growth and death, host metabolism and virus replication. Together, this study has shown the establishment of a clinically relevant primary human cell model that paves the way for the further analysis of host factors and their involvement in the various stages of CHIKV replication cycle and viral pathogenesis. PMID:26892458

  8. Correlation analysis on alpha attenuation and nasal skin temperature

    NASA Astrophysics Data System (ADS)

    Nozawa, Akio; Tacano, Munecazu

    2009-01-01

    Some serious accidents caused by declines in arousal level, such as traffic accidents and mechanical control mistakes, have become issues of social concern. The physiological index obtained by human body measurement is expected to offer a leading tool for evaluating arousal level as an objective indicator. In this study, declines in temporal arousal levels were evaluated by nasal skin temperature. As arousal level declines, sympathetic nervous activity is decreased and blood flow in peripheral vessels is increased. Since peripheral vessels exist just under the skin on the fingers and nose, the psychophysiological state can be judged from the displacement of skin temperature caused by changing blood flow volume. Declining arousal level is expected to be observable as a temperature rise in peripheral parts of the body. The objective of this experiment was to obtain assessment criteria for judging declines in arousal level by nasal skin temperature using the alpha attenuation coefficient (AAC) of electroencephalography (EEG) as a reference benchmark. Furthermore, a psychophysical index of sleepiness was also measured using a visual analogue scale (VAS). Correlations between nasal skin temperature index and EEG index were analyzed. AAC and maximum displacement of nasal skin temperature displayed a clear negative correlation, with a correlation coefficient of -0.55.

  9. Nasal reconstruction using porous polyethylene implants.

    PubMed

    Romo, T; Sclafani, A P; Jacono, A A

    2000-01-01

    Nasal reconstruction presents a significant challenge to the facial plastic surgeon. The dual goals of reconstruction are restoration of the desired aesthetic nasal contour and an improved nasal airway. Autologous cartilage and bone are considered optimal grafting material, but their supply is often limited and harvesting entails additional morbidity. Many synthetic materials have been introduced in nasal reconstruction, but high infection and extrusion rates limited their use. Porous high density polyethylene implants present an alternative to autologous material as they allow for fibrovascular ingrowth, leading to stability of the implant and decreased rates of infection. Herein we describe the use of porous high density polyethylene implants for reconstruction of the platyrrhine nose and in revision rhinoplasty. The use of preformed nasal-dorsal tip and alar batten implants are described, as well as the use of columellar strut and premaxillary plumper implants. We believe that porous high density polyethylene implants provide a safe, desirable alternative in functional and aesthetic nasal reconstruction.

  10. Post Septorhinoplasty Custom-Made Unilateral Nasal Stent for Nasal Cleft Deformity

    PubMed Central

    Rathee, Manu; Bhoria, Mohaneesh; Boora, Priyanka

    2015-01-01

    Context: Nasal cleft deformity is a complicated problem. Utilization of nasal stent in post septorhinoplastyaims at establishing and maintaining airway patency, tissue position, and reduces tissue contracture after surgery. Case Report: A 16-year-old female patient presented with history of surgical reconstruction of congenital cleft lip and cleft palate with secondary septorhinoplasty of nasal cleft deformity. Patient was referred for nasal stent 1 week after septorhinoplasty. This case report provides a novel technique for fabrication of esthetic nasal stent after postseptorhinoplasty for secondary cleft nose deformity correction. Conclusion: This case report presents a simple, convenient technique for nasal stent fabrication for prevention of restenosis for cleft nose deformity post secondary septorhinoplasty. Provision of nasal stent allows breathing, maintains esthetics, comfort, nasal patency, and contour with minimal discomfort. PMID:25789253

  11. Simvastatin impairs ADP-stimulated respiration and increases mitochondrial oxidative stress in primary human skeletal myotubes.

    PubMed

    Kwak, Hyo-Bum; Thalacker-Mercer, Anna; Anderson, Ethan J; Lin, Chien-Te; Kane, Daniel A; Lee, Nam-Sihk; Cortright, Ronald N; Bamman, Marcas M; Neufer, P Darrell

    2012-01-01

    Statins, the widely prescribed cholesterol-lowering drugs for the treatment of cardiovascular disease, cause adverse skeletal muscle side effects ranging from fatigue to fatal rhabdomyolysis. The purpose of this study was to determine the effects of simvastatin on mitochondrial respiration, oxidative stress, and cell death in differentiated primary human skeletal muscle cells (i.e., myotubes). Simvastatin induced a dose-dependent decrease in viability of proliferating and differentiating primary human muscle precursor cells, and a similar dose-dependent effect was noted in differentiated myoblasts and myotubes. Additionally, there were decreases in myotube number and size following 48 h of simvastatin treatment (5 μM). In permeabilized myotubes, maximal ADP-stimulated oxygen consumption, supported by palmitoylcarnitine+malate (PCM, complex I and II substrates) and glutamate+malate (GM, complex I substrates), was 32-37% lower (P<0.05) in simvastatin-treated (5 μM) vs control myotubes, providing evidence of impaired respiration at complex I. Mitochondrial superoxide and hydrogen peroxide generation were significantly greater in the simvastatin-treated human skeletal myotube cultures compared to control. In addition, simvastatin markedly increased protein levels of Bax (proapoptotic, +53%) and Bcl-2 (antiapoptotic, +100%, P<0.05), mitochondrial PTP opening (+44%, P<0.05), and TUNEL-positive nuclei in human skeletal myotubes, demonstrating up-regulation of mitochondrial-mediated myonuclear apoptotic mechanisms. These data demonstrate that simvastatin induces myotube atrophy and cell loss associated with impaired ADP-stimulated maximal mitochondrial respiratory capacity, mitochondrial oxidative stress, and apoptosis in primary human skeletal myotubes, suggesting that mitochondrial dysfunction may underlie human statin-induced myopathy.

  12. Phosphatase inhibitor 2 promotes acetylation of tubulin in the primary cilium of human retinal epithelial cells

    PubMed Central

    Wang, Weiping; Brautigan, David L

    2008-01-01

    Background Primary cilia are flagella-like projections from the centriole of mammalian cells that have a key role in cell signaling. Human diseases are linked to defects in primary cilia. Microtubules make up the axoneme of cilia and are selectively acetylated and this is thought to contribute to the stability of the structure. However, mechanisms to regulate tubulin acetylation in cilia are poorly understood. Results Endogenous phosphatase inhibitor-2 (I-2) was found concentrated in cilia of human epithelial cells, and was localized to cilia early in the process of formation, prior to the full acetylation of microtubules. Knockdown of I-2 by siRNA significantly reduced the acetylation of microtubules in cilia, without a net decrease in whole cell tubulin acetylation. There was a reduction in the percentage of I-2 knockdown cells with a primary cilium, but no apparent alteration in the cilium length, suggesting no change in microtubule-based transport processes. Inhibition of either histone deacetylases with trichostatin A, or protein phosphatase-1 with calyculin A in I-2 knockdown cells partially rescued the acetylation of microtubules in cilia and the percentage of cells with a primary cilium. Conclusion The regulatory protein I-2 localizes to the primary cilium where it affects both Ser/Thr phosphorylation and is required for full tubulin acetylation. Rescue of tubulin acetylation in I-2 knockdown cells by different chemical inhibitors shows that deacetylases and phosphatases are functionally interconnected to regulate microtubules. As a multifunctional protein, I-2 may link cell cycle progression to structure and stability of the primary cilium. PMID:19036150

  13. 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.

  14. Human antibodies against dengue enhance dengue viral infectivity without suppressing type I interferon secretion in primary human monocytes.

    PubMed

    Kou, Zhihua; Lim, Joanne Y H; Beltramello, Martina; Quinn, Matthew; Chen, Huiyuan; Liu, Shengyong; Liu, Shengyo-ng; Martinez-Sobrido, Luis; Martnez-Sobrido, Luis; Diamond, Michael S; Schlesinger, Jacob J; de Silva, Aravinda; Sallusto, Federica; Jin, Xia

    2011-02-05

    It remains unclear whether antibody-dependent-enhancement (ADE) of dengue infection merely augments viral attachment and entry through Fcγ receptors or immune complex binding to Fcγ receptors triggers an intrinsic signaling cascade that changes the viral permissiveness of the cell. Using human dengue-immune sera and novel human monoclonal antibodies against dengue in combination with virologic and immunologic techniques, we found that ADE infection increased the proportion of infected primary human monocytes modestly from 0.2% ± 0.1% (no Ab) to 1.7% ± 1.6% (with Ab) but the total virus output markedly from 2 ± 2 (× 10(3)) FFU to 120 ± 153 (× 10(3))FFU. However, this increased virus production was not associated with a reduced secretion of type I interferon or an elevated secretion of anti-inflammatory cytokine, IL-10. These results demonstrate that the regulation of virus production in ADE infection of primary human monocytes is more complex than previously appreciated.

  15. Cell-to-Cell Contact and Nectin-4 Govern Spread of Measles Virus from Primary Human Myeloid Cells to Primary Human Airway Epithelial Cells

    PubMed Central

    Singh, Brajesh K.; Li, Ni; Mark, Anna C.; Mateo, Mathieu; Cattaneo, Roberto

    2016-01-01

    ABSTRACT Measles is a highly contagious, acute viral illness. Immune cells within the airways are likely first targets of infection, and these cells traffic measles virus (MeV) to lymph nodes for amplification and subsequent systemic dissemination. Infected immune cells are thought to return MeV to the airways; however, the mechanisms responsible for virus transfer to pulmonary epithelial cells are poorly understood. To investigate this process, we collected blood from human donors and generated primary myeloid cells, specifically, monocyte-derived macrophages (MDMs) and dendritic cells (DCs). MDMs and DCs were infected with MeV and then applied to primary cultures of well-differentiated airway epithelial cells from human donors (HAE). Consistent with previous results obtained with free virus, infected MDMs or DCs were incapable of transferring MeV to HAE when applied to the apical surface. Likewise, infected MDMs or DCs applied to the basolateral surface of HAE grown on small-pore (0.4-μm) support membranes did not transfer virus. In contrast, infected MDMs and DCs applied to the basolateral surface of HAE grown on large-pore (3.0-μm) membranes successfully transferred MeV. Confocal microscopy demonstrated that MDMs and DCs are capable of penetrating large-pore membranes but not small-pore membranes. Further, by using a nectin-4 blocking antibody or recombinant MeV unable to enter cells through nectin-4, we demonstrated formally that transfer from immune cells to HAE occurs in a nectin-4-dependent manner. Thus, both infected MDMs and DCs rely on cell-to-cell contacts and nectin-4 to efficiently deliver MeV to the basolateral surface of HAE. IMPORTANCE Measles virus spreads rapidly and efficiently in human airway epithelial cells. This rapid spread is based on cell-to-cell contact rather than on particle release and reentry. Here we posit that MeV transfer from infected immune cells to epithelial cells also occurs by cell-to-cell contact rather than through cell

  16. RNA interference mediated in human primary cells via recombinant baculoviral vectors.

    PubMed

    Nicholson, Linda J; Philippe, Marie; Paine, Alan J; Mann, Derek A; Dolphin, Colin T

    2005-04-01

    The success of RNA interference (RNAi) in mammalian cells, mediated by siRNAs or shRNA-generating plasmids, is dependent, to an extent, upon transfection efficiency. This is a particular problem with primary cells, which are often difficult to transfect using cationic lipid vehicles. Effective RNAi in primary cells is thus best achieved with viral vectors, and retro-, adeno-, and lentivirus RNAi systems have been described. However, the use of such human viral vectors is inherently problematic, e.g., Class 2 status and requirement of secondary helper functions. Although insect cells are their natural host, baculoviruses also transduce a range of vertebrate cell lines and primary cells with high efficiency. The inability of baculoviral vectors to replicate in mammalian cells, their Class 1 status, and the simplicity of their construction make baculovirus an attractive alternative gene delivery vector. We have developed a baculoviral-based RNAi system designed to express shRNAs and GFP from U6 and CMV promoters, respectively. Transduction of Saos2, HepG2, Huh7, and primary human hepatic stellate cells with a baculoviral construct expressing shRNAs targeting lamin A/C resulted in effective knockdown of the corresponding mRNA and protein. Development of this baculoviral-based system provides an additional shRNA delivery option for RNAi-based investigations in mammalian cells.

  17. Effect of Human and Sheep Lung Orientation on Primary Blast Injury Induced by Single Blast

    DTIC Science & Technology

    2010-09-01

    kPa 200 500 700 Positive phase duration, ms 2 2 2 From the wo rk do ne by O ’ Brien et al. an d Coop er et al. [ Refs. 5, 6], pressure w...Effect of human and sheep lung orientation on primary blast injury induced by single blast A. Bouamoul, K. Williams DRDC Valcartier, 2459 Pie...main goal o f this stud y is to verify if the injuries observed in the animal are trul y representative of human lung injuries for simple blast

  18. Reconstruction of Small Soft Tissue Nasal Defects

    PubMed Central

    Wolfswinkel, Erik M.; Weathers, William M.; Cheng, David; Thornton, James F.

    2013-01-01

    Nasal defect repair has been one of the more challenging areas of reconstructive surgery due to the lack of uniform nasal skin thickness and complex contours. Currently, algorithms for medium to large nasal soft tissue defects have been well defined by various authors. Small defects, arbitrarily defined as 1 cm or less, still present significant challenges. In this article, the authors examine the options available to repair small soft tissue nasal defects and the appropriate situations in which each method is best suited. PMID:24872751

  19. Perception of Better Nasal Patency Correlates with Increased Mucosal Cooling after Surgery for Nasal Obstruction

    NASA Astrophysics Data System (ADS)

    Garcia, Guilherme; Sullivan, Corbin; Frank-Ito, Dennis; Kimbell, Julia; Rhee, John

    2014-11-01

    Nasal airway obstruction (NAO) is a common health problem with 340,000 patients undergoing surgery annually in the United States. Traditionally, otolaryngologists have focused on airspace cross-sectional areas and nasal resistance to airflow as objective measures of nasal patency, but neither of these variables correlated consistently with patients' symptoms. Given that the sensation of nasal airflow is also associated with mucosal cooling (i.e., heat loss) during inspiration, we investigated the correlation between the sensation of nasal obstruction and mucosal cooling in 10 patients before and after NAO surgery. Three-dimensional models of the nasal anatomy were created based on pre- and post-surgery computed tomography scans. Computational fluid dynamics (CFD) simulations were conducted to quantify nasal resistance and mucosal cooling. Patient-reported symptoms were measured by a visual analog scale and the Nasal Obstruction Symptom Evaluation (NOSE), a disease-specific quality of life questionnaire. Our results revealed that the subjective sensation of nasal obstruction correlated with both nasal resistance and heat loss, but the strongest correlation was between the NOSE score and the nasal surface area where heat flux exceeds 50 W /m2 . In conclusion, a significant post-operative increase in mucosal cooling correlates well with patients' perception of better nasal patency after NAO surgery.

  20. Clinical Practice Guideline: Improving Nasal Form and Function after Rhinoplasty.

    PubMed

    Ishii, Lisa E; Tollefson, Travis T; Basura, Gregory J; Rosenfeld, Richard M; Abramson, Peter J; Chaiet, Scott R; Davis, Kara S; Doghramji, Karl; Farrior, Edward H; Finestone, Sandra A; Ishman, Stacey L; Murphy, Robert X; Park, John G; Setzen, Michael; Strike, Deborah J; Walsh, Sandra A; Warner, Jeremy P; Nnacheta, Lorraine C

    2017-02-01

    Objective Rhinoplasty, a surgical procedure that alters the shape or appearance of the nose while preserving or enhancing the nasal airway, ranks among the most commonly performed cosmetic procedures in the United States, with >200,000 procedures reported in 2014. While it is difficult to calculate the exact economic burden incurred by rhinoplasty patients following surgery with or without complications, the average rhinoplasty procedure typically exceeds $4000. The costs incurred due to complications, infections, or revision surgery may include the cost of long-term antibiotics, hospitalization, or lost revenue from hours/days of missed work. The resultant psychological impact of rhinoplasty can also be significant. Furthermore, the health care burden from psychological pressures of nasal deformities/aesthetic shortcomings, surgical infections, surgical pain, side effects from antibiotics, and nasal packing materials must also be considered for these patients. Prior to this guideline, limited literature existed on standard care considerations for pre- and postsurgical management and for standard surgical practice to ensure optimal outcomes for patients undergoing rhinoplasty. The impetus for this guideline is to utilize current evidence-based medicine practices and data to build unanimity regarding the peri- and postoperative strategies to maximize patient safety and to optimize surgical results for patients. Purpose The primary purpose of this guideline is to provide evidence-based recommendations for clinicians who either perform rhinoplasty or are involved in the care of a rhinoplasty candidate, as well as to optimize patient care, promote effective diagnosis and therapy, and reduce harmful or unnecessary variations in care. The target audience is any clinician or individual, in any setting, involved in the management of these patients. The target patient population is all patients aged ≥15 years. The guideline is intended to focus on knowledge gaps, practice

  1. 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.

  2. 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.

  3. Sclerosing cholangitis in baboons (Papio spp) resembling primary sclerosing cholangitis of humans.

    PubMed

    Arenas-Gamboa, A M; Bearss, J J; Hubbard, G B; Porter, B F; Owston, M A; Dick, E J

    2012-05-01

    Primary sclerosing cholangitis is a chronic and progressive cholestatic liver disease that has been extensively documented in the human literature. Although it shares many features in common with chronic lymphocytic cholangitis in cats, primary sclerosing cholangitis has never been reported in a nonhuman primate. Primary sclerosing cholangitis is characterized by the presence of intrahepatic and/or extrahepatic inflammation and concentric fibrosis of bile ducts, eventually leading to cirrhosis and hepatic failure. The pathogenesis and cause remain unknown, but the disease likely involves a multifactorial mechanism with genetic- and immune-mediated components. The authors report 2 cases that histologically resemble the condition in humans; they consist of 2 adult male baboons with a clinical history of chronic elevated liver enzymes. In both cases, the liver was histologically characterized by thick bands of fibrosis and mild lymphoplasmacytic periportal cholangiohepatitis with concentric periductal fibrosis, resulting in atrophy and loss of bile ducts. Immunohistochemical analysis revealed positivity of hepatocytes to cytokeratin 7. Masson stain demonstrated marked biliary fibrosis. This is the first report that resembles sclerosing cholangitis in a nonhuman primate, and it suggests that the baboon may provide a useful animal model for this condition in humans.

  4. An expression atlas of human primary cells: inference of gene function from coexpression networks

    PubMed Central

    2013-01-01

    Background The specialisation of mammalian cells in time and space requires genes associated with specific pathways and functions to be co-ordinately expressed. Here we have combined a large number of publically available microarray datasets derived from human primary cells and analysed large correlation graphs of these data. Results Using the network analysis tool BioLayout Express3D we identify robust co-associations of genes expressed in a wide variety of cell lineages. We discuss the biological significance of a number of these associations, in particular the coexpression of key transcription factors with the genes that they are likely to control. Conclusions We consider the regulation of genes in human primary cells and specifically in the human mononuclear phagocyte system. Of particular note is the fact that these data do not support the identity of putative markers of antigen-presenting dendritic cells, nor classification of M1 and M2 activation states, a current subject of debate within immunological field. We have provided this data resource on the BioGPS web site (http://biogps.org/dataset/2429/primary-cell-atlas/) and on macrophages.com (http://www.macrophages.com/hu-cell-atlas). PMID:24053356

  5. Cigarette smoke extract reduces VEGF in primary human airway epithelial cells.

    PubMed

    Thaikoottathil, J V; Martin, R J; Zdunek, J; Weinberger, A; Rino, J G; Chu, H W

    2009-04-01

    Reduced vascular endothelial growth factor (VEGF) has been reported in bronchoalveolar lavage fluid and lungs of severe emphysema patients. Airway epithelial cells (AEC) are exposed to various environmental insults like cigarette smoke and bacterial infections, but their direct effect on VEGF production in well-differentiated primary human AEC remains unclear. The current authors determined the effect of cigarette smoke extract (CSE) alone and in combination with Mycoplasma pneumoniae (Mp) on VEGF production in well-differentiated primary normal human bronchial epithelial (NHBE) and small airway epithelial cells (SAEC) in air-liquid interface cultures. Secretion and expression of VEGF were determined by ELISA and real-time RT-PCR, respectively. Cell growth, apoptosis, extracellular signal-regulated kinase (ERK)1/2 and protein kinase (PK)C signalling pathways were evaluated to further dissect VEGF regulation under CSE treatment. CSE significantly reduced VEGF secretion in NHBE and SAEC. In SAEC, Mp alone significantly increased the VEGF, while the presence of CSE attenuated Mp-induced VEGF production. While ERK inhibitor reduced VEGF secretion only in NHBE, a PKC inhibitor significantly decreased VEGF secretion in both NHBE and SAEC. In conclusion, direct cigarette smoke extract exposure significantly reduced vascular endothelial growth factor production in well-differentiated primary human airway epithelial cells, in part through modifying extracellular signal-regulated kinase 1/2 and protein kinase C signalling pathways.

  6. 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.

  7. Desloratadine citrate disodium injection, a potent histamine H(1) receptor antagonist, inhibits chemokine production in ovalbumin-induced allergic rhinitis guinea pig model and histamine-induced human nasal epithelial cells via inhibiting the ERK1/2 and NF-kappa B signal cascades.

    PubMed

    Chen, Meiling; Xu, Shuhong; Zhou, Peipei; He, Guangwei; Jie, Qiong; Wu, Yulin

    2015-11-15

    Chemokines have chemotactic properties on leukocyte subsets whose modulation plays a pivotal role in allergic inflammatory processes. Our present study was designed to investigate the anti-allergic and anti-inflammatory properties of desloratadine citrate disodium injection (DLC) and elucidate the molecular mechanisms of its anti-inflammatory properties. The anti-allergic effects of DLC were evaluated based on allergic symptoms, serological marker production and histological changes of the nasal mucosa in guinea pigs model of allergic rhinitis. The anti-inflammatory properties and molecular mechanisms of DLC were explored by studying the regulation of a set of chemokines and extracellular signal-regulated kinase (ERK)1/2 and nuclear factor-kappa B (NF-κB) pathways, after DLC treatment in guinea pigs model of allergic rhinitis in vivo and histamine-activated human nasal epithelial cells (HNECs) in vitro. In vivo model in guinea pigs, DLC alleviated the rhinitis symptoms, inhibited inflammatory cells infiltration in nasal lavage fluid (NLF) and histamine, monocyte chemotactic protein (MCP)-1, regulated on activation normal T cell expressed, and presumably secreted (RANTEs) and interleukin (IL)-8 release in sera and P-ERK1/2 and NF-κB activation in nasal mucosa. In vitro, DLC markedly inhibited histamine-induced production of MCP-1, RANTEs and IL-8 and suppressed c-Raf, mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) and ERK1/2 activation in HNECs. These results provide evidence that DLC possesses potent anti-allergic and anti-inflammatory properties. The mechanism of action underlying DLC in allergic inflammation appears to be inhibition of the phosphorylation of ERK1/2, in addition to blocking of the NF-κB pathway.

  8. Histamine H3 receptor activation inhibits neurogenic sympathetic vasoconstriction in porcine nasal mucosa.

    PubMed

    Varty, LoriAnn M; Hey, John A

    2002-10-11

    Histamine release from mast cells is a primary mediator of rhinorrhea, nasal mucosal swelling, increased secretion, sneezing, pruritus and congestion that occur in allergic rhinitis. It is well known that histamine H(1) receptor antagonists inhibit the itch and rhinorhea, but do not block the allergic nasal congestion. A growing body of evidence shows that in addition to histamine H(1) receptors, activation of H(3) receptors may contribute to the procongestant nasal actions of histamine. Activation of the prejunctional histamine H(3) receptor modulates sympathetic control of nasal vascular tone and resistance. The present study was conducted to further characterize the role of histamine H(3) receptors on neurogenic sympathetic vascular contractile responses in isolated porcine nasal turbinate mucosa. We presently found that the histamine H(3) receptor agonist, (R)-alpha-methylhistamine (10-1000 nM), inhibited electrical field stimulation-induced sympathetic vasomotor contractions in a concentration-dependent fashion. Pretreatment with either of the selective histamine H(3) receptor antagonists, thioperamide and clobenpropit, blocked the sympathoinhibitory effect of (R)-alpha-methylhistamine in porcine turbinate mucosa. The effect of compound 48/80, an agent that elicits the release of endogenous histamine from mast cells on nasal sympathetic contractile responses, was also tested. The action of compound 48/80 to release mast cell-derived histamine in the nose mimics many of the nasal responses associated with allergic rhinitis, extravascular leakage and decreased nasal patency. We presently found that compound 48/80 also inhibited the electrical field stimulation-induced sympathetic response. Pretreatment with the H(3) receptor antagonist clobenpropit blocked the sympathoinhibitory action of compound 48/80 on sympathetic contractile responses in nasal mucosa. Taken together, these studies indicate that histamine H(3) receptors modulate vascular contractile

  9. Tumours of the nasal cavity*

    PubMed Central

    Stünzi, H.; Hauser, B.

    1976-01-01

    Tumours of the nasal cavity are rare in domestic animals, most cases occurring in the dog. Epithelial tumours are the most common type in carnivores (dogs and cats). In general, the same types of tumour occur in domestic animals as occur in man. There was no significant predisposition for breed in dogs, but in both dogs and cats far more males than females were affected. Metastases occurred only rarely. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 9Fig. 10Fig. 11Fig. 12Fig. 5Fig. 6Fig. 7Fig. 8 PMID:1086156

  10. Neurilemmoma of lateral nasal wall.

    PubMed

    Bharti, Jyotsna Naresh; Gautam, Parul; Arora, Prerna

    2015-01-01

    Neurilemmoma is a benign tumour of nerve sheath origin that can arise from myelinated nerve. The Head and neck is the most frequent site involved and other sites are scalp, face, oral cavity, pharynx, larynx, trachea and ear. Neurilemmoma usually occur as solitary lesions and in association with NF type 2. Malignant transformation is very rare. We report a case of 18 year old male presented with complaint of nasal obstruction and swelling in right side of nose. We discuss the clinical presentation, histologic features, and therapeutic options for such a rare benign lesion.

  11. Autophagy: a cyto-protective mechanism which prevents primary human hepatocyte apoptosis during oxidative stress.

    PubMed

    Bhogal, Ricky H; Weston, Christopher J; Curbishley, Stuart M; Adams, David H; Afford, Simon C

    2012-04-01

    The role of autophagy in the response of human hepatocytes to oxidative stress remains unknown. Understanding this process may have important implications for the understanding of basic liver epithelial cell biology and the responses of hepatocytes during liver disease. To address this we isolated primary hepatocytes from human liver tissue and exposed them ex vivo to hypoxia and hypoxia-reoxygenation (H-R). We showed that oxidative stress increased hepatocyte autophagy in a reactive oxygen species (ROS) and class III PtdIns3K-dependent manner. Specifically, mitochondrial ROS and NADPH oxidase were found to be key regulators of autophagy. Autophagy involved the upregulation of BECN1, LC3A, Atg7, Atg5 and Atg 12 during hypoxia and H-R. Autophagy was seen to occur within the mitochondria of the hepatocyte and inhibition of autophagy resulted in the lowering a mitochondrial membrane potential and onset of cell death. Autophagic responses were primarily observed in the large peri-venular (PV) hepatocyte subpopulation. Inhibition of autophagy, using 3-methyladenine, increased apoptosis during H-R. Specifically, PV human hepatocytes were more susceptible to apoptosis after inhibition of autophagy. These findings show for the first time that during oxidative stress autophagy serves as a cell survival mechanism for primary human hepatocytes.

  12. Differentiation of primary human submandibular gland cells cultured on basement membrane extract.

    PubMed

    Szlávik, Vanda; Szabó, Bálint; Vicsek, Tamás; Barabás, József; Bogdán, Sándor; Gresz, Veronika; Varga, Gábor; O'Connell, Brian; Vág, János

    2008-11-01

    There is no effective treatment for the loss of functional salivary tissue after irradiation for head and neck cancer or the autoimmune disease Sjögren's syndrome. One possible approach is the regeneration of salivary glands from stem cells. The present study aimed to investigate whether small pieces of human submandiblar gland tissue contain elements necessary for the reconstruction of salivary rudiments in vitro via acinar and ductal cell differentiation. Primary submandibular gland (primary total human salivary gland; PTHSG) cells were isolated from human tissue and cultured in vitro using a new method in which single cells form an expanding epithelial monolayer on plastic substrates. Differentiation, morphology, number, and organization of these cells were then followed on basement membrane extract (BME) using RNA quantitation (amylase, claudin-1 (CLN1), CLN3, kallikrein, vimentin), immunohistochemistry (amylase and occludin), viability assay, and videomicroscopy. On the surface of BME, PTHSG cells formed acinotubular structures within 24 h, did not proliferate, and stained for amylase. In cultures derived from half of the donors, the acinar markers amylase and CLN3 were upregulated. The PTHSG culture model suggests that human salivary gland may be capable of regeneration via reorganization and differentiation and that basement membrane components play a crucial role in the morphological and functional differentiation of salivary cells.

  13. 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.

  14. Partial primary structure of human pregnancy zone protein: extensive sequence homology with human alpha 2-macroglobulin.

    PubMed Central

    Sottrup-Jensen, L; Folkersen, J; Kristensen, T; Tack, B F

    1984-01-01

    Human pregnancy zone protein (PZP) is a major pregnancy-associated protein. Its quaternary structure (two covalently bound 180-kDa subunits, which are further non-covalently assembled into a tetramer of 720 kDa) is similar to that of human alpha 2-macroglobulin (alpha 2M). Here we show, from the results of complete or partial sequence determination of a random selection of 38 tryptic peptides covering 685 residues of the subunit of PZP, that PZP and alpha 2M indeed are extensively homologous. In the stretches of PZP sequenced so far, the degree of identically placed residues in the two proteins is 68%, indicating a close evolutionary relationship between PZP and alpha 2M. Although the function of PZP in pregnancy is largely unknown, its close structural relationship to alpha 2M suggests analogous proteinase binding properties and a potential for being taken up in cells by receptor-mediated endocytosis. In this regard our studies indicate a bait region in PZP significantly different from that present in alpha 2M. PZP could be the human equivalent of the acute-phase alpha-macroglobulins (e.g., rat alpha 2M and rabbit alpha 1M) described earlier. PMID:6209714

  15. 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

  16. Gibbon ape leukemia virus poorly replicates in primary human T lymphocytes: implications for safety testing of primary human T lymphocytes transduced with GALV-pseudotyped vectors.

    PubMed

    Lamers, Cor H J; Willemsen, Ralph A; van Elzakker, Pascal M M L; Gratama, Jan Willem; Debets, Reno

    2009-04-01

    The Food and Drug Administration/Center for Biologics Evaluation and Research has defined that for retroviral gene therapy, the vector-producing cell, the vector preparation, and the ex vivo gene-transduced cells have to be tested for absence of replication-competent retrovirus (RCR) if the transduced cells are cultured for >4 days. We assessed the sensitivity of the "extended PG4(S+L-) assay" to detect gibbon ape leukemia virus (GALV) RCR, and applied this assay to measure GALV RCR spread in retrovirally transduced T cells. To this end, T cells were expanded for 12 days after transduction with a GALV-envelope pseudotyped retroviral vector expressing single chain variable fragment (anticarbonic anhydrase IX) in presence or absence of GALV RCR. Results showed that: (1) the "extended PG4(S+L-) assay" detects 1 focus-forming unit (ffu) GALV RCR and thus is applicable and sufficiently sensitive to screen human T-cell cultures for absence of infectious GALV RCR; (2) although GALV RCR infect human T cells, it very poorly replicate in T cells; (3) GALV RCR, when present at low levels immediately upon gene transduction (ie, 100 ffu/20x10 T cells in 100 mL), did not spread during a 12-day T-cell culture at clinical scale. Our observation that GALV RCR poorly spreads in primary human T-cell cultures questions the relevance of testing T-cell transductants for RCR on top of testing the vector-producing cells and the clinical vector batch for RCR and warrants evaluation of the current policy for safety testing of ex vivo retrovirally transduced T lymphocytes for GALV RCR.

  17. 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.

  18. Astrocytes As the Main Players in Primary Degenerative Disorders of the Human Central Nervous System

    PubMed Central

    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

  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.

  20. Biokinetics of chlorpromazine in primary rat and human hepatocytes and human HepaRG cells after repeated exposure.

    PubMed

    Broeders, Jessica J W; Parmentier, Céline; Truisi, Germaine L; Jossé, Rozenn; Alexandre, Eliane; Savary, Camille C; Hewitt, Philip G; Mueller, Stefan O; Guillouzo, André; Richert, Lysiane; van Eijkeren, Jan C H; Hermens, Joop L M; Blaauboer, Bas J

    2015-12-25

    Since drug induced liver injury is difficult to predict in animal models, more representative tests are needed to better evaluate these effects in humans. Existing in vitro systems hold great potential to detect hepatotoxicity of pharmaceuticals. In this study, the in vitro biokinetics of the model hepatotoxicant chlorpromazine (CPZ) were evaluated in three different liver cell systems after repeated exposure in order to incorporate repeated-dose testing into an in vitro assay. Primary rat and human hepatocytes, cultured in sandwich configuration and the human HepaRG cell line were treated daily with CPZ for 14 days. Samples were taken from medium, cells and well plastic at specific time points after the first and last exposure. The samples were analysed by HPLC-UV to determine the amount of CPZ in these samples. Based on cytotoxicity assays, the three models were tested at 1-2 μM CPZ, while the primary rat hepatocytes and the HepaRG cell line were in addition exposed to a higher concentration of 15-20 μM. Overall, the mass balance of CPZ decreased in the course of 24 h, indicating the metabolism of the compound within the cells. The largest decrease in parent compound was seen in the primary cultures; in the HepaRG cell cultures the mass balance only decreased to 50%. CPZ accumulated in the cells during the 14-day repeated exposure. Possible explanations for the accumulation of CPZ are a decrease in metabolism over time, inhibition of efflux transporters or binding to phospholipids. The biokinetics of CPZ differed between the three liver cell models and were influenced by specific cell properties as well as culture conditions. These results support the conclusion that in vitro biokinetics data are necessary to better interpret chemical-induced cytotoxicity data.

  1. Bortezomib sensitizes primary human esthesioneuroblastoma cells to TRAIL-induced apoptosis.

    PubMed

    Koschny, Ronald; Holland, Heidrun; Sykora, Jaromir; Erdal, Hande; Krupp, Wolfgang; Bauer, Manfred; Bockmuehl, Ulrike; Ahnert, Peter; Meixensberger, Jürgen; Stremmel, Wolfgang; Walczak, Henning; Ganten, Tom M

    2010-04-01

    TNF-related apoptosis-inducing ligand (TRAIL), a promising novel anti-cancer cytokine of the TNF superfamily, and Bortezomib, the first-in-class clinically used proteasome inhibitor, alone or in combination have been shown to efficiently kill numerous tumor cell lines. However, data concerning primary human tumor cells are very rare. Using primary esthesioneuroblastoma cells we analyzed the anti-tumor potential and the mechanism employed by Bortezomib in combination with TRAIL for the treatment of this rare but aggressive tumor. Expression of components of the TRAIL pathway was analyzed in tumor specimens and isolated primary tumor cells at the protein level. Cells were treated with TRAIL, Bortezomib, and a combination thereof, and apoptosis induction was quantified. Clonogenicity assays were performed to elucidate the long-term effect of this treatment. Despite expressing all components of the TRAIL pathway, freshly isolated primary esthesioneuroblastoma cells were completely resistant to TRAIL-induced apoptosis. They could, however, be very efficiently sensitized by subtoxic doses of Bortezomib. The influence of Bortezomib on the TRAIL pathway was analyzed and showed upregulation of TRAIL death receptor expression, enhancement of the TRAIL death-inducing signaling complex (DISC), and downregulation of anti-apoptotic proteins of the TRAIL pathway. Of clinical relevance, TRAIL-resistant primary tumor cells could be repeatedly sensitized by Bortezomib, providing the basis for repeated clinical application schedules. This is the first report on the highly synergistic induction of apoptosis in primary esthesioneuroblastoma cells by Bortezomib and TRAIL. This combination, therefore, represents a promising novel therapeutic option for esthesioneuroblastoma.

  2. 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.

  3. 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

  4. Global human appropriation of net primary production doubled in the 20th century.

    PubMed

    Krausmann, Fridolin; Erb, Karl-Heinz; Gingrich, Simone; Haberl, Helmut; Bondeau, Alberte; Gaube, Veronika; Lauk, Christian; Plutzar, Christoph; Searchinger, Timothy D

    2013-06-18

    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.

  5. Generation of knock-in primary human T cells using Cas9 ribonucleoproteins

    DOE PAGES

    Schumann, Kathrin; Lin, Steven; Boyer, Eric; ...

    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

  6. 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.

  7. Generation of knock-in primary human T cells using Cas9 ribonucleoproteins

    PubMed Central

    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

    2015-01-01

    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. PMID:26216948

  8. Changes in nasal airflow and heat transfer correlate with symptom improvement after surgery for nasal obstruction.

    PubMed

    Kimbell, J S; Frank, D O; Laud, Purushottam; Garcia, G J M; Rhee, J S

    2013-10-18

    Surgeries to correct nasal airway obstruction (NAO) often have less than desirable outcomes, partly due to the absence of an objective tool to select the most appropriate surgical approach for each patient. Computational fluid dynamics (CFD) models can be used to investigate nasal airflow, but variables need to be identified that can detect surgical changes and correlate with patient symptoms. CFD models were constructed from pre- and post-surgery computed tomography scans for 10 NAO patients showing no evidence of nasal cycling. Steady-state inspiratory airflow, nasal resistance, wall shear stress, and heat flux were computed for the main nasal cavity from nostrils to posterior nasal septum both bilaterally and unilaterally. Paired t-tests indicated that all CFD variables were significantly changed by surgery when calculated on the most obstructed side, and that airflow, nasal resistance, and heat flux were significantly changed bilaterally as well. Moderate linear correlations with patient-reported symptoms were found for airflow, heat flux, unilateral allocation of airflow, and unilateral nasal resistance as a fraction of bilateral nasal resistance when calculated on the most obstructed nasal side, suggesting that these variables may be useful for evaluating the efficacy of nasal surgery objectively. Similarity in the strengths of these correlations suggests that patient-reported symptoms may represent a constellation of effects and that these variables should be tracked concurrently during future virtual surgery planning.

  9. Nasal allergen challenge and mediators release.

    PubMed

    Carlos, A G; Carlos, M L; Ferreira, M B; Santos, A S; Santos, M C; Pedro, E

    1997-11-01

    Nasal allergen challenges, despite not reproducing exactly natural allergen exposure, are a very useful method to understand the complex cellular kinetics and cellular interactions that occur in allergic rhinitis. Cell-specific soluble mediator measurements can give useful diagnostic information. In this paper we present data concerning eosinophil cationic protein (ECP) and tryptase measurements after nasal allergen challenge.

  10. Transnasal microsurgical ethmoidectomy in nasal polyposis.

    PubMed

    Bagatella, F; Mazzoni, A

    1980-03-01

    A technique of microsurgical ethmoidectomy by a nasal route was devised for and applied to the treatment of nasal polyposis. A description of the operative procedure and the results in 30 cases with a 3-5 years of follow-up are reported.

  11. Color and surface temperature variation during bleaching in human devitalized primary teeth: an in vitro study.

    PubMed

    Gontijo, Isa T; Navarro, Ricardo S; Ciamponi, Ana Lídia; Miyakawa, Walter; Zezell, Denise Maria

    2008-01-01

    This study's purpose was to make an in vitro assessment of 2 whitening techniques in primary teeth, regarding color and temperature surface variation, during dental bleaching using different catalytic sources. Twenty-one extracted human upper central deciduous incisors were used in this in vitro study. The teeth were darkened with human blood for a period of 21 days. After preparing the teeth, they were randomly distributed into 2 groups, according to bleaching source of activation: (1) a diode laser (DL) group; and (2) a halogen lamp (HL) group. The bleaching process was performed, according to the manufacturer's guidelines, using Whiteness HP (FGM, Joinville, Brazil). The color was assessed by spectrophotometer (CIELab) and the VITA scale (3M) before and immediately after tooth whitening. The temperature increase in the radicular surface during the bleaching was registered with a thermographic camera ThermaCAM SC 3000 (Flir Systems, Danderyd, Sweden) at the Nuclear and Energy Research Institute, IPEN-CNEN (São Paulo, Brazil). There was no significant difference between the groups in terms of color changes, but there was a statistically significant difference for temperature variation. The use of a diode laser and halogen lamp both promoted whitening in devitalized primary teeth in vitro. As a catalytic source of energy, the diode laser--with the applied parameters--promoted a smaller temperature increase compared to the halogen lamp during the bleaching procedure on nonvital primary teeth.

  12. Primary outgrowth cultures are a reliable source of human pancreatic stellate cells.

    PubMed

    Han, Song; Delitto, Daniel; Zhang, Dongyu; Sorenson, Heather L; Sarosi, George A; Thomas, Ryan M; Behrns, Kevin E; Wallet, Shannon M; Trevino, Jose G; Hughes, Steven J

    2015-11-01

    Recent advances demonstrate a critical yet poorly understood role for the pancreatic stellate cell (PSC) in the pathogenesis of chronic pancreatitis (CP) and pancreatic cancer (PC). Progress in this area has been hampered by the availability, fidelity, and/or reliability of in vitro models of PSCs. We examined whether outgrowth cultures from human surgical specimens exhibited reproducible phenotypic and functional characteristics of PSCs. PSCs were cultured from surgical specimens of healthy pancreas, CP and PC. Growth dynamics, phenotypic characteristics, soluble mediator secretion profiles and co-culture with PC cells both in vitro and in vivo were assessed. Forty-seven primary cultures were established from 52 attempts, demonstrating universal α-smooth muscle actin and glial fibrillary acidic protein but negligible epithelial surface antigen expression. Modification of culture conditions consistently led to cytoplasmic lipid accumulation, suggesting induction of a quiescent phenotype. Secretion of growth factors, chemokines and cytokines did not significantly differ between donor pathologies, but did evolve over time in culture. Co-culture of PSCs with established PC cell lines resulted in significant changes in levels of multiple secreted mediators. Primary PSCs co-inoculated with PC cells in a xenograft model led to augmented tumor growth and metastasis. Therefore, regardless of donor pathology, outgrowth cultures produce PSCs that demonstrate consistent growth and protein secretion properties. Primary cultures from pancreatic surgical specimens, including malignancies, may represent a reliable source of human PSCs.

  13. Tuning in to sound: frequency-selective attentional filter in human primary auditory cortex.

    PubMed

    Da Costa, Sandra; van der Zwaag, Wietske; Miller, Lee M; Clarke, Stephanie; Saenz, Melissa

    2013-01-30

    Cocktail parties, busy streets, and other noisy environments pose a difficult challenge to the auditory system: how to focus attention on selected sounds while ignoring others? Neurons of primary auditory cortex, many of which are sharply tuned to sound frequency, could help solve this problem by filtering selected sound information based on frequency-content. To investigate whether this occurs, we used high-resolution fMRI at 7 tesla to map the fine-scale frequency-tuning (1.5 mm isotropic resolution) of primary auditory areas A1 and R in six human participants. Then, in a selective attention experiment, participants heard low (250 Hz)- and high (4000 Hz)-frequency streams of tones presented at the same time (dual-stream) and were instructed to focus attention onto one stream versus the other, switching back and forth every 30 s. Attention to low-frequency tones enhanced neural responses within low-frequency-tuned voxels relative to high, and when attention switched the pattern quickly reversed. Thus, like a radio, human primary auditory cortex is able to tune into attended frequency channels and can switch channels on demand.

  14. Primary Human Placental Trophoblasts are Permissive for Zika Virus (ZIKV) Replication

    PubMed Central

    Aagaard, Kjersti M.; Lahon, Anismrita; Suter, Melissa A.; Arya, Ravi P.; Seferovic, Maxim D.; Vogt, Megan B.; Hu, Min; Stossi, Fabio; Mancini, Michael A.; Harris, R. Alan; Kahr, Maike; Eppes, Catherine; Rac, Martha; Belfort, Michael A.; Park, Chun Shik; Lacorazza, Daniel; Rico-Hesse, Rebecca

    2017-01-01

    Zika virus (ZIKV) is an emerging mosquito-borne (Aedes genus) arbovirus of the Flaviviridae family. Although ZIKV has been predominately associated with a mild or asymptomatic dengue-like disease, its appearance in the Americas has been accompanied by a multi-fold increase in reported incidence of fetal microcephaly and brain malformations. The source and mode of vertical transmission from mother to fetus is presumptively transplacental, although a causal link explaining the interval delay between maternal symptoms and observed fetal malformations following infection has been missing. In this study, we show that primary human placental trophoblasts from non-exposed donors (n = 20) can be infected by primary passage ZIKV-FLR isolate, and uniquely allowed for ZIKV viral RNA replication when compared to dengue virus (DENV). Consistent with their being permissive for ZIKV infection, primary trophoblasts expressed multiple putative ZIKV cell entry receptors, and cellular function and differentiation were preserved. These findings suggest that ZIKV-FLR strain can replicate in human placental trophoblasts without host cell destruction, thereby serving as a likely permissive reservoir and portal of fetal transmission with risk of latent microcephaly and malformations. PMID:28128342

  15. Primary Cilia Negatively Regulate Melanogenesis in Melanocytes and Pigmentation in a Human Skin Model

    PubMed Central

    Kim, Eun Sung; Park, So Jung; Bae, Il-Hong; Jo, Yoon Kyung; Jeong, In Young; Kim, Hyoung-June; Lee, Youngjin; Park, Hea Chul; Jeon, Hong Bae; Kim, Ki Woo; Lee, Tae Ryong; Cho, Dong-Hyung

    2016-01-01

    The primary cilium is an organelle protruding from the cell body that senses external stimuli including chemical, mechanical, light, osmotic, fluid flow, and gravitational signals. Skin is always exposed to the external environment and responds to external stimuli. Therefore, it is possible that primary cilia have an important role in skin. Ciliogenesis was reported to be involved in developmental processes in skin, such as keratinocyte differentiation and hair formation. However, the relation between skin pigmentation and primary cilia is largely unknown. Here, we observed that increased melanogenesis in melanocytes treated with a melanogenic inducer was inhibited by a ciliogenesis inducer, cytochalasin D, and serum-free culture. However, these inhibitory effects disappeared in GLI2 knockdown cells. In addition, activation of sonic hedgehog (SHH)-smoothened (Smo) signaling pathway by a Smo agonist, SAG inhibited melanin synthesis in melanocytes and pigmentation in a human skin model. On the contrary, an inhibitor of primary cilium formation, ciliobrevin A1, activated melanogenesis in melanocytes. These results suggest that skin pigmentation may be regulated partly by the induction of ciliogenesis through Smo-GLI2 signaling. PMID:27941997

  16. Squamous cell carcinoma with sarcomatous stroma in the nasal cavity of a dog.

    PubMed

    Bosward, K L; Kessell, A E; Lucy, R J

    2004-09-01

    This is a report of an unusual squamous cell carcinoma in the nasal cavity of a dog. A 13-year-old Golden Retriever was presented with a unilateral nasal and ocular discharge. Although a nasal tumour was suspected, initial diagnostic investigations were unrewarding, and, with worsening clinical signs, the dog was euthanatized. Necropsy examination confirmed the presence of a nasal tumour that was composed histologically of both a well-differentiated squamous cell carcinoma component blending with a predominant spindle cell component. Immunohistochemical staining with anti-human keratin/cytokeratin (AE1/AE3, CAM 5.2 and broad spectrum cytokeratin), Vimentin, Desmin, smooth muscle actin and S-100 protein supported a diagnosis of a squamous cell carcinoma with (pseudo) sarcomatous stroma.

  17. Herpes simplex virus type 2 infection increases human immunodeficiency virus type 1 entry into human primary macrophages.

    PubMed

    Sartori, Elena; Calistri, Arianna; Salata, Cristiano; Del Vecchio, Claudia; Palù, Giorgio; Parolin, Cristina

    2011-04-12

    Epidemiological and clinical data indicate that genital ulcer disease (GUD) pathogens are associated with an increased risk of human immunodeficiency virus type 1 (HIV-1) acquisition and/or transmission. Among them, genital herpes simplex virus type 2 (HSV-2) seems to play a relevant role. Indeed, the ability of HSV-2 to induce massive infiltration at the genital level of cells which are potential targets for HIV-1 infection may represent one of the mechanisms involved in this process. Here we show that infection of human primary macrophages (MDMs) by HSV-2 results in an increase of CCR5 expression levels on cell surface and allows higher efficiency of MDMs to support entry of R5 HIV-1 strains. This finding could strengthen, at the molecular level, the evidence linking HSV-2 infection to an increased susceptibility to HIV-1 acquisition.

  18. Assessment of nasalance and nasality in patients with a repaired cleft palate.

    PubMed

    Sinko, Klaus; Gruber, Maike; Jagsch, Reinhold; Roesner, Imme; Baumann, Arnulf; Wutzl, Arno; Denk-Linnert, Doris-Maria

    2017-03-15

    In patients with a repaired cleft palate, nasality is typically diagnosed by speech language pathologists. In addition, there are various instruments to objectively diagnose nasalance. To explore the potential of nasalance measurements after cleft palate repair by NasalView(®), we correlated perceptual nasality and instrumentally measured nasalance of eight speech items and determined the relationship between sensitivity and specificity of the nasalance measures by receiver-operating characteristics (ROC) analyses and AUC (area under the curve) computation for each single test item and specific item groups. We recruited patients with a primarily repaired cleft palate receiving speech therapy during follow-up. During a single day visit, perceptive and instrumental assessments were obtained in 36 patients and analyzed. The individual perceptual nasality was assigned to one of four categories; the corresponding instrumental nasalance measures for the eight specific speech items were expressed on a metric scale (1-100). With reference to the perceptual diagnoses, we observed 3 nasal and one oral test item with high sensitivity. However, the specificity of the nasality indicating measures was rather low. The four best speech items with the highest sensitivity provided scores ranging from 96.43 to 100%, while the averaged sensitivity of all eight items was below 90%. We conclude that perceptive evaluation of nasality remains state of the art. For clinical follow-up, instrumental nasalance assessment can objectively document subtle changes by analysis of four speech items only. Further studies are warranted to determine the applicability of instrumental nasalance measures in the clinical routine, using discriminative items only.

  19. Fabrication of a provisional nasal prosthesis.

    PubMed

    Rosen, Evan B; Golden, Marjorie; Huryn, Joseph M

    2014-11-01

    A technique for making a provisional nasal prosthesis for interim use after the ablation of a midface tumor is described. The technique is especially useful for the re-creation of a nasal form in an expedient and cost-effective manner. A preoperative definitive cast, or moulage, of the patient that includes a nasal form is used to fabricate a vacuum form of the midface. The vacuum form is evaluated on the patient, the extension is adjusted, and an external adhesive knit liner is applied to give the appearance of a contoured nasal bandage. The provisional nasal prosthesis is attached with medical adhesive tape and removed daily by the patient. The prosthesis is easily replaced during the course of treatment and has been found to be functional and esthetically acceptable to those patients receiving care from the Dental Service at Memorial Sloan Kettering Cancer Center.

  20. Nasal foreign body removal in children.

    PubMed

    Kiger, James R; Brenkert, Timothy E; Losek, Joseph D

    2008-11-01

    Nasal foreign bodies in children are often managed in the pediatric emergency department. The child is usually between 2 and 4 years old, and the foreign body is most commonly a plastic toy or bead. Nasal foreign bodies are removed by a number of techniques. Positive-pressure expulsion is accomplished by orally applied pressure via a parent's mouth or an Ambu bag or by nasally applied pressure via a catheter or an oxygen source. The object can be washed out with nasally applied saline. Direct mechanical extraction is possible with a variety of tools, including forceps, hooks, or balloon-tipped catheters. Each method carries its own risks and benefits. Serious complications of nasal foreign bodies include posterior dislodgement and aspiration, trauma caused by the object itself or removal attempts, infection, and choanal stenosis. Magnets and button batteries require emergent removal as they carry the risk of septal perforation or necrosis, which may develop within a relatively short time.

  1. Nasal Reshaping with Hyaluronic Acid: An Alternative or Complement to Surgery

    PubMed Central

    2016-01-01

    Background: Rhinoplasty has traditionally been preferred for correction of nasal defects. Long-term clinical experience with hyaluronic acid (HA) injection as an alternative or complement to rhinoplasty is presented. Methods: A retrospective review of the author’s clinical experience with HA gel for nasal reshaping from 1997 to 2012 was conducted, with treatments performed during 1998, 2005, and 2012 selected for detailed review. Results: More than 250 patients were treated for nasal reshaping with HA since 1997. In addition to being a complement to surgery, HA injection successfully addressed nasal defects that would have been difficult to correct surgically. The effect persisted for >1 year in most patients (>5 y in some patients), with individual variations. No serious complications occurred. When comparing the 3 years reviewed in detail, new indications for nasal reshaping with HA gel became evident over time, which was also reflected by the increase in number of patients treated (1998: n = 2; 2005: n = 22; 2012: n = 51). Of these patients, 55 (73%) received HA injection instead of rhinoplasty, 20 (27%) received HA injection after rhinoplasty, and 5 (7%) underwent rhinoplasty after HA injection. The mean injection volume was 0.4 mL HA gel/treatment. All patients were satisfied with the primary outcome of treatment. Retreatment was performed in 32 patients (43%). Conclusions: Injection of HA gel is a valuable tool for nasal reshaping. It can also be used for correction of minor postrhinoplasty defects in appropriate patients. PMID:27975025

  2. Gamma scintigraphy for testing bioequivalence: a case study on two cromolyn sodium nasal spray preparations.

    PubMed

    Al-Ghananeem, Abeer M; Sandefer, Erik P; Doll, Walter J; Page, Richard C; Chang, Yunik; Digenis, George A

    2008-06-05

    The present work was carried out to study the deposition patterns and clearance of technetium-99m (99mTc) DTPA labeled cromolyn sodium (CS) solutions when administered from two different CS nasal products using gamma scintigraphy. Five healthy volunteers received a single dose with complete crossover design involving treatment A (test formulation) and treatment B (reference formulation). The deposition patterns as well as the changes in distribution of the radiolabeled CS solutions due to the mucociliary transport were monitored by gamma scintigraphy. Primary deposition of the aforementioned nasal solutions occurred in the anterior portion of the nose. After migration into the posterior nasal cavity, the solutions were rapidly cleared by ciliary action into the nasopharynx where it was swallowed. The test product of cromolyn sodium was shown to be equivalent to the reference product with regard to nasal deposition and clearance. The results from this study indicate that external gamma scintigraphy can be used to demonstrate the equivalence of nasal sprays that are intended for local therapeutic action where the drug is not systemically absorbed into the blood circulation. Furthermore, a non-invasive imaging method such as rhinoscintigraphy may prove to be a useful technique to be utilized during the regulatory approval process for local-acting nasal products, and may facilitate the early introduction of these products to the market.

  3. Modeling of oropharyngeal articulatory adaptation to compensate for the acoustic effects of nasalization.

    PubMed

    Rong, Panying; Kuehn, David P; Shosted, Ryan K

    2016-09-01

    Hypernasality is one of the most detrimental speech disturbances that lead to declines of speech intelligibility. Velopharyngeal inadequacy, which is associated with anatomic defects such as cleft palate or neuromuscular disorders that affect velopharygneal function, is the primary cause of hypernasality. A simulation study by Rong and Kuehn [J. Speech Lang. Hear. Res. 55(5), 1438-1448 (2012)] demonstrated that properly adjusted oropharyngeal articulation can reduce nasality for vowels synthesized with an articulatory model [Mermelstein, J. Acoust. Soc. Am. 53(4), 1070-1082 (1973)]. In this study, a speaker-adaptive articulatory model was developed to simulate speaker-customized oropharyngeal articulatory adaptation to compensate for the acoustic effects of nasalization on /a/, /i/, and /u/. The results demonstrated that (1) the oropharyngeal articulatory adaptation effectively counteracted the effects of nasalization on the second lowest formant frequency (F2) and partially compensated for the effects of nasalization on vowel space (e.g., shifting and constriction of vowel space) and (2) the articulatory adaptation strategies generated by the speaker-adaptive model might be more efficacious for counteracting the acoustic effects of nasalization compared to the adaptation strategies generated by the standard articulatory model in Rong and Kuehn. The findings of this study indicated the potential of using oropharyngeal articulatory adaptation as a means to correct maladaptive articulatory behaviors and to reduce nasality.

  4. The fluid dynamics of canine olfaction: unique nasal airflow patterns as an explanation of macrosmia

    PubMed Central

    Craven, Brent A.; Paterson, Eric G.; Settles, Gary S.

    2010-01-01

    The canine nasal cavity contains hundreds of millions of sensory neurons, located in the olfactory epithelium that lines convoluted nasal turbinates recessed in the rear of the nose. Traditional explanations for canine olfactory acuity, which include large sensory organ size and receptor gene repertoire, overlook the fluid dynamics of odorant transport during sniffing. But odorant transport to the sensory part of the nose is the first critical step in olfaction. Here we report new experimental data on canine sniffing and demonstrate allometric scaling of sniff frequency, inspiratory airflow rate and tidal volume with body mass. Next, a computational fluid dynamics simulation of airflow in an anatomically accurate three-dimensional model of the canine nasal cavity, reconstructed from high-resolution magnetic resonance imaging scans, reveals that, during sniffing, spatially separate odour samples are acquired by each nostril that may be used for bilateral stimulus intensity comparison and odour source localization. Inside the nose, the computation shows that a unique nasal airflow pattern develops during sniffing, which is optimized for odorant transport to the olfactory part of the nose. These results contrast sharply with nasal airflow in the human. We propose that mammalian olfactory function and acuity may largely depend on odorant transport by nasal airflow patterns resulting from either the presence of a highly developed olfactory recess (in macrosmats such as the canine) or the lack of one (in microsmats including humans). PMID:20007171

  5. Public perspectives on health human resources in primary healthcare: context, choices and change.

    PubMed

    Regan, Sandra; Wong, Sabrina T; Watson, Diane E

    2010-02-01

    The purpose of this study was to examine factors identified by patients as relevant to health human resources (HHR) planning for primary healthcare (PHC). Eleven focus groups were conducted in British Columbia and a thematic analysis was undertaken, informed by a needs-based HHR planning framework. Three themes emerged: (a) the importance of geographic context, (b) change management at the practice level and (c) the need for choices and changes in delivery of PHC. Findings suggest that more attention could be focused on overcoming geographic barriers to providing services, change management within office-based practices, and providing support structures that allow primary care providers to work closer to their full scope of practice. That these factors align with many strategic directions set out by government and planners signals the readiness for change in how PHC is delivered and HHR planned.

  6. 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

  7. Functional nasal morphology of chimaerid fishes.

    PubMed

    Howard, Lauren E; Holmes, William M; Ferrando, Sara; Maclaine, James S; Kelsh, Robert N; Ramsey, Andrew; Abel, Richard L; Cox, Jonathan P L

    2013-09-01

    Holocephalans (chimaeras) are a group of marine fishes comprising three families: the Callorhinchidae (callorhinchid fishes), the Rhinochimaeridae (rhinochimaerid fishes) and the Chimaeridae (chimaerid fishes). We have used X-ray microcomputed tomography and magnetic resonance imaging to characterise in detail the nasal anatomy of three species of chimaerid fishes: Chimaera monstrosa, C. phantasma and Hydrolagus colliei. We have shown that the nasal chamber of these three species is linked to the external environment by an incurrent channel and to the oral cavity by an excurrent channel via an oral groove. A protrusion of variable morphology is present on the medial wall of the incurrent channel in all three species, but is absent in members of the two other holocephalan families that we inspected. A third nasal channel, the lateral channel, functionally connects the incurrent nostril to the oral cavity, by-passing the nasal chamber. From anatomical reconstructions, we have proposed a model for the circulation of water, and therefore the transport of odorant, in the chimaerid nasal region. In this model, water could flow through the nasal region via the nasal chamber or the lateral channel. In either case, the direction of flow could be reversed. Circulation through the entire nasal region is likely to be driven primarily by the respiratory pump. We have identified several anatomical features that may segregate, distribute, facilitate and regulate flow in the nasal region and have considered the consequences of flow reversal. The non-sensory cilia lining the olfactory sensory channels appear to be mucus-propelling, suggesting that these cilia have a common protective role in cartilaginous fishes (sharks, rays and chimaeras). The nasal region of chimaerid fishes shows at least two adaptations to a benthic lifestyle, and suggests good olfactory sensitivity, with secondary folding enhancing the hypothetical flat sensory surface area by up to 70%.

  8. 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

  9. Experimental study on the behavior of primary human osteoblasts on laser-cused pure titanium surfaces.

    PubMed

    Markwardt, Jutta; Friedrichs, Jens; Werner, Carsten; Davids, Andreas; Weise, Hartmut; Lesche, Raoul; Weber, Anke; Range, Ursula; Meißner, Heike; Lauer, Günther; Reitemeier, Bernd

    2014-05-01

    Mandibular tumor resection can lead to a mandibular segmental defect. LaserCUSING® is used to produce a mandibular implant, designed to be identical to the shape of the mandibular defect. Novel microrough surfaces result from this generative technology. In the current study, the behavior of human osteoblasts on untreated laser-cused titanium specimens or on specimens conditioned with different blasting agents was analyzed. The conditioning of these specimens resulted in surfaces with graded roughness. White light confocal microscopy and single-cell force spectroscopy were used to characterize the surface of the specimens and to quantify the initial adhesion of primary human osteoblasts to the specimens, respectively. Furthermore, cell growth, viability, apoptosis as well as mineralization of the specimens were analyzed over a time-period of 2 months. Compared to specimens that were treated with blasting agents, untreated specimens had the highest surface roughness. Quantitative SCFS measurements demonstrated that the adhesion of human primary osteoblasts was the highest on these specimens. Additionally, the untreated specimens allowed the highest number of osteoblasts to colonize. Mineralization studies showed increasing calcium and phosphor elemental composition for all specimen series. It can be concluded that untreated laser-cused titanium specimens are superior to promote the initial adhesion and subsequent colonization by osteoblast cells.

  10. Identification and Validation of Novel Contraction-Regulated Myokines Released from Primary Human Skeletal Muscle Cells

    PubMed Central

    Raschke, Silja; Eckardt, Kristin; Bjørklund Holven, Kirsten; Jensen, Jørgen; Eckel, Jürgen

    2013-01-01

    Proteins secreted by skeletal muscle, so called myokines, have been shown to affect muscle physiology and additionally exert systemic effects on other tissues and organs. Although recent profiling studies have identified numerous myokines, the amount of overlap from these studies indicates that the secretome of skeletal muscle is still incompletely characterized. One limitation of the models used is the lack of contraction, a central characteristic of muscle cells. Here we aimed to characterize the secretome of primary human myotubes by cytokine antibody arrays and to identify myokines regulated by contraction, which was induced by electrical pulse stimulation (EPS). In this study, we validated the regulation and release of two selected myokines, namely pigment epithelium derived factor (PEDF) and dipeptidyl peptidase 4 (DPP4), which were recently described as adipokines. This study reveals that both factors, DPP4 and PEDF, are secreted by primary human myotubes. PEDF is a contraction-regulated myokine, although PEDF serum levels from healthy young men decrease after 60 min cycling at VO2max of 70%. Most interestingly, we identified 52 novel myokines which have not been described before to be secreted by skeletal muscle cells. For 48 myokines we show that their release is regulated by contractile activity. This profiling study of the human skeletal muscle secretome expands the number of myokines, identifies novel contraction-regulated myokines and underlines the overlap between proteins which are adipokines as well as myokines. PMID:23637948

  11. Human prion protein-induced autophagy flux governs neuron cell damage in primary neuron cells.

    PubMed

    Moon, Ji-Hong; Lee, Ju-Hee; Nazim, Uddin Md; Lee, You-Jin; Seol, Jae-Won; Eo, Seong-Kug; Lee, John-Hwa; Park, Sang-Youel

    2016-05-24

    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.

  12. Brd4 Activates Early Viral Transcription upon Human Papillomavirus 18 Infection of Primary Keratinocytes

    PubMed Central

    McKinney, Caleb C.; Kim, Min Jung; Chen, Dan

    2016-01-01

    ABSTRACT  Human papillomaviruses (HPVs) replicate in the cutaneous and mucosal epithelia, and the infectious cycle is synchronous with the differentiation program of the host keratinocytes. The virus initially infects dividing cells in the lower layers of the epithelium, where it establishes a persistent infection. The viral genome is maintained as a low-copy-number, extrachromosomal element in these proliferating cells but switches to the late stage of the life cycle in differentiated cells. The cellular chromatin adaptor protein Brd4 is involved in several stages and processes of the viral life cycle. In concert with the viral transcriptional regulator E2, Brd4 can repress transcription from the early viral promoter. Brd4 and E2 form a complex with the viral genome that associates with host chromosomes to partition the viral genome in dividing cells; Brd4 also localizes to active sites of productive HPV DNA replication. However, because of the difficulties in producing HPV viral particles, the role of Brd4 in modulating viral transcription and replication at the initial stage of infection is unclear. In this study, we have used an HPV18 quasivirus-based genome delivery system to assess the role of Brd4 in the initial infectivity of primary human keratinocytes. We show that, upon infection of primary human keratinocytes with HPV18 quasivirus, Brd4 activates viral transcription and replication. Furthermore, this activation is independent of the functional interaction between Brd4 and the HPV18 E2 protein. PMID:27879331

  13. The performance of primary human renal cells in hollow fiber bioreactors for bioartificial kidneys.

    PubMed

    Oo, Zay Yar; Deng, Rensheng; Hu, Min; Ni, Ming; Kandasamy, Karthikeyan; bin Ibrahim, Mohammed Shahrudin; Ying, Jackie Y; Zink, Daniele

    2011-12-01

    Bioartificial kidneys (BAKs) containing human primary renal proximal tubule cells (HPTCs) have been applied in clinical trials. The results were encouraging, but also showed that more research is required. Animal cells or cell lines are not suitable for clinical applications, but have been mainly used in studies on BAK development as large numbers of such cells could be easily obtained. It is difficult to predict HPTC performance based on data obtained with other cell types. To enable more extensive studies on HPTCs, we have developed a bioreactor containing single hollow fiber membranes that requires relatively small amounts of cells. Special hollow fiber membranes with the skin layer on the outer surface and consisting of polyethersulfone/polyvinylpyrrolidone were developed. The results suggested that such hollow fiber membranes were more suitable for the bioreactor unit of BAKs than membranes with an inner skin layer. An HPTC-compatible double coating was applied to the insides of the hollow fiber membranes, which sustained the formation of functional epithelia under bioreactor conditions. Nevertheless, the state of differentiation of the primary human cells remained a critical issue and should be further addressed. The bioreactor system described here will facilitate further studies on the relevant human cell type.

  14. Entry of hepatitis B virus into immortalized human primary hepatocytes by clathrin-dependent endocytosis.

    PubMed

    Huang, Hsiu-Chen; Chen, Chun-Chi; Chang, Wen-Cheng; Tao, Mi-Hua; Huang, Cheng

    2012-09-01

    The lack of a suitable in vitro hepatitis B virus (HBV) infectivity model has limited examination of the early stages of the virus-cell interaction. In this study, we used an immortalized cell line derived from human primary hepatocytes, HuS-E/2, to study the mechanism of HBV infection. HBV infection efficiency was markedly increased after dimethyl sulfoxide (DMSO)-induced differentiation of the cells. Transmission electron microscopy demonstrated the presence of intact HBV particles in DMSO-treated HBV-infected HuS-E/2 cells, which could be infected with HBV for up to at least 50 passages. The pre-S1 domain of the large HBsAg (LHBsAg) protein specifically interacted with clathrin heavy chain (CHC) and clathrin adaptor protein AP-2. Short hairpin RNA knockdown of CHC or AP-2 in HuS-E/2 cells significantly reduced their susceptibility to HBV, indicating that both are necessary for HBV infection. Furthermore, HBV entry was inhibited by chlorpromazine, an inhibitor of clathrin-mediated endocytosis. LHBsAg also interfered with the clathrin-mediated endocytosis of transferrin by human hepatocytes. This infection system using an immortalized human primary hepatocyte cell line will facilitate investigations into HBV entry and in devising therapeutic strategies for manipulating HBV-associated liver disorders.

  15. Generation of Endoderm derived Human iPS cells from Primary Hepatocytes

    PubMed Central

    Liu, Hua; Ye, Zhaohui; Kim, Yong-Hak; Sharkis, Saul; Jang, Yoon-Young

    2010-01-01

    Recent advances in induced pluripotent stem (iPS) cell research significantly changed our perspective on regenerative medicine. Patient specific iPS cells have been derived not only for disease modeling but also as sources for cell replacement therapy. However, there have been insufficient data to prove that iPS cells are functionally equivalent to hES cells or safer than hES cells. There are several important issues which need to be addressed and foremost are the safety and efficacy of human iPS cells from different origins. Human iPS cells have been derived mostly from cells originated from mesoderm, with a few cases from ectoderm. So far there has been no report of endoderm derived human iPS cells, preventing comprehensive comparative investigations on the quality of human iPS cells from different origins. Here we show for the first time reprogramming of human endoderm derived cells (i.e. primary hepatocytes) to pluripotency. Hepatocyte-derived iPS cells appear indistinguishable from human embryonic stem cells in colony morphology, growth properties, expression of pluripotency-associated transcription factors and surface markers, and differentiation potential in embryoid body formation and teratoma assays. In addition, these cells were able to directly differentiate into definitive endoderm, hepatic progenitors, and mature hepatocytes. The technology to develop endoderm derived human iPS cell lines, together with other established cell lines, will provide a foundation to elucidate the mechanisms of cellular reprogramming and to study the safety and efficacy of differentially originated human iPS cells for cell therapy. For studying liver disease pathogenesis, this technology also provides a potentially more amenable system to generate liver disease specific iPS cells. PMID:20432258

  16. 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

  17. Activity of Protease-Activated Receptors in Primary Cultured Human Myenteric Neurons

    PubMed Central

    Kugler, Eva M.; Mazzuoli, Gemma; Demir, Ihsan E.; Ceyhan, Güralp O.; Zeller, Florian; Schemann, Michael

    2012-01-01

    Activity of the four known protease-activated receptors (PARs) has been well studied in rodent enteric nervous system and results in animal models established an important role for neuronal PAR2. We recently demonstrated that, unlike in rodents, PAR1 is the dominant neuronal protease receptor in the human submucous plexus. With this study we investigated whether this also applies to the human myenteric plexus. We used voltage sensitive dye recordings to detect action potential discharge in primary cultures of human myenteric neurons in response to PAR activating peptides (APs). Application of the PAR1-AP (TFLLR) or PAR4-AP (GYPGQV) evoked spike discharge in 79 or 23% of myenteric neurons, respectively. The PAR1-AP response was mimicked by the endogenous PAR1 activator thrombin and blocked by the PAR1 antagonists SCH79797. Human myenteric neurons did not respond to PAR2-AP. This was not due to culture conditions because all three PAR-APs evoked action potentials in cultured guinea pig myenteric neurons. Consecutive application of PAR-APs revealed coexpression (relative to the population responding to PAR-APs) of PAR1/PAR2 in 51%, PAR1/PAR4 in 43%, and of PAR2/PAR4 in 29% of guinea pig myenteric neurons. Our study provided further evidence for the prominent role of neuronal PAR1 in the human enteric nervous system. PMID:22988431

  18. 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.

  19. Evaluating the Role of Viral Proteins in HIV-Mediated Neurotoxicity Using Primary Human Neuronal Cultures

    PubMed Central

    Rao, Vasudev R.; Eugenin, Eliseo A.; Prasad, Vinayaka R.

    2016-01-01

    Despite the inability of HIV-1 to infect neurons, over half of the HIV-1-infected population in the USA suffers from neurocognitive dysfunction. HIV-infected immune cells in the periphery enter the central nervous system by causing a breach in the blood–brain barrier. The damage to the neurons is mediated by viral and host toxic products released by activated and infected immune and glial cells. To evaluate the toxicity of any viral isolate, viral protein, or host inflammatory protein, we describe a protocol to assess the neuronal apoptosis and synaptic compromise in primary cultures of human neurons and astrocytes. PMID:26714725

  20. Evaluating the Role of Viral Proteins in HIV-Mediated Neurotoxicity Using Primary Human Neuronal Cultures.

    PubMed

    Rao, Vasudev R; Eugenin, Eliseo A; Prasad, Vinayaka R

    2016-01-01

    Despite the inability of HIV-1 to infect neurons, over half of the HIV-1-infected population in the USA suffers from neurocognitive dysfunction. HIV-infected immune cells in the periphery enter the central nervous system by causing a breach in the blood-brain barrier. The damage to the neurons is mediated by viral and host toxic products released by activated and infected immune and glial cells. To evaluate the toxicity of any viral isolate, viral protein, or host inflammatory protein, we describe a protocol to assess the neuronal apoptosis and synaptic compromise in primary cultures of human neurons and astrocytes.

  1. Manipulation of Human Primary Endothelial Cell and Osteoblast Coculture Ratios to Augment Vasculogenesis and Mineralization.

    PubMed

    Shah, Amita R; Wenke, Joseph C; Agrawal, Chandra Mauli

    2016-01-01

    Tissue-engineering scaffolds are often seeded with a single type of cell, but there has been more focus on cocultures to improve angiogenesis and bone formation for craniofacial applications. Investigation of bone-derived osteoblasts (OBs) is important because of the use of bone grafts and migration of OBs from native bone into constructs in vivo and therefore, their contribution to bone formation in vivo. The limitation of primary OBs has been their inability to mineralize without osteogenic factors in vitro. Through coculture of OBs and endothelial cells (ECs) and manipulation of the coculture ratio, mineralization can be achieved without osteogenic media or additional growth factors, thus enhancing their utility for tissue-engineering applications. An optimal ratio of EC/OB for vasculogenesis and mineralization has not been determined for human primary cells. Human umbilical vein ECs were cultured with normal human primary OBs in different EC/OB ratios, namely, 10:1, 5:1, 1:1, 1:5, and 1:10 with EC and OB monocultures as controls. The number of vasculogenic networks in a collagen matrix was highest in ratios of 5:1 and 1:1. ECs lined up and formed capillary-like networks by day 10, which was not seen in the other groups. On polystyrene, cells were cocultured with ECs and OBs in direct contact (direct coculture) or separated by a transwell membrane (indirect coculture). At day 21, Alizarin Red staining showed mineralization on the 1:5 and 1:10 direct coculture ratios, with 1:5 having more mineralization nodules present than 1:10. No mineralization was seen in other direct coculture ratios or in any of the indirect coculture ratios. Alkaline phosphatase secretion was highest in the 1:5 direct coculture group. Vascular endothelial growth factor secretion from OBs was present in the 1:5 and 1:10 direct coculture ratios at all time points and inhibited after day 1 in other coculture groups. To improve vasculogenesis, cocultures of primary human ECs and OBs in ratios

  2. Novel Analysis of Immune Cells from Nasal Microbiopsy Demonstrates Reliable, Reproducible Data for Immune Populations, and Superior Cytokine Detection Compared to Nasal Wash

    PubMed Central

    Rylance, Jamie; Adler, Hugh; Carniel, Beatriz F.; Collins, Andrea; Gritzfeld, Jenna F.; Hancock, Carole; Hill, Helen; Reiné, Jesus; Seddon, Alexandra; Solórzano, Carla; Sunny, Syba; Trimble, Ashleigh; Wright, Angela D.; Zaidi, Seher; Gordon, Stephen B.; Ferreira, Daniela M.

    2017-01-01

    The morbidity and mortality related to respiratory tract diseases is enormous, with hundreds of millions of individuals afflicted and four million people dying each year. Understanding the immunological processes in the mucosa that govern outcome following pathogenic encounter could lead to novel therapies. There is a need to study responses at mucosal surfaces in humans for two reasons: (i) Immunological findings in mice, or other animals, often fail to translate to humans. (ii) Compartmentalization of the immune system dictates a need to study sites where pathogens reside. In this manuscript, we describe two novel non-invasive nasal mucosal microsampling techniques and their use for measuring immunological parameters: 1) using nasal curettes to collect cells from the inferior turbinate and; 2) absorptive matrices to collect nasal lining fluid. Both techniques were well tolerated and yielded reproducible and robust data. We demonstrated differences in immune populations and activation state in nasal mucosa compared to blood as well as compared to nasopharyngeal lumen in healthy adults. We also found superior cytokine detection with absorptive matrices compared to nasal wash. These techniques are promising new tools that will facilitate studies of the immunological signatures underlying susceptibility and resistance to respiratory infections. PMID:28107457

  3. Teaching about Human Relationships Education for Primary School Student-Teachers Using an Interactive CD-ROM

    ERIC Educational Resources Information Center

    Goldman, Juliette D. G.; Torrisi-Steele, Geraldine

    2009-01-01

    Human Relationships Education is a very important part of primary school student-teacher education. All primary school children need sound guidance and enhanced knowledge about puberty, growing up successfully, and feeling competent and confident in themselves. An interactive multimedia CD-ROM was designed and developed for some Australian…

  4. 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.

  5. 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.

  6. Bcl-2 upregulation by HIV-1 Tat during infection of primary human macrophages in culture.

    PubMed

    Zhang, Mingjie; Li, Xingxiang; Pang, Xiaowu; Ding, Lina; Wood, Owen; Clouse, Kathleen A; Hewlett, Indira; Dayton, Andrew I

    2002-01-01

    The ability of cells of the human monocyte/macrophage lineage to host HIV-1 replication while resisting cell death is believed to significantly contribute to their ability to serve as a reservoir for viral replication in the host. Although macrophages are generally resistant to apoptosis, interruption of anti-apoptotic pathways can render them susceptible to apoptosis. Here we report that HIV-1(BAL )infection of primary human monocyte-derived macrophages (MDM) upregulates the mRNA and protein levels of the anti-apoptic gene, Bcl-2. Furthermore, this upregulation can be quantitatively mimicked by treating MDM with soluble HIV-1 Tat-86 protein. These results suggest that in infecting cells of the monocyte/macrophage lineage, HIV-1 may be benefiting from additional protection against apoptosis caused by specific upregulation of cellular anti-apoptotic genes.

  7. 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.

  8. 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

  9. 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.

  10. Polypoidal Lesions in the Nasal Cavity

    PubMed Central

    Kumari M.K., Kalpana; K.C., Mahadeva

    2013-01-01

    Introduction: Nasal polyps are polypoidal masses arising from mucous membranes of nose and paranasal sinuses. They are overgrowths of the mucosa that frequently accompany allergic rhinitis. They are freely movable and nontender. Aims and Objectives: The purpose of this study was to study the histopathologic spectrum of polypoidal lesions of the nasal cavity. Materials and Methods: The study comprised of 100 consecutive cases of polypoidal lesions in the nasal cavity, received in the department of pathology. The age and sex of the patients were recorded. The tissues were routinely processed for histopathologic sections and stained with haematoxylin and eosin stains. Special stains like Periodic acid Schiff (PAS) was done wherever applicable. The cases were classified into neoplastic and nonneoplastic lesions. The neoplastic lesions were further classified according to WHO classification on histopathologic examination. Results: Analysis of 100 polypoidal lesions in the nose and paranasal sinuses with clinical diagnosis of nasal polyps, revealed 66 cases were nonneoplastic and 34 were neoplastic;17 (50%)were benign and 17(50%) were malignant. True nasal polyps both inflammatory and allergic together comprised 44 cases of the 100 polypoidal lesions in the nasal cavity. Angiofibroma and inverted papilloma were the most frequent benign tumour accounting for 12/17(0.7%). The most common malignant tumour was anaplastic carcinoma 7/17(0.4%). Nonneoplastic and benign tumours were common in younger age groups whereas malignant tumours were most common in older males. Conclusion: The majority of polypoidal lesions in the nasal cavity are nonneoplastic. PMID:23905098

  11. 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

  12. Adjuncts to Improve Nasal Reconstruction Results.

    PubMed

    Gordon, Shayna Lee; Hurst, Eva A

    2017-02-01

    The final cosmetic appearance of nasal reconstruction scars is of paramount importance to both the patient and surgeon. Ideal postreconstruction nasal scars are flat and indistinguishable from surrounding skin. Unfortunately, even with meticulous surgical execution, nasal scars can occasionally be suboptimal. Abnormal fibroblast response can lead to hypertrophic nasal scars, and excessive angiogenesis may lead to telangiectasias or an erythematous scar. Imperfect surgical closure or poor postoperative management can lead to surgical outcomes with step-offs, depressions, suture marks, or dyspigmentation. Aesthetically unacceptable nasal scars can cause pruritus, tenderness, pain, sleep disturbance, and anxiety and depression in postsurgical patients. Fortunately, there are several minimally invasive or noninvasive techniques that allow for enhancement and improvement of cosmetic results with minimal risk and associated downtime. This article provides an overview of adjuncts to improve nasal reconstruction with a focus on techniques to be used in the postoperative period. Armed with an understanding of relevant available therapies, skillful surgeons may drastically improve the final cosmesis and outcome of nasal reconstruction scars.

  13. Canine and feline nasal neoplasia.

    PubMed

    Malinowski, Christine

    2006-05-01

    Dogs and cats of our society have outgrown their status as merely pets and are now considered our close companions and even family members. This shift in their roles has led to pet owners seeking improved preventative medicine for their four-legged friends. Subsequently, dogs and cats are living longer lives than ever before and developing more old-age-related diseases. One of the most devastating diseases of older animals is cancer. Once a veterinarian has detected cancer in a pet, pet owners seek advice on their next course of action. This article is intended to provide concise information regarding the diagnosis and treatment of intranasal tumors of the dog and cat. This article outlines the forms of nasal tumors that are the most common, the recommended imaging and biopsy techniques to diagnose the tumor, and the most appropriate treatments of them.

  14. Sino-nasal T-cell lymphoma invading the brain: A case study

    PubMed Central

    Reddy, Srikanth; Kumar, Ashish; Allugolu, Rajesh; Uppin, Megha; Ramgopal, Keshav

    2014-01-01

    Lesions occupying the anterior cranial fossa may arise de novo or are extensions from the sino-nasal areas with a handful of differentials in either group. The imaging findings, though to a large extent standardized are not full proof. Primary central nervous system lymphoma and sino-nasal lymphoma are uncommon variants of extranodal non-Hodgkin's lymphoma (NHL). We encountered a 35-year-old lady presenting with headache and seizures with a mass lesion involving the ethmoids with invasion into the anterior cranial fossa diagnosed as T-cell extranodal NHL. Gross total resection and reconstruction of the skull base were done. She was treated with chemotherapy and radiotherapy and is doing well at 6 months follow-up. This is the first report of a sino-nasal T-cell lymphoma invading the brain-parenchyma in an immuno-competent person. Sino-nasal primary T-cell lymphoma presenting as skull base pathology should form an essential differential diagnosis along with other routine lesions of anterior cranial fossa. Since these lesions have a good response to chemo and radiotherapy, a trans-nasal biopsy may obviate the need of a craniotomy if neurosurgeons are aware of this rare entity. PMID:25685223

  15. Intrapulmonary Versus Nasal Transduction of Murine Airways With GP64-pseudotyped Viral Vectors

    PubMed Central

    Oakland, Mayumi; Maury, Wendy; McCray, Paul B; Sinn, Patrick L

    2013-01-01

    Persistent viral vector-mediated transgene expression in the airways requires delivery to cells with progenitor capacity and avoidance of immune responses. Previously, we observed that GP64-pseudotyped feline immunodeficiency virus (FIV)-mediated gene transfer was more efficient in the nasal airways than the large airways of the murine lung. We hypothesized that in vivo gene transfer was limited by immunological and physiological barriers in the murine intrapulmonary airways. Here, we systematically investigate multiple potential barriers to lentiviral gene transfer in the airways of mice. We show that GP64-FIV vector transduced primary cultures of well-differentiated murine nasal epithelia with greater efficiency than primary cultures of murine tracheal epithelia. We further demonstrate that neutrophils, type I interferon (IFN) responses, as well as T and B lymphocytes are not the major factors limiting the transduction of murine conducting airways. In addition, we observed better transduction of GP64-pseudotyped vesicular stomatitis virus (VSV) in the nasal epithelia compared with the intrapulmonary airways in mice. VSVG glycoprotein pseudotyped VSV transduced intrapulmonary epithelia with similar efficiency as nasal epithelia. Our results suggest that the differential transduction efficiency of nasal versus intrapulmonary airways by FIV vector is not a result of immunological barriers or surface area, but rather differential expression of cellular factors specific for FIV vector transduction. PMID:23360952

  16. The nose revisited: a brief review of the comparative structure, function, and toxicologic pathology of the nasal epithelium.

    PubMed

    Harkema, Jack R; Carey, Stephan A; Wagner, James G

    2006-01-01

    The nose is a very complex organ with multiple functions that include not only olfaction, but also the conditioning (e.g., humidifying, warming, and filtering) of inhaled air. The nose is also a "scrubbing tower" that removes inhaled chemicals that may be harmful to the more sensitive tissues in the lower tracheobronchial airways and pulmonary parenchyma. Because the nasal airway may also be a prime target for many inhaled toxicants, it is important to understand the comparative aspects of nasal structure and function among laboratory animals commonly used in inhalation toxicology studies, and how nasal tissues and cells in these mammalian species may respond to inhaled toxicants. The surface epithelium lining the nasal passages is often the first tissue in the nose to be directly injured by inhaled toxicants. Five morphologically and functionally distinct epithelia line the mammalian nasal passages--olfactory, respiratory, squamous, transitional, and lymphoepithelial--and each nasal epithelium may be injured by an inhaled toxicant. Toxicant-induced epithelial lesions in the nasal passages of laboratory animals (and humans) are often site-specific and dependent on the intranasal regional dose of the inhaled chemical and the sensitivity of the nasal epithelial tissue to the specific chemical. In this brief review, we present examples of nonneoplastic epithelial lesions (e.g., cell death, hyperplasia, metaplasia) caused by single or repeated exposure to various inhaled chemical toxicants. In addition, we provide examples of how nasal maps may be used to record the character, magnitude and distribution of toxicant-induced epithelial injury in the nasal airways of laboratory animals. Intranasal mapping of nasal histopathology (or molecular and biochemical alterations to the nasal mucosa) may be used along with innovative dosimetric models to determine dose/response relationships and to understand if site-specific lesions are driven primarily by airflow, by tissue

  17. Effects of Nd:YAG laser pulpotomy on human primary molars.

    PubMed

    Liu, Jeng-fen

    2006-05-01

    The purpose of this study was to compare the effects of Nd:YAG laser pulpotomy to formocresol pulpotomy on human primary teeth. Patients with a primary tooth that required pulpotomy because of pulpal exposure to caries, were selected for this study. After removal of coronal pulpal tissue, Nd:YAG laser at 2 W, 20 Hz, 100 mJ or a 1:5 dilution of formocresol was introduced into the canal orifice for complete hemostasis. IRM paste was then placed over the pulp stump, and the tooth was restored either with composite resin or stainless steel crown. Sixty-eight teeth were treated with Nd:YAG laser and followed up for 6 to 64 months. Clinical success was achieved in 66 out of the 68 teeth (97 %), and 94.1 % were radiographically successful. In the control group, 69 primary molars were treated with formocresol and followed up for 9 to 66 months; 85.5 and 78.3% achieved clinical and radiographic success, respectively. The success rate of Nd:YAG laser pulpotomy was significantly higher than that of formocresol pulpotomy. The permanent successors of the laser-treated teeth erupted without any complications.

  18. Quantitative proteomics of extracellular vesicles derived from human primary and metastatic colorectal cancer cells.

    PubMed

    Choi, Dong-Sic; Choi, Do-Young; Hong, Bok Sil; Jang, Su Chul; Kim, Dae-Kyum; Lee, Jaewook; Kim, Yoon-Keun; Kim, Kwang Pyo; Gho, Yong Song

    2012-01-01

    Cancer cells actively release extracellular vesicles (EVs), including exosomes and microvesicles, into surrounding tissues. These EVs play pleiotropic roles in cancer progression and metastasis, including invasion, angiogenesis, and immune modulation. However, the proteomic differences between primary and metastatic cancer cell-derived EVs remain unclear. Here, we conducted comparative proteomic analysis between EVs derived from human primary colorectal cancer cells (SW480) and their metastatic derivatives (SW620). Using label-free quantitation, we identified 803 and 787 proteins in SW480 EVs and SW620 EVs, respectively. Based on comparison between the estimated abundance of EV proteins, we identified 368 SW480 EV-enriched and 359 SW620 EV-enriched proteins. SW480 EV-enriched proteins played a role in cell adhesion, but SW620 EV-enriched proteins were associated with cancer progression and functioned as diagnostic indicators of metastatic cancer; they were overexpressed in metastatic colorectal cancer and played roles in multidrug resistance. As the first proteomic analysis comparing primary and metastatic cancer-derived EVs, this study increases our understanding of the pathological function of EVs in the metastatic process and provides useful biomarkers for cancer metastasis.

  19. 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.

  20. 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.

  1. Non-primary motor areas in the human frontal lobe are connected directly to hand muscles.

    PubMed

    Teitti, S; Määttä, S; Säisänen, L; Könönen, M; Vanninen, R; Hannula, H; Mervaala, E; Karhu, J

    2008-04-15

    Structural studies in primates have shown that, in addition to the primary motor cortex (M1), premotor areas are a source of corticospinal tracts. The function of these putative corticospinal neuronal tracts in humans is still unclear. We found frontal non-primary motor areas (NPMAs), which react to targeted non-invasive magnetic pulses and activate peripheral muscles as fast as or even faster than those in M1. Hand muscle movements were observed in all our subjects about 20 ms after transcranial stimulation of the superior frontal gyrus (Brodmann areas 6 and 8). Stimulation of NPMA could activate both proximal and distal upper limb muscles with the same delay as a stimulation of the M1, indicating converging motor representations with direct functional connections to the hand. We suggest that these non-primary cortical motor representations provide additional capacity for the fast execution of movements. Such a capacity may play a role in motor learning and in recovery from motor deficits.

  2. Cytotoxicity evaluation using cryopreserved primary human hepatocytes in various culture formats.

    PubMed

    Richert, Lysiane; Baze, Audrey; Parmentier, Céline; Gerets, Helga H J; Sison-Young, Rowena; Dorau, Martina; Lovatt, Cerys; Czich, Andreas; Goldring, Christopher; Park, B Kevin; Juhila, Satu; Foster, Alison J; Williams, Dominic P

    2016-09-06

    Sixteen training compounds selected in the IMI MIP-DILI consortium, 12 drug-induced liver injury (DILI) positive compounds and 4 non-DILI compounds, were assessed in cryopreserved primary human hepatocytes. When a ten-fold safety margin threshold was applied, the non-DILI-compounds were correctly identified 2h following a single exposure to pooled human hepatocytes (n=13 donors) in suspension and 14-days following repeat dose exposure (3 treatments) to an established 3D-microtissue co-culture (3D-MT co-culture, n=1 donor) consisting of human hepatocytes co-cultured with non-parenchymal cells (NPC). In contrast, only 5/12 DILI-compounds were correctly identified 2h following a single exposure to pooled human hepatocytes in suspension. Exposure of the 2D-sandwich culture human hepatocyte monocultures (2D-sw) for 3days resulted in the correct identification of 11/12 DILI-positive compounds, whereas exposure of the human 3D-MT co-cultures for 14days resulted in identification of 9/12 DILI-compounds; in addition to ximelagatran (also not identified by 2D-sw monocultures, Sison-Young et al., 2016), the 3D-MT co-cultures failed to detect amiodarone and bosentan. The sensitivity of the 2D human hepatocytes co-cultured with NPC to ximelagatran was increased in the presence of lipopolysaccharide (LPS), but only at high concentrations, therefore preventing its classification as a DILI positive compound. In conclusion (1) despite suspension human hepatocytes having the greatest metabolic capacity in the short term, they are the least predictive of clinical DILI across the MIP-DILI test compounds, (2) longer exposure periods than 72h of human hepatocytes do not allow to increase DILI-prediction rate, (3) co-cultures of human hepatocytes with NPC, in the presence of LPS during the 72h exposure period allow the assessment of innate immune system involvement of a given drug.

  3. Regulation of indoleamine 2,3-dioxygenase in primary human saphenous vein endothelial cells

    PubMed Central

    Mouratidis, Petros XE; George, Andrew JT

    2015-01-01

    Background Indoleamine 2,3-dioxygenase (IDO) is an enzyme associated with the regulation of immune responses. Cytokines such as IFNγ induce its expression in endothelial cells originating from immune-privileged sites. In this study, we investigate regulators of IDO in primary endothelial cells from a non-immune-privileged site and determine whether IDO expression affects immune cell behavior. Methods IDO expression was determined using real-time quantitative polymerase chain reaction and immunoblotting. IDO activity was estimated using an IDO enzyme assay. Primary cells were transfected using microporation, and T-cell migration was determined using a cell transmigration assay. Results IDO is expressed in human saphenous vein endothelial cells after stimulation with IFNγ but not after treatment with TNFα, IL-1β, IL-2, IL-4, IL-6, or IL-10. VEGFβ and heparin negatively regulate IFNγ-driven increases in IDO. Overexpression of IDO in endothelial cells does not affect transmigration of T-cells. Conclusion IDO is expressed in human saphenous vein endothelial cells after stimulation with IFNγ. Heparin and angiogenesis stimulators such as VEGFβ negatively regulate its expression. PMID:26056484

  4. 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.

  5. A method for establishing human primary gastric epithelial cell culture from fresh surgical gastric tissues.

    PubMed

    Aziz, Faisal; Yang, Xuesong; Wen, Qingping; Yan, Qiu

    2015-08-01

    At present, biopsy specimens, cancer cell lines and tissues obtained by gastric surgery are used in the study and analysis of gastric cancer, including the molecular mechanisms and proteomics. However, fibroblasts and other tissue components may interfere with these techniques. Therefore, the present study aimed to develop a procedure for the isolation of viable human gastric epithelial cells from gastric surgical tissues. A method was developed to culture human gastric epithelial cells using fresh, surgically excised tissues and was evaluated using immunocytochemistry, periodic acid-Schiff (PAS) staining and cell viability assays. Low cell growth was observed surrounding the gastric tissue on the seventh day of tissue explant culture. Cell growth subsequently increased, and at 12 days post-explant a high number of pure epithelial cells were detected. The gastric cancer cells exhibited rapid growth with a doubling time of 13-52 h, as compared to normal cells, which had a doubling time of 20-53 h. Immunocytochemical analyses of primary gastric cells revealed positive staining for cytokeratin 18 and 19, which indicated that the culture was comprised of pure epithelial cells and contained no fibroblasts. Furthermore, PAS staining demonstrated that the cultured gastric cells produced neutral mucin. Granulin and carbohydrate antigen 724 staining confirmed the purity of gastric cancer and normal cells in culture. This method of cell culture indicated that the gastric cells in primary culture consisted of mucin-secreting gastric epithelial cells, which may be useful for the study of gastric infection with Helicobacter pylori and gastric cancer.

  6. 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.

  7. Layer-specific diffusion weighted imaging in human primary visual cortex in vitro.

    PubMed

    Kleinnijenhuis, Michiel; Zerbi, Valerio; Küsters, Benno; Slump, Cornelis H; Barth, Markus; van Cappellen van Walsum, Anne-Marie

    2013-10-01

    One of the most prominent characteristics of the human neocortex is its laminated structure. The first person to observe this was Francesco Gennari in the second half the 18th century: in the middle of the depth of primary visual cortex, myelinated fibres are so abundant that he could observe them with bare eyes as a white line. Because of its saliency, the stria of Gennari has a rich history in cyto- and myeloarchitectural research as well as in magnetic resonance (MR) microscopy. In the present paper we show for the first time the layered structure of the human neocortex with ex vivo diffusion weighted imaging (DWI). To achieve the necessary spatial and angular resolution, primary visual cortex samples were scanned on an 11.7 T small-animal MR system to characterize the diffusion properties of the cortical laminae and the stria of Gennari in particular. The results demonstrated that fractional anisotropy varied over cortical depth, showing reduced anisotropy in the stria of Gennari, the inner band of Baillarger and the deepest layer of the cortex. Orientation density functions showed multiple components in the stria of Gennari and deeper layers of the cortex. Potential applications of layer-specific diffusion imaging include characterization of clinical abnormalities, cortical mapping and (intra)cortical tractography. We conclude that future high-resolution in vivo cortical DWI investigations should take into account the layer-specificity of the diffusion properties.

  8. 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

  9. 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

  10. 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

  11. Osteopontin improves adhesion and migration of human primary renal cortical epithelial cells during wound healing

    PubMed Central

    Wu, Jinfeng; Wang, Zuolin

    2016-01-01

    The aim of the present study was to investigate the effect of osteopontin (OPN) on adhesion and migration in human primary renal cortical epithelial cells during wound healing and Transwell assays. MTT assay was used to examine the cell viability and western blot analysis was used to examine the expression of cytoskeletal proteins and cell adhesion molecules. The results showed that overexpression of OPN had positive effects on the viability, proliferation, adhesion and migration of the human primary renal cortical epithelial cells. In addition, the integrity of the cell membrane and cytoskeleton of the epithelial cells was negatively affected by knockdown of OPN expression. The Transwell migration and a wound healing assays performed using OPN-knockdown cells suggested that OPN had a significant impact on cell migration (P=0.0421) and wound healing (P=0.0333). Therefore, OPN may be a potential target for the therapeutic modulation of skin repair to improve the healing rate and quality of wound healing. PMID:28101213

  12. Efficiency of isolation of human rotavirus in primary African green monkey kidney cells.

    PubMed

    Aboudy, Y; Shif, I; Silberstein, I; Gotlieb-Stematsky, T

    1989-09-01

    Out of 212 human rotavirus (HRV) containing fecal specimens, 173 (81.6%) yielded virus on first passage in primary African Green monkey kidney cells (AGMK), while additional 34 specimens, did not yield virus on first passage. However, following blind passages, 18 of the 34 yielded virus in passage levels 2-8, thus raising the overall isolation rate to 90.1%. The isolation rate of HRV strains obtained in embryonic Rhesus monkey kidney cell line (MA-104), was only 41.4%. ELISA tests performed on fluids from infected cell cultures proved to be an efficient tool to measure virus replication. No differences were encountered in the isolation rates between subgroup I and II strains, while viruses lacking the antigenic determinants of both subgroups did not grow at all. However, one of those unusual group A strains was isolated and grew well in AGMK cells. Primary AGMK and MA-104 cells supported the growth of tissue culture adapted virus most efficiently when compared with six human and primate cell types.

  13. Attentional load modulates responses of human primary visual cortex to invisible stimuli.

    PubMed

    Bahrami, Bahador; Lavie, Nilli; Rees, Geraint

    2007-03-20

    Visual neuroscience has long sought to determine the extent to which stimulus-evoked activity in visual cortex depends on attention and awareness. Some influential theories of consciousness maintain that the allocation of attention is restricted to conscious representations [1, 2]. However, in the load theory of attention [3], competition between task-relevant and task-irrelevant stimuli for limited-capacity attention does not depend on conscious perception of the irrelevant stimuli. The critical test is whether the level of attentional load in a relevant task would determine unconscious neural processing of invisible stimuli. Human participants were scanned with high-field fMRI while they performed a foveal task of low or high attentional load. Irrelevant, invisible monocular stimuli were simultaneously presented peripherally and were continuously suppressed by a flashing mask in the other eye [4]. Attentional load in the foveal task strongly modulated retinotopic activity evoked in primary visual cortex (V1) by the invisible stimuli. Contrary to traditional views [1, 2, 5, 6], we found that availability of attentional capacity determines neural representations related to unconscious processing of continuously suppressed stimuli in human primary visual cortex. Spillover of attention to cortical representations of invisible stimuli (under low load) cannot be a sufficient condition for their awareness.

  14. Evidence that calcineurin is rate-limiting for primary human lymphocyte activation.

    PubMed Central

    Batiuk, T D; Kung, L; Halloran, P F

    1997-01-01

    Cyclosporine (CsA) is both a clinical immunosuppressive drug and a probe to dissect intracellular signaling pathways. In vitro, CsA inhibits lymphocyte gene activation by inhibiting the phosphatase activity of calcineurin (CN). In clinical use, CsA treatment inhibits 50-75% of CN activity in circulating leukocytes. We modeled this degree of CN inhibition in primary human leukocytes in vitro in order to study the effect of partial CN inhibition on the downstream signaling events that lead to gene activation. In CsA-treated leukocytes stimulated by calcium ionophore, the degree of reduction in CN activity was accompanied by a similar degree of inhibition of each event tested: dephosphorylation of nuclear factor of activated T cell proteins, nuclear DNA binding, activation of a transfected reporter gene construct, IFN-gamma and IL-2 mRNA accumulation, and IFN-gamma production. Furthermore, the degree of CN inhibition was reflected by a similar degree of reduction in lymphocyte proliferation and IFN-gamma production in the allogeneic mixed lymphocyte cultures. These data support the conclusion that CN activity is rate-limiting for the activation of primary human T lymphocytes. Thus, the reduction of CN activity observed in CsA-treated patients is accompanied by a similar degree of reduction in lymphocyte gene activation, and accounts for the immunosuppression observed. PMID:9312192

  15. Advances in the quantification of mitochondrial function in primary human immune cells through extracellular flux analysis

    PubMed Central

    Ip, Blanche C.; Habib, Chloe; Ritou, Eleni; Grammatopoulos, Tom N.; Steenkamp, Devin; Dooms, Hans; Apovian, Caroline M.; Lauffenburger, Douglas A.

    2017-01-01

    Numerous studies show that mitochondrial energy generation determines the effectiveness of immune responses. Furthermore, changes in mitochondrial function may regulate lymphocyte function in inflammatory diseases like type 2 diabetes. Analysis of lymphocyte mitochondrial function has been facilitated by introduction of 96-well format extracellular flux (XF96) analyzers, but the technology remains imperfect for analysis of human lymphocytes. Limitations in XF technology include the lack of practical protocols for analysis of archived human cells, and inadequate data analysis tools that require manual quality checks. Current analysis tools for XF outcomes are also unable to automatically assess data quality and delete untenable data from the relatively high number of biological replicates needed to power complex human cell studies. The objectives of work presented herein are to test the impact of common cellular manipulations on XF outcomes, and to develop and validate a new automated tool that objectively analyzes a virtually unlimited number of samples to quantitate mitochondrial function in immune cells. We present significant improvements on previous XF analyses of primary human cells that will be absolutely essential to test the prediction that changes in immune cell mitochondrial function and fuel sources support immune dysfunction in chronic inflammatory diseases like type 2 diabetes. PMID:28178278

  16. Advances in the quantification of mitochondrial function in primary human immune cells through extracellular flux analysis.

    PubMed

    Nicholas, Dequina; Proctor, Elizabeth A; Raval, Forum M; Ip, Blanche C; Habib, Chloe; Ritou, Eleni; Grammatopoulos, Tom N; Steenkamp, Devin; Dooms, Hans; Apovian, Caroline M; Lauffenburger, Douglas A; Nikolajczyk, Barbara S

    2017-01-01

    Numerous studies show that mitochondrial energy generation determines the effectiveness of immune responses. Furthermore, changes in mitochondrial function may regulate lymphocyte function in inflammatory diseases like type 2 diabetes. Analysis of lymphocyte mitochondrial function has been facilitated by introduction of 96-well format extracellular flux (XF96) analyzers, but the technology remains imperfect for analysis of human lymphocytes. Limitations in XF technology include the lack of practical protocols for analysis of archived human cells, and inadequate data analysis tools that require manual quality checks. Current analysis tools for XF outcomes are also unable to automatically assess data quality and delete untenable data from the relatively high number of biological replicates needed to power complex human cell studies. The objectives of work presented herein are to test the impact of common cellular manipulations on XF outcomes, and to develop and validate a new automated tool that objectively analyzes a virtually unlimited number of samples to quantitate mitochondrial function in immune cells. We present significant improvements on previous XF analyses of primary human cells that will be absolutely essential to test the prediction that changes in immune cell mitochondrial function and fuel sources support immune dysfunction in chronic inflammatory diseases like type 2 diabetes.

  17. 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...

  18. 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...

  19. Pharmacology of Nasal Medications: An Update

    PubMed Central

    Martin, G. F.

    1988-01-01

    The author of this article reviews the pharmacology of nasal medication, focusing on the indications and side-effects. The newer group of non-sedating antihistamines proves to be a useful supplement to disodium cromoglycate and the traditional antihistamines in the treatment of allergic rhinitis. The topical steroids (flunisolide and beclomethasone dipropionate) did not produce a significant incidence of adrenal suppression, mucosal atrophy, or nasal candidiasis. The anticholinergic ipatropium bromide shows promise in the treatment of rhinorrhea. The author also reviews the use of decongestants and emollients and remarks on the factors that affect patient compliance when nasal medications are prescribed. PMID:20469495

  20. Microsurgery in nasal polyposis transnasal ethmoidectomy.

    PubMed

    Bagatella, F; Mazzoni, A

    1986-01-01

    Transnasal ethmoidectomy is a current treatment in selected cases of nasal polyposis, and with its complicated anatomy offers a proper opportunity for microsurgery. Ten years' experience of microsurgical ethmoidectomy in 155 patients with nasal polyposis is reported. The surgical anatomy of the ethmoid sinus is reviewed with attention to the requirements of the microsurgical approach, and the operative procedure is described. The microsurgical approach is discussed both as a part of the treatment of nasal polyposis and as a new development in rhinologic surgery. Advantages of the technique are the objective safety against risks of the ethmoid area and enhanced sense of security for the surgeon.

  1. Evaluation and Reduction of Nasal Trauma

    PubMed Central

    Kelley, Brian P.; Downey, Cara R.; Stal, Samuel

    2010-01-01

    Nasal trauma plays a large and important role in the field of craniofacial trauma. The resulting aesthetic, structural, and functional sequelae associated with these injuries necessitate a thorough understanding of the topic. This includes an appreciation for the unique anatomic features of the region, the important aspects of the initial history and examination, nasal injury classification, and subsequent treatment timing and options. While a large body of literature has accumulated on the topic, the purpose of this article is to focus on both clinically relevant information and pearls of management. Additionally, age-specific concerns, secondary procedures, and nasal fracture grafting, will be addressed as well. PMID:22550458

  2. 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.

  3. Efficient nanoparticle mediated sustained RNA interference in