Responses of primary human nasal epithelial cells to EDIII-DENV stimulation: the first step to intranasal dengue vaccination.

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Nantachit, Nattika; Sunintaboon, Panya; Ubol, Sukathida

2016-08-18

About half of the world's population are living in the endemic area of dengue viruses implying that a rapid-mass vaccination may be required. In addition, a major target of dengue vaccine are children, thus, a needle-free administration is more attractive. These problems may be overcome by the alternative route of vaccination such as topical, oral and intranasal vaccination. Here, we investigated the possibility to deliver a dengue immunogen intranasally, a painless route of vaccination. The tested immunogen was the domain III of dengue serotype-3 E protein (EDIII-D3) loaded into trimethyl chitosan nanoparticles (EDIII-D3 TMC NPs). The primary human nasal epithelial cells, HNEpCs, were used as an in vitro model for nasal responses. At tested concentrations, EDIII-D3 TMC NPs not only exerted no detectable toxicity toward HNEpC cultures but also efficiently delivered EDIII-D3 immunogens into HNEpCs. Moreover, HNEpCs quickly and strongly produced proinflammatory cytokines (IL-1β, IL-6, TNF-α), type-I IFN, the growth factors (GM-CSF, IL-7), the chemokines (MCP-1, MIP-1β, IL-8), Th1-related cytokines (IL-2, IL-12p70, IL-17, IFN-γ) and Th2-related cytokine (IL-4) in response to EDIII-D3 TMC NPs treatment. A potential mucosal delivery system for dengue immunogens was revealed and found to stimulate a strong local innate antiviral response which possibly leading to a systemic adaptive immunity.

Absorption and Clearance of Pharmaceutical Aerosols in the Human Nose: Effects of Nasal Spray Suspension Particle Size and Properties.

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Rygg, Alex; Hindle, Michael; Longest, P Worth

2016-04-01

The objective of this study was to use a recently developed nasal dissolution, absorption, and clearance (DAC) model to evaluate the extent to which suspended drug particle size influences nasal epithelial drug absorption for a spray product. Computational fluid dynamics (CFD) simulations of mucociliary clearance and drug dissolution were used to calculate total and microscale epithelial absorption of drug delivered with a nasal spray pump. Ranges of suspended particle sizes, drug solubilities, and partition coefficients were evaluated. Considering mometasone furoate as an example, suspended drug particle sizes in the range of 1-5 μm did not affect the total nasal epithelial uptake. However, the microscale absorption of suspended drug particles with low solubilities was affected by particle size and this controlled the extent to which the drug penetrated into the distal nasal regions. The nasal-DAC model was demonstrated to be a useful tool in determining the nasal exposure of spray formulations with different drug particle sizes and solubilities. Furthermore, the model illustrated a new strategy for topical nasal drug delivery in which drug particle size is selected to increase the region of epithelial surface exposure using mucociliary clearance while minimizing the drug dose exiting the nasopharynx.

Epithelial cells as alternative human biomatrices for comet assay.

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Rojas, Emilio; Lorenzo, Yolanda; Haug, Kristiane; Nicolaissen, Bjørn; Valverde, Mahara

2014-01-01

The comet assay is a valuable experimental tool aimed at mapping DNA damage in human cells in vivo for environmental and occupational monitoring, as well as for therapeutic purposes, such as storage prior to transplant, during tissue engineering, and in experimental ex vivo assays. Furthermore, due to its great versatility, the comet assay allows to explore the use of alternative cell types to assess DNA damage, such as epithelial cells. Epithelial cells, as specialized components of many organs, have the potential to serve as biomatrices that can be used to evaluate genotoxicity and may also serve as early effect biomarkers. Furthermore, 80% of solid cancers are of epithelial origin, which points to the importance of studying DNA damage in these tissues. Indeed, studies including comet assay in epithelial cells have either clear clinical applications (lens and corneal epithelial cells) or examine genotoxicity within human biomonitoring and in vitro studies. We here review improvements in determining DNA damage using the comet assay by employing lens, corneal, tear duct, buccal, and nasal epithelial cells. For some of these tissues invasive sampling procedures are needed. Desquamated epithelial cells must be obtained and dissociated prior to examination using the comet assay, and such procedures may induce varying amounts of DNA damage. Buccal epithelial cells require lysis enriched with proteinase K to obtain free nucleosomes. Over a 30 year period, the comet assay in epithelial cells has been little employed, however its use indicates that it could be an extraordinary tool not only for risk assessment, but also for diagnosis, prognosis of treatments and diseases.

Characterization of epithelial domains in the nasal passages of chick embryos: spatial and temporal mapping of a range of extracellular matrix and cell surface molecules during development of the nasal placode.

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Croucher, S J; Tickle, C

1989-07-01

The formation of the nasal passages involves complex morphogenesis and their lining develops a spatially ordered pattern of differentiation, with distinct domains of olfactory and respiratory epithelium. Using antibodies to the neural cell adhesion molecule (N-CAM), keratan sulphate and heparan sulphate proteoglycan (HSPG) and a panel of lectins (agglutinins of Canavalia ensiformis (ConA), Dolichos biflorus (DBA), peanut (PNA), Ricinis communis (RCA1), soybean (SBA), Ulex europaeus (UEA1), and wheatgerm (WGA], we have documented cell surface characteristics of each epithelial domain. Binding of antibodies to N-CAM and to keratan sulphate, and the lectins ConA, PNA, RCA1, SBA and WGA marks the olfactory epithelial domain only. The restriction of N-CAM to the sensory region of the epithelium has also been reported in the developing ear. This striking similarity is consistent with the idea that N-CAM may be involved in the division of functionally and histologically distinct cell groups within an epithelium. We traced the olfactory-specific cell markers during development to gain insights into the origin of the epithelial lining of the nasal passages. All reagents bind at early stages to the thickened nasal placode and surrounding head ectoderm and then become progressively restricted to the olfactory domain. The expression of these characteristics appears to be modulated during development rather than being cell autonomous. The distribution of keratan sulphate was compared with collagen type II in relation to the specification of the chondrocranium. Keratan sulphate and collagen type II are only colocalized at the epithelial-mesenchymal interface during early nasal development. At later stages, only collagen type II is expressed at the interface throughout the nasal passages, whereas keratan sulphate is absent beneath the respiratory epithelium.

The effects of gas humidification with high-flow nasal cannula on cultured human airway epithelial cells.

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

2012-01-01

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

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

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Aaron Chidekel

2012-01-01

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

Poly(I:C) reduces expression of JAM-A and induces secretion of IL-8 and TNF-α via distinct NF-κB pathways in human nasal epithelial cells

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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 3 CSK 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-α. Both the reduction of JAM-A expression and the induction of secretion of IL-8 and TNF-α 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-κB 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.

Responses of well-differentiated nasal epithelial cells exposed to particles: Role of the epithelium in airway inflammation

International Nuclear Information System (INIS)

Auger, Floriane; Gendron, Marie-Claude; Chamot, Christophe; Marano, Francelyne; Dazy, Anne-Catherine

2006-01-01

Numerous epidemiological studies support the contention that ambient air pollution particles can adversely affect human health. To explain the acute inflammatory process in airways exposed to particles, a number of in vitro studies have been performed on cells grown submerged on plastic and poorly differentiated, and on cell lines, the physiology of which is somewhat different from that of well-differentiated cells. In order to obtain results using a model system in which epithelial cells are similar to those of the human airway in vivo, apical membranes of well-differentiated human nasal epithelial (HNE) cells cultured in an air-liquid interface (ALI) were exposed for 24 h to diesel exhaust particles (DEP) and Paris urban air particles (PM 2.5 ). DEP and PM 2.5 (10-80 μg/cm 2 ) stimulated both IL-8 and amphiregulin (ligand of EGFR) secretion exclusively towards the basal compartment. In contrast, there was no IL-1β secretion and only weak non-reproducible secretion of TNF-α. IL-6 and GM-CSF were consistently stimulated towards the apical compartment and only when cells were exposed to PM 2.5 . ICAM-1 protein expression on cell surfaces remained low after particle exposure, although it increased after TNF-α treatment. Internalization of particles, which is believed to initiate oxidative stress and proinflammatory cytokine expression, was restricted to small nanoparticles (≤ 40 nm). Production of reactive oxygen species (ROS) was detected, and DEP were more efficient than PM 2.5 . Collectively, our results suggest that airway epithelial cells exposed to particles augment the local inflammatory response in the lung but cannot alone initiate a systemic inflammatory response

Reduced expression IRF7 in nasal epithelial cells from smokers as a potential mechanism mediating enhanced susceptibility to influenza

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Rationale: Smokers are more susceptible to viral infections, including influenza virus, yet the mechanisms mediating this effect are not known. Methods: We have established an in vitro model of differentiated nasal epithelial cells from smokers, which maintain enhanced levels...

Regional deposition of mometasone furoate nasal spray suspension in humans.

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Shah, Samir A; Berger, Robert L; McDermott, John; Gupta, Pranav; Monteith, David; Connor, Alyson; Lin, Wu

2015-01-01

Nasal deposition studies can demonstrate whether nasal sprays treating allergic rhinitis and polyposis reach the ciliated posterior nasal cavity, where turbinate inflammation and other pathology occurs. However, quantifying nasal deposition is challenging, because in vitro tests do not correlate to human nasal deposition; gamma scintigraphy studies are thus used. For valid data, the radiolabel must distribute, as the drug, into different-sized droplets, remain associated with the drug in the formulation after administration, and not alter its deposition. Some nasal deposition studies have demonstrated this using homogenous solutions. However, most commercial nasal sprays are heterogeneous suspensions. Using mometasone furoate nasal suspension (MFS), we developed a technique to validate radiolabel deposition as a surrogate for nasal cavity drug deposition and characterized regional deposition and nasal clearance in humans. Mometasone furoate (MF) formulation was spiked with diethylene triamine pentacaetic acid. Both unlabeled and radiolabeled formulations (n = 3) were sprayed into a regionally divided nasal cast. Drug deposition was quantified by high pressure liquid chromatography within each region; radiolabel deposition was determined by gamma camera. Healthy subjects (n = 12) were dosed and imaged for six hours. Scintigraphic images were coregistered with magnetic resonance imaging scans to quantify anterior and posterior nasal cavity deposition and mucociliary clearance. The ratio of radiolabel to unlabeled drug was 1.05 in the nasal cast and regionally appeared to match, indicating that in vivo radiolabel deposition could represent drug deposition. In humans, MFS delivered 86% (9.2) of metered dose to the nasal cavity, approximately 60% (9.1) of metered dose to the posterior nasal cavity. After 15 minutes, mucociliary clearance removed 59% of the initial radiolabel in the nasal cavity, consistent with clearance rates from the ciliated posterior surface. MFS

In vivo effects of dexamethasone and indomethacin on neutrophil-induced alterations of nasal epithelial mucosubstances

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Hotchkiss, J A; Portereiko, J V; Harkema, J R

1988-12-01

Previous studies have shown that neutrophils migrating through rat nasal mucosal epithelium, in response to intranasal instillation of endotoxin, induce a transient decrease in stored epithelial mucosubstances. Prostaglandins and leukotrienes can either increase or decrease mucous secretion of airway epithelia in vitro. In this study, rats were treated with indomethacin a specific inhibitor of prostaglandin synthesis, or with dexamethasone, a general inhibitor of arachidonic acid metabolism, and challenged with intranasally instilled endotoxin. Dexamethasone alone or in combination with indomethacin, but not indomethacin alone, significantly altered the neutrophil response to intranasally instilled endotoxin and may have inhibited the neutrophil-induced decrease in stored mucosubstances. These data suggest that leukotrienes and possibly prostaglandins play a significant role in the coordinated response of the nasal mucosal epitholium to an acute inflammatory stimulus. (author)

In vivo effects of dexamethasone and indomethacin on neutrophil-induced alterations of nasal epithelial mucosubstances

International Nuclear Information System (INIS)

Hotchkiss, J.A.; Portereiko, J.V.; Harkema, J.R.

1988-01-01

Previous studies have shown that neutrophils migrating through rat nasal mucosal epithelium, in response to intranasal instillation of endotoxin, induce a transient decrease in stored epithelial mucosubstances. Prostaglandins and leukotrienes can either increase or decrease mucous secretion of airway epithelia in vitro. In this study, rats were treated with indomethacin a specific inhibitor of prostaglandin synthesis, or with dexamethasone, a general inhibitor of arachidonic acid metabolism, and challenged with intranasally instilled endotoxin. Dexamethasone alone or in combination with indomethacin, but not indomethacin alone, significantly altered the neutrophil response to intranasally instilled endotoxin and may have inhibited the neutrophil-induced decrease in stored mucosubstances. These data suggest that leukotrienes and possibly prostaglandins play a significant role in the coordinated response of the nasal mucosal epitholium to an acute inflammatory stimulus. (author)

Expression and functional activity of P-glycoprotein in passaged primary human nasal epithelial cell monolayers cultured by the air-liquid interface method for nasal drug transport study.

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Cho, Hyun-Jong; Choi, Min-Koo; Lin, Hongxia; Kim, Jung Sun; Chung, Suk-Jae; Shim, Chang-Koo; Kim, Dae-Duk

2011-03-01

P-glycoprotein (P-gp) is an efflux transporter encoded by the multidrug resistance gene (MDR1), which is also known as the human ABCB1 gene (ATP-binding cassette, subfamily-B). The objectives of this study were to investigate the expression of P-gp in passaged primary human nasal epithelial (HNE) cell monolayer, cultured by the air-liquid interface (ALI) method, and to evaluate its feasibility as an in-vitro model for cellular uptake and transport studies of P-gp substrates. Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to verify the expression of the MDR1 gene. Transport and cellular uptake studies with P-gp substrate (rhodamine123) and P-gp inhibitors (verapamil and cyclosporin A) were conducted to assess the functional activity of P-gp in HNE cell monolayers cultured by the ALI method. MDR1 gene expression in primary HNE cell monolayers cultured by ALI method was confirmed by RT-PCR. The apparent permeability coefficient (P(app) ) of the P-gp substrate (rhodamine123) in the basolateral to apical (B to A) direction was 6.9 times higher than that in the apical to basolateral (A to B) direction. B to A transport was saturated at high rhodamine123 concentration, and the treatment of P-gp inhibitors increased cellular uptake of rhodamine123 in a time- and concentration-dependent manner. These results support the MDR1 gene expression and the functional activity of P-gp in primary HNE cell monolayers cultured by the ALI method. © 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.

Herpes viruses and human papilloma virus in nasal polyposis and controls

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Dimitrios Ioannidis

2015-12-01

Full Text Available ABSTRACT INTRODUCTION: Chronic rhinosinusitis with nasal polyps is a multifactorial disease entity with an unclear pathogenesis. Contradictory data exist in the literature on the potential implication of viral elements in adult patients with chronic rhinosinusitis. OBJECTIVE: To compare the prevalence of human herpes viruses (1-6 and Human Papilloma Virus in adult patients with chronic rhinosinusitis with nasal polyps and healthy controls. METHODS: Viral DNA presence was evaluated by real-time polymerase chain reaction application to nasal polyps specimens from 91 chronic rhinosinusitis with nasal polyps patients and nasal turbinate mucosa from 38 healthy controls. RESULTS: Epstein-Barr virus positivity was higher in nasal polyps (24/91; 26.4% versus controls (4/38; 10.5%, but the difference did not reach significance (p = 0.06. Human herpes virus-6 positivity was lower in nasal polyps (13/91; 14.29% versus controls (10/38; 26.32%,p = 0.13. In chronic rhinosinusitis with nasal polyps group, 1 sample was herpes simplex virus-1-positive (1/91; 1.1%, and another was cytomegalovirus-positive (1/91; 1.1%, versus none in controls. No sample was positive for herpes simplex virus-2, varicella-zoster virus, high-risk-human papilloma viruses (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and low-risk-human papilloma viruses (6, 11. CONCLUSION: Differences in Epstein-Barr virus and human herpes virus-6 positivity among patients with chronic rhinosinusitis with nasal polyps and healthy controls are not statistically significant, weakening the likelihood of their implication in chronic rhinosinusitis with nasal polyps pathogenesis.

Interaction of Mycobacterium leprae with human airway epithelial cells: adherence, entry, survival, and identification of potential adhesins by surface proteome analysis.

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Silva, Carlos A M; Danelishvili, Lia; McNamara, Michael; Berredo-Pinho, Márcia; Bildfell, Robert; Biet, Franck; Rodrigues, Luciana S; Oliveira, Albanita V; Bermudez, Luiz E; Pessolani, Maria C V

2013-07-01

This study examined the in vitro interaction between Mycobacterium leprae, the causative agent of leprosy, and human alveolar and nasal epithelial cells, demonstrating that M. leprae can enter both cell types and that both are capable of sustaining bacterial survival. Moreover, delivery of M. leprae to the nasal septum of mice resulted in macrophage and epithelial cell infection in the lung tissue, sustaining the idea that the airways constitute an important M. leprae entry route into the human body. Since critical aspects in understanding the mechanisms of infection are the identification and characterization of the adhesins involved in pathogen-host cell interaction, the nude mouse-derived M. leprae cell surface-exposed proteome was studied to uncover potentially relevant adhesin candidates. A total of 279 cell surface-exposed proteins were identified based on selective biotinylation, streptavidin-affinity purification, and shotgun mass spectrometry; 11 of those proteins have been previously described as potential adhesins. In vitro assays with the recombinant forms of the histone-like protein (Hlp) and the heparin-binding hemagglutinin (HBHA), considered to be major mycobacterial adhesins, confirmed their capacity to promote bacterial attachment to epithelial cells. Taking our data together, they suggest that the airway epithelium may act as a reservoir and/or portal of entry for M. leprae in humans. Moreover, our report sheds light on the potentially critical adhesins involved in M. leprae-epithelial cell interaction that may be useful in designing more effective tools for leprosy control.

Herpes viruses and human papilloma virus in nasal polyposis and controls.

Science.gov (United States)

Ioannidis, Dimitrios; Lachanas, Vasileios A; Florou, Zoe; Bizakis, John G; Petinaki, Efthymia; Skoulakis, Charalampos E

2015-01-01

Chronic rhinosinusitis with nasal polyps is a multifactorial disease entity with an unclear pathogenesis. Contradictory data exist in the literature on the potential implication of viral elements in adult patients with chronic rhinosinusitis. To compare the prevalence of human herpes viruses (1-6) and Human Papilloma Virus in adult patients with chronic rhinosinusitis with nasal polyps and healthy controls. Viral DNA presence was evaluated by real-time polymerase chain reaction application to nasal polyps specimens from 91 chronic rhinosinusitis with nasal polyps patients and nasal turbinate mucosa from 38 healthy controls. Epstein-Barr virus positivity was higher in nasal polyps (24/91; 26.4%) versus controls (4/38; 10.5%), but the difference did not reach significance (p=0.06). Human herpes virus-6 positivity was lower in nasal polyps (13/91; 14.29%) versus controls (10/38; 26.32%, p=0.13). In chronic rhinosinusitis with nasal polyps group, 1 sample was herpes simplex virus-1-positive (1/91; 1.1%), and another was cytomegalovirus-positive (1/91; 1.1%), versus none in controls. No sample was positive for herpes simplex virus-2, varicella-zoster virus, high-risk-human papilloma viruses (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59) and low-risk-human papilloma viruses (6, 11). Differences in Epstein-Barr virus and human herpes virus-6 positivity among patients with chronic rhinosinusitis with nasal polyps and healthy controls are not statistically significant, weakening the likelihood of their implication in chronic rhinosinusitis with nasal polyps pathogenesis. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Nasal cytochrome P4502A: Identification in rats and humans

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Thornton-Manning, J.R.; Hotchkiss, J.A. [Michigan State Univ., East Lansing, MI (United States); Ding, Xinxin [Wadsworth Center for Laboratories and Research, Albany, NY (United States)] [and others

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.

Biological safety of nasal thallium-201 administration. A preclinical study for olfacto-scintigraphy

International Nuclear Information System (INIS)

Washiyama, Kohshin; Shiga, Hideaki; Hirota, Kyoko

2011-01-01

Nasal administration of thallium-201 ( 201 Tl) has previously been shown to be useful for the assessment of olfactory nerve connectivity in vivo. We assessed the biological effects of nasal 201 Tl administration in mice to determine its safety before conducting clinical trials on humans. 201 Tl uptake was evaluated in normal mice (n=5) in vivo by using a high-resolution gamma camera and radiography 15 min, 1, 2 and 9 d after administration of 201 TlCl to the right side of the nasal cavity (10 μl 201 TlCl per nostril, 74 MBq/ml). Murine olfactory epithelial thickness (n=5) was measured 9 d following nasal administration of 201 TlCl. We assessed the odor detection ability of normal mice (n=8) following nasal administration of 201 TlCl to both sides of the nasal cavity, by observing cycloheximide solution avoidance behavior. We subsequently administrated 201 TlCl (n=4) or saline (n=4) to both nostrils to assess the odor detection ability of mice following bilateral olfactory nerve transection. 201 Tl uptake by the nasal cavity decreased immediately following nasal administration of 201 Tl in normal mice. Nasal administration of 201 Tl did not affect the olfactory epithelial thickness or the odor detection ability of normal mice. Recovery of odor detection ability following olfactory nerve transection was not significantly different between mice nasally administered with 201 Tl, and mice administered with saline. Thus, nasal administration of 201 Tl for the diagnosis of traumatic olfactory impairment did not produce harmful biological effects in vivo. (author)

Zicam-induced damage to mouse and human nasal tissue.

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Jae H Lim

Full Text Available Intranasal medications are used to treat various nasal disorders. However, their effects on olfaction remain unknown. Zicam (zinc gluconate; Matrixx Initiatives, Inc, a homeopathic substance marketed to alleviate cold symptoms, has been implicated in olfactory dysfunction. Here, we investigated Zicam and several common intranasal agents for their effects on olfactory function. Zicam was the only substance that showed significant cytotoxicity in both mouse and human nasal tissue. Specifically, Zicam-treated mice had disrupted sensitivity of olfactory sensory neurons to odorant stimulation and were unable to detect novel odorants in behavioral testing. These findings were long-term as no recovery of function was observed after two months. Finally, human nasal explants treated with Zicam displayed significantly elevated extracellular lactate dehydrogenase levels compared to saline-treated controls, suggesting severe necrosis that was confirmed on histology. Our results demonstrate that Zicam use could irreversibly damage mouse and human nasal tissue and may lead to significant smell dysfunction.

Correlation of nasal geometry with aerosol deposition in human volunteers

International Nuclear Information System (INIS)

Cheng, Yung-Seng; Simpson, S.Q.; Cheng, Kuo-His; Swift, D.L.; Yeh, Hsu-Chi; Guilmette, R.A.

1994-01-01

The nasal airways act as the first filter in the respiratory tract to remove very large or small particles, that would otherwise penetrate to the lower airways. Aerosol deposition data obtained with human volunteers vary considerably under comparable experimental conditions. Reasons for the intersubject variations have been frequently attributed to the geometry of the nasal passages. Because there is no direct proof of this hypothesis, nasal deposition of ultrafine particles in human volunteers has been studied in our laboratory. Preliminary results obtained with four adult volunteers also vary considerably between subjects. The purpose of this part of the study was to establish a theoretical equation relating diffusional deposition in nasal airways to the geometrical dimensions of the individual nasal airways. This relationship was then applied to the experimental deposition data and measurement of airway morphometry for correlation

Electronic cigarette liquid increases inflammation and virus infection in primary human airway epithelial cells.

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Wu, Qun; Jiang, Di; Minor, Maisha; Chu, Hong Wei

2014-01-01

The use of electronic cigarettes (e-cigarettes) is rapidly increasing in the United States, especially among young people since e-cigarettes have been perceived as a safer alternative to conventional tobacco cigarettes. However, the scientific evidence regarding the human health effects of e-cigarettes on the lung is extremely limited. The major goal of our current study is to determine if e-cigarette use alters human young subject airway epithelial functions such as inflammatory response and innate immune defense against respiratory viral (i.e., human rhinovirus, HRV) infection. We examined the effects of e-cigarette liquid (e-liquid) on pro-inflammatory cytokine (e.g., IL-6) production, HRV infection and host defense molecules (e.g., short palate, lung, and nasal epithelium clone 1, SPLUNC1) in primary human airway epithelial cells from young healthy non-smokers. Additionally, we examined the role of SPLUNC1 in lung defense against HRV infection using a SPLUNC1 knockout mouse model. We found that nicotine-free e-liquid promoted IL-6 production and HRV infection. Addition of nicotine into e-liquid further amplified the effects of nicotine-free e-liquid. Moreover, SPLUNC1 deficiency in mice significantly increased lung HRV loads. E-liquid inhibited SPLUNC1 expression in primary human airway epithelial cells. These findings strongly suggest the deleterious health effects of e-cigarettes in the airways of young people. Our data will guide future studies to evaluate the impact of e-cigarettes on lung health in human populations, and help inform the public about potential health risks of e-cigarettes.

Electronic cigarette liquid increases inflammation and virus infection in primary human airway epithelial cells.

Directory of Open Access Journals (Sweden)

Qun Wu

Full Text Available The use of electronic cigarettes (e-cigarettes is rapidly increasing in the United States, especially among young people since e-cigarettes have been perceived as a safer alternative to conventional tobacco cigarettes. However, the scientific evidence regarding the human health effects of e-cigarettes on the lung is extremely limited. The major goal of our current study is to determine if e-cigarette use alters human young subject airway epithelial functions such as inflammatory response and innate immune defense against respiratory viral (i.e., human rhinovirus, HRV infection.We examined the effects of e-cigarette liquid (e-liquid on pro-inflammatory cytokine (e.g., IL-6 production, HRV infection and host defense molecules (e.g., short palate, lung, and nasal epithelium clone 1, SPLUNC1 in primary human airway epithelial cells from young healthy non-smokers. Additionally, we examined the role of SPLUNC1 in lung defense against HRV infection using a SPLUNC1 knockout mouse model. We found that nicotine-free e-liquid promoted IL-6 production and HRV infection. Addition of nicotine into e-liquid further amplified the effects of nicotine-free e-liquid. Moreover, SPLUNC1 deficiency in mice significantly increased lung HRV loads. E-liquid inhibited SPLUNC1 expression in primary human airway epithelial cells. These findings strongly suggest the deleterious health effects of e-cigarettes in the airways of young people. Our data will guide future studies to evaluate the impact of e-cigarettes on lung health in human populations, and help inform the public about potential health risks of e-cigarettes.

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

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

2009-09-01

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

Mechanics of airflow in the human nasal airways.

Science.gov (United States)

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.

In vitro systems toxicology approach to investigate the effects of repeated cigarette smoke exposure on human buccal and gingival organotypic epithelial tissue cultures.

Science.gov (United States)

Schlage, Walter K; Iskandar, Anita R; Kostadinova, Radina; Xiang, Yang; Sewer, Alain; Majeed, Shoaib; Kuehn, Diana; Frentzel, Stefan; Talikka, Marja; Geertz, Marcel; Mathis, Carole; Ivanov, Nikolai; Hoeng, Julia; Peitsch, Manuel C

2014-10-01

Smoking has been associated with diseases of the lung, pulmonary airways and oral cavity. Cytologic, genomic and transcriptomic changes in oral mucosa correlate with oral pre-neoplasia, cancer and inflammation (e.g. periodontitis). Alteration of smoking-related gene expression changes in oral epithelial cells is similar to that in bronchial and nasal epithelial cells. Using a systems toxicology approach, we have previously assessed the impact of cigarette smoke (CS) seen as perturbations of biological processes in human nasal and bronchial organotypic epithelial culture models. Here, we report our further assessment using in vitro human oral organotypic epithelium models. We exposed the buccal and gingival organotypic epithelial tissue cultures to CS at the air-liquid interface. CS exposure was associated with increased secretion of inflammatory mediators, induction of cytochrome P450s activity and overall weak toxicity in both tissues. Using microarray technology, gene-set analysis and a novel computational modeling approach leveraging causal biological network models, we identified CS impact on xenobiotic metabolism-related pathways accompanied by a more subtle alteration in inflammatory processes. Gene-set analysis further indicated that the CS-induced pathways in the in vitro buccal tissue models resembled those in the in vivo buccal biopsies of smokers from a published dataset. These findings support the translatability of systems responses from in vitro to in vivo and demonstrate the applicability of oral organotypical tissue models for an impact assessment of CS on various tissues exposed during smoking, as well as for impact assessment of reduced-risk products.

Nasal obstruction and human communication.

Science.gov (United States)

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.

Puerarin transport across rat nasal epithelial cells and the influence of compatibility with paeoniflorin and menthol

Directory of Open Access Journals (Sweden)

Zhang L

2017-09-01

Full Text Available Lin Zhang, Shou-Ying Du, Yang Lu, Chang Liu, Hui-Chao Wu, Zhi-Hao Tian, Min Wang, Chang Yang School of Chinese Materia Medica, Beijing University of Chinese Medicine, Chaoyang District, Beijing, People’s Republic of China Abstract: Nose-to-brain transport can provide an excellent pathway for drugs of the central nervous system. Consequently, how to make full use of this pathway in practical applications has become a focus of drug design. However, many aspects affecting drug delivery from the nose to the brain remain unclear. This study aimed to more deeply investigate the transport of puerarin and to explore the mechanism underlying the influence of compatible drugs on puerarin permeability in a primary cell model simulating the nasal mucosa. In this research, based on rat nasal epithelial cells (RNECs cultured in vitro and cytotoxicity assays, the bidirectional transport of puerarin across RNEC monolayers and the effect of its compatibility with peoniflorin and menthol were analyzed. The apparent permeability coefficient was <1.5×10–6 cm/s, and the efflux ratio of puerarin was <2, indicating that puerarin had poor absorption and that menthol but not peoniflorin significantly improved puerarin transport. Simultaneously, through experiments, such as immunofluorescence staining, transepithelial electrical resistance measurement, rhodamine 123 efflux evaluation, the cell membrane fluorescence recovery after photobleaching test, and ATPase activity determination, the permeability promoting mechanism of menthol was confirmed to be closely related to disruption of the tight junction protein structure, to the P-glycoprotein inhibitory effect, to increased membrane fluidity, and to the promotion of enzyme activity. These results provide reliable data on nasal administration of the studied drugs and lay the foundation for a deeper investigation of the nose–brain pathway and nasal administration. Keywords: Chinese herbal compound

Modulation of epithelial sodium channel in human alveolar epithelial ...

African Journals Online (AJOL)

Modulation of epithelial sodium channel in human alveolar epithelial cells by lipoxin A4 through AhR-cAMP-dependent pathway. Bi-Huan Cheng1,2, Li-Wei Pan2, Sheng-Rong Zhang3, Bin-Yu Ying2, Ben-Ji. Wang2, Guo-Liang Lin2 and Shi-Fang Ding1*. 1Department of Critical Care Medicine, Qilu Hospital of Shandong ...

Ultrastructural nasal pathology in children chronically and sequentially exposed to air pollutants.

Science.gov (United States)

Calderón-Garcidueñas, L; Valencia-Salazar, G; Rodríguez-Alcaraz, A; Gambling, T M; García, R; Osnaya, N; Villarreal-Calderón, A; Devlin, R B; Carson, J L

2001-02-01

Southwest Metropolitan Mexico City (SWMMC) children are repeatedly exposed to a complex mixture of air pollutants, including ozone, particulate matter, and aldehydes. Nasal biopsies taken from these children exhibit a wide range of histopathologic alterations: marked changes in ciliated and goblet cell populations, basal cell hyperplasia, squamous metaplasia, and mild dysplasias. We studied the ultrastructural features of 15 nasal biopsies obtained from clinically healthy children 4 to 15 yr of age, growing up in SWMMC. The results were compared with nasal biopsies from 11 children growing up in Veracruz and exposed to low pollutant levels. Ultrathin sections of nasal biopsies revealed an unremarkable mucociliary epithelium in control children, whereas SWMMC children showed an epithelium comprised of variable numbers of basal, ciliated, goblet, and squamous metaplastic as well as intermediate cells. Nascent ciliated cells, as evidenced by the presence of migratory kinetosomes, were common, as were ciliary abnormalities, including absent central microtubules, supernumerary central and peripheral tubules, ciliary microtubular discontinuities, and compound cilia. Dyskinesia associated with these abnormal cilia was suggested by the altered orientation of the central microtubules in closely adjacent cilia. A transudate was evident between epithelial cells, suggesting potential deficiencies in epithelial junction integrity. Particulate matter was present in heterolysosomal bodies in epithelial cells and it was also deposited in intercellular spaces. The severe structural alteration of the nasal epithelium together with the prominent acquired ciliary defects are likely the result of chronic airway injury in which ozone, particulate matter, and aldehydes are thought to play a crucial role. The nasal epithelium in SWMMC children is fundamentally disordered, and their mucociliary defense mechanisms are no longer intact. A compromised nasal epithelium has less ability to

Characterization of deposition from nasal spray devices using a computational fluid dynamics model of the human nasal passages.

Science.gov (United States)

Kimbell, Julia S; Segal, Rebecca A; Asgharian, Bahman; Wong, Brian A; Schroeter, Jeffry D; Southall, Jeremy P; Dickens, Colin J; Brace, Geoff; Miller, Frederick J

2007-01-01

Many studies suggest limited effectiveness of spray devices for nasal drug delivery due primarily to high deposition and clearance at the front of the nose. Here, nasal spray behavior was studied using experimental measurements and a computational fluid dynamics model of the human nasal passages constructed from magnetic resonance imaging scans of a healthy adult male. Eighteen commercially available nasal sprays were analyzed for spray characteristics using laser diffraction, high-speed video, and high-speed spark photography. Steadystate, inspiratory airflow (15 L/min) and particle transport were simulated under measured spray conditions. Simulated deposition efficiency and spray behavior were consistent with previous experimental studies, two of which used nasal replica molds based on this nasal geometry. Deposition fractions (numbers of deposited particles divided by the number released) of 20- and 50-microm particles exceeded 90% in the anterior part of the nose for most simulated conditions. Predicted particle penetration past the nasal valve improved when (1) the smaller of two particle sizes or the lower of two spray velocities was used, (2) the simulated nozzle was positioned 1.0 rather than 0.5 or 1.5 cm into the nostril, and (3) inspiratory airflow was present rather than absent. Simulations also predicted that delaying the appearance of normal inspiratory airflow more than 1 sec after the release of particles produced results equivalent to cases in which no inspiratory airflow was present. These predictions contribute to more effective design of drug delivery devices through a better understanding of the effects of nasal airflow and spray characteristics on particle transport in the nose.

On the relation of nasal cycling with nasal airway dimensions

Energy Technology Data Exchange (ETDEWEB)

Guilmette, R A; Wolff, R K

1988-12-01

The size and configuration of the nasal airways of humans change with time as a result of the normal process of congestion/decongestion of the erectile tissue of the nasal mucosa. To determine the extent to which airway areas change in vivo, we used magnetic resonance imaging (MRI) to quantitate both the cross-sectional area and perimeter of coronal sections of the entire nasal airway of a human subject. Changes in airway size or patency were indexed to measured changes in unilateral nasal airway resistance determined by posterior rhino manometry. The results of this study in which two MRI scans were performed for presumed left-side patency and two for right-side patency, showed that changes in nasal airway resistance were difficult to ascribe to systematic changes In the sizes of the airways. (author)

On the relation of nasal cycling with nasal airway dimensions

International Nuclear Information System (INIS)

Guilmette, R.A.; Wolff, R.K.

1988-01-01

The size and configuration of the nasal airways of humans change with time as a result of the normal process of congestion/decongestion of the erectile tissue of the nasal mucosa. To determine the extent to which airway areas change in vivo, we used magnetic resonance imaging (MRI) to quantitate both the cross-sectional area and perimeter of coronal sections of the entire nasal airway of a human subject. Changes in airway size or patency were indexed to measured changes in unilateral nasal airway resistance determined by posterior rhino manometry. The results of this study in which two MRI scans were performed for presumed left-side patency and two for right-side patency, showed that changes in nasal airway resistance were difficult to ascribe to systematic changes In the sizes of the airways. (author)

Early remodeling of nasal mucosa in rat model after radiation injury

International Nuclear Information System (INIS)

Xiao Mang; Tang Jianguo; Luo Baozhen; Zhao Li'na; Shi Guozhi

2008-01-01

Objective: To explore the feature of nasal mucosa remodeling in experimental radiation injury. Methods: Fourty male rats were randomly divided into five groups, as control group and radiation injury groups (radiation dose were 20 Gy, 30 Gy, 40 Gy and 50 Gy). Each group had 8 rats. Two weeks after the last irradiation, the rats were killed and the nasal middle turbinates of the animals were removed. The tissue blocks were embedded in paraffin. The paraffin sections were stained with hematoxylin and eosin (HE), alcian blue- periodic acid-Schif (AB-PAS), and Masson Trichrome (MT). The infiltrating eosinophils in nasal mucosa were examined. AB-PAS positive cells in the surface epithelium in nasal mucosa were counted. The percentage of area in MT stained extracellular matrix in nasal mucosa and damage of epithelium were determined by an image analyzer. Results: The control group only presented a few eosinophils. Significant eosinophil infiltration was observed in the radiation injury groups, especially for the 30 Gy radiation injury group. Compared with the control group, there was no significant epithelial damage in 20 Gy radiation injury group. Significant epithelial damage were observed in the rest of radiation injury groups. The epithelial damage became more severe as the radiation dose increasing. A little but not significant increase in AB-PAS positive cells was observed in the mucos of the 20 Gy radiation injury group and significant increase in the 30 and 40 Gy groups. But in the 50 Gy radiation injury group, the AB-PAS positive cells were decreased compared with control group. The collagen fibrils in the mucosa of nasal middle turbinate in 20 Gy radiation injury group did not significantly increase.. But in the other groups, the increase was significant compared with that of control group. Furthermore, collagen fibrils increased as the radiation dose increased. Conclusions: Epithelial damage, goblet cells hyperplasia and extracellular matrix deposition are the

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

Science.gov (United States)

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

2016-10-01

In this study, the effects of nasal drug delivery device and the spray nozzle orientation on sprayed droplets deposition in a realistic human nasal cavity were numerically studied. Prior to performing the numerical investigation, an in-house designed automated actuation system representing mean adults actuation force was developed to produce realistic spray plume. Then, the spray plume development was filmed by high speed photography system, and spray characteristics such as spray cone angle, break-up length, and average droplet velocity were obtained through off-line image analysis. Continuing studies utilizing those experimental data as boundary conditions were applied in the following numerical spray simulations using a commercially available nasal spray device, which was inserted into a realistic adult nasal passage with external facial features. Through varying the particle releasing direction, the deposition fractions of selected particle sizes on the main nasal passage for targeted drug delivery were compared. The results demonstrated that the middle spray direction showed superior spray efficiency compared with upper or lower directions, and the 10µm agents were the most suitable particle size as the majority of sprayed agents can be delivered to the targeted area, the main passage. This study elaborates a comprehensive approach to better understand nasal spray mechanism and evaluate its performance for existing nasal delivery practices. Results of this study can assist the pharmaceutical industry to improve the current design of nasal drug delivery device and ultimately benefit more patients through optimized medications delivery. Copyright © 2016 Elsevier Ltd. All rights reserved.

Shared Gene Expression Alterations in Nasal and Bronchial Epithelium for Lung Cancer Detection.

Science.gov (United States)

2017-07-01

We previously derived and validated a bronchial epithelial gene expression biomarker to detect lung cancer in current and former smokers. Given that bronchial and nasal epithelial gene expression are similarly altered by cigarette smoke exposure, we sought to determine if cancer-associated gene expression might also be detectable in the more readily accessible nasal epithelium. Nasal epithelial brushings were prospectively collected from current and former smokers undergoing diagnostic evaluation for pulmonary lesions suspicious for lung cancer in the AEGIS-1 (n = 375) and AEGIS-2 (n = 130) clinical trials and gene expression profiled using microarrays. All statistical tests were two-sided. We identified 535 genes that were differentially expressed in the nasal epithelium of AEGIS-1 patients diagnosed with lung cancer vs those with benign disease after one year of follow-up ( P  cancer-associated gene expression alterations between the two airway sites ( P  lung cancer classifier derived in the AEGIS-1 cohort that combined clinical factors (age, smoking status, time since quit, mass size) and nasal gene expression (30 genes) had statistically significantly higher area under the curve (0.81; 95% confidence interval [CI] = 0.74 to 0.89, P  = .01) and sensitivity (0.91; 95% CI = 0.81 to 0.97, P  = .03) than a clinical-factor only model in independent samples from the AEGIS-2 cohort. These results support that the airway epithelial field of lung cancer-associated injury in ever smokers extends to the nose and demonstrates the potential of using nasal gene expression as a noninvasive biomarker for lung cancer detection. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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

Energy Technology Data Exchange (ETDEWEB)

Yeh, Hsu-Chi; Swift, D.L. [John Hopkins Univ., Baltimore, MD (United States); Simpson, S.Q. [Univ. of New Mexico, Albuquerque, NM (United States)] [and others

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.

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

International Nuclear Information System (INIS)

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

1995-01-01

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 μm particles in 10 human subjects and in our preliminary studies using 0.004-0.15 μm 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 μm with the nasal dimensions of each subject

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

Science.gov (United States)

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

2004-08-01

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

The human nasal microbiota and Staphylococcus aureus carriage.

Directory of Open Access Journals (Sweden)

Daniel N Frank

Full Text Available BACKGROUND: Colonization of humans with Staphylococcus aureus is a critical prerequisite of subsequent clinical infection of the skin, blood, lung, heart and other deep tissues. S. aureus persistently or intermittently colonizes the nares of approximately 50% of healthy adults, whereas approximately 50% of the general population is rarely or never colonized by this pathogen. Because microbial consortia within the nasal cavity may be an important determinant of S. aureus colonization we determined the composition and dynamics of the nasal microbiota and correlated specific microorganisms with S. aureus colonization. METHODOLOGY/PRINCIPAL FINDINGS: Nasal specimens were collected longitudinally from five healthy adults and a cross-section of hospitalized patients (26 S. aureus carriers and 16 non-carriers. Culture-independent analysis of 16S rRNA sequences revealed that the nasal microbiota of healthy subjects consists primarily of members of the phylum Actinobacteria (e.g., Propionibacterium spp. and Corynebacterium spp., with proportionally less representation of other phyla, including Firmicutes (e.g., Staphylococcus spp. and Proteobacteria (e.g. Enterobacter spp. In contrast, inpatient nasal microbiotas were enriched in S. aureus or Staphylococcus epidermidis and diminished in several actinobacterial groups, most notably Propionibacterium acnes. Moreover, within the inpatient population S. aureus colonization was negatively correlated with the abundances of several microbial groups, including S. epidermidis (p = 0.004. CONCLUSIONS/SIGNIFICANCE: The nares environment is colonized by a temporally stable microbiota that is distinct from other regions of the integument. Negative association between S. aureus, S. epidermidis, and other groups suggests microbial competition during colonization of the nares, a finding that could be exploited to limit S. aureus colonization.

Chromosome aberration induction in human diploid fibroblast and epithelial cells

International Nuclear Information System (INIS)

Scott, D.

1986-01-01

The relative sensitivity of cultured human fibroblasts and epithelial cells to radiation-induced chromosomal aberrations was investigated. Lung fibroblast and kidney epithelial cells from the same fetus were compared, as were skin fibroblasts and epithelial keratinocytes from the same foreskin sample. After exposure of proliferating fetal cells to 1.5 Gy X-rays there was a very similar aberration yield in the fibroblasts and epithelial cells. Observations of either little or no difference in chromosomal sensitivity between human fibroblasts and epithelial cells give added confidence that quantitative cytogenetic data obtained from cultured fibroblasts are relevant to the question of sensitivity of epithelial cells which are the predominant cell type in human cancers. (author)

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.

Science.gov (United States)

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. Copyright © 2015 Elsevier B.V. All rights reserved.

Unsteady flow characteristics through a human nasal airway.

Science.gov (United States)

Lee, Jong-Hoon; Na, Yang; Kim, Sung-Kyun; Chung, Seung-Kyu

2010-07-31

Time-dependent characteristics of the flow in a human nasal airway constructed from the CT image of a healthy volunteer were investigated using a computational fluid dynamics (CFD) technique. To capture the time-varying nature of the flow as well as pressure and temperature fields, the large eddy simulation (LES) technique instead of the RANS (Reynolds Averaged Navier-Stokes) approach was adopted. To make the present analysis more relevant to a real human breathing cycle, the flow was designed to be induced by the pressure difference and the time-varying pressure at the end of trachea was described to reproduce the flow rate data from the measurement. Comparison of the present results with those of typical steady simulations showed that the difference in flow characteristics is magnified in the expiration phase. This fact may suggest that the inertial effect associated with unsteady flow is more important during the expiration period. Also, the fact that the distribution of the flow rate in a given cross-section of the airway changes significantly with time implies the importance of unsteady data for clinical decision. The wall shear stress was found to have relatively high values at the locations near nasopharynx and larynx but the magnitude changes with time during the whole respiratory cycle. Analysis of the temperature field showed that most of the temperature change occurs in the nasal cavity when the air is incoming and thus, the nasal cavity acts as a very efficient heat exchanger during an inspiration period. Copyright 2010 Elsevier B.V. All rights reserved.

The role of human papilloma virus and herpes viruses in the etiology of nasal polyposis.

Science.gov (United States)

Koçoğlu, Mücahide Esra; Mengeloğlu, Fırat Zafer; Apuhan, Tayfun; Özsoy, Şeyda; Yilmaz, Beyhan

2016-02-17

The aim of this study was to investigate the etiological role of human papilloma virus (HPV), herpes simplex virus (HSV), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpes virus-6 (HHV-6) and -7 (HHV-7) in the occurrence of nasal polyposis. Nasal polyp samples from 30 patients with nasal polyposis and normal nasal mucosa from 10 patients without nasal polyps were obtained. DNA was extracted from tissues. Real-time polymerase chain reaction was performed for all runs. No HSV-1, HSV-2, or VZV was detected in the samples. Among the patient samples, EBV and HHV-7 DNA were detected in 18 (60%), HHV-6 was detected in 20 (66.7%), and HPV was detected in 4 (13.3%) samples. Among the controls, CMV DNA was positive in one (10%). EBV was positive in 5 (50%), HHV-6 and HHV-7 were positive in 7 (70%), and HPV was positive in 2 (20%) samples. No significant difference was found among the groups with any test in terms of positivity. The association of Herpesviridae and HPV with the pathogenesis of nasal polyps was investigated in this study and no relationship was found. Thus, these viruses do not play a significant role in the formation of nasal polyps.

Dispersions of geometric TiO2 nanomaterials and their toxicity to RPMI 2650 nasal epithelial cells

Science.gov (United States)

Tilly, Trevor B.; Kerr, Lei L.; Braydich-Stolle, Laura K.; Schlager, John J.; Hussain, Saber M.

2014-11-01

Titanium dioxide (TiO2) based nanofilaments—nanotube, nanowire, nanorod—have gained interest for industrial, electrical, and as of recent, medical applications due to their superior performance over TiO2 nanoparticles. Safety assessment of these nanomaterials is critical to protect workers, patients, and bystanders as these technologies become widely implemented. Additionally, TiO2 based nanofilaments can easily be inhaled by humans and their high aspect ratio, much like asbestos fibers, may make them toxic in the respiratory system. The tendency of TiO2 nanofilaments to aggregate makes evaluating their nanotoxicity difficult and the results controversial, because incomplete dispersion results in larger particle sizes that are no longer in the nano dimensional size range. TiO2 nanofilaments are aggregated and difficult to disperse homogeneously in solution by conventional methods, such as sonication and vortexing. In this study, a microfluidic device was utilized to produce stable, homogeneous dosing solutions necessary for in vitro toxicity evaluation by eliminating any toxicity caused by aggregated TiO2 nanomaterials. The toxicity results could then be directly correlated to the TiO2 nanostructure itself. The toxicity of four TiO2 nanogeometries—nanotube, nanowire, nanorod, and nanoparticle—were assessed in RPMI 2650 human nasal epithelial cells at representative day, week, and month in vitro exposure dosages of 10, 50, 100 μg/ml, respectively. All TiO2 based nanomaterials dispersed by the microfluidic method were nontoxic to RPMI 2650 cells at the concentrations tested, whereas higher concentrations of 100 μg/ml of nanowires and nanotubes dispersed by sonication reduced viability up to 27 %, indicating that in vitro toxicity results may be controlled by the dispersion of dosing solutions.

Staphylococcus aureus α-Toxin Induces Actin Filament Remodeling in Human Airway Epithelial Model Cells.

Science.gov (United States)

Ziesemer, Sabine; Eiffler, Ina; Schönberg, Alfrun; Müller, Christian; Hochgräfe, Falko; Beule, Achim G; Hildebrandt, Jan-Peter

2018-04-01

Exposure of cultured human airway epithelial model cells (16HBE14o-, S9) to Staphylococcus aureus α-toxin (hemolysin A, Hla) induces changes in cell morphology and cell layer integrity that are due to the inability of the cells to maintain stable cell-cell or focal contacts and to properly organize their actin cytoskeletons. The aim of this study was to identify Hla-activated signaling pathways involved in regulating the phosphorylation level of the actin-depolymerizing factor cofilin. We used recombinant wild-type hemolysin A (rHla) and a variant of Hla (rHla-H35L) that is unable to form functional transmembrane pores to treat immortalized human airway epithelial cells (16HBE14o-, S9) as well as freshly isolated human nasal tissue. Our results indicate that rHla-mediated changes in cofilin phosphorylation require the formation of functional Hla pores in the host cell membrane. Formation of functional transmembrane pores induced hypophosphorylation of cofilin at Ser3, which was mediated by rHla-induced attenuation of p21-activated protein kinase and LIM kinase activities. Because dephosphorylation of pSer3-cofilin results in activation of this actin-depolymerizing factor, treatment of cells with rHla resulted in loss of actin stress fibers from the cells and destabilization of cell shape followed by the appearance of paracellular gaps in the cell layers. Activation of protein kinase A or activation of small GTPases (Rho, Rac, Cdc42) do not seem to be involved in this response.

Geographic variation in nasal cavity form among three human groups from the Japanese Archipelago: Ecogeographic and functional implications.

Science.gov (United States)

Fukase, Hitoshi; Ito, Tsuyoshi; Ishida, Hajime

2016-05-01

Geographic variation in human nasal form has often been interpreted as a climatic adaptation, owing to the nasal air-conditioning function. The aim of this study was to further address morphofunctional issues of the nasal cavity, using three human groups from subarctic, temperate, and subtropical regions of the Japanese Archipelago: prehistoric Okhotsk, early-modern Honshu and Okinawa groups. Using three-dimensional coordinates of craniometric landmarks surrounding the nasal cavity, we compared linear measurements regarding nasal cavity form among the three groups and also conducted 3D geometric morphometrics. Both linear measurements and morphometric analyses corroborate the previously reported covariation pattern of nasal cavity shape with climate, where humans from a cold/dry climate tend to possess a relatively tall, narrow, and deep nasal cavity compared with those from a warm/humid environment. The northern Okhotsk group had overall larger cranial airways, which may be attributable to their large facial skeleton. However, the ratio of nasal/bimaxillary breadth was significantly lower in the Okhotsk group, indicating that maxillary size does not necessarily constrain the nasal breadth. In addition, despite the presence of obvious geographic clines in anterior nasal shape, posterior choanal shape lacked the north-south geographic cline. This suggests a certain level of morphofunctional independence between the anterior and posterior nasal openings. The observed geographic variations must, however, be partly considered as a reflection of different ancestral traits and population histories of the three groups. Nevertheless, the results indicate that intergroup variations in nasal cavity morphology can be largely explained by climatic conditions. Am. J. Hum. Biol. 28:343-351, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

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

Directory of Open Access Journals (Sweden)

Armstrong Dianna

2004-12-01

Full Text Available Abstract 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.

Adenoma pleomórfico de septo nasal: relato de caso Pleomorphic adenoma of the nasal septum: a case report

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Mauren P. Rocha

2004-06-01

Full Text Available As neoplasias nasais são bastante raras. Os tumores mais observados na cavidade nasal são papilomas epiteliais, angiomas, carcinoma de células transicionais, carcinoma pavimentoso e adenocarcinoma. O adenoma pleomórfico pertence ao grupo de tumores que aparecem com menor freqüência na fossa nasal, e é o tumor benigno glandular mais comum originado na cabeça e pescoço. A apresentação clínica típica dos pacientes com adenoma pleomórfico do septo nasal é de obstrução nasal unilateral, epistaxe e massa indolor na cavidade nasal. Em vista da raridade da apresentação clínica do adenoma pleomórfico nesta localização, os autores descrevem um caso de adenoma pleomórfico nasal em um paciente do sexo masculino, com 69 anos de idade, onde relatam os achados clínicos, critérios diagnósticos, tratamento, prognóstico e revisão da literatura.Nasal tumours are very rare. The neoplasms most frequently seen in the nasal cavity are epithelial papillomas, angiomas, transitional cells carcinoma, pavement carcinoma and adenocarcinoma. The pleomorphic adenoma belongs to the group of tumours less commonly observed in the nasal cavity, and is the most common head and neck benign glandular tumour. The typical clinical presentation of the nasal pleomorphic adenoma is of unilateral nasal obstruction, epistaxis and a painless mass in the nasal cavity. The authors reported an adenoma pleomorphic case that highlights itself by its unusual nasal presentation in the nasal septum of a 45-year-old male patient who was submitted to surgical treatment, and discuss the clinical findings, diagnostic criteria, treatment, prognosis and literature review.

Non‐diluted seawater enhances nasal ciliary beat frequency and wound repair speed compared to diluted seawater and normal saline

Science.gov (United States)

Bonnomet, Arnaud; Luczka, Emilie; Coraux, Christelle

2016-01-01

Background The regulation of mucociliary clearance is a key part of the defense mechanisms developed by the airway epithelium. If a high aggregate quality of evidence shows the clinical effectiveness of nasal irrigation, there is a lack of studies showing the intrinsic role of the different irrigation solutions allowing such results. This study investigated the impact of solutions with different pH and ionic compositions, eg, normal saline, non‐diluted seawater and diluted seawater, on nasal mucosa functional parameters. Methods For this randomized, controlled, blinded, in vitro study, we used airway epithelial cells obtained from 13 nasal polyps explants to measure ciliary beat frequency (CBF) and epithelial wound repair speed (WRS) in response to 3 isotonic nasal irrigation solutions: (1) normal saline 0.9%; (2) non‐diluted seawater (Physiomer®); and (3) 30% diluted seawater (Stérimar). The results were compared to control (cell culture medium). Results Non‐diluted seawater enhanced the CBF and the WRS when compared to diluted seawater and to normal saline. When compared to the control, it significantly enhanced CBF and slightly, though nonsignificantly, improved the WRS. Interestingly, normal saline markedly reduced the number of epithelial cells and ciliated cells when compared to the control condition. Conclusion Our results suggest that the physicochemical features of the nasal wash solution is important because it determines the optimal conditions to enhance CBF and epithelial WRS thus preserving the respiratory mucosa in pathological conditions. Non‐diluted seawater obtains the best results on CBF and WRS vs normal saline showing a deleterious effect on epithelial cell function. PMID:27101776

induced acute cytotoxicity in human cervical epithelial carcinoma cells

African Journals Online (AJOL)

Molecular basis of arsenite (As +3 )-induced acute cytotoxicity in human cervical epithelial carcinoma cells. ... Libyan Journal of Medicine ... Methods: After performing cytotoxic assays on a human epithelial carcinoma cell line, expression analysis was done by quantitative polymerase chain reaction, western blotting, and ...

Yield Strength Testing in Human Cadaver Nasal Septal Cartilage and L-Strut Constructs.

Science.gov (United States)

Liu, Yuan F; Messinger, Kelton; Inman, Jared C

2017-01-01

To our knowledge, yield strength testing in human nasal septal cartilage has not been reported to date. An understanding of the basic mechanics of the nasal septum may help surgeons decide how much of an L-strut to preserve and how much grafting is needed. To determine the factors correlated with yield strength of the cartilaginous nasal septum and to explore the association between L-strut width and thickness in determining yield strength. In an anatomy laboratory, yield strength of rectangular pieces of fresh cadaver nasal septal cartilage was measured, and regression was performed to identify the factors correlated with yield strength. To measure yield strength in L-shaped models, 4 bonded paper L-struts models were constructed for every possible combination of the width and thickness, for a total of 240 models. Mathematical modeling using the resultant data with trend lines and surface fitting was performed to quantify the associations among L-strut width, thickness, and yield strength. The study dates were November 1, 2015, to April 1, 2016. The factors correlated with nasal cartilage yield strength and the associations among L-strut width, thickness, and yield strength in L-shaped models. Among 95 cartilage pieces from 12 human cadavers (mean [SD] age, 67.7 [12.6] years) and 240 constructed L-strut models, L-strut thickness was the only factor correlated with nasal septal cartilage yield strength (coefficient for thickness, 5.54; 95% CI, 4.08-7.00; P cadaver nasal septal cartilage, L-strut thickness was significantly associated with yield strength. In a bonded paper L-strut model, L-strut thickness had a more important role in determining yield strength than L-strut width. Surgeons should consider the thickness of potential L-struts when determining the amount of cartilaginous septum to harvest and graft. NA.

Visualization of nasal airflow patterns in a patient affected with atrophic rhinitis using particle image velocimetry

Energy Technology Data Exchange (ETDEWEB)

Garcia, G J M [Hamner Institutes for Health Sciences, NC (United States); Mitchell, G [The Queens University of Belfast, Belfast (United Kingdom); Bailie, N [The Queens University of Belfast, Belfast (United Kingdom); Thornhill, D [The Queens University of Belfast, Belfast (United Kingdom); Watterson, J [The Queens University of Belfast, Belfast (United Kingdom); Kimbell, J S [Hamner Institutes for Health Sciences, NC (United States)

2007-10-15

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.

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

International Nuclear Information System (INIS)

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

2010-01-01

Cytotoxicity and genotoxicity of nitrogen dioxide (NO 2 ) as part of urban exhaust pollution are widely discussed as potential hazards to human health. This study focuses on toxic effects of NO 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 2 , 0.1 ppm NO 2 , 1 ppm NO 2 , 10 ppm NO 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 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 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.

Health risks associated with inhaled nasal toxicants

NARCIS (Netherlands)

Feron, VJ; Arts, JHE; Kuper, CF; Slootweg, PJ; Woutersen, RA

2001-01-01

Health risks of inhaled nasal toxicants were reviewed with emphasis on chemically induced nasal lesions in humans, sensory irritation, olfactory and trigeminal nerve toxicity, nasal immunopathology and carcinogenesis, nasal responses to chemical mixtures, in vitro models, and nasal dosimetry- and

Angioleiomyoma of nasal septum: Case report and literature review

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Varun V. Varadarajan, M.D.

2016-12-01

Conclusion: Angioleiomyoma of the nasal septum is a rare and challenging clinical diagnosis that requires detailed histopathologic examination. The differential diagnosis includes a variety of epithelial and mesenchymal derived tumors. Literature review suggests a female predilection with possible hormonal influence.

DNA repair in human bronchial epithelial cells

International Nuclear Information System (INIS)

Fornace, A.J. Jr.; Lechner, J.F.; Grafstrom, R.C.; Harris, C.C.

1982-01-01

The purpose of this investigation was to compare the response of human cell types (bronchial epithelial cells and fibroblasts and skin fibroblasts) to various DNA damaging agents. Repair of DNA single strand breaks (SSB) induced by 5 krads of X-ray was similar for all cell types; approximately 90% of the DNA SSB were rejoined within one hour. During excision repair of DNA damage from u.v.-radiation, the frequencies of DNA SSB as estimated by the alkaline elution technique, were similar in all cell types. Repair replication as measured by BND cellulose chromatography was also similar in epithelial and fibroblastic cells after u.v.-irradiation. Similar levels of SSB were also observed in epithelial and fibroblastic cells after exposure to chemical carcinogens: 7,12-dimethylbenz[a]anthracene; benzo[a]pyrene diol epoxide (BPDE); or N-methyl-N-nitro-N-nitrosoguanidine. Significant repair replication of BPDE-induced DNA damage was detected in both bronchial epithelial and fibroblastic cells, although the level in fibroblasts was approximately 40% of that in epithelial cells. The pulmonary carcinogen asbestos did not damage DNA. DNA-protein crosslinks induced by formaldehyde were rapidly removed in bronchial cells. Further, epithelial and fibroblastic cells, which were incubated with formaldehyde and the polymerase inhibitor combination of cytosine arabinoside and hydroxyurea, accumulated DNA SSB at approximately equal frequencies. These results should provide a useful background for further investigations of the response of human bronchial cells to various DNA damaging agents

Non-diluted seawater enhances nasal ciliary beat frequency and wound repair speed compared to diluted seawater and normal saline.

Science.gov (United States)

Bonnomet, Arnaud; Luczka, Emilie; Coraux, Christelle; de Gabory, Ludovic

2016-10-01

The regulation of mucociliary clearance is a key part of the defense mechanisms developed by the airway epithelium. If a high aggregate quality of evidence shows the clinical effectiveness of nasal irrigation, there is a lack of studies showing the intrinsic role of the different irrigation solutions allowing such results. This study investigated the impact of solutions with different pH and ionic compositions, eg, normal saline, non-diluted seawater and diluted seawater, on nasal mucosa functional parameters. For this randomized, controlled, blinded, in vitro study, we used airway epithelial cells obtained from 13 nasal polyps explants to measure ciliary beat frequency (CBF) and epithelial wound repair speed (WRS) in response to 3 isotonic nasal irrigation solutions: (1) normal saline 0.9%; (2) non-diluted seawater (Physiomer®); and (3) 30% diluted seawater (Stérimar). The results were compared to control (cell culture medium). Non-diluted seawater enhanced the CBF and the WRS when compared to diluted seawater and to normal saline. When compared to the control, it significantly enhanced CBF and slightly, though nonsignificantly, improved the WRS. Interestingly, normal saline markedly reduced the number of epithelial cells and ciliated cells when compared to the control condition. Our results suggest that the physicochemical features of the nasal wash solution is important because it determines the optimal conditions to enhance CBF and epithelial WRS thus preserving the respiratory mucosa in pathological conditions. Non-diluted seawater obtains the best results on CBF and WRS vs normal saline showing a deleterious effect on epithelial cell function. © 2016 The Authors International Forum of Allergy & Rhinology, published by ARSAAOA, LLC.

Ozone-Induced Nasal Type 2 Immunity in Mice Is Dependent on Innate Lymphoid Cells.

Science.gov (United States)

Kumagai, Kazuyoshi; Lewandowski, Ryan; Jackson-Humbles, Daven N; Li, Ning; Van Dyken, Steven J; Wagner, James G; Harkema, Jack R

2016-06-01

Epidemiological studies suggest that elevated ambient concentrations of ozone are associated with activation of eosinophils in the nasal airways of atopic and nonatopic children. Mice repeatedly exposed to ozone develop eosinophilic rhinitis and type 2 immune responses. In this study, we determined the role of innate lymphoid cells (ILCs) in the pathogenesis of ozone-induced eosinophilic rhinitis by using lymphoid-sufficient C57BL/6 mice, Rag2(-/-) mice that are devoid of T cells and B cells, and Rag2(-/-)Il2rg(-/-) mice that are depleted of all lymphoid cells including ILCs. The animals were exposed to 0 or 0.8 ppm ozone for 9 consecutive weekdays (4 h/d). Mice were killed 24 hours after exposure, and nasal tissues were selected for histopathology and gene expression analysis. ILC-sufficient C57BL/6 and Rag2(-/-) mice exposed to ozone developed marked eosinophilic rhinitis and epithelial remodeling (e.g., epithelial hyperplasia and mucous cell metaplasia). Chitinase-like proteins and alarmins (IL-33, IL-25, and thymic stromal lymphopoietin) were also increased morphometrically in the nasal epithelium of ozone-exposed C57BL/6 and Rag2(-/-) mice. Ozone exposure elicited increased expression of Il4, Il5, Il13, St2, eotaxin, MCP-2, Gob5, Arg1, Fizz1, and Ym2 mRNA in C57BL/6 and Rag2(-/-) mice. In contrast, ozone-exposed ILC-deficient Rag2(-/-)Il2rg(-/-) mice had no nasal lesions or overexpression of Th2- or ILC2-related transcripts. These results indicate that ozone-induced eosinophilic rhinitis, nasal epithelial remodeling, and type 2 immune activation are dependent on ILCs. To the best of our knowledge, this is the first study to demonstrate that ILCs play an important role in the nasal pathology induced by repeated ozone exposure.

Influence of essential and fatty oils on ciliary beat frequency of human nasal epithelial cells.

Science.gov (United States)

Neher, Andreas; Gstöttner, Michaela; Thaurer, Michael; Augustijns, Patrick; Reinelt, Monika; Schobersberger, Wolfgang

2008-01-01

In alternative and complementary medicine, the use of essential and fatty oils has become more and more popular. In addition to conventional medical therapies, self-medication is showing increasing popularity, using agents with unclear compounds and poorly controlled dosages. Among other disorders, these alternative treatments are used in bronchitis and rhinitis, including some topical applications. Thus, the influence on ciliated epithelia should be evaluated, because a disturbance of the ciliary function can lead to recurrent sinusitis and chronic rhinosinusitis. The aim of this study was to test the influence of fatty and essential oils on the ciliary beat frequency (CBF) of nasal mucosa in vivo. The influence of sesame oil, soy oil, peanut oil, Miglyol 840, thyme oil, lavender oil, eucalyptus oil, and menthol on the ciliary activity of nasal brushings was evaluated by digital high-speed imaging. The presence of most fatty oils resulted in an increase in CBF, the effect being highest for peanut oil. Miglyol 840 had no significant influence on CBF. The essential oils were tested at a concentration of 0.2 and 2%. Thyme oil did not affect CBF, whereas the presence of all other essentials oils resulted in an increase in CBF; the effect was higher at 0.2% than at 2%. Except thyme oil and Miglyol 840, all tested oils caused an increase in CBF. Interestingly, the 0.2% concentrations of essential oils resulted in stronger effects when compared with the 2% concentrations.

Role of the Akt/mTOR signaling pathway in human papillomavirus-associated nasal and sinonasal inverted papilloma.

Science.gov (United States)

Liu, Yongliang; Duan, Lihua; Tian, Jie; Song, Daoliang; Zhang, Min; Zhao, Shenlin; Yin, Zhaofu; Xiang, Xinxin; Li, Xuezhong

2017-12-01

Nasal and sinonasal inverted papilloma (NSIP) is a benign tumor in which surface epithelial cells grow downward into the underlying supportive tissue with varying degrees of metaplasia. Human papillomavirus (HPV) has been proposed as the causal agent in the pathogenesis of this disease. Many studies have shown that HPV can activate the Akt/mechanistic target of rapamycin (mTOR) signaling pathway, but the role of this pathway in HPV-associated NSIP is largely unknown. In this study, we enrolled 40 control tissue samples and 80 NSIP tissue samples. HPV genotyping showed that 47 of the 80 examined cases of NSIP were HPV-positive (58.8%), and the most common subtype was HPV11 (20/53, 37.7%). The immunohistochemistry showed statistically significant differences in phosphorylated Akt and phosphorylated S6 ribosomal protein staining among control samples, HPV-positive NSIP and HPV-negative NSIP. The HPV11 L1-L2 plasmid increased the proliferation of normal human nasopharyngeal epithelial NP69-SV40T cells and human nasopharyngeal cancer CNE1 cells. Meanwhile, rapamycin, an mTOR inhibitor, reversed the increased cell proliferation induced by the HPV11 L1-L2 plasmid. Western blot analysis showed that Akt/mTOR/S6 were overexpressed in NP69-SV40T cells and CNE1 cells infected with the HPV11 L1-L2 plasmid. These data demonstrate that HPV promotes cell proliferation through the Akt/mTOR signaling pathway in NSIP. © The Author 2017. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Comparison of Nasal Epithelial Smoking-Induced Gene Expression on Affymetrix Exon 1.0 and Gene 1.0 ST Arrays

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Xiaoling Zhang

2013-01-01

Full Text Available We have previously defined the impact of tobacco smoking on nasal epithelium gene expression using Affymetrix Exon 1.0 ST arrays. In this paper, we compared the performance of the Affymetrix GeneChip Human Gene 1.0 ST array with the Human Exon 1.0 ST array for detecting nasal smoking-related gene expression changes. RNA collected from the nasal epithelium of five current smokers and five never smokers was hybridized to both arrays. While the intersample correlation within each array platform was relatively higher in the Gene array than that in the Exon array, the majority of the genes most changed by smoking were tightly correlated between platforms. Although neither array dataset was powered to detect differentially expressed genes (DEGs at a false discovery rate (FDR <0.05, we identified more DEGs than expected by chance using the Gene ST array. These findings suggest that while both platforms show a high degree of correlation for detecting smoking-induced differential gene expression changes, the Gene ST array may be a more cost-effective platform in a clinical setting for gene-level genomewide expression profiling and an effective tool for exploring the host response to cigarette smoking and other inhaled toxins.

Sequestration of human cytomegalovirus by human renal and mammary epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Twite, Nicolas [Institute for Medical Immunology, Université Libre de Bruxelles, Rue A. Bolland 8, B-6041 Charleroi (Belgium); Andrei, Graciela [Laboratory of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven (Belgium); Kummert, Caroline [ImmuneHealth, Rue A. Bolland 8, B-6041 Charleroi (Belgium); Donner, Catherine [Department of Obstetrics and Gynecology, Erasme Hospital, Route de Lennik 808, 1070 Brussels (Belgium); Perez-Morga, David [Laboratory of Molecular Parasitology, Institut de Biologie et Médecine Moléculaires, Université Libre de Bruxelles, Gosselies (Belgium); De Vos, Rita [Pathology Department, U.Z. Leuven, Minderbroedersstraat 12, Leuven (Belgium); Snoeck, Robert, E-mail: Robert.Snoeck@Rega.kuleuven.be [Laboratory of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven (Belgium); Marchant, Arnaud, E-mail: arnaud.marchant@ulb.ac.be [Institute for Medical Immunology, Université Libre de Bruxelles, Rue A. Bolland 8, B-6041 Charleroi (Belgium); ImmuneHealth, Rue A. Bolland 8, B-6041 Charleroi (Belgium)

2014-07-15

Urine and breast milk represent the main routes of human cytomegalovirus (HCMV) transmission but the contribution of renal and mammary epithelial cells to viral excretion remains unclear. We observed that kidney and mammary epithelial cells were permissive to HCMV infection and expressed immediate early, early and late antigens within 72 h of infection. During the first 24 h after infection, high titers of infectious virus were measured associated to the cells and in culture supernatants, independently of de novo synthesis of virus progeny. This phenomenon was not observed in HCMV-infected fibroblasts and suggested the sequestration and the release of HCMV by epithelial cells. This hypothesis was supported by confocal and electron microscopy analyses. The sequestration and progressive release of HCMV by kidney and mammary epithelial cells may play an important role in the excretion of the virus in urine and breast milk and may thereby contribute to HCMV transmission. - Highlights: • Primary renal and mammary epithelial cells are permissive to HCMV infection. • HCMV is sequestered by epithelial cells and this phenomenon does not require viral replication. • HCMV sequestration by epithelial cells is reduced by antibodies and IFN-γ.

Characteristics of nasal-associated lymphoid tissue (NALT) and nasal absorption capacity in chicken.

Science.gov (United States)

Kang, Haihong; Yan, Mengfei; Yu, Qinghua; Yang, Qian

2013-01-01

As the main mucosal immune inductive site of nasal cavity, nasal-associated lymphoid tissue (NALT) plays an important role in both antigen recognition and immune activation after intranasal immunization. However, the efficiency of intranasal vaccines is commonly restricted by the insufficient intake of antigen by the nasal mucosa, resulting from the nasal mucosal barrier and the nasal mucociliary clearance. The distribution of NALT and the characteristic of nasal cavity have already been described in humans and many laboratory rodents, while data about poultry are scarce. For this purpose, histological sections of the chicken nasal cavities were used to examine the anatomical structure and histological characteristics of nasal cavity. Besides, the absorptive capacity of chicken nasal mucosa was also studied using the materials with different particle size. Results showed that the NALT of chicken was located on the bottom of nasal septum and both sides of choanal cleft, which mainly consisted of second lymphoid follicle. A large number of lymphocytes were distributed under the mucosal epithelium of inferior nasal meatus. In addition, there were also diffuse lymphoid tissues located under the epithelium of the concha nasalis media and the walls of nasal cavity. The results of absorption experiment showed that the chicken nasal mucosa was capable to absorb trypan blue, OVA, and fluorescent latex particles. Inactivated avian influenza virus (IAIV) could be taken up by chicken nasal mucosa except for the stratified squamous epithelium sites located on the forepart of nasal cavity. The intake of IAIV by NALT was greater than that of the nasal mucosa covering on non-lymphoid tissue, which could be further enhanced after intranasal inoculation combined with sodium cholate or CpG DNA. The study on NALT and nasal absorptive capacity will be benefit for further understanding of immune mechanisms after nasal vaccination and development of nasal vaccines for poultry.

Human airway xenograft models of epithelial cell regeneration

Directory of Open Access Journals (Sweden)

Puchelle Edith

2000-10-01

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

Resident aerobic microbiota of the adult human nasal cavity

DEFF Research Database (Denmark)

Rasmussen, TT; Kirkeby Nielsen, LP; Poulsen, Knud

2000-01-01

Recent evidence strongly suggests that the microbiota of the nasal cavity plays a crucial role in determining the reaction patterns of the mucosal and systemic immune system. However, little is known about the normal microbiota of the nasal cavity. The purpose of this study was to determine...... the microbiota in different parts of the nasal cavity and to develop and evaluate methods for this purpose. Samples were collected from 10 healthy adults by nasal washes and by swabbing of the mucosa through a sterile introduction device. Both methods gave results that were quantitatively and qualitatively...... reproducible, and revealed significant differences in the density of the nasal microbiota between individuals. The study revealed absence of gram-negative bacteria that are regular members of the commensal microbiota of the pharynx. Likewise, viridans type streptococci were sparsely represented. The nasal...

The expression of Egfl7 in human normal tissues and epithelial tumors.

Science.gov (United States)

Fan, Chun; Yang, Lian-Yue; Wu, Fan; Tao, Yi-Ming; Liu, Lin-Sen; Zhang, Jin-Fan; He, Ya-Ning; Tang, Li-Li; Chen, Guo-Dong; Guo, Lei

2013-04-23

To investigate the expression of Egfl7 in normal adult human tissues and human epithelial tumors.
 RT-PCR and Western blot were employed to detect Egfl7 expression in normal adult human tissues and 10 human epithelial tumors including hepatocellular carcinoma (HCC), lung cancer, breast cancer, prostate cancer, colorectal cancer, gastric cancer, esophageal cancer, malignant glioma, ovarian cancer and renal cancer. Immunohistochemistry and cytoimmunofluorescence were subsequently used to determine the localization of Egfl7 in human epithelial tumor tissues and cell lines. ELISA was also carried out to examine the serum Egfl7 levels in cancer patients. In addition, correlations between Egfl7 expression and clinicopathological features as well as prognosis of HCC and breast cancer were also analyzed on the basis of immunohistochemistry results.
 Egfl7 was differentially expressed in 19 adult human normal tissues and was overexpressed in all 10 human epithelial tumor tissues. The serum Egfl7 level was also significantly elevated in cancer patients. The increased Egfl7 expression in HCC correlated with vein invasion, absence of capsule formation, multiple tumor nodes and poor prognosis. Similarly, upregulation of Egfl7 in breast cancer correlated strongly with TNM stage, lymphatic metastasis, estrogen receptor positivity, Her2 positivity and poor prognosis. 
 Egfl7 is significantly upregulated in human epithelial tumor tissues, suggesting Egfl7 to be a potential biomarker for human epithelial tumors, especially HCC and breast cancer.

Methods for Diagnosing Some Malignant Neoplasms of the Canine Nasal Mucosa

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Emilia Florica Balint

2016-11-01

Full Text Available Abstract The aim of this study is to highlight the easiest method of investigation (nasal lavage or rhinoscopy depending on the animal condition. 18 dogs were investigated, which presented at the Faculty of Veterinary Medicine Bucharest, with respiratory distress due to obstruction of the nasal cavities. The sampling for cytological diagnosis was done using the two techniques, the nasal lavage and rhinoscopy. It is most useful to try the lavage first, because it is less invasive, and only then, if case of poor cellularity after centrifugation, or in case of a inflammatory process with unfavourable post-treatment evolution, endoscopy will be used. Cytomorphological diagnosis using, after rhinoscopy or nasal lavage, have evidentiated the following forms of nasal cancer: 10 cases out of 18 were epithelial neoplasms of the olfactory mucosa; 6 cases out of 18 were nerve tumors (malignant melanoma, estesiocarcinoma; 2 cases out of 18 were mesenchymal tumors (osteosarcoma, fibrosarcoma. The nasal lavage is a good sampling method but has the disadvantage of sometimes encountering an acute or chronic inflammatory process that can shield the tumor process.

[Characterization of epithelial primary culture from human conjunctiva].

Science.gov (United States)

Rivas, L; Blázquez, A; Muñoz-Negrete, F J; López, S; Rebolleda, G; Domínguez, F; Pérez-Esteban, A

2014-01-01

To evaluate primary cultures from human conjunctiva supplemented with fetal bovine serum, autologous serum, and platelet-rich autologous serum, over human amniotic membrane and lens anterior capsules. One-hundred and forty-eight human conjunctiva explants were cultured in CnT50(®) supplemented with 1, 2.5, 5 and 10% fetal bovine serum, autologous serum and platelet-rich autologous serum. Conjunctival samples were incubated at 37°C, 5% CO2 and 95% HR, for 3 weeks. The typical phenotype corresponding to conjunctival epithelial cells was present in all primary cultures. Conjunctival cultures had MUC5AC-positive secretory cells, K19-positive conjunctival cells, and MUC4-positive non-secretory conjunctival cells, but were not corneal phenotype (cytokeratin K3-negative) and fibroblasts (CD90-negative). Conjunctiva epithelial progenitor cells were preserved in all cultures; thus, a cell culture in CnT50(®) supplemented with 1 to 5% autologous serum over human amniotic membrane can provide better information of epithelial cell differentiation for the conjunctival surface reconstruction. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

Sodium transport and intracellular sodium activity in cultured human nasal epithelium

DEFF Research Database (Denmark)

Willumsen, Niels J.; Boucher, Richard C.

1991-01-01

 human nasal epithelium (HNE). Under control conditions, intracellular Na+ activity (acNa) was 23 +/- 1 mM (n = 44 preparations, 393 impalements).Amiloride (10(-4) M) hyperpolarized the apical membrane and increased the fractional apical membrane resistance but did not affect acNa. Exposure to...

Human nasal rhinosporidiosis: a case report from Malawi | Sefu ...

African Journals Online (AJOL)

Patient presented with long standing history of nasal obstruction and intermittent epistaxis for three years. Diagnosis was confirmed by histopathological examination and he was successfully treated by complete surgical excision. This was a very unusual cause of nasal masses in our setting. Nasal rhinosporidioss lesions ...

Epithelial cell specific properties and genetic complementation in a delta F508 cystic fibrosis nasal polyp cell line.

Science.gov (United States)

Kunzelmann, K; Lei, D C; Eng, K; Escobar, L C; Koslowsky, T; Gruenert, D C

1995-09-01

Analysis of vectorial ion transport and protein trafficking in transformed cystic fibrosis (CF) epithelial cells has been limited because the cells tend to lose their tight junctions with multiple subcultures. To elucidate ion transport and protein trafficking in CF epithelial cells, a polar cell line with apical and basolateral compartments will facilitate analysis of the efficacy of different gene therapy strategies in a "tight epithelium" in vitro. This study investigates the genotypic and phenotypic properties of a CF nasal polyp epithelial, delta F508 homozygote, cell line that has tight junctions pre-crisis. The cells (sigma CFNPE14o-) were transformed with an origin-of-replication defective SV40 plasmid. They develop transepithelial resistance in Ussing chambers and are defective in cAMP-dependent Cl- transport as measured by efflux of radioactive Cl-, short circuit current (Isc), or whole-cell patch clamp. Stimulation of the cells by bradykinin, histamine, or ATP seems to activate both K(+)- and Ca(+2)-dependent Cl- transport. Measurement of 36Cl- efflux following stimulation with A23187 and ionomycin indicate a Ca(+2)-dependent Cl- transport. Volume regulatory capacity of the cells is indicated by cell swelling conductance. Expression of the CF transmembrane conductance regulator mRNA was indicated by RT-PCR amplification. When cells are grown at 26 degrees C for 48 h there is no indication of cAMP-dependent Cl- as has been previously indicated in heterologous expression systems. Antibodies specific for secretory cell antigens indicate the presence of antigens found in goblet, serous, and mucous cells; in goblet and serous cells; or in goblet and mucous cells; but not antigens found exclusively in mucous or serous cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Histone deacetylase inhibitors up-regulate LL-37 expression independent of toll-like receptor mediated signalling in airway epithelial cells.

Science.gov (United States)

Liu, Quan; Liu, Juan; Roschmann, Kristina Irene Lisolette; van Egmond, Danielle; Golebski, Korneliusz; Fokkens, Wytske Johanna; Wang, Dehui; van Drunen, Cornelis Maria

2013-04-11

HDAC inhibitors have been proposed as anticancer agents. However, their roles in innate genes expression remain not well known. Cathelicidin LL-37 is one of the few human bactericidal peptides, but the regulation of histone acetylation on LL-37 expression in airway epithelium remains largely unknown. Therefore, we investigated the effects of two non-selective HDACi, trichostatin A (TSA) and sodium butyrate (SB), on the expression of the cathelicidin LL-37 in human airway epithelial cells. LL37 in human NCI-H292 airway epithelial cells and the primary cultures of normal nasal epithelial cells(PNEC) in response to HDAC inhibitors with or without poly (I:C) stimulation was assessed using real-time PCR and western blot. In parallel, IL-6 expression was evaluated by ELISA. Our results showed that HDAC inhibitors up-regulated LL-37 gene expression independent of poly (I:C) stimulation in PNEC as well as in NCI-H292 cells. HDAC inhibitors increased LL37 protein expression in NCI-H292 cells but not in PNEC. In addition, HDAC inhibitors significantly inhibited poly (I:C)-induced IL-6 production in both of the epithelial cells. In conclusion, HDAC inhibitors directly up-regulated LL-37 gene expression in human airway epithelial cells.

Paramyxovirus Infection Mimics In Vivo Cellular Dynamics in Three-Demensional Human Bronchio-Epithelial Tissue-Like Assemblies

Science.gov (United States)

Deatly, Anne M.; Lin, Yen-Huei; McCarthy, Maureen; Chen, Wei; Miller, Lynn Z.; Quiroz, Jorge; Nowak, Becky M.; Lerch, Robert A.; Udem, Stephen A.; Goodwin, Thomas J.

2012-01-01

, cotton rat, guinea pig, ferret, and hamster) fail to accurately imitate viral replication and human disease states (8). Lacking an authentic model has impeded the development and evaluation of live, attenuated vaccine candidates. Development of a physiologically relevant in vitro tissue culture model that reproduces characteristics of the HRE, the primary target of RSV and PIV3, would aid in predicting clinical attenuation and safety of vaccine candidates. Successful tissue engineering of a 3D human intestinal model using novel NASA technology inspired the development of a tri-culture 3D model for the HRE. Sequential layering of primary mesenchymal cells (comprised of normal human fibroblasts and endothelial cells) followed by BEAS-2B epithelial cells derived from human bronchi and tracheae were recapitulated on Cultisphere and/or cytodex3 microcarriers in cylindrical vessels that rotate horizontally creating an organized epithelial structure. Horizontal rotation randomizes the gravity vector modeling aspects of microgravity. Mesenchymal and epithelial cells grown under these conditions reproduce the structural organization, multi-cellular complexity, and differentiation state of the HRE. The opportunity to study respiratory viruses in a nasal epithelium model is invaluable because the most promising respiratory virus vaccine candidates are live attenuated viruses for intranasal administration. Here we characterize the interactions of respiratory viruses and epithelial cells grown under modeled microgravity in comparison to gravity-ladened monolayers. 3D HBE TLAs and traditional monolayers (2D) are infected at 35 C, the upper temperature of the upper HRE, to simulate in vivo infection conditions. Growth kinetics of wild type (wt) RSV and PIV3 viruses were compared in 2D and 3D cells to that of strains attenuated in humans or rhesus macaques. This novel 3D HBE model also offers an opportunity to study whether the epithelial cell function, especially in host defenses

Carcinome hybride de la fosse nasale | Ben Mhamed | Journal ...

African Journals Online (AJOL)

Hybrid carcinoma is a rare neoplasm, accounting for less than 0.1% of all registered tumors in salivary glands. Up to now, only one case of hybrid carcinoma of the nasal cavity has been described. In this report, we describe a case of hybrid carcinoma composed of epithelial-myoepithelial carcinoma with an adenoid cystic ...

Nasal airway epithelial cell IL-6 and FKBP51 gene expression and steroid sensitivity in asthmatic children.

Directory of Open Access Journals (Sweden)

Michael Fayon

Full Text Available Many asthmatic patients exhibit uncontrolled asthma despite high-dose inhaled corticosteroids (ICS. Airway epithelial cells (AEC have distinct activation profiles that can influence ICS response.A pilot study to identify gene expression markers of AEC dysfunction and markers of corticosteroid sensitivity in asthmatic and non-asthmatic control children, for comparison with published reports in adults.AEC were obtained by nasal brushings and primary submerged cultures, and incubated in control conditions or in the presence of 10 ng/ml TNFalpha, 10-8M dexamethasone, or both. RT-PCR-based expression of FKBP51 (a steroid hormone receptor signalling regulator, NF-kB, IL-6, LIF (an IL-6 family neurotrophic cytokine, serpinB2 (which inhibits plasminogen activation and promotes fibrin deposition and porin (a marker of mitochondrial mass were determined.6 patients without asthma (median age 11yr; min-max: 7-13, 8 with controlled asthma (11yr, 7-13; median daily fluticasone dose = 100 μg, and 4 with uncontrolled asthma (12yr, 7-14; 1000 μg fluticasone daily were included. Baseline expression of LIF mRNA was significantly increased in uncontrolled vs controlled asthmatic children. TNFalpha significantly increased LIF expression in uncontrolled asthma. A similar trend was observed regarding IL-6. Dexamethasone significantly upregulated FKBP51 expression in all groups but the response was blunted in asthmatic children. No significant upregulation was identified regarding NF-kB, serpinB2 and porin.LIF and FKBP51 expression in epithelial cells were the most interesting markers of AEC dysfunction/response to corticosteroid treatment.

Smoking-induced gene expression changes in the bronchial airway are reflected in nasal and buccal epithelium

Directory of Open Access Journals (Sweden)

Zhang Xiaohui

2008-05-01

Full Text Available Abstract Background Cigarette smoking is a leading cause of preventable death and a significant cause of lung cancer and chronic obstructive pulmonary disease. Prior studies have demonstrated that smoking creates a field of molecular injury throughout the airway epithelium exposed to cigarette smoke. We have previously characterized gene expression in the bronchial epithelium of never smokers and identified the gene expression changes that occur in the mainstem bronchus in response to smoking. In this study, we explored relationships in whole-genome gene expression between extrathorcic (buccal and nasal and intrathoracic (bronchial epithelium in healthy current and never smokers. Results Using genes that have been previously defined as being expressed in the bronchial airway of never smokers (the "normal airway transcriptome", we found that bronchial and nasal epithelium from non-smokers were most similar in gene expression when compared to other epithelial and nonepithelial tissues, with several antioxidant, detoxification, and structural genes being highly expressed in both the bronchus and nose. Principle component analysis of previously defined smoking-induced genes from the bronchus suggested that smoking had a similar effect on gene expression in nasal epithelium. Gene set enrichment analysis demonstrated that this set of genes was also highly enriched among the genes most altered by smoking in both nasal and buccal epithelial samples. The expression of several detoxification genes was commonly altered by smoking in all three respiratory epithelial tissues, suggesting a common airway-wide response to tobacco exposure. Conclusion Our findings support a relationship between gene expression in extra- and intrathoracic airway epithelial cells and extend the concept of a smoking-induced field of injury to epithelial cells that line the mouth and nose. This relationship could potentially be utilized to develop a non-invasive biomarker for

Human papillomavirus: cause of epithelial lacrimal sac neoplasia?

DEFF Research Database (Denmark)

Sjö, Nicolai Christian; von Buchwald, Christian; Cassonnet, Patricia

2007-01-01

PURPOSE: Epithelial tumours of the lacrimal sac are rare but important entities that may carry grave prognoses. In this study the prevalence and possible role of human papillomavirus (HPV) infection in epithelial tumours of the lacrimal sac were evaluated. METHODS: Five papillomas and six...... 11 RNA was demonstrated in two papillomas. CONCLUSIONS: By analysing 11 epithelial lacrimal sac papillomas and carcinomas using PCR, DNA ISH and RNA ISH, we found HPV DNA in all investigated transitional epithelium tumours of the lacrimal sac. HPV RNA was present in two of eight epithelial lacrimal...... sac tumours positive for HPV DNA. As RNA degrades fast in paraffin-embedded tissue, only a small fraction of DNA-positive tumours can be expected to be RNA-positive. We therefore suggest that HPV infection is associated with the development of lacrimal sac papillomas and carcinomas....

Human thymic epithelial cells express functional HLA-DP molecules

DEFF Research Database (Denmark)

Jørgensen, A; Röpke, C; Nielsen, M

1996-01-01

T lymphocytes, we examined whether human thymic epithelial cells (TEC) expressed HLA-DP molecules. We present evidence that TEC obtained from short time culture express low but significant levels of HLA-DP molecules. The expression of HLA-DP molecules was comparable to or higher than the expression...... of HLA-DP allospecific primed lymphocyte typing (PLT) CD4 T cell lines. IFN-gamma treatment strongly upregulated the HLA-DP allospecific PLT responses whereas other PLT responses remained largely unchanged. In conclusion, these data indicate that human thymus epithelial cells express significant levels...

Decellularization of Human Nasal Septal Cartilage for the Novel Filler Material of Vocal Fold Augmentation.

Science.gov (United States)

Kang, Dae-Woon; Shin, Sung-Chan; Jang, Jeon-Yeob; Park, Hee-Young; Lee, Jin-Choon; Wang, Soo-Geun; Lee, Byung-Joo

2017-01-01

The clinical application of allogenic and/or xenogenic cartilage for vocal fold augmentation requires to remove the antigenic cellular component. The objective of this study was to assess the effect of cartilage decellularization and determine the change in immunogenicity after detergent treatment in human nasal septal cartilage flakes made by the freezing and grinding method. Human nasal septal cartilages were obtained from surgical cases. The harvested cartilages were treated by the freezing and grinding technique. The obtained cartilage flakes were treated with 1% Triton X-100 or 2% sodium dodecyl sulfate (SDS) for decellularization of the cartilage flakes. Hematoxylin and eosin stain (H&E stain), surface electric microscopy, immunohistochemical stain for major histocompatibility complex I and II, and ELISA for DNA contents were performed to assess the effect of cartilage decellularization after detergent treatment. A total of 10 nasal septal cartilages were obtained from surgical cases. After detergent treatment, the average size of the cartilage flakes was significantly decreased. With H&E staining, the cell nuclei of decellularized cartilage flakes were not observed. The expression of major histocompatibility complex (MHC)-I and II antigens was not identified in the decellularized cartilage flakes after treatment with detergent. DNA content was removed almost entirely from the decellularized cartilage flakes. Treatment with 2% SDS or 1% Triton X-100 for 1 hour appears to be a promising method for decellularization of human nasal septal cartilage for vocal fold augmentation. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Infection and HLA-G Molecules in Nasal Polyposis

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Roberta Rizzo

2014-01-01

Full Text Available Sinonasal polyposis (SNP is a chronic inflammatory pathology with an unclear aetiopathogenesis. Human papillomavirus (HPV infection is one candidate for the development of SNP for its epithelial cell trophism, hyperproliferative effect, and the induction of immune-modulatory molecules as HLA-G. We enrolled 10 patients with SNP without concomitant allergic diseases (SNP-WoAD, 10 patients with SNP and suffering from allergic diseases (SNP-WAD, and 10 control subjects who underwent rhinoplasty. We analyzed the presence of high- and low-risk HPV DNA and the expression of membrane HLA-G (mHLA-G and IL-10 receptor (IL-10R and of soluble HLA-G (sHLA-G and IL-10 by polyp epithelial cells. The results showed the presence of HPV-11 in 50% of SNP-WoAD patients (OR:5.5, all characterized by a relapsing disease. HPV-11 infection was absent in nonrelapsing SNP-WoAD patients, in SNP-WAD patients and in controls, supporting the hypothesis that HPV-11 increases risk of relapsing disease. HPV-11 positive SNP-WoAD patients presented with mHLA-G and IL-10R on epithelial cells from nasal polyps and showed secretion of sHLA-G and IL-10 in culture supernatants. No HLA-G expression was observed in HPV negative polyps. These data highlight new aspects of polyposis aetiopathogenesis and suggest HPV-11 and HLA-G/IL-10 presence as prognostic markers in the follow-up of SNP-WoAD.

Interleukin-4 and interleukin-13 compromise the sinonasal epithelial barrier and perturb intercellular junction protein expression.

Science.gov (United States)

Wise, Sarah K; Laury, Adrienne M; Katz, Elizabeth H; Den Beste, Kyle A; Parkos, Charles A; Nusrat, Asma

2014-05-01

Altered expression of epithelial intercellular junction proteins has been observed in sinonasal biopsies from nasal polyps and epithelial layers cultured from nasal polyp patients. These alterations comprise a "leaky" epithelial barrier phenotype. We hypothesize that T helper 2 (Th2) cytokines interleukin (IL)-4 and IL-13 modulate epithelial junction proteins, thereby contributing to the leaky epithelial barrier. Differentiated primary sinonasal epithelial layers cultured at the air-liquid interface were exposed to IL-4, IL-13, and controls for 24 hours at 37°C. Epithelial resistance measurements were taken every 4 hours during cytokine exposure. Western blot and immunofluorescence staining/confocal microscopy were used to assess changes in a panel of tight and adherens junction proteins. Western blot densitometry was quantified with image analysis. IL-4 and IL-13 exposure resulted in a mean decrease in transepithelial resistance at 24 hours to 51.6% (n = 6) and 68.6% (n = 8) of baseline, respectively. Tight junction protein junctional adhesion molecule-A (JAM-A) expression decreased 42.2% with IL-4 exposure (n = 9) and 37.5% with IL-13 exposure (n = 9). Adherens junction protein E-cadherin expression decreased 35.3% with IL-4 exposure (n = 9) and 32.9% with IL-13 exposure (n = 9). Tight junction protein claudin-2 showed more variability but had a trend toward higher expression with Th2 cytokine exposure. There were no appreciable changes in claudin-1, occludin, or zonula occludens-1 (ZO-1) with IL-4 or IL-13 exposure. Sinonasal epithelial exposure to Th2 cytokines IL-4 and IL-13 results in alterations in intercellular junction proteins, reflecting increased epithelial permeability. Such changes may explain some of the phenotypic manifestations of Th2-mediated sinonasal disease, such as edema, nasal discharge, and environmental reactivity. © 2014 ARS-AAOA, LLC.

IL-4 and IL-13 Compromise the Sinonasal Epithelial Barrier and Perturb Intercellular Junction Protein Expression

Science.gov (United States)

Wise, Sarah K.; Laury, Adrienne M.; Katz, Elizabeth H.; Den Beste, Kyle A.; Parkos, Charles A.; Nusrat, Asma

2014-01-01

Introduction Altered expression of epithelial intercellular junction proteins has been observed in sinonasal biopsies from nasal polyps and epithelial layers cultured from nasal polyp patients. These alterations comprise a “leaky” epithelial barrier phenotype. We hypothesize that Th2 cytokines IL-4 and IL-13 modulate epithelial junction proteins thereby contributing to the leaky epithelial barrier. Methods Differentiated primary sinonasal epithelial layers cultured at the air-liquid interface were exposed to IL-4, IL-13, and controls for 24 hours at 37°C. Epithelial resistance measurements were taken every 4 hours during cytokine exposure. Western blot and immunofluorescence staining/confocal microscopy were used to assess changes in a panel of tight and adherens junction proteins. Western blot densitometry was quantified with image analysis. Results IL-4 and IL-13 exposure resulted in a mean decrease in transepithelial resistance at 24 hours to 51.6% (n=6) and 68.6% (n=8) of baseline, respectively. Tight junction protein JAM-A expression decreased 42.2% with IL-4 exposure (n=9) and 37.5% with IL-13 exposure (n=9). Adherens junction protein E-cadherin expression decreased 35.3% with IL-4 exposure (n=9) and 32.9% with IL-13 exposure (n=9). Tight junction protein claudin-2 showed more variability but had a trend toward higher expression with Th2 cytokine exposure. There were no appreciable changes in claudin-1, occludin, or ZO-1 with IL-4 or IL-13 exposure. Conclusion Sinonasal epithelial exposure to Th2 cytokines IL-4 and IL-13 results in alterations in intercellular junction proteins, reflecting increased epithelial permeability. Such changes may explain some of the phenotypic manifestations of Th2-mediated sinonasal disease, such as edema, nasal discharge, and environmental reactivity. PMID:24510479

ANTHROPOMETRIC STUDY OF NASAL INDEX OF EGYPTIANS

OpenAIRE

Abdelmonem Awad Hegazy

2014-01-01

Background: The nasal index determination is one of the most commonly used anthropometric parameters in classifying human races. There are few reports in medical literature concerning nasal index that specifically address particular Egyptian populations. The objective of this study was to determine the normal parameters of external nose (width, height and nasal index) in Egyptians. Methods: The study was conducted randomly on healthy Egyptian subjects of both sexes. Nasal height and width ...

Human corneal epithelial subpopulations

DEFF Research Database (Denmark)

Søndergaard, Chris Bath

2013-01-01

Corneal epithelium is being regenerated throughout life by limbal epithelial stem cells (LESCs) believed to be located in histologically defined stem cell niches in corneal limbus. Defective or dysfunctional LESCs result in limbal stem cell deficiency (LSCD) causing pain and decreased visual acuity...... subpopulations in human corneal epithelium using a combination of laser capture microdissection and RNA sequencing for global transcriptomic profiling. We compared dissociation cultures, using either expansion on γ-irradiated NIH/3T3 feeder cells in serum-rich medium or expansion directly on plastic in serum...

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

DEFF Research Database (Denmark)

Kirkeby, L; Rasmussen, TT; Reinholdt, Jesper

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...

Differential growth factor induction and modulation of human gastric epithelial regeneration

International Nuclear Information System (INIS)

Tetreault, Marie-Pier; Chailler, Pierre; Rivard, Nathalie; Menard, Daniel

2005-01-01

While several autocrine/paracrine growth factors (GFs) can all stimulate epithelial regeneration in experimentally wounded primary gastric cultures, clinical relevance for their non-redundant cooperative actions in human gastric ulcer healing is suggested by the sequential pattern of GF gene induction in vivo. Using new HGE cell lines able to form a coherent monolayer with tight junctions as well as using primary human gastric epithelial cultures, we show that EGF, TGFα, HGF and IGFs accelerate epithelial restitution upon wounding, independently of the TGFβ pathway (as opposed to intestinal cells). However, they differently modulate cell behavior: TGFα exerts strong effects (even more than EGF) on cytoplasmic spreading and non-oriented protruding activity of bordering cells whereas HGF preferentially coordinates single lamella formation, cell elongation and migration into the wound. IGF-I and IGF-II rather induce the alignment of bordering cells and maintain a compact monolayer front. The number of mitotic cells maximally increases with EGF, followed by TGFα and IGF-I,-II. The current study demonstrates that GFs differentially regulate the regeneration of human gastric epithelial cells through specific modulation of cell shape adaptation, migration and proliferation, further stressing that a coordination of GF activities would be necessary for the normal progression of post-wounding epithelial repair

The role of L-type amino acid transporters in the uptake of glyphosate across mammalian epithelial tissues.

Science.gov (United States)

Xu, Jiaqiang; Li, Gao; Wang, Zhuoyi; Si, Luqin; He, Sijie; Cai, Jialing; Huang, Jiangeng; Donovan, Maureen D

2016-02-01

Glyphosate is one of the most commonly used herbicides worldwide due to its broad spectrum of activity and reported low toxicity to humans. Glyphosate has an amino acid-like structure that is highly polar and shows low bioavailability following oral ingestion and low systemic toxicity following intravenous exposures. Spray applications of glyphosate in agricultural or residential settings can result in topical or inhalation exposures to the herbicide. Limited systemic exposure to glyphosate occurs following skin contact, and pulmonary exposure has also been reported to be low. The results of nasal inhalation exposures, however, have not been evaluated. To investigate the mechanisms of glyphosate absorption across epithelial tissues, the permeation of glyphosate across Caco-2 cells, a gastrointestinal epithelium model, was compared with permeation across nasal respiratory and olfactory tissues excised from cows. Saturable glyphosate uptake was seen in all three tissues, indicating the activity of epithelial transporters. The uptake was shown to be ATP and Na(+) independent, and glyphosate permeability could be significantly reduced by the inclusion of competitive amino acids or specific LAT1/LAT2 transporter inhibitors. The pattern of inhibition of glyphosate permeability across Caco-2 and nasal mucosal tissues suggests that LAT1/2 play major roles in the transport of this amino-acid-like herbicide. Enhanced uptake into the epithelial cells at barrier mucosae, including the respiratory and gastrointestinal tracts, may result in more significant local and systemic effects than predicted from glyphosate's passive permeability, and enhanced uptake by the olfactory mucosa may result in further CNS disposition, potentially increasing the risk for brain-related toxicities. Copyright © 2015 Elsevier Ltd. All rights reserved.

Human Parvovirus 4 in Nasal and Fecal Specimens from Children, Ghana

Science.gov (United States)

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

2012-01-01

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 log10 copies/mL suggest respiratory or fecal–oral modes of PARV4 transmission. PMID:23018024

Nasal Lipopolysaccharide Challenge and Cytokine Measurement Reflects Innate Mucosal Immune Responsiveness.

Directory of Open Access Journals (Sweden)

Jaideep Dhariwal

Full Text Available Practical methods of monitoring innate immune mucosal responsiveness are lacking. Lipopolysaccharide (LPS is a component of the cell wall of Gram negative bacteria and a potent activator of Toll-like receptor (TLR-4. To measure LPS responsiveness of the nasal mucosa, we administered LPS as a nasal spray and quantified chemokine and cytokine levels in mucosal lining fluid (MLF.We performed a 5-way cross-over, single blind, placebo-controlled study in 15 healthy non-atopic subjects (n = 14 per protocol. Doses of ultrapure LPS (1, 10, 30 or 100μg/100μl or placebo were administered by a single nasal spray to each nostril. Using the recently developed method of nasosorption with synthetic adsorptive matrices (SAM, a series of samples were taken. A panel of seven cytokines/chemokines were measured by multiplex immunoassay in MLF. mRNA for intercellular cell adhesion molecule-1 (ICAM-1 was quantified from nasal epithelial curettage samples taken before and after challenge.Topical nasal LPS was well tolerated, causing no symptoms and no visible changes to the nasal mucosa. LPS induced dose-related increases in MLF levels of IL-1β, IL-6, CXCL8 (IL-8 and CCL3 (MIP-1α (AUC at 0.5 to 10h, compared to placebo, p<0.05 at 30 and 100μg LPS. At 100μg LPS, IL-10, IFN-α and TNF-α were also increased (p<0.05. Dose-related changes in mucosal ICAM-1 mRNA were also seen after challenge, and neutrophils appeared to peak in MLF at 8h. However, 2 subjects with high baseline cytokine levels showed prominent cytokine and chemokine responses to relatively low LPS doses (10μg and 30μg LPS.Topical nasal LPS causes dose-dependent increases in cytokines, chemokines, mRNA and cells. However, responsiveness can show unpredictable variations, possibly because baseline innate tone is affected by environmental factors. We believe that this new technique will have wide application in the study of the innate immune responses of the respiratory mucosa.Ultrapure LPS was used

Human Mammary Luminal Epithelial Cells Contain Progenitors to Myoepithelial Cells

Energy Technology Data Exchange (ETDEWEB)

Pechoux, Christine; Gudjonsson, Thorarinn; Ronnov-Jessen, Lone; Bissell, Mina J; Petersen, Ole

1999-02-01

The origin of the epithelial and myoepithelial cells in the human breast has not been delineated. In this study we have addressed whether luminal epithelial cells and myoepithelial cells are vertically connected, i.e., whether one is the precursor for the other. We used a primary culture assay allowing preservation of basic phenotypic traits of luminal epithelial and myoepithelial cells in culture. The two cell types were then separated immunomagnetically using antibodies directed against lineage-specific cell surface antigens into at best 100% purity. The cellular identity was ascertained by cytochemistry, immunoblotting, and 2-D gel electrophoresis. Luminal epithelial cells were identified by strong expression of cytokeratins 18 and 19 while myoepithelial cells were recognized by expression of vimentin and {alpha}-smooth muscle actin. We used a previously devised culture medium (CDM4) that allows vigorous expansion of proliferative myoepithelial cells and also devised a medium (CDM6) that allowed sufficient expansion of differentiated luminal epithelial cells based on addition of hepatocyte growth factor/scatter factor. The two different culture media supported each lineage for at least five passages without signs of interconversion. We used parallel cultures where we switched culture media, thus testing the ability of each lineage to convert to the other. Whereas the myoepithelial lineage showed no signs of interconversion, a subset of luminal epithelial cells, gradually, but distinctly, converted to myoepithelial cells. We propose that in the mature human breast, it is the luminal epithelial cell compartment that gives rise to myoepithelial cells rather than the other way around.

Platinum levels in nasal lavage fluid as a biomarker for traffic-related exposure and inflammation in children

Energy Technology Data Exchange (ETDEWEB)

Schins, R.P.F.; Polat, D.; Begerow, J.; Turfeld, M.; Becker, A.; Borm, P.J.A

2004-12-01

Platinum (Pt) is a well-known constituent of particles emitted by catalytic converters during car operation. To evaluate Pt as a potential marker for traffic related particle exposure, we investigated Pt content along with metals vanadium (V) and chromium (Cr) in coarse and fine particulate matter (PM), sampled in four areas with different traffic density, as well as in the nasal lavage (NAL) of 67 children (average age: 6 years) living in these areas. The different sites were characterised by significant differences in air pollutants including PM, NO, NO{sub 2}, CO and Cr, but differences in V or Pt were absent. No significant differences in neutrophil and epithelial cell counts or concentrations of the neutrophil chemoattractant interleukin-8 (IL-8) were found in the NAL of children living in the different areas. In addition, the concentrations of V, Cr and Pt, which were detectable in 64%, 73% and 93% of the individuals, respectively, did not differ between the different locations. However, in the NAL of the children, a significant correlation between Pt and the number of neutrophils/ml (r=0.40, p<0.001) as well as of epithelial cells/ml (r=0.41, p<0.001) was found. No relation was present between nasal inflammation and nasal Cr levels, whereas a relatively weak association was observed between V and epithelial cells counts (r=0.30, p=0.018). In conclusion, our data suggests a role for nasal lavage Pt as a candidate biomarker for traffic-related PM, which is able to induce inflammation in the upper respiratory tract.

Nasal Physiology

Science.gov (United States)

... Caregivers Contact ARS HOME ANATOMY Nasal Anatomy Sinus Anatomy Nasal Physiology Nasal Endoscopy Skull Base Anatomy Virtual Anatomy Disclosure ... Patient Education About this Website Font Size + - Home > ANATOMY > Nasal Physiology Nasal Anatomy Sinus Anatomy Nasal Physiology Nasal Endoscopy ...

Nasal Anatomy

Science.gov (United States)

... Caregivers Contact ARS HOME ANATOMY Nasal Anatomy Sinus Anatomy Nasal Physiology Nasal Endoscopy Skull Base Anatomy Virtual Anatomy Disclosure ... Size + - Home > ANATOMY > Nasal Anatomy Nasal Anatomy Sinus Anatomy Nasal Physiology Nasal Endoscopy Skull Base Anatomy Virtual Anatomy Disclosure ...

Nasal packing with ventilated nasal packs; a comparison with traditional vaseline nasal pack

International Nuclear Information System (INIS)

Alam, J.; Siddiqui, M.W.; Abbas, A.; Sami, M.; Ayub, Z.

2017-01-01

To compare the benefits of ventilated nasal packing with traditional vaseline guaze nasal packing. Study Design: Randomized controlled trial. Place and Duration of Study: This study was conducted at CMH Multan, from Jun 2014 to Dec 2014. Material and Methods: In this study, sample size of 80 patients was calculated using WHO calculator. Patients were divided in two groups using lottery method endotracheal tube and piece of surgical glove filled with ribbon guaze was utilized for fabricated ventilated nasal pack and compared with traditional nasal packs. Nasal obstruction and sleep disturbance were studied at eight hours and twenty-four hours following surgery using visual analog scale. Results: Mean nasal obstruction with ventilated nasal pack was 45.62 +- 6.17 and with Vaseline nasal pack was 77.67 +- 4.85 which was statistically significant (p=0.001) in both the groups. Mean sleep disturbance in both the groups was 46.32 +- 5.23 and 68.75 +- 2.70 respectively which was statistically significant (p=0.001) in both the groups. Conclusion: Patients with ventilated nasal packs were found to have better tolerance to nasal packs due to less nasal obstruction and sleep disturbance

CXCL9 Regulates TGF-β1-Induced Epithelial to Mesenchymal Transition in Human Alveolar Epithelial Cells.

Science.gov (United States)

O'Beirne, Sarah L; Walsh, Sinead M; Fabre, Aurélie; Reviriego, Carlota; Worrell, Julie C; Counihan, Ian P; Lumsden, Robert V; Cramton-Barnes, Jennifer; Belperio, John A; Donnelly, Seamas C; Boylan, Denise; Marchal-Sommé, Joëlle; Kane, Rosemary; Keane, Michael P

2015-09-15

Epithelial to mesenchymal cell transition (EMT), whereby fully differentiated epithelial cells transition to a mesenchymal phenotype, has been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). CXCR3 and its ligands are recognized to play a protective role in pulmonary fibrosis. In this study, we investigated the presence and extent of EMT and CXCR3 expression in human IPF surgical lung biopsies and assessed whether CXCR3 and its ligand CXCL9 modulate EMT in alveolar epithelial cells. Coexpression of the epithelial marker thyroid transcription factor-1 and the mesenchymal marker α-smooth muscle actin and CXCR3 expression was examined by immunohistochemical staining of IPF surgical lung biopsies. Epithelial and mesenchymal marker expression was examined by quantitative real-time PCR, Western blotting, and immunofluorescence in human alveolar epithelial (A549) cells treated with TGF-β1 and CXCL9, with Smad2, Smad3, and Smad7 expression and cellular localization examined by Western blotting. We found that significantly more cells were undergoing EMT in fibrotic versus normal areas of lung in IPF surgical lung biopsy samples. CXCR3 was expressed by type II pneumocytes and fibroblasts in fibrotic areas in close proximity to cells undergoing EMT. In vitro, CXCL9 abrogated TGF-β1-induced EMT. A decrease in TGF-β1-induced phosphorylation of Smad2 and Smad3 occurred with CXCL9 treatment. This was associated with increased shuttling of Smad7 from the nucleus to the cytoplasm where it inhibits Smad phosphorylation. This suggests a role for EMT in the pathogenesis of IPF and provides a novel mechanism for the inhibitory effects of CXCL9 on TGF-β1-induced EMT. Copyright © 2015 by The American Association of Immunologists, Inc.

Nasal application of HSV encoding human preproenkephalin blocks craniofacial pain in a rat model of traumatic brain injury

DEFF Research Database (Denmark)

Sørensen, Jens Christian Hedemann; Meidahl, Anders Christian Nørgaard; Tzabazis

2017-01-01

pain using nasal application of a herpes simplex virus (HSV)-based vector expressing human proenkephalin (SHPE) to target the trigeminal ganglia. Mild TBI was induced in rats by the use of a modified fluid percussion model. Two days after mild TBI, following the development of facial mechanical...... lasting at least 45 days. On the other hand, nasal SHPE application 2 days post-TBI attenuated facial allodynia, reaching significance by day 4–7 and maintaining this effect throughout the duration of the experiment. Immunohistochemical examination revealed strong expression of human proenkephalin...

Response of cultured normal human mammary epithelial cells to X rays

International Nuclear Information System (INIS)

Yang, T.C.; Stampfer, M.R.; Smith, H.S.

1983-01-01

The effect of X rays on the reproductive death of cultured normal human mammary epithelial cells was examined. Techniques were developed for isolating and culturing normal human mammary epithelial cells which provide sufficient cells at second passage for radiation studies, and an efficient clonogenic assay suitable for measuring radiation survival curves. It was found that the survival curves for epithelial cells from normal breast tissue were exponential and had D 0 values of about 109-148 rad for 225 kVp X rays. No consistent change in cell radiosensitivity with the age of donor was observed, and no sublethal damage repair in these cells could be detected with the split-dose technique

Culture of human intestinal epithelial cell using the dissociating enzyme thermolysin and endothelin-3

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Z. Liu

2010-05-01

Full Text Available Epithelium, a highly dynamic system, plays a key role in the homeostasis of the intestine. However, thus far a human intestinal epithelial cell line has not been established in many countries. Fetal tissue was selected to generate viable cell cultures for its sterile condition, effective generation, and differentiated character. The purpose of the present study was to culture human intestinal epithelial cells by a relatively simple method. Thermolysin was added to improve the yield of epithelial cells, while endothelin-3 was added to stimulate their growth. By adding endothelin-3, the achievement ratio (viable cell cultures/total cultures was enhanced to 60% of a total of 10 cultures (initiated from 8 distinct fetal small intestines, allowing the generation of viable epithelial cell cultures. Western blot, real-time PCR and immunofluorescent staining showed that cytokeratins 8, 18 and mouse intestinal mucosa-1/39 had high expression levels in human intestinal epithelial cells. Differentiated markers such as sucrase-isomaltase, aminopeptidase N and dipeptidylpeptidase IV also showed high expression levels in human intestinal epithelial cells. Differentiated human intestinal epithelial cells, with the expression of surface markers (cytokeratins 8, 18 and mouse intestinal mucosa-1/39 and secretion of cytokines (sucrase-isomaltase, aminopeptidase N and dipeptidylpeptidase IV, may be cultured by the thermolysin and endothelin-3 method and maintained for at least 20 passages. This is relatively simple, requiring no sophisticated techniques or instruments, and may have a number of varied applications.

Non-Eosinophilic Nasal Polyps Shows Increased Epithelial Proliferation and Localized Disease Pattern in the Early Stage.

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Dong-Kyu Kim

Full Text Available Non-eosinophilic nasal polyps (NPs show less inflammatory changes and are less commonly associated with lower airway inflammatory disorders such as asthma, compared with eosinophilic NPs. However, the development of non-eosinophilic NPs which is a predominant subtype in Asian population still remains unclear.A total of 81 patients (45 with non-eosinophilic NPs and 36 with eosinophilic NPs were enrolled. Clinical information and computed tomography (CT, endoscopic, and histological findings were investigated. Tissue samples were analyzed for total IgE levels and for mRNA expression levels of interleukin (IL-4, IL-5, IL-13, interferon (IFN-γ, tumor necrosis factor (TNF-α, IL-17A, IL-22, IL-23p19, transforming growth factor (TGF-β1, TGF-β2, TGF-β3, and periostin. Immunostaining assessment of Ki-67 as a proliferation marker was performed.We found that epithelial in-growing patterns such as pseudocysts were more frequently observed in histological and endoscopic evaluations of non-eosinophilic NPs, which was linked to increase epithelial staining of Ki-67, a proliferating marker. Eosinophilic NPs were characterized by high infiltration of inflammatory cells, compared with non-eosinophilic NPs. To investigate the developmental course of each subtype, CT was analyzed according to CT scores and subtypes. Non-eosinophilic NPs showed more localized pattern and maxillary sinus involvement, but lesser olfactory involvement in early stage whereas eosinophilic NPs were characterized by diffuse ethmoidal and olfactory involvement. In addition, high ethmoidal/maxillary (E/M CT scores, indicating ethmoidal dominant involvement, were one of surrogate markers for eosinophilic NP. E/M CT scores was positively correlated with levels of TH2 inflammatory markers, including IL-4, IL-5, periostin mRNA expression and total IgE levels in NPs, whereas levels of the TH1 cytokine, IFN- γ were inversely correlated. Moreover, if the combinatorial algorithm meet the three

Chronic Exposure to Particulate Nickel Induces Neoplastic Transformation in Human Lung Epithelial Cells

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Amie L. Holmes

2013-11-01

Full Text Available Nickel is a well-known human lung carcinogen with the particulate form being the most potent; however, the carcinogenic mechanism remains largely unknown. Few studies have investigated the genotoxicity and carcinogenicity of nickel in its target cell, human bronchial epithelial cells. Thus, the goal of this study was to investigate the effects of particulate nickel in human lung epithelial cells. We found that nickel subsulfide induced concentration- and time-dependent increases in both cytotoxicity and genotoxicity in human lung epithelial cells (BEP2D. Chronic exposure to nickel subsulfide readily induced cellular transformation, inducing 2.55, 2.9 and 2.35 foci per dish after exposure to 1, 2.5 and 5 μg/cm2 nickel subsulfide, respectively. Sixty-one, 100 and 70 percent of the foci isolated from 1, 2.5, and 5 μg/cm2 nickel subsulfide treatments formed colonies in soft agar and the degree of soft agar colony growth increased in a concentration-dependent manner. Thus, chronic exposure to particulate nickel induces genotoxicity and cellular transformation in human lung epithelial cells.

Nasal biopsies of children exposed to air pollutants.

Science.gov (United States)

Calderón-Garcidueñas, L; Rodriguez-Alcaraz, A; Valencia-Salazar, G; Mora-Tascareño, A; García, R; Osnaya, N; Villarreal-Calderón, A; Devlin, R B; Van Dyke, T

2001-01-01

Southwest Metropolitan Mexico City (SWMMC) atmosphere is a complex mixture of air pollutants, including ozone, particulate matter, and aldehydes. Children in SWMMC are exposed chronically and sequentially to numerous toxicants, and they exhibit significant nasal damage. The objective of this study was to assess p53 accumulation by immunohistochemistry in nasal biopsies of SWMMC children. We evaluated 111 biopsies from 107 children (83 exposed SWMMC children and 24 control children residents in a pollutant-compliant Caribbean island). Complete clinical histories and physical examinations, including an ear-nose-throat (ENT) exam were done. There was a significant statistical difference in the upper and lower respiratory symptomatology and ENT findings between control and exposed children (p < 0.001). Control children gave no respiratory symptomatology in the 3 months prior to the study; their biopsies exhibited normal ciliated respiratory epithelium and were p53-negative. SWMMC children complained of epistaxis, nasal obstruction. and crusting. Irregular areas of whitish-gray recessed mucosa over the inferior and middle turbinates were seen in 25% of SWMMC children, and their nasal biopsies displayed basal cell hyperplasia, decreased numbers of ciliated and goblet cells, neutrophilic epithelial infiltrates, squamous metaplasia. and mild dysplasia. Four of 21 SWMMC children with grossly abnormal mucosal changes exhibited strong transmural nuclear p53 staining in their nasal biopsies (p 0.005, odds ratio 26). In the context of lifetime exposures to toxic and potentially carcinogenic air pollutants, p53 nasal induction in children could potentially represent. a) a checkpoint response to toxic exposures, setting up a selective condition for p53 mutation, or b) a p53 mutation has already occurred as a result of such selection. Because the biological significance of p53 nuclear accumulation in the nasal biopsies of these children is not clear at this point, we strongly

Interleukin (IL) 36 gamma induces mucin 5AC, oligomeric mucus/gel-forming expression via IL-36 receptor-extracellular signal regulated kinase 1 and 2, and p38-nuclear factor kappa-light-chain-enhancer of activated B cells in human airway epithelial cells.

Science.gov (United States)

Bae, Chang Hoon; Choi, Yoon Seok; Na, Hyung Gyun; Song, Si-Youn; Kim, Yong-Dae

2018-03-01

Mucin 5AC, oligomeric mucus/gel-forming (MUC5AC) expression is significantly increased in allergic and inflammatory airway diseases. Interleukin (IL) 36 gamma is predominantly expressed in airway epithelial cells and plays an important role in innate and adaptive immune responses. IL-36 gamma is induced by many inflammatory mediators, including cytokines and bacterial and viral infections. However, the association between IL-36 gamma and mucin secretion in human airway epithelial cells has not yet been fully investigated. The objective of this study was to determine whether IL-36 gamma might play a role in the regulation of mucin secretion in airway epithelial cells. We investigated the effect and brief signaling pathway of IL-36 gamma on MUC5AC expression in human airway epithelial cells. Enzyme immunoassay, immunoblot analysis, immunofluorescence staining, reverse transcriptase-polymerase chain reaction (PCR), and real-time PCR were performed in mucin-producing human airway epithelial NCI-H292 cells and in human nasal epithelial cells after pretreatment with IL-36 gamma, several specific inhibitors, or small interfering RNAs (siRNA). IL-36 gamma induced MUC5AC expression and activated the phosphorylation of extracellular signal regulated kinase (ERK) 1 and 2, p38, and nuclear factor-kappa-light-chain-enhancer of activated B cells (NF-kappa B). IL-36 receptor antagonist significantly attenuated these effects. The specific inhibitor and siRNA of ERK1, ERK2, p38, and NF-kappa B significantly attenuated IL-36 gamma induced MUC5AC expression. These results indicated that IL-36 gamma induced MUC5AC expression via the IL-36 receptor-mediated ERK1/2 and p38/NF-kappa B pathway in human airway epithelial cells.

The Effect of Menstrual Cycle on Nasal Resonance Characteristics in Females

Science.gov (United States)

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"…

Bio-synthesis of gold nanoparticles by human epithelial cells, in vivo

International Nuclear Information System (INIS)

Larios-Rodriguez, E; Rangel-Ayon, C; Herrera-Urbina, R; Castillo, S J; Zavala, G

2011-01-01

Healthy epithelial cells, in vivo, have the ability to synthesize gold nanoparticles when aqueous tetrachloroauric acid is made to react with human skin. Neither a reducing agent nor a protecting chemical is needed for this bio-synthesis method. The first indication of gold nanoparticle formation is the staining of the skin, which turns deep purple. Stereoscopic optical micrographs of human skin tissue in contact with aqueous tetrachloroauric acid clearly show the staining of the epithelial cells. The UV-Vis spectrum of these epithelial cells shows an absorption band with a maximum at 553 nm. This absorption peak is within the wavelength region where the surface plasmon resonance (SPR) band of aqueous colloidal gold exhibits a maximum. Transmission electron micrographs show that gold nanoparticles synthesized by epithelial cells have sizes between 1 and 100 nm. The electron diffraction pattern of these nanoparticles reveals a crystalline structure whose interplanar distances correspond to fcc metallic gold. Transmission electron micrographs of ultra-thin (70 nm thick) slices of epithelial cells clearly and undoubtedly demonstrate that gold nanoparticles are inside the cell. According to high resolution transmission electron micrographs of intracellular single gold nanoparticles, they have the shape of a polyhedron.

Bio-synthesis of gold nanoparticles by human epithelial cells, in vivo

Energy Technology Data Exchange (ETDEWEB)

Larios-Rodriguez, E; Rangel-Ayon, C; Herrera-Urbina, R [Departamento de Ingenieria Quimica y Metalurgia, Universidad de Sonora, Rosales y Luis Encinas S/N, Hermosillo, Sonora, C.P. 83000 (Mexico); Castillo, S J [Departamento de Investigacion en Fisica, Universidad de Sonora, Rosales y Luis Encinas S/N, Hermosillo, Sonora, C.P. 83000 (Mexico); Zavala, G, E-mail: elarios@polimeros.uson.mx [Instituto de Biotecnologia, Universidad Nacional Autonoma de Mexico, Cuernavaca, Morelos (Mexico)

2011-09-02

Healthy epithelial cells, in vivo, have the ability to synthesize gold nanoparticles when aqueous tetrachloroauric acid is made to react with human skin. Neither a reducing agent nor a protecting chemical is needed for this bio-synthesis method. The first indication of gold nanoparticle formation is the staining of the skin, which turns deep purple. Stereoscopic optical micrographs of human skin tissue in contact with aqueous tetrachloroauric acid clearly show the staining of the epithelial cells. The UV-Vis spectrum of these epithelial cells shows an absorption band with a maximum at 553 nm. This absorption peak is within the wavelength region where the surface plasmon resonance (SPR) band of aqueous colloidal gold exhibits a maximum. Transmission electron micrographs show that gold nanoparticles synthesized by epithelial cells have sizes between 1 and 100 nm. The electron diffraction pattern of these nanoparticles reveals a crystalline structure whose interplanar distances correspond to fcc metallic gold. Transmission electron micrographs of ultra-thin (70 nm thick) slices of epithelial cells clearly and undoubtedly demonstrate that gold nanoparticles are inside the cell. According to high resolution transmission electron micrographs of intracellular single gold nanoparticles, they have the shape of a polyhedron.

Adrenomedullin stimulates cyclic AMP production in the airway epithelial cells of guinea-pigs and in the human epithelial cell line

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Takashi Kawaguchi

1999-01-01

Full Text Available This study was designed to examine the effects of adrenomedullin (AM on airway epithelial cells. Primary cultures of guinea-pig tracheal epithelial cells and the human bronchiolar epithelial cell line NCI-H441 were used. Intracellular cyclic adenosine monophosphate (cAMP, cyclic guanosine monophosphate (cGMP, prostaglandin E2 (PGE2, and stable end-products of nitric oxide were assayed. Adrenomedullin (10−6 mol/L stimulated cAMP production in guinea-pig epithelial cells. Indomethacin (10−5 mol/L significantly decreased the basal level of intracellular cAMP in guinea-pig epithelial cells, but not in NCI-H441 cells. However, AM did not stimulate production of PGE2, a major product that can increase cAMP formation. In the case of NCI-H441 cells, AM (10−8 – 10−6 mol/L did not significantly affect intracellular cGMP levels or nitrite content in conditioned medium. Adrenomedullin and calcitonin gene-related peptide (CGRP each stimulated cAMP production in NCI-H441 cells, but AM-stimulated cAMP production was antagonized by the CGRP fragment CGRP8–37. These findings suggest that AM stimulates cAMP production and functionally competes with CGRP for binding sites in airway epithelial cells, at least in human epithelial cells, but that it does not stimulate the release of PGE2 and nitric oxide. Though cyclooxygenase products contribute to some extent to cAMP formation in guinea-pigs, AM independently stimulates intracellular cAMP formation in airway epithelial cells.

Airway epithelial NF-κB activation promotes Mycoplasma pneumoniae clearance in mice.

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Di Jiang

Full Text Available Respiratory infections including atypical bacteria Mycoplasma pneumoniae (Mp contribute to the pathobiology of asthma and chronic obstructive pulmonary disease (COPD. Mp infection mainly targets airway epithelium and activates various signaling pathways such as nuclear factor κB (NF-κB. We have shown that short palate, lung, and nasal epithelium clone 1 (SPLUNC1 serves as a novel host defense protein and is up-regulated upon Mp infection through NF-κB activation in cultured human and mouse primary airway epithelial cells. However, the in vivo role of airway epithelial NF-κB activation in host defense against Mp infection has not been investigated. In the current study, we investigated the effects of in vivo airway epithelial NF-κB activation on lung Mp clearance and its association with airway epithelial SPLUNC1 expression.Non-antimicrobial tetracycline analog 9-t-butyl doxycycline (9-TB was initially optimized in mouse primary tracheal epithelial cell culture, and then utilized to induce in vivo airway epithelial specific NF-κB activation in conditional NF-κB transgenic mice (CC10-(CAIKKβ with or without Mp infection. Lung Mp load and inflammation were evaluated, and airway epithelial SPLUNC1 protein was examined by immunohistochemistry. We found that 9-TB treatment in NF-κB transgene positive (Tg+, but not transgene negative (Tg- mice significantly reduced lung Mp load. Moreover, 9-TB increased airway epithelial SPLUNC1 protein expression in NF-κB Tg+ mice.By using the non-antimicrobial 9-TB, our study demonstrates that in vivo airway epithelial NF-κB activation promotes lung bacterial clearance, which is accompanied by increased epithelial SPLUNC1 expression.

Chitin stimulates expression of acidic mammalian chitinase and eotaxin-3 by human sinonasal epithelial cells in vitro.

Science.gov (United States)

Lalaker, Ashley; Nkrumah, Louis; Lee, Won-Kyung; Ramanathan, Murugappan; Lane, Andrew P

2009-01-01

Sinonasal epithelial cells participate in host defense by initiating innate immune mechanisms against potential pathogens. Antimicrobial innate mechanisms have been shown to involve Th1-like inflammatory responses. Although epithelial cells can also be induced by Th2 cytokines to express proeosinophilic mediators, no environmental agents have been identified that promote this effect. Human sinonasal epithelial cells from patients with chronic rhinosinusitis with nasal polyps (CRSwNPs) and controls were harvested and grown in primary culture. Cell cultures were exposed to a range of concentrations of chitin for 24 hours, and mRNA for acidic mammalian chitinase (AMCase), eotaxin-3, and thymic stromal-derived lymphopoietin (TSLP) were assessed. Other cultures were exposed to interleukin 4 (IL- 4) alone and in combination with dust-mite antigen (DMA) for 36 hours. Extracted mRNA and cell culture supernatant were analyzed for expression of AMCase and eotaxin-3. Chitin induced a dose-dependent expression of AMCase and eotaxin-3 mRNA but not TSLP. Patients with recalcitrant CRSwNPs showed lower baseline expression of AMCase when compared with treatment-responsive CRSwNP and less induction of AMCase expression by chitin. DMA did not directly induce expression of AMCase or eotaxin-3. Expression of eotaxin-3 was stimulated by IL-4 and further enhanced with the addition of DMA. Levels of AMCase were not significantly affected by either IL-4 or DMA exposure. In some cases, the combination of IL-4 and DMA was able to induce AMCase expression in cell cultures not producing AMCase at baseline. The abundant biopolymer chitin appears to be recognized by a yet uncharacterized receptor on sinonasal epithelial cells. Chitin stimulates production of AMCase and eotaxin-3, two pro-Th2 effector proteins. This finding suggests the existence of a novel innate immune pathway for local defense against chitin-containing organisms in the sinonasal tract. Dysregulation of this function could

Staphylococcus aureus and the ecology of the nasal microbiome

DEFF Research Database (Denmark)

Liu, Cindy M; Price, Lance B; Hungate, Bruce A

2015-01-01

The human microbiome can play a key role in host susceptibility to pathogens, including in the nasal cavity, a site favored by Staphylococcus aureus. However, what determines our resident nasal microbiota-the host or the environment-and can interactions among nasal bacteria determine S. aureus...

Effects of scaffold composition and architecture on human nasal chondrocyte redifferentiation and cartilaginous matrix deposition

NARCIS (Netherlands)

Miot, Sylvie; Woodfield, T.B.F.; Daniels, Alma U.; Suetterlin, Rosemarie; Peterschmitt, Iman; Heberer, Michael; van Blitterswijk, Clemens; Riesle, J.U.; Martin, Ivan

2005-01-01

We investigated whether the post-expansion redifferentiation and cartilage tissue formation capacity of adult human nasal chondrocytes can be regulated by controlled modifications of scaffold composition and architecture. As a model system, we used poly(ethylene

Studies of blood flow in human nasal mucosa with /sup133/Xe washout technique and laser doppler flowmetry

International Nuclear Information System (INIS)

Olsson, P.

1986-01-01

The techniques were applied for studies of the influence of environmental temperature on the human nasal mucosa, for studies of mediators in nasal allergy and for studies of the sympathetic neurogenic control of blood flow in the nasal mucosa. The results show that the two techniques are complementary to one another. The /sup133/Xe washout technique is useful for semiquantitative estimations of blood flow in the deeper parts of the mucosa, while the laser doppler technique is especially suited for continuous recordings of relative blood flow changes in the superficial part of the mucosa. Vascular changes may take part in body temperature regulation changes may take part in body temperature regulation as well as in conditioning of respiratory air. The results support the theories that changes in nasal mucosal blood flow are related to body temperature control, while conditioning of inspiratory air may be more dependent on mucosal blood content. The observed dissociation between changes in the resistance and the capacitance vessels also illustrates that these vascular segments are regulated in different ways. The present results indicate that leukotriene D/sub4/ might contribute to an increased blood flow in the nasal mucosa and to blockage of the nasal airway in the acute allergic reaction. Vasomotion is demonstrated to be present in the nasal mucosa, and it appears to be partly dependent on sympathetic neurogenic activity. The development of the present techniques, means that vascular changes involved in normal nasal function and in nasal disease may be evaluated by a new approach. (author)

The plasticity of human breast carcinoma cells is more than epithelial to mesenchymal conversion

DEFF Research Database (Denmark)

Petersen, Ole William; Nielsen, Helga Lind; Gudjonsson, Thorarinn

2001-01-01

The human breast comprises three lineages: the luminal epithelial lineage, the myoepithelial lineage, and the mesenchymal lineage. It has been widely accepted that human breast neoplasia pertains only to the luminal epithelial lineage. In recent years, however, evidence has accumulated that neopl...

Studies Using an in Vitro Model Show Evidence of Involvement of Epithelial-Mesenchymal Transition of Human Endometrial Epithelial Cells in Human Embryo Implantation*

Science.gov (United States)

Uchida, Hiroshi; Maruyama, Tetsuo; Nishikawa-Uchida, Sayaka; Oda, Hideyuki; Miyazaki, Kaoru; Yamasaki, Akiko; Yoshimura, Yasunori

2012-01-01

Human embryo implantation is a critical multistep process consisting of embryo apposition/adhesion, followed by penetration and invasion. Through embryo penetration, the endometrial epithelial cell barrier is disrupted and remodeled by an unknown mechanism. We have previously developed an in vitro model for human embryo implantation employing the human choriocarcinoma cell line JAR and the human endometrial adenocarcinoma cell line Ishikawa. Using this model we have shown that stimulation with ovarian steroid hormones (17β-estradiol and progesterone, E2P4) and suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, enhances the attachment and adhesion of JAR spheroids to Ishikawa. In the present study we showed that the attachment and adhesion of JAR spheroids and treatment with E2P4 or SAHA individually induce the epithelial-mesenchymal transition (EMT) in Ishikawa cells. This was evident by up-regulation of N-cadherin and vimentin, a mesenchymal cell marker, and concomitant down-regulation of E-cadherin in Ishikawa cells. Stimulation with E2P4 or SAHA accelerated Ishikawa cell motility, increased JAR spheroid outgrowth, and enhanced the unique redistribution of N-cadherin, which was most prominent in proximity to the adhered spheroids. Moreover, an N-cadherin functional blocking antibody attenuated all events but not JAR spheroid adhesion. These results collectively provide evidence suggesting that E2P4- and implanting embryo-induced EMT of endometrial epithelial cells may play a pivotal role in the subsequent processes of human embryo implantation with functional control of N-cadherin. PMID:22174415

CriticalSorb: a novel efficient nasal delivery system for human growth hormone based on Solutol HS15.

Science.gov (United States)

Illum, Lisbeth; Jordan, Faron; Lewis, Andrew L

2012-08-20

The absorption enhancing efficiency of CriticalSorb for human growth hormone (MW 22 kDa) was investigated in the conscious rat model. The principle absorption enhancing component of CriticalSorb, Solutol HS15, comprises polyglycol mono- and di-esters of 12-hydroxystearic acid combined with free polyethylene glycol. When administering hGH nasally in rats with increasing concentrations of Solutol HS15, it was found that for a 10%w/v solution formulation a bioavailability of 49% was obtained in the first 2h after administration. Furthermore it was shown that the most effective ratio of Solutol HS15 to hGH was 4:1 on a mg to mg basis. Histopathology studies in rats after 5 days repeated nasal administration showed that Solutol HS15 had no toxic effect on the nasal mucosa. These results have been confirmed in a 6 month repeat nasal toxicity study in rats. It can be concluded that the principle absorption enhancing component of CriticalSorb - Solutol HS15 - is a potent and non- toxic nasal absorption enhancer that warrants further development. Copyright © 2012 Elsevier B.V. All rights reserved.

Effects of 0.12 and 0.80 ppm ozone on rat nasal and nasopharyngeal epithelial mucosubstances: Quantitative histochemistry

International Nuclear Information System (INIS)

Harkema, J.R.; Hotchkiss, J.A.; Henderson, R.F.

1989-01-01

The present study was designed to characterize the quantity of mucosubstances in surface epithelia of the rat nasal cavity and nasopharynx after short-term ozone exposure. Rats were exposure. Nasal cavities were processed for morphometric analysis of intraepithelial mucosubstances. Compared to controls, rats exposed to 0.12 ppm ozone had increased amounts of stored mucosubstances within epithelium lining the medial aspect of the nasal turbinate, but no change within the epithelium of the nasopharynx. Rats exposed to 0.8 ppm ozone had increased quantities of stored mucosubstances within the transitional and respiratory epithelia lining turbinates and lateral walls of the anterior nasal airway, and significant decreases in stored mucosubstances within the epithelium of the nasal septum at the end of exposure. Seven days after the end of exposure, the amounts of intraepithelial mucosubstances returned to control levels along the septum, but remained greater than those of controls along the turbinates and nasopharynx. We conclude that exposures to ambient levels of ozone induce significant changes in the stored secretory product of nasal epithelium in the rat, and that these changes persist for at least 7 days after cessation of exposure

Impaired Air Conditioning within the Nasal Cavity in Flat-Faced Homo.

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Takeshi Nishimura

2016-03-01

Full Text Available 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

Cellular changes in tears associated with keratoconjunctival responses induced by nasal allergy.

Science.gov (United States)

Pelikan, Z

2014-04-01

Allergic keratoconjunctivitis occurs in a primary form, caused by an allergic reaction localized in the conjunctiva, and in a secondary form, induced by an allergic reaction originating in the nasal mucosa. Various hypersensitivity mechanisms involved in the keratoconjunctivitis forms result in different keratoconjunctival response types. To investigate the cytologic changes in tears during the secondary immediate (SIKCR), late (SLKCR), and delayed (SDYKCR) keratoconjunctival responses. In 61 patients, comprising 20 SIKCRs, 23 SLKCRs, and 18 SDYKCRs, nasal provocation tests (NPTs) with allergens and 61 phosphate-buffered control challenges were repeated and supplemented with cell counting in the tears. The SIKCR (Ptears. The SLKCR (Ptears. The cells, except mast, epithelial and goblet cells, displaying no intracellular changes, migrated probably from the conjunctival capillaries, in response to the factors released during the primary allergic reaction in the nasal mucosa and subsequently penetrating into the conjunctiva. These results demonstrate a causal role of nasal allergy and diagnostic value of NPT combined with recording of ocular features and cellular profiles in tears in some keratoconjunctivitis patients.

Solitary chemoreceptor cells in the nasal cavity serve as sentinels of respiration.

Science.gov (United States)

Finger, Thomas E; Böttger, Bärbel; Hansen, Anne; Anderson, Karl T; Alimohammadi, Hessamedin; Silver, Wayne L

2003-07-22

Inhalation of irritating substances leads to activation of the trigeminal nerve, triggering protective reflexes that include apnea or sneezing. Receptors for trigeminal irritants are generally assumed to be located exclusively on free nerve endings within the nasal epithelium, requiring that trigeminal irritants diffuse through the junctional barrier at the epithelial surface to activate receptors. We find, in both rats and mice, an extensive population of chemosensory cells that reach the surface of the nasal epithelium and form synaptic contacts with trigeminal afferent nerve fibers. These chemosensory cells express T2R "bitter-taste" receptors and alpha-gustducin, a G protein involved in chemosensory transduction. Functional studies indicate that bitter substances applied to the nasal epithelium activate the trigeminal nerve and evoke changes in respiratory rate. By extending to the surface of the nasal epithelium, these chemosensory cells serve to expand the repertoire of compounds that can activate trigeminal protective reflexes. The trigeminal chemoreceptor cells are likely to be remnants of the phylogenetically ancient population of solitary chemoreceptor cells found in the epithelium of all anamniote aquatic vertebrates.

Translocation of SiO2-NPs across in vitro human bronchial epithelial monolayer

International Nuclear Information System (INIS)

George, I; Vranic, S; Boland, S; Borot, M C; Marano, F; Baeza-Squiban, A

2013-01-01

Safe development and application of nanotechnologies in many fields require better knowledge about their potential adverse effects on human health. Evidence of abilities of nanoparticles (NPs) to cross epithelial barriers and reach secondary organs via the bloodstream led us to investigate the translocation of SiO 2 NPs of 50 nm (50 nm-SiO 2 -NPs) across human bronchial epithelial cells that are primary targets after exposure to inhaled NPs. We quantified the translocation of fluorescently labelled SiO 2 NPs at non-cytotoxic concentrations (5 and 10 μg/cm 2 ) across Calu-3 epithelial monolayer. After 14 days in culture Calu-3 cells seeded onto 3 μm-polycarbonate Transwell membranes formed an efficient bronchial barrier assessed by measurement of the transepithelial electric resistance and quantification of the permeability of the monolayer. After 24 hours of exposure, we observed a significant translocation of NPs that was more important when the initial NP concentration decreased. Confocal microscopy observations revealed NP uptake by cells and an important NP retention inside the porous membrane. In conclusion, 50 nm-SiO 2 -NPs can cross the human bronchial epithelial barrier without affecting the integrity of the epithelial cell monolayer.

Alkaline phosphatase in nasal secretion of cattle: biochemical and molecular characterisation.

Science.gov (United States)

Ghazali, M Faizal; Koh-Tan, H H Caline; McLaughlin, Mark; Montague, Paul; Jonsson, Nicholas N; Eckersall, P David

2014-09-05

Nasal secretion (NS) was investigated as a source of information regarding the mucosal and systemic immune status of cattle challenged by respiratory disease. A method for the collection of substantial volumes (~12 ml) of NS from cattle was developed to establish a reference range of analytes that are present in the NS of healthy cattle. Biochemical profiles of NS from a group of 38 healthy Holstein-Friesian cows revealed high alkaline phosphatase (AP) activity of up to 2392 IU/L. The character and source of the high activity of AP in bovine NS was investigated. Histochemical analysis confirmed the localization of the AP enzyme activity to epithelial cells and serous glands of the nasal respiratory mucosa. Analysis of mRNA levels from nasal mucosa by end point RT-PCR and PCR product sequencing confirmed that the AP was locally produced and is identical at the nucleotide level to the non-specific AP splice variant found in bovine liver, bone and kidney. Analysis by isoelectric focussing confirmed that AP was produced locally at a high level in nasal epithelium demonstrating that AP from nasal secretion and nasal mucosa had similar pI bands, though differing from those of the liver, kidney, bone and intestine, suggesting different post-translational modification (PTM) of AP in these tissues. A nasal isozyme of AP has been identified that is present at a high activity in NS, resulting from local production and showing distinctive PTM and may be active in NS as an anti-endotoxin mediator.

Human epithelial cells increase their rigidity with ageing in vitro: direct measurements

International Nuclear Information System (INIS)

Berdyyeva, Tamara K; Woodworth, Craig D; Sokolov, Igor

2005-01-01

The decrease in elasticity of epithelial tissues with ageing contributes to many human diseases. This change was previously attributed to increased crosslinking of extracellular matrix proteins. Here we show that individual human epithelial cells also become significantly more rigid during ageing in vitro. Using atomic force microscopy (AFM), we found that the Young's modulus of viable cells was consistently increased two- to four-fold in older versus younger cells. Direct visualization of the cytoskeleton using a novel method involving the AFM suggested that increased rigidity of ageing cells was due to a higher density of cytoskeletal fibres. Our results identify a unique mechanism that might contribute to the age-related loss of elasticity in epithelial tissues

Oxytetracycline Inhibits Mucus Secretion and Inflammation in Human Airway Epithelial Cells.

Science.gov (United States)

Shah, Said Ahmad; Ishinaga, Hajime; Takeuchi, Kazuhiko

2017-01-01

Oxytetracycline is a broad-spectrum antibiotic, but its nonantibacterial effects in the human respiratory tract are unknown. In this study, the effects of oxytetracycline on mucus secretion and inflammation were examined by PCR and ELISA in the human airway epithelial cell line NCI-H292. Oxytetracycline (10 μg/mL) significantly inhibited TNF-α-induced MUC5AC gene expression and MUC5AC protein levels in NCI-H292 cells. It also downregulated IL-8 and IL-1β gene expression and IL-1β protein levels. Our findings demonstrated that oxytetracycline suppressed mucus production and inflammation in human respiratory epithelial cells, providing further evidence for the usefulness of oxytetracycline for human airway inflammatory diseases. © 2017 S. Karger AG, Basel.

The human airway epithelial basal cell transcriptome.

Directory of Open Access Journals (Sweden)

Neil R Hackett

2011-05-01

Full Text Available The human airway epithelium consists of 4 major cell types: ciliated, secretory, columnar and basal cells. During natural turnover and in response to injury, the airway basal cells function as stem/progenitor cells for the other airway cell types. The objective of this study is to better understand human airway epithelial basal cell biology by defining the gene expression signature of this cell population.Bronchial brushing was used to obtain airway epithelium from healthy nonsmokers. Microarrays were used to assess the transcriptome of basal cells purified from the airway epithelium in comparison to the transcriptome of the differentiated airway epithelium. This analysis identified the "human airway basal cell signature" as 1,161 unique genes with >5-fold higher expression level in basal cells compared to differentiated epithelium. The basal cell signature was suppressed when the basal cells differentiated into a ciliated airway epithelium in vitro. The basal cell signature displayed overlap with genes expressed in basal-like cells from other human tissues and with that of murine airway basal cells. Consistent with self-modulation as well as signaling to other airway cell types, the human airway basal cell signature was characterized by genes encoding extracellular matrix components, growth factors and growth factor receptors, including genes related to the EGF and VEGF pathways. Interestingly, while the basal cell signature overlaps that of basal-like cells of other organs, the human airway basal cell signature has features not previously associated with this cell type, including a unique pattern of genes encoding extracellular matrix components, G protein-coupled receptors, neuroactive ligands and receptors, and ion channels.The human airway epithelial basal cell signature identified in the present study provides novel insights into the molecular phenotype and biology of the stem/progenitor cells of the human airway epithelium.

Mechanism research of miR-181 regulating human lens epithelial cell apoptosis

Directory of Open Access Journals (Sweden)

Yu Qin

2015-05-01

Full Text Available AIM: To investigate the expression of miR-181 in the lens tissue of cataract and the regulating mechanism of miR-181 on apoptosis of human lens epithelial cell.METHODS:Real time q-PCR was used to measure the expression of miR-181 in the anterior lens capsules of age-related cataract and human lens epithelial cell apoptosis model. miR-181 mimic and inhibitor were transfected using Lipofectamine 2 000 to regulate the expression of miR-181, and then Real time q-PCR was used to verify transfection efficiency. Flow cytometry was used to detect the change of cell apoptosis rate. RESULTS: Compared with control group, the expression of miR-181 was significantly higher in both the anterior lens capsules of age-related cataract and human lens epithelial cell apoptosis model; the relative expression of miR-181 in lens epithelial cells transfected with miR-181 mimic was increased, whereas decreased in cells transfected with miR-181 inhibitor; the apoptosis rate of cells transfected with miR-181 mimic was increased, while reduced in miR-181 inhibitor group. Each result was statistically significant(PCONCLUSION: High expression of miR-181 is detected in anterior lens capsule of age-related cataract. miR-181 might play a certain role in the pathogenesis of cataract via promoting human lens epithelial cell apoptosis. miR-181 probably becomes a new approach for the nonoperative treatment of cataract, but the concrete mechanism still needs to be further studied.

Effects of 0.12 and 0.80 PPM ozone on rat nasal and nasopharyngeal epithelial mucosubstances: Quantitative histochemistry

International Nuclear Information System (INIS)

Harkema, J.R.; Hotchkiss, J.A.; Henderson, R.F.

1988-01-01

The present study was designed to characterize changes in the quantity of mucosubstances in surface epithelia of rat nasal airways after short- term ozone exposure. Rats were exposed for 7 days (6 h/day) to 0.0, 0.12, or 0.8 ppm ozone, and killed immediately or 7 days after the last exposure. Nasal cavities were processed for morphometric analysis of intraepithelial mucosubstances. Compared to controls, rats exposed to 0.12 ppm ozone had increased amounts of stored mucosubstances within epithelium lining the medial aspect of the nasal turbinate immediately after exposure, but no change within epithelia of the nasopharynx. Rats exposed to 0.8 ppm ozone had increased quantities of stored mucosubstances within transitional and respiratory epithelium lining turbinates and lateral walls of the anterior nasal airway and significant decreases in stored mucosubstances within epithelia of the nasal septum at the end of exposure. Seven days after the end of exposure, the amounts of intraepithelial mucosubstances returned to control levels along the septum, but remained greater than those of controls along the turbinates. We demonstrated that exposures to ambient levels of ozone induce significant changes in the stored secretory product of nasal epithelium in the rat, and that these changes persist for at least 7 days post-exposure. (author)

Platelets are a possible regulator of human endometrial re-epithelialization during menstruation.

Science.gov (United States)

Suginami, Koh; Sato, Yukiyasu; Horie, Akihito; Matsumoto, Hisanori; Kyo, Satoru; Araki, Yoshihiko; Konishi, Ikuo; Fujiwara, Hiroshi

2017-01-01

The human endometrium periodically breaks down and regenerates. As platelets have been reported to contribute to the tissue remodeling process, we examined the possible involvement of platelets in endometrial regeneration. The distribution of extravasating platelets throughout the menstrual cycle was immunohistochemically examined using human endometrial tissues. EM-E6/E7/hTERT cells, a human endometrial epithelial cell-derived immortalized cell line, were co-cultured with platelets, and the effects of platelets on the epithelialization response of EM-E6/E7/hTERT cells were investigated by attachment and permeability assays, immunohistochemical staining, and Western blot analysis. Immunohistochemical study showed numerous extravasated platelets in the subluminar stroma during the menstrual phase. The platelets promoted the cell-to-matrigel attachment of EM-E6/E7/hTERT cells concomitantly with the phosphorylation of focal adhesion kinase. They also promoted cell-to-cell contact among EM-E6/E7/hTERT cells in parallel with E-cadherin expression. These results indicate the possible involvement of platelets in the endometrial epithelial re-epithelialization process. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

E-cigarette use results in suppression of immune and inflammatory-response genes in nasal epithelial cells similar to cigarette smoke.

Science.gov (United States)

Martin, Elizabeth M; Clapp, Phillip W; Rebuli, Meghan E; Pawlak, Erica A; Glista-Baker, Ellen; Benowitz, Neal L; Fry, Rebecca C; Jaspers, Ilona

2016-07-01

Exposure to cigarette smoke is known to result in impaired host defense responses and immune suppressive effects. However, the effects of new and emerging tobacco products, such as e-cigarettes, on the immune status of the respiratory epithelium are largely unknown. We conducted a clinical study collecting superficial nasal scrape biopsies, nasal lavage, urine, and serum from nonsmokers, cigarette smokers, and e-cigarette users and assessed them for changes in immune gene expression profiles. Smoking status was determined based on a smoking history and a 3- to 4-wk smoking diary and confirmed using serum cotinine and urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) levels. Total RNA from nasal scrape biopsies was analyzed using the nCounter Human Immunology v2 Expression panel. Smoking cigarettes or vaping e-cigarettes resulted in decreased expression of immune-related genes. All genes with decreased expression in cigarette smokers (n = 53) were also decreased in e-cigarette smokers. Additionally, vaping e-cigarettes was associated with suppression of a large number of unique genes (n = 305). Furthermore, the e-cigarette users showed a greater suppression of genes common with those changed in cigarette smokers. This was particularly apparent for suppressed expression of transcription factors, such as EGR1, which was functionally associated with decreased expression of 5 target genes in cigarette smokers and 18 target genes in e-cigarette users. Taken together, these data indicate that vaping e-cigarettes is associated with decreased expression of a large number of immune-related genes, which are consistent with immune suppression at the level of the nasal mucosa. Copyright © 2016 the American Physiological Society.

Application of nitrogen plasma immersion ion implantation to titanium nasal implants with nanonetwork surface structure

Energy Technology Data Exchange (ETDEWEB)

Sun, Ying-Sui; Yang, Wei-En [Department of Dentistry, National Yang-Ming University, Taipei 112, Taiwan (China); Zhang, Lan [State Key Laboratory for Mechanical Behavior of Materials, Xi' an Jiaotong University, Xi' an 710049 (China); Zhu, Hongqin [State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050 (China); Lan, Ming-Ying [Division of Rhinology, Department of Otolaryngology Head and Neck Surgery, Taipei Veterans General Hospital, Taipei 112, Taiwan and School of Medicine, National Yang-Ming University, Taipei 112, Taiwan (China); Lee, Sheng-Wei [Institute of Materials Science and Engineering, National Central University, Taoyuan 320, Taiwan (China); Huang, Her-Hsiung, E-mail: hhhuang@ym.edu.tw [Department of Dentistry, National Yang-Ming University, Taipei 112, Taiwan (China); Institute of Oral Biology, National Yang-Ming University, Taipei 112, Taiwan (China); Graduate Institute of Basic Medical Science, China Medical University, Taichung 404, Taiwan (China); Department of Medical Research, China Medical University Hospital, Taichung 407, Taiwan (China); Department of Bioinformatics and Medical Engineering, Asia University, Taichung 413, Taiwan (China); Department of Stomatology, Taipei Veterans General Hospital, Taipei 112, Taiwan (China)

2016-07-15

In nasal reconstruction, the response of cells to titanium (Ti) implants is mainly determined by surface features of the implant. In a pilot study, the authors applied electrochemical anodization to Ti surfaces in an alkaline solution to create a network of nanoscale surface structures. This nanonetwork was intended to enhance the responses of primary human nasal epithelial cell (HNEpC) to the Ti surface. In this study, the authors then treated the anodized, nanonetwork-structured Ti surface using nitrogen plasma immersion ion implantation (NPIII) in order to further improve the HNEpC response to the Ti surface. Subsequently, surface characterization was performed to elucidate morphology, roughness, wettability, and chemistry of specimens. Cytotoxicity, blood, and HNEpC responses were also evaluated. Our results demonstrate that NPIII treatment led to the formation of a noncytotoxic TiN-containing thin film (thickness <100 nm) on the electrochemically anodized Ti surface with a nanonetwork-structure. NPIII treatment was shown to improve blood clotting and the adhesion of platelets to the anodized Ti surface as well as the adhesion and proliferation of hNEpC. This research spreads our understanding of the fact that a TiN-containing thin film, produced using NPIII treatment, could be used to improve blood and HNEpC responses to anodized, nanonetwork-structured Ti surfaces in nasal implant applications.

Human papilloma virus DNAs immortalize normal human mammary epithelial cells and reduce their growth factor requirements

International Nuclear Information System (INIS)

Band, V.; Zajchowski, D.; Kulesa, V.; Sager, R.

1990-01-01

Human papilloma virus (HPV) types 16 and 18 are most commonly associated with cervical carcinoma in patients and induce immortalization of human keratinocytes in culture. HPV has not been associated with breast cancer. This report describes the immortalization of normal human mammary epithelial cells (76N) by plasmid pHPV18 or pHPV16, each containing the linearized viral genome. Transfectants were grown continuously for more than 60 passages, whereas 76N cells senesce after 18-20 passages. The transfectants also differ from 76N cells in cloning in a completely defined medium called D2 and growing a minimally supplemented defined medium (D3) containing epidermal growth factor. All transfectant tested contain integrated HPV DNA, express HPV RNA, and produce HPV E7 protein. HPV transfectants do not form tumors in a nude mouse assay. It is concluded that products of the HPV genome induce immortalization of human breast epithelial cells and reduce their growth factor requirements. This result raises the possibility that HPV might be involved in breast cancer. Furthermore, other tissue-specific primary epithelial cells that are presently difficult to grown and investigate may also be immortalized by HPV

Nasal deposition of ciclesonide nasal aerosol and mometasone aqueous nasal spray in allergic rhinitis patients.

Science.gov (United States)

Emanuel, Ivor A; Blaiss, Michael S; Meltzer, Eli O; Evans, Philip; Connor, Alyson

2014-01-01

Sensory attributes of intranasal corticosteroids, such as rundown to the back of the throat, may influence patient treatment preferences. This study compares the nasal deposition and nasal retention of a radiolabeled solution of ciclesonide nasal aerosol (CIC-hydrofluoroalkane [HFA]) with a radiolabeled suspension of mometasone furoate monohydrate aqueous nasal spray (MFNS) in subjects with either perennial allergic rhinitis (AR) or seasonal AR. In this open-label, single-dose, randomized, crossover scintigraphy study, 14 subjects with symptomatic AR received a single dose of radiolabeled 74-μg CIC-HFA (37 μg/spray, 1 spray/each nostril) via a nasal metered-dose inhaler or a single dose of radiolabeled 200-μg MFNS (50 μg/spray, 2 sprays/each nostril), with a minimum 5-day washout period between treatments. Initial deposition (2 minutes postdose) of radiolabeled CIC-HFA and MFNS in the nasal cavity, nasopharynx, and on nasal wipes, and retention of radioactivity in the nasal cavity and nasal run-out on nasal wipes at 2, 4, 6, 8, and 10 minutes postdose were quantified with scintigraphy. At 2 and 10 minutes postdose, deposition of radiolabeled CIC-HFA was significantly higher in the nasal cavity versus radiolabeled MFNS (99.42% versus 86.50% at 2 minutes, p = 0.0046; and 81.10% versus 54.31% at 10 minutes, p Deposition of radioactivity on nasal wipes was significantly higher with MFNS versus CIC-HFA at all five time points, and posterior losses of radiolabeled formulation were significantly higher with MFNS at 6, 8, and 10 minutes postdose. In this scintigraphic study, significantly higher nasal deposition and retention of radiolabeled aerosol CIC-HFA were observed versus radiolabeled aqueous MFNS in subjects with AR.

Chromosomal changes in cultured human epithelial cells transformed by low- and high-LET radiation

Energy Technology Data Exchange (ETDEWEB)

Yang, Tracy Chui-hsu; Craise, L.M; Prioleau, J.C.; Stampfer, M.R.; Rhim, J.S.

1990-11-01

For a better assessment of radiation risk in space, an understanding of the responses of human cells, especially the epithelial cells, to low- and high-LET radiation is essential. In our laboratory, we have successfully developed techniques to study the neoplastic transformation of two human epithelial cell systems by ionizing radiation. These cell systems are human mammary epithelial cells (H184B5) and human epidermal keratinocytes (HEK). Both cell lines are immortal, anchorage dependent for growth, and nontumorigenic in athymic nude nice. Neoplastic transformation was achieved by irradiation cells successively. Our results showed that radiogenic cell transformation is a multistep process and that a single exposure of ionizing radiation can cause only one step of transformation. It requires, therefore, multihits to make human epithelial cells fully tumorigenic. Using a simple karyotyping method, we did chromosome analysis with cells cloned at various stages of transformation. We found no consistent large terminal deletion of chromosomes in radiation-induced transformants. Some changes of total number of chromosomes, however, were observed in the transformed cells. These transformants provide an unique opportunity for further genetic studies at a molecular level. 15 refs., 9 figs., 2 tabs.

Chromosomal changes in cultured human epithelial cells transformed by low- and high-LET radiation

International Nuclear Information System (INIS)

Yang, Tracy Chui-hsu; Craise, L.M; Prioleau, J.C.; Stampfer, M.R.; Rhim, J.S.

1990-11-01

For a better assessment of radiation risk in space, an understanding of the responses of human cells, especially the epithelial cells, to low- and high-LET radiation is essential. In our laboratory, we have successfully developed techniques to study the neoplastic transformation of two human epithelial cell systems by ionizing radiation. These cell systems are human mammary epithelial cells (H184B5) and human epidermal keratinocytes (HEK). Both cell lines are immortal, anchorage dependent for growth, and nontumorigenic in athymic nude nice. Neoplastic transformation was achieved by irradiation cells successively. Our results showed that radiogenic cell transformation is a multistep process and that a single exposure of ionizing radiation can cause only one step of transformation. It requires, therefore, multihits to make human epithelial cells fully tumorigenic. Using a simple karyotyping method, we did chromosome analysis with cells cloned at various stages of transformation. We found no consistent large terminal deletion of chromosomes in radiation-induced transformants. Some changes of total number of chromosomes, however, were observed in the transformed cells. These transformants provide an unique opportunity for further genetic studies at a molecular level. 15 refs., 9 figs., 2 tabs

Surfactant Proteins A, B, C and D in the Human Nasal Airway

DEFF Research Database (Denmark)

Gaunsbaek, Maria Q; Kjeldsen, Anette D; Svane-Knudsen, Viggo

2014-01-01

Aims: To investigate the presence of surfactant protein (SP) A, B, C and D in nasal airways and to determine whether the proteins exert their main functions in nasal secretions or in the deeper layers of the nasal mucosa. Methods: Volunteers were recruited from the Department of ENT Head and Neck...

Keratoacanthoma of the Nasal Septum Secondary to Ranibizumab Use

Directory of Open Access Journals (Sweden)

Jason E. Cohn

2017-01-01

Full Text Available Keratoacanthoma (KA is a benign epithelial tumor that typically presents as a firm, cone-shaped, flesh-colored nodule with a central horn-filled crater. KA is considered to be a low-grade variant of squamous cell carcinoma (SCC. We report a rare case of a 72-year-old male who presented with a KA involving the nasal septum, possibly related to ranibizumab use. A flesh-colored lesion on the right anterior nasal septum lesion was visualized on examination. Histologic examination revealed a well-circumscribed, dome-shaped central crater filled with keratin, well-differentiated squamous epithelium with ground-glass cytoplasm with pushing margins, and intraepithelial microabscesses establishing the diagnosis of KA. KA of the nasal septum has only been reported once in the literature. This case is unusual because it normally presents on sun-exposed areas. Additionally, this patient was taking ranibizumab, a vascular endothelial growth factor (VEGF inhibitor for macular degeneration. Despite ranibizumab not being directly linked to precancerous and cancerous skin lesions, agents in this medication class have been. Although it is difficult to prove associations in this isolated case, the role of ranibizumab causing cutaneous lesions should be further investigated.

Maxillary bone epithelial cyst in an adult miniature schnauzer.

Science.gov (United States)

Lin, Chung-Tien; Tasi, Wen-Chih; Hu, Chun-Kun; Lin, Nien-Ting; Huang, Pei-Yun; Yeh, Lih-Seng

2008-09-01

Maxillary bone epithelial cyst is rare in dogs. A 5-year-old, spayed female miniature schnauzer developed a swelling below the nasal canthus of left eye. Plain radiograph demonstrated a 1.5 cm diameter of radiolucent lesion on the maxillary bone anteroventral to the eye, and contrast dacryocystorhinography confirmed an obstructed nasolarcrimal duct. The swelling showed poor response to antibiotic treatment but responded well to oral prednisolone. Exploratory surgery revealed a cyst-like structure filled with brown serous fluid. Histopathological examination of the removed cyst revealed a double cuboidal epithelial cyst. The dog recovered rapidly after surgery, and the swelling had not recurred for a 36-month follow-up. It is the first case of periorbital bone epithelial cyst reported in an adult miniature schnauzer.

Engineered human broncho-epithelial tissue-like assemblies

Science.gov (United States)

Goodwin, Thomas J. (Inventor)

2012-01-01

Three-dimensional human broncho-epithelial tissue-like assemblies (TLAs) are produced in a rotating wall vessel (RWV) with microcarriers by coculturing mesenchymal bronchial-tracheal cells (BTC) and bronchial epithelium cells (BEC). These TLAs display structural characteristics and express markers of in vivo respiratory epithelia. TLAs are useful for screening compounds active in lung tissues such as antiviral compounds, cystic fibrosis treatments, allergens, and cytotoxic compounds.

PLGA/DPPC/trimethylchitosan spray-dried microparticles for the nasal delivery of ropinirole hydrochloride: in vitro, ex vivo and cytocompatibility assessment

Energy Technology Data Exchange (ETDEWEB)

Karavasili, Christina [Laboratory of Pharmaceutical Technology, Department of Pharmacy, Aristotle University of Thessaloniki, 54124 (Greece); Bouropoulos, Nikolaos [Department of Materials Science, University of Patras, 26504 Rio, Patras (Greece); Foundation for Research and Technology, Hellas-Institute of Chemical Engineering and High Temperature, P.O. Box 1414, 26504 Patras (Greece); Sygellou, Lamprini [Foundation for Research and Technology, Hellas-Institute of Chemical Engineering and High Temperature, P.O. Box 1414, 26504 Patras (Greece); Amanatiadou, Elsa P.; Vizirianakis, Ioannis S. [Laboratory of Pharmacology, Department of Pharmaceutical Sciences, Aristotle University of Thessaloniki, GR-54124 Thessaloniki (Greece); Fatouros, Dimitrios G., E-mail: dfatouro@pharm.auth.gr [Laboratory of Pharmaceutical Technology, Department of Pharmacy, Aristotle University of Thessaloniki, 54124 (Greece)

2016-02-01

In the present study we investigated polymer-lipid microparticles loaded with ropinirole hydrochloride (RH) for nasal delivery. RH microparticles were further evaluated by means of scanning electron microscopy (SEM), ζ-potential measurements, Fourier-transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS) and x-ray diffraction (XRD). In vitro release studies were performed in simulated nasal electrolyte solution (SNES) pH 5.5 at 35 °C. Ex vivo permeation studies were conducted across sheep nasal mucosa. Cytocompatibility was tested in cultured human airway epithelial cells (Calu-3). SEM studies revealed spheroid microparticles in the range of 2.09 μm to 2.41 μm. The presence of trimethylchitosan (TMC) induced a slight shift towards less negative ζ-potential values. Surface chemistry (XPS) revealed the presence of dipalmitoylphospatidylcholine (DPPC) and poly(lactic-co-glycolic acid) (PLGA) onto microparticles' surface, further corroborating the FT-IR and XRD findings. In vitro release studies showed that the microparticle composition can partly modulate the release of RH. Ex vivo studies demonstrated a 2.35-folded enhancement of RH permeation when RH was co-formulated with TMC of low molecular weight, compared to the control. All formulations tested were found to be non-toxic to cells. The results suggest that polymer-lipid microparticles may be a promising carrier for the nasal delivery of RH. - Highlights: • Development of microparticles comprising PLGA/DPPC/TMC for nasal drug delivery. • Physicochemical characterization showed that DPPC dominated microparticles' surface. • Microparticles enhanced permeation of ropinirole across sheep nasal epithelium. • The cytotoxicity assay with Calu-3 cells demonstrated satisfactory cell viability.

PLGA/DPPC/trimethylchitosan spray-dried microparticles for the nasal delivery of ropinirole hydrochloride: in vitro, ex vivo and cytocompatibility assessment

International Nuclear Information System (INIS)

Karavasili, Christina; Bouropoulos, Nikolaos; Sygellou, Lamprini; Amanatiadou, Elsa P.; Vizirianakis, Ioannis S.; Fatouros, Dimitrios G.

2016-01-01

In the present study we investigated polymer-lipid microparticles loaded with ropinirole hydrochloride (RH) for nasal delivery. RH microparticles were further evaluated by means of scanning electron microscopy (SEM), ζ-potential measurements, Fourier-transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS) and x-ray diffraction (XRD). In vitro release studies were performed in simulated nasal electrolyte solution (SNES) pH 5.5 at 35 °C. Ex vivo permeation studies were conducted across sheep nasal mucosa. Cytocompatibility was tested in cultured human airway epithelial cells (Calu-3). SEM studies revealed spheroid microparticles in the range of 2.09 μm to 2.41 μm. The presence of trimethylchitosan (TMC) induced a slight shift towards less negative ζ-potential values. Surface chemistry (XPS) revealed the presence of dipalmitoylphospatidylcholine (DPPC) and poly(lactic-co-glycolic acid) (PLGA) onto microparticles' surface, further corroborating the FT-IR and XRD findings. In vitro release studies showed that the microparticle composition can partly modulate the release of RH. Ex vivo studies demonstrated a 2.35-folded enhancement of RH permeation when RH was co-formulated with TMC of low molecular weight, compared to the control. All formulations tested were found to be non-toxic to cells. The results suggest that polymer-lipid microparticles may be a promising carrier for the nasal delivery of RH. - Highlights: • Development of microparticles comprising PLGA/DPPC/TMC for nasal drug delivery. • Physicochemical characterization showed that DPPC dominated microparticles' surface. • Microparticles enhanced permeation of ropinirole across sheep nasal epithelium. • The cytotoxicity assay with Calu-3 cells demonstrated satisfactory cell viability.

A Rare Nasal Bone Fracture: Anterior Nasal Spine Fracture

Directory of Open Access Journals (Sweden)

Egemen Kucuk

2014-04-01

Full Text Available Anterior nasal spine fractures are a quite rare type of nasal bone fractures. Associated cervical spine injuries are more dangerous than the nasal bone fracture. A case of the anterior nasal spine fracture, in a 18-year-old male was presented. Fracture of the anterior nasal spine, should be considered in the differential diagnosis of the midface injuries and also accompanying cervical spine injury should not be ignored.

The effect of topical treatments for CRS on the sinonasal epithelial barrier.

Science.gov (United States)

Ramezanpour, M; Rayan, A; Smith, J L P; Vreugde, S

2017-06-01

Several topical treatments are used in the management of Chronic Rhinosinusitis (CRS), some of which the safety and efficacy has yet to be determined. The purpose of this study was to investigate the effect of commonly used topical treatments on the sinonasal epithelial barrier. Normal saline (0.9% Sodium Chloride), hypertonic saline (3% Sodium Chloride), FESS Sinu-Cleanse Hypertonic, FLO Sinus Care and Budesonide 1 mg/ 2 ml were applied to the apical side of air-liquid interface (ALI) cultures of primary human nasal epithelial cells (HNECs) from CRS patients (n=3) and non-CRS controls (n=3) for 24 hours. Epithelial barrier structure and function was assessed using trans-epithelial electrical resistance (TEER), measuring the passage of Fluorescein Isothiocyanate labelled Dextrans (FITC-Dextrans) and assessing the expression of the tight junction protein Zona Occludens-1 (ZO-1) using immunofluorescence. Toxicity was assessed using a Lactate Dehydrogenase (LDH) assay. Data was analysed using ANOVA, followed by Tukey HSD post hoc test. Hypertonic solution and budesonide significantly increased TEER values in CRS derived HNECs. In contrast, FESS Sinu-Cleanse Hypertonic significantly reduced TEER 5 minutes after application of the solution followed by an increase in paracellular permeability of FITC-Dextrans (30 minutes) and increased LDH levels 6 hours after application of the solution. Our findings confirm that isotonic and hypertonic saline solutions do not compromise epithelial barrier function in vitro but underscore the importance of examining safety and efficacy of over-the-counter wash solutions.

Nasal Oxytocin Treatment Biases Dogs’ Visual Attention and Emotional Response toward Positive Human Facial Expressions

Directory of Open Access Journals (Sweden)

Sanni Somppi

2017-10-01

Full Text Available The neuropeptide oxytocin plays a critical role in social behavior and emotion regulation in mammals. The aim of this study was to explore how nasal oxytocin administration affects gazing behavior during emotional perception in domestic dogs. Looking patterns of dogs, as a measure of voluntary attention, were recorded during the viewing of human facial expression photographs. The pupil diameters of dogs were also measured as a physiological index of emotional arousal. In a placebo-controlled within-subjects experimental design, 43 dogs, after having received either oxytocin or placebo (saline nasal spray treatment, were presented with pictures of unfamiliar male human faces displaying either a happy or an angry expression. We found that, depending on the facial expression, the dogs’ gaze patterns were affected selectively by oxytocin treatment. After receiving oxytocin, dogs fixated less often on the eye regions of angry faces and revisited (glanced back at more often the eye regions of smiling (happy faces than after the placebo treatment. Furthermore, following the oxytocin treatment dogs fixated and revisited the eyes of happy faces significantly more often than the eyes of angry faces. The analysis of dogs’ pupil diameters during viewing of human facial expressions indicated that oxytocin may also have a modulatory effect on dogs’ emotional arousal. While subjects’ pupil sizes were significantly larger when viewing angry faces than happy faces in the control (placebo treatment condition, oxytocin treatment not only eliminated this effect but caused an opposite pupil response. Overall, these findings suggest that nasal oxytocin administration selectively changes the allocation of attention and emotional arousal in domestic dogs. Oxytocin has the potential to decrease vigilance toward threatening social stimuli and increase the salience of positive social stimuli thus making eye gaze of friendly human faces more salient for dogs. Our

Objective Measure of Nasal Air Emission Using Nasal Accelerometry

Science.gov (United States)

Cler, Meredith J.; Lien, Yu-An, S.; Braden, Maia N.; Mittleman, Talia; Downing, Kerri; Stepp, Cara, E.

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…

Characterisation of Bergeyella spp. isolated from the nasal cavities of piglets.

Science.gov (United States)

Lorenzo de Arriba, M; Lopez-Serrano, S; Galofre-Mila, N; Aragon, V

2018-04-01

The aim of this study was to characterise bacteria in the genus Bergeyella isolated from the nasal passages of healthy piglets. Nasal swabs from 3 to 4 week-old piglets from eight commercial domestic pig farms and one wild boar farm were cultured under aerobic conditions. Twenty-nine Bergeyella spp. isolates were identified by partial 16S rRNA gene sequencing and 11 genotypes were discriminated by enterobacterial repetitive intergenic consensus (ERIC)-PCR. Bergeyella zoohelcum and Bergeyella porcorum were identified within the 11 genotypes. Bergeyella spp. isolates exhibited resistance to serum complement and phagocytosis, poor capacity to form biofilms and were able to adhere to epithelial cells. Maneval staining was consistent with the presence of a capsule. Multiple drug resistance (resistance to three or more classes of antimicrobial agents) was present in 9/11 genotypes, including one genotype isolated from wild boar with no history of antimicrobial use. In conclusion, Bergeyella spp. isolates from the nasal cavities of piglets showed some in vitro features indicative of a potential for virulence. Further studies are necessary to identify the role of Bergeyella spp. in disease and within the nasal microbiota of pigs. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Solitary chemoreceptor cells in the nasal cavity serve as sentinels of respiration

OpenAIRE

Finger, Thomas E.; Böttger, Bärbel; Hansen, Anne; Anderson, Karl T.; Alimohammadi, Hessamedin; Silver, Wayne L.

2003-01-01

Inhalation of irritating substances leads to activation of the trigeminal nerve, triggering protective reflexes that include apnea or sneezing. Receptors for trigeminal irritants are generally assumed to be located exclusively on free nerve endings within the nasal epithelium, requiring that trigeminal irritants diffuse through the junctional barrier at the epithelial surface to activate receptors. We find, in both rats and mice, an extensive population of chemosensory...

Human factor in Staphylococcus aureus nasal carriage

NARCIS (Netherlands)

J.L. Nouwen (Jan); H.A.M. Boelens (Hélène); A.F. van Belkum (Alex); H.A. Verbrugh (Henri)

2004-01-01

textabstractPersistent nasal carriers and noncarriers of Staphylococcus aureus were inoculated with a mixture of different S. aureus strains. The majority of noncarriers and nearly all persistent carriers returned to their original carrier state after artificial inoculation. Furthermore, the

Esthetic rhinoplasty as an adjunctive technique in nasal oncoplastic ...

African Journals Online (AJOL)

Adham Farouk

2016-01-15

Jan 15, 2016 ... Esthetic rhinoplasty;. Oncoplastic surgery nose;. Basal cell carcinoma;. Squamous cell carcinoma;. Nonmelanoma skin cancer;. Nasal reconstruction ... Conclusions: Esthetic rhinoplasty is a useful adjunctive technique in nasal oncoplastic surgery. .... All procedures performed in the study involving human.

Nasal chondromesenchymal hamartoma with no nasal symptoms.

LENUS (Irish Health Repository)

Uzomefuna, Vincent

2012-01-01

The authors present a case of nasal chondromesenchymal hamartoma (NCMH) in an 8-year-old boy with a 4-month history of frontal headache and no symptoms of nasal obstruction, rhinorrhoea or postnasal drip. An ENT examination as well as ophthalmology assessment presented normal results. CT scan showed a lesion involving the sphenoid and ethmoid sinuses. The patient had an endoscopic resection of the lesion that was confirmed histologically to be a NCMH. Though NCMH is known to present usually in infants with obstructing nasal mass, an unusual presentation of a patient with throbbing headache without any nasal symptoms is reported here.

Anti-inflammatory effects of embelin in A549 cells and human asthmatic airway epithelial tissues.

Science.gov (United States)

Lee, In-Seung; Cho, Dong-Hyuk; Kim, Ki-Suk; Kim, Kang-Hoon; Park, Jiyoung; Kim, Yumi; Jung, Ji Hoon; Kim, Kwanil; Jung, Hee-Jae; Jang, Hyeung-Jin

2018-02-01

Allergic asthma is the most common type in asthma, which is defined as a chronic inflammatory disease of the lung. In this study, we investigated whether embelin (Emb), the major component of Ardisia japonica BL. (AJB), exhibits anti-inflammatory effects on allergic asthma via inhibition of NF-κB activity using A549 cells and asthmatic airway epithelial tissues. Inflammation was induced in A549 cells, a human airway epithelial cell line, by IL-1β (10 ng/ml) treatment for 4 h. The effects of Emb on NF-κB activity and COX-2 protein expression in inflamed airway epithelial cells and human asthmatic airway epithelial tissues were analyzed via western blot. The secretion levels of NF-κB-mediated cytokines/chemokines, including IL-4, 6, 9, 13, TNF-α and eotaxin, were measured by a multiplex assay. Emb significantly blocked NF-κB activity in IL-1β-treated A549 cells and human asthmatic airway epithelial tissues. COX-2 expression was also reduced in both IL-1β-treated A549 cells and asthmatic tissues Emb application. Emb significantly reduced the secretion of IL-4, IL-6 and eotaxin in human asthmatic airway epithelial tissues by inhibiting activity of NF-κB. The results of this study suggest that Emb may be used as an anti-inflammatory agent via inhibition of NF-κB and related cytokines.

Overexpression of human sperm protein 17 increases migration and decreases the chemosensitivity of human epithelial ovarian cancer cells

International Nuclear Information System (INIS)

Li, Fang-qiu; Han, Yan-ling; Liu, Qun; Wu, Bo; Huang, Wen-bin; Zeng, Su-yun

2009-01-01

Most deaths from ovarian cancer are due to metastases that are resistant to conventional therapies. But the factors that regulate the metastatic process and chemoresistance of ovarian cancer are poorly understood. In the current study, we investigated the aberrant expression of human sperm protein 17 (HSp17) in human epithelial ovarian cancer cells and tried to analyze its influences on the cell behaviors like migration and chemoresistance. Immunohistochemistry and immunocytochemistry were used to identify HSp17 in paraffin embedded ovarian malignant tumor specimens and peritoneal metastatic malignant cells. Then we examined the effect of HSp17 overexpression on the proliferation, migration, and chemoresistance of ovarian cancer cells to carboplatin and cisplatin in a human ovarian carcinoma cell line, HO8910. We found that HSp17 was aberrantly expressed in 43% (30/70) of the patients with primary epithelial ovarian carcinomas, and in all of the metastatic cancer cells of ascites from 8 patients. The Sp17 expression was also detected in the metastatic lesions the same as in ovarian lesions. None of the 7 non-epithelial tumors primarily developed in the ovaries was immunopositive for HSp17. Overexpression of HSp17 increased the migration but decreased the chemosensitivity of ovarian carcinoma cells to carboplatin and cisplatin. HSp17 is aberrantly expressed in a significant proportion of epithelial ovarian carcinomas. Our results strongly suggest that HSp17 plays a role in metastatic disease and resistance of epithelial ovarian carcinoma to chemotherapy

TLR-dependent human mucosal epithelial cell responses to microbial pathogens.

Directory of Open Access Journals (Sweden)

Paola eMassari

2014-08-01

Full Text Available AbstractToll-Like Receptor (TLR signaling represents one of the best studied pathways to implement defense mechanisms against invading microbes in humans as well as in animals. TLRs respond to specific microbial ligands and to danger signals produced by the host during infection, and initiate downstream cascades that activate both innate and adaptive immunity. TLRs are expressed by professional immune cells and by the large majority of non-hematopoietic cells, including epithelial cells. In epithelial tissues, TLR functions are particularly important because these sites are constantly exposed to microorganisms, due to their location at the host interface with the environment. While at these sites, specific defense mechanisms and inflammatory responses are initiated via TLR signaling against pathogens, suppression or lack of TLR activation is also observed in response to the commensal microbiota. The mechanisms by which TLR signaling is regulated in mucosal epithelial cells include differential expression and levels of TLRs (and their signaling partners, their cellular localization and positioning within the tissue in a fashion that favors responses to pathogens while dampening responses to commensals and maintaining tissue homeostasis in physiologic conditions. In this review, the expression and activation of TLRs in mucosal epithelial cells of several sites of the human body are examined. Specifically, the oral cavity, the ear canal and eye, the airways, the gut and the reproductive tract are discussed, along with how site-specific host defense mechanisms are implemented via TLR signaling.

Transfection of normal human bronchial epithelial cells with the bcl-2 oncogene

Energy Technology Data Exchange (ETDEWEB)

Kennedy, C.H.; Kenyon, K.D.; Tesfaigzi, J. [and others

1995-12-01

In vitro, studies examining the transformation of virus-immortalized human bronchial epithelial (HBE) cells after exposure to chemical and physical carcinogens have contributed to our understanding of the mechanisms that underlie the development of lung cancer. Virus-immortalized HBE cells have been used because of both the limited life span of normal human bronchial epithelial (NHBE) cells in culture (approximately 30-35 population doublins) and their resistance to in vitro malignant transformation. For example, human papillomavirus (HPV)-immortalized HBE cells have been used to study the genetic changes that occur after exposure to {alpha}-particles in vitro. Although this model may prove to be useful for studying the 18% or less of bronchogenic carcinomas found to contain HPV sequences, it is not an appropriate model for studying the majority of lung epithelial malignancies in which HPV DNA is not detected. This view is supported by the fact that HPV-immortalized cell lines commonly exhibit aneuploidy. This results of this study suggest that: (1) NHBE cells can be transiently transfected with the pCMV{Beta} vector; and (2) the antibiotic hygromycin-resistant transfected cells.

Transfection of normal human bronchial epithelial cells with the bcl-2 oncogene

International Nuclear Information System (INIS)

Kennedy, C.H.; Kenyon, K.D.; Tesfaigzi, J.

1995-01-01

In vitro, studies examining the transformation of virus-immortalized human bronchial epithelial (HBE) cells after exposure to chemical and physical carcinogens have contributed to our understanding of the mechanisms that underlie the development of lung cancer. Virus-immortalized HBE cells have been used because of both the limited life span of normal human bronchial epithelial (NHBE) cells in culture (approximately 30-35 population doublins) and their resistance to in vitro malignant transformation. For example, human papillomavirus (HPV)-immortalized HBE cells have been used to study the genetic changes that occur after exposure to α-particles in vitro. Although this model may prove to be useful for studying the 18% or less of bronchogenic carcinomas found to contain HPV sequences, it is not an appropriate model for studying the majority of lung epithelial malignancies in which HPV DNA is not detected. This view is supported by the fact that HPV-immortalized cell lines commonly exhibit aneuploidy. This results of this study suggest that: (1) NHBE cells can be transiently transfected with the pCMVΒ vector; and (2) the antibiotic hygromycin-resistant transfected cells

The effect of OK-432 (Picibanil) injection on the histopathology of nasal turbinate.

Science.gov (United States)

Sengul, S; Kaygusuz, I; Akin, M M; Yalcin, Ş; Karlidag, T; Keles, E; Arslan, I

2015-12-01

This study aimed to assess the histopathological effect of OK-432 (Picibanil) on rabbit nasal turbinates. A total of 21 rabbits were divided into 3 treatment groups and various parts of both nasal turbinates were injected with 0.5 ml OK-432, 0.2 ml OK-432 or 0.6 ml saline (control). Bilateral nasal turbinates were later excised and studied under light microscopy to assess any histopathological changes. Animals in the 0.2 ml and 0.5 ml OK-432 groups exhibited mild ciliary loss, goblet cell loss and epithelial damage, and a marked increase in inflammatory cell infiltration, submucosal vascularisation and fibrosis. There was a significant difference in histopathological changes between the two OK-432 treated groups. In addition, each OK-432 treated group had significantly more inflammatory cell infiltration, increased submucosal vascularisation and fibrosis compared with controls. The marked fibrosis observed in OK-432-injected turbinates may be responsible for a reduction in turbinate size.

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.

Science.gov (United States)

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. Copyright © 2015 Elsevier Ltd. All rights reserved.

Structure of neuro-endocrine and neuro-epithelial interactions in human foetal pancreas.

Science.gov (United States)

Krivova, Yuliya; Proshchina, Alexandra; Barabanov, Valeriy; Leonova, Olga; Saveliev, Sergey

2016-12-01

In the pancreas of many mammals including humans, endocrine islet cells can be integrated with the nervous system components into neuro-insular complexes. The mechanism of the formation of such complexes is not clearly understood. The present study evaluated the interactions between the nervous system components, epithelial cells and endocrine cells in the human pancreas. Foetal pancreas, gestational age 19-23 weeks (13 cases) and 30-34 weeks (7 cases), were studied using double immunohistochemical labeling with neural markers (S100 protein and beta III tubulin), epithelial marker (cytokeratin 19 (CK19)) and antibodies to insulin and glucagon. We first analyse the structure of neuro-insular complexes using confocal microscopy and provide immunohistochemical evidences of the presence of endocrine cells within the ganglia or inside the nerve bundles. We showed that the nervous system components contact with the epithelial cells located in ducts or in clusters outside the ductal epithelium and form complexes with separate epithelial cells. We observed CK19-positive cells inside the ganglia and nerve bundles which were located separately or were integrated with the islets. Therefore, we conclude that neuro-insular complexes may forms as a result of integration between epithelial cells and nervous system components at the initial stages of islets formation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sensitivity and specificity of hypopnoea detection using nasal pressure in the presence of a nasal expiratory resistive device (Provent®)

International Nuclear Information System (INIS)

Milne, Stephen; Amis, Terence C; Wheatley, John R; Kairaitis, Kristina

2014-01-01

Nasal expiratory resistive valves (Provent ® ) have been proposed as novel therapy for obstructive sleep apnea. We compared pressure measurements from a standard nasal pressure catheter used to assess nasal airflow during sleep with those from nasal expiratory resistive device with attached proprietary nasal pressure cannula. Nasal pressure cannula or Provent ® + proprietary nasal pressure cannula were attached to a bench model of human anterior nares and nasal passages, and pressure measured (P). Respiratory airflows generated by a subject breathing were applied to rear of model and airflow ( V-dot ) measured via pneumotachograph. Airflow amplitude (Δ V-dot ) was plotted against pressure amplitude (ΔP). Hypopnoea detection (<50% Δ V-dot ) sensitivity and specificity was tested by expressing ΔP in terms of two reference breaths: reference breath 1, Δ V-dot 0.55 L s −1  = 100%; and reference breath 2, Δ V-dot 0.45 L s −1  = 100%. ΔP/Δ V-dot relationships were linear for Δ V-dot  ≤ 0.55 L s −1 ; ΔP = 0.37ΔV + 0.16 (nasal pressure cannula), ΔP = 2.7ΔV + 0.12 (Provent ® + proprietary nasal pressure cannula); both R 2  > 0.65, p < 0.0001; p < 0.0001 for between slope difference). For nasal pressure cannula, specificity of hypopnoea detection differed between reference breaths one and two (80.2% and 40.0%, respectively), and Provent ® + proprietary nasal pressure cannula (30.3% and 74.2%, respectively). Quantification of airflow obstruction in the presence of Provent ® + proprietary nasal pressure cannula is greatly influenced by the reference breath chosen to determine a reduction in nasal airflow. Reported variability in therapeutic response to nasal expiratory resistive devices may relate to differences in measurement technique specificity used to quantify the severity of sleep disordered breathing. (paper)

The protective effect of resveratrol on human lens epithelial cells against ultraviolet-induced apoptosis

Directory of Open Access Journals (Sweden)

Xue - Fang Chen

2013-06-01

Full Text Available AIM: To investigate the protective effect of resveratrol on human lens epithelial cells against ultraviolet-induced apoptosis. METHODS:Subcultured human lens epithelial cell line, ultraviolet induced cell apoptosis, 20μmol/L resveratrol pretreated cell, the indicators change was observed: rate of apoptosis was detected by flow cytometry and apoptosis-related factors of caspses-3 and caspase-9 were detected by colorimetric detection, ultrastructure changes were observed under transmission electron microscope. RESULTS: Flow cytometry instrument testing found that resveratrol can suppress the apoptosis induced by ultraviolet irradiation, caspses-3 and caspase-9 content in positive control group were significantly higher than that of the negative control group at the same time period, the difference was statistically significant(P<0.05; caspses-3 and caspase-9 content in experimental group were lower than that in the positive control group at the same time, the difference was statistically significant(P<0.05. In addition, the damage of human lens epithelial cells was alleviated with the incubation time of resveratrol elongated. CONCLUSION:Resveratrol may inhibit ultraviolet-induced apoptosis of human lens epithelial cells, it has preventive function against radioactive cataract, and it can provide reliable evidence for pursuing effective medicine to prevent and treat cataract.

Regulation of hTERT Expression and Function in Newly Immortalized p53(+) Human Mammary Epithelial Cell Lines

Science.gov (United States)

2007-06-01

human mammary epithelial cell types by human papilloma virus 16 e6 or e7. Proc Nat Acad Sci USA 1995; 92:3687-91. 54. Shay JW, Pereira-Smith OM, Wright...Liu X-L, Chu Q, Gao Q, Band V. Immortalization of distinct human mammary epithelial cell types by human papilloma virus 16 e6 or e7. Proc Nat Acad

The plasticity of human breast carcinoma cells is more than epithelial to mesenchymal conversion

International Nuclear Information System (INIS)

William Petersen, Ole; Lind Nielsen, Helga; Gudjonsson, Thorarinn; Villadsen, René; Rønnov-Jessen, Lone; Bissell, Mina J

2001-01-01

The human breast comprises three lineages: the luminal epithelial lineage, the myoepithelial lineage, and the mesenchymal lineage. It has been widely accepted that human breast neoplasia pertains only to the luminal epithelial lineage. In recent years, however, evidence has accumulated that neoplastic breast epithelial cells may be substantially more plastic in their differentiation repertoire than previously anticipated. Thus, along with an increasing availability of markers for the myoepithelial lineage, at least a partial differentiation towards this lineage is being revealed frequently. It has also become clear that conversions towards the mesenchymal lineage actually occur, referred to as epithelial to mesenchymal transitions. Indeed, some of the so-called myofibroblasts surrounding the tumor may have an epithelial origin rather than a mesenchymal origin. Because myoepithelial cells, epithelial to mesenchymal transition-derived cells, genuine stromal cells and myofibroblasts share common markers, we now need to define a more ambitious set of markers to distinguish these cell types in the microenvironment of the tumors. This is necessary because the different microenvironments may confer different clinical outcomes. The aim of this commentary is to describe some of the inherent complexities in defining cellular phenotypes in the microenvironment of breast cancer and to expand wherever possible on the implications for tumor suppression and progression

The plasticity of human breast carcinoma cells is more than epithelial to mesenchymal conversion

Energy Technology Data Exchange (ETDEWEB)

Petersen, Ole William; Nielsen, Helga Lind; Gudjonsson, Thorarinn; Villadsen, Ren& #233; ; Ronnov-Jessen, Lone; Bissell, Mina J.

2001-05-12

The human breast comprises three lineages: the luminal epithelial lineage, the myoepithelial lineage, and the mesenchymal lineage. It has been widely accepted that human breast neoplasia pertains only to the luminal epithelial lineage. In recent years, however, evidence has accumulated that neoplastic breast epithelial cells may be substantially more plastic in their differentiation repertoire than previously anticipated. Thus, along with an increasing availability of markers for the myoepithelial lineage, at least a partial differentiation towards this lineage is being revealed frequently. It has also become clear that conversions towards the mesenchymal lineage actually occur, referred to as epithelial to mesenchymal transitions. Indeed, some of the so-called myofibroblasts surrounding the tumor may indeed have an epithelial origin rather than a mesenchymal origin. Because myoepithelial cells, epithelial to mesenchymal transition-derived cells, genuine stromal cells and myofibroblasts share common markers, we now need to define a more ambitious set of markers to distinguish these cell types in the microenvironment of the tumors. This is necessary because the different microenvironments may confer different clinical outcomes. The aim of this commentary is to describe some of the inherent complexities in defining cellular phenotypes in the microenvironment of breast cancer and to expand wherever possible on the implications for tumor suppression and progression.

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

Science.gov (United States)

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

Relation between epistaxis, external nasal deformity, and septal deviation following nasal trauma

Science.gov (United States)

Daniel, M; Raghavan, U

2005-01-01

Objectives: To find if the presence of epistaxis after nasal trauma can be used to predict post-traumatic external nasal deformity or a symptomatic deviated nasal septum. Methods: Retrospective analysis of all patients seen in the fractured nose clinic by the first author between 17 October 2003 and 27 February 2004. Presence of epistaxis, newly developed external nasal deformity, and the presence of a deviated nasal septum with new symptoms of nasal obstruction were noted. Results: A total of 139 patients were included in the study. Epistaxis following injury was noted in 106 (76%). Newly developed external nasal deformity was noted in 71 (51%), and 33 (24%) had a deviated nasal septum with new symptoms of nasal obstruction. Of the 106 patients with post-trauma epistaxis, 50 (67%) had newly developed external nasal deformity and of the 33 patients without post-traumatic epistaxis, 11 (33%) had nasal deformity (pepistaxis was not associated with the presence of a newly symptomatic deviated septum (25% in patients with epistaxis after injury versus 18% if there was no epistaxis). Conclusions: Presence of epistaxis after nasal trauma is associated with a statistically significant increase in external nasal deformity. However, one third of patients without epistaxis following nasal trauma also had external nasal deformity and hence all patients with a swollen nose after injury, irrespective of post-trauma epistaxis, still need to be referred to the fractured nose clinic. PMID:16244333

Interaction of chitin/chitosan with salivary and other epithelial cells-An overview.

Science.gov (United States)

Patil, Sharvari Vijaykumar; Nanduri, Lalitha S Y

2017-11-01

Chitin and its deacetylated form, chitosan, have been widely used for tissue engineering of both epithelial and mesenchymal tissues. Epithelial cells characterised by their sheet-like tight cellular arrangement and polarised nature, constitute a major component in various organs and play a variety of roles including protection, secretion and maintenance of tissue homeostasis. Regeneration of damaged epithelial tissues has been studied using biomaterials such as chitin, chitosan, hyaluronan, gelatin and alginate. Chitin and chitosan are known to promote proliferation of various embryonic and adult epithelial cells. However it is not clearly understood how this activity is achieved or what are the mechanisms involved in the chitin/chitosan driven proliferation of epithelial cells. Mechanistic understanding of influence of chitin/chitosan on epithelial cells will guide us to develop more targeted regenerative scaffold/hydrogel systems. Therefore, current review attempts to elicit a mechanistic insight into how chitin and chitosan interact with salivary, mammary, skin, nasal, lung, intestinal and bladder epithelial cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Culture of human intestinal epithelial cell using the dissociating enzyme thermolysin and endothelin-3

OpenAIRE

Liu, Z.; Zhang, P.; Zhou, Y.; Qin, H.; Shen, T.

2010-01-01

Epithelium, a highly dynamic system, plays a key role in the homeostasis of the intestine. However, thus far a human intestinal epithelial cell line has not been established in many countries. Fetal tissue was selected to generate viable cell cultures for its sterile condition, effective generation, and differentiated character. The purpose of the present study was to culture human intestinal epithelial cells by a relatively simple method. Thermolysin was added to improve the yield of epithel...

Invasion of Human Oral Epithelial Cells by Prevotella intermedia

Science.gov (United States)

Dorn, Brian R.; Leung, K.-P.; Progulske-Fox, Ann

1998-01-01

Invasion of oral epithelial cells by pathogenic oral bacteria may represent an important virulence factor in the progression of periodontal disease. Here we report that a clinical isolate of Prevotella intermedia, strain 17, was found to invade a human oral epithelial cell line (KB), whereas P. intermedia 27, another clinical isolate, and P. intermedia 25611, the type strain, were not found to invade the cell line. Invasion was quantified by the recovery of viable bacteria following a standard antibiotic protection assay and observed by electron microscopy. Cytochalasin D, cycloheximide, monodansylcadaverine, and low temperature (4°C) inhibited the internalization of P. intermedia 17. Antibodies raised against P. intermedia type C fimbriae and against whole cells inhibited invasion, but the anti-type-C-fimbria antibody inhibited invasion to a greater extent than the anti-whole-cell antibody. This work provides evidence that at least one strain of P. intermedia can invade an oral epithelial cell line and that the type C fimbriae and a cytoskeletal rearrangement are required for this invasion. PMID:9826397

Personalized medicine for cystic fibrosis: establishing human model systems.

Science.gov (United States)

Mou, Hongmei; Brazauskas, Karissa; Rajagopal, Jayaraj

2015-10-01

With over 1,500 identifiable mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that result in distinct functional and phenotypical abnormalities, it is virtually impossible to perform randomized clinical trials to identify the best therapeutics for all patients. Therefore, a personalized medicine approach is essential. The only way to realistically accomplish this is through the development of improved in vitro human model systems. The lack of a readily available and infinite supply of human CFTR-expressing airway epithelial cells is a key bottleneck. We propose that a concerted two-pronged approach is necessary for patient-specific cystic fibrosis research to continue to prosper and realize its potential: (1) more effective culture and differentiation conditions for growing primary human airway and nasal epithelial cells and (2) the development of collective protocols for efficiently differentiating disease- and patient-specific induced pluripotent stem cells (iPSC) into pure populations of adult epithelial cells. Ultimately, we need a personalized human model system for cystic fibrosis with the capacity for uncomplicated bankability, widespread availability, and universal applicability for patient-specific disease modeling, novel pharmacotherapy investigation and screening, and readily executable genetic modification. © 2015 Wiley Periodicals, Inc.

Quantitative expression of osteopontin in nasal mucosa of patients with allergic rhinitis: effects of pollen exposure and nasal glucocorticoid treatment

Directory of Open Access Journals (Sweden)

O'Neil Serena E

2010-11-01

Full Text Available Abstract Background Osteopontin (OPN is a multifunctional cytokine that has been primarily investigated in Th1 diseases. Recently, it has also been implicated in Th2-mediated allergic diseases, such as asthma. The expression of OPN in allergic rhinitis (AR is currently unknown, as is the effect of intranasal glucocorticosteroids (GCs on that expression. Methods Subjects with AR were randomised to receive treatment with fluticasone propionate (FP (n = 12 or a placebo (n = 16 over the grass pollen season and nasal biopsies were taken prior to, and during the season. OPN expression in the nasal mucosa was examined with immunohistochemistry. Healthy non-AR controls (n = 5 were used as a comparator. Results OPN expression was detected in epithelial cells, subepithelial infiltrating/inflammatory cells and cells lining the vessels and glands of all subjects. Comparison of the pre- and peak-pollen season biopsy sections in placebo treated patients revealed no increase in OPN expression during the grass pollen season (5.7% vs 6.4%. Treatment with a local glucocorticosteroid did not alter the expression of OPN during pollen exposure (6.2% vs 6.7%. Conclusion OPN has been increasingly associated with the pathogenesis of various Th2-mediated diseases. However, our finding that the OPN expression in the nasal mucosa of AR patients is not significantly affected by allergen exposure and is comparable to that of the healthy controls, suggests that intracellular OPN is not directly involved in the pathogenesis of allergic rhinitis.

Engineering stromal-epithelial interactions in vitro for ...

Science.gov (United States)

Background: Crosstalk between epithelial and stromal cells drives the morphogenesis of ectodermal organs during development and promotes normal mature adult epithelial tissue function. Epithelial-mesenchymal interactions (EMIs) have been examined using mammalian models, ex vivo tissue recombination, and in vitro co-cultures. Although these approaches have elucidated signaling mechanisms underlying morphogenetic processes and adult mammalian epithelial tissue function, they are limited by the availability of human tissue, low throughput, and human developmental or physiological relevance. Objectives: Bioengineering strategies to promote EMIs using human epithelial and mesenchymal cells have enabled the development of human in vitro models of adult epidermal and glandular tissues. In this review, we describe recent bioengineered models of human epithelial tissue and organs that can instruct the design of organotypic models of human developmental processes.Methods: We reviewed current bioengineering literature and here describe how bioengineered EMIs have enabled the development of human in vitro epithelial tissue models.Discussion: Engineered models to promote EMIs have recapitulated the architecture, phenotype, and function of adult human epithelial tissue, and similar engineering principles could be used to develop models of developmental morphogenesis. We describe how bioengineering strategies including bioprinting and spheroid culture could be implemented to

Characterization of nasal cavity-associated lymphoid tissue in ducks.

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Kang, Haihong; Yan, Mengfei; Yu, Qinghua; Yang, Qian

2014-05-01

The nasal mucosa is involved in immune defense, as it is the first barrier for pathogens entering the body through the respiratory tract. The nasal cavity-associated lymphoid tissue (NALT), which is found in the mucosa of the nasal cavity, is considered to be the main mucosal immune inductive site in the upper respiratory tract. NALT has been found in humans and many mammals, which contributes to local and systemic immune responses after intranasal vaccination. However, there are very few data on NALT in avian species, especially waterfowl. For this study, histological sections of the nasal cavities of Cherry Valley ducks were used to examine the anatomical location and histological characteristics of NALT. The results showed that several lymphoid aggregates are present in the ventral wall of the nasal cavity near the choanal cleft, whereas several more lymphoid aggregates were located on both sides of the nasal septum. In addition, randomly distributed intraepithelial lymphocytes and isolated lymphoid follicles were observed in the regio respiratoria of the nasal cavity. There were also a few lymphoid aggregates located in the lamina propria of the regio vestibularis, which was covered with a stratified squamous epithelium. This study focused on the anatomic and histological characteristics of the nasal cavity of the duck and performed a systemic overview of NALT. This will be beneficial for further understanding of immune mechanisms after nasal vaccination and the development of effective nasal vaccines for waterfowls. Copyright © 2014 Wiley Periodicals, Inc.

Expression of IGF-1R and iNOS in nasal polyps; epithelial cell homeostasis and innate immune mechanisms in pathogenesis of nasal polyposis

Czech Academy of Sciences Publication Activity Database

Fundová, P.; Filipovský, T.; Funda, David P.; Hovorka, Ondřej; Holý, R.; Navara, M.; Tlaskalová, Helena

2008-01-01

Roč. 53, č. 6 (2008), s. 558-562 ISSN 0015-5632 R&D Projects: GA MZd NR8517 Institutional research plan: CEZ:AV0Z50200510 Keywords : nasal polyposis * igf -1r * inos Subject RIV: EC - Immunology Impact factor: 1.172, year: 2008

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

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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...

Nasal solitary chemoreceptor cell responses to bitter and trigeminal stimulants in vitro

OpenAIRE

Gulbransen, Brian D; Clapp, Tod R; Kinnamon, Sue C; Finger, Thomas E

2008-01-01

Nasal trigeminal chemosensitivity in mice and rats is mediated in part by epithelial solitary chemoreceptor (chemosensory) cells (SCCs), but the exact role of these cells in chemoreception is unclear (Finger et al. 2003). Histological evidence suggests that SCCs express elements of the bitter taste transduction pathway including T2R (bitter taste) receptors, the G protein α-gustducin, PLCβ2, and TRPM5, leading to speculation that SCCs are the receptor cells that mediate trigeminal nerve respo...

Bone marrow contributes to epithelial cancers in mice and humans as developmental mimicry.

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Cogle, Christopher R; Theise, Neil D; Fu, Dongtao; Ucar, Deniz; Lee, Sean; Guthrie, Steven M; Lonergan, Jean; Rybka, Witold; Krause, Diane S; Scott, Edward W

2007-08-01

Bone marrow cells have the capacity to contribute to distant organs. We show that marrow also contributes to epithelial neoplasias of the small bowel, colon, and lung, but not the skin. In particular, epithelial neoplasias found in patients after hematopoietic cell transplantations demonstrate that human marrow incorporates into neoplasias by adopting the phenotype of the surrounding neoplastic environment. To more rigorously evaluate marrow contribution to epithelial cancer, we employed mouse models of intestinal and lung neoplasias, which revealed specifically that the hematopoietic stem cell and its progeny incorporate within cancer. Furthermore, this marrow involvement in epithelial cancer does not appear to occur by induction of stable fusion. Whereas previous claims have been made that marrow can serve as a direct source of epithelial neoplasia, our results indicate a more cautionary note, that marrow contributes to cancer as a means of developmental mimicry. Disclosure of Potential Conflicts of Interest is found at the end of this article.

Interleukin-13-induced MUC5AC is regulated by 15-lipoxygenase 1 pathway in human bronchial epithelial cells.

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Zhao, Jinming; Maskrey, Ben; Balzar, Silvana; Chibana, Kazuyuki; Mustovich, Anthony; Hu, Haizhen; Trudeau, John B; O'Donnell, Valerie; Wenzel, Sally E

2009-05-01

15-Lipoxygenase-1 (15LO1) and MUC5AC are highly expressed in asthmatic epithelial cells. IL-13 is known to induce 15LO1 and MUC5AC in human airway epithelial cells in vitro. Whether 15LO1 and/or its product 15-HETE modulate MUC5AC expression is unknown. To determine the expression of 15LO1 in freshly harvested epithelial cells from subjects with asthma and normal control subjects and to determine whether IL-13-induced 15LO1 expression and activation regulate MUC5AC expression in human bronchial epithelial cells in vitro. Human airway epithelial cells from subjects with asthma and normal subjects were evaluated ex vivo for 15LO1 and MUC5AC expression. The impact of 15LO1 on MUC5AC expression in vitro was analyzed by inhibiting 15LO1 through pharmacologic (PD146176) and siRNA approaches in human bronchial epithelial cells cultured under air-liquid interface. We analyzed 15 hydroxyeicosatetraenoic acid (15-HETE) by liquid chromatography/UV/mass spectrometry. MUC5AC and 15LO1 were analyzed by real-time RT-PCR, immunofluoresence, and Western blot. Epithelial 15LO1 expression increased with asthma severity (P < 0.0001). 15LO1 significantly correlated with MUC5AC ex vivo and in vitro. IL-13 increased 15LO1 expression and stimulated formation of two molecular species of 15-HETE esterified to phosphotidylethanolamine (15-HETE-PE). Inhibition of 15LO1 suppressed 15-HETE-PE and decreased MUC5AC expression in the presence of IL-13 stimulation. The addition of exogenous 15-HETE partially restored MUC5AC expression. Epithelial 15LO1 expression increases with increasing asthma severity. IL-13 induction of 15-HETE-PE enhances MUC5AC expression in human airway epithelial cells. High levels of 15LO1 activity could contribute to the increases of MUC5AC observed in asthma.

Generation of folliculogenic human epithelial stem cells from induced pluripotent stem cells

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Yang, Ruifeng; Zheng, Ying; Burrows, Michelle; Liu, Shujing; Wei, Zhi; Nace, Arben; Guo, Wei; Kumar, Suresh; Cotsarelis, George; Xu, Xiaowei

2014-01-01

Epithelial stem cells (EpSCs) in the hair follicle bulge are required for hair follicle growth and cycling. The isolation and propagation of human EpSCs for tissue engineering purposes remains a challenge. Here we develop a strategy to differentiate human iPSCs (hiPSCs) into CD200+/ITGA6+ EpSCs that can reconstitute the epithelial components of the hair follicle and interfollicular epidermis. The hiPSC-derived CD200+/ITGA6+ cells show a similar gene expression signature as EpSCs directly isolated from human hair follicles. Human iPSC-derived CD200+/ITGA6+ cells are capable of generating all hair follicle lineages including the hair shaft, and the inner and outer root sheaths in skin reconstitution assays. The regenerated hair follicles possess a KRT15+ stem cell population and produce hair shafts expressing hair-specific keratins. These results suggest an approach for generating large numbers of human EpSCs for tissue engineering and new treatments for hair loss, wound healing and other degenerative skin disorders.

Human retinal pigment epithelial cell-induced apoptosis in activated T cells

DEFF Research Database (Denmark)

Jørgensen, A; Wiencke, A K; la Cour, M

1998-01-01

human retinal pigment epithelial (RPE) cells can induce apoptosis in activated T cells. METHODS: Fas ligand (FasL) expression was detected by flow cytometry and immunohistochemistry. Cultured RPE cells were cocultured with T-cell lines and peripheral blood lymphocytes for 6 hours to 2 days. Induction...... of apoptosis was detected by 7-amino-actinomycin D and annexin V staining. RESULTS: Retinal pigment epithelial cells expressed FasL and induced apoptosis in activated Fas+ T cells. Blocking of Fas-FasL interaction with antibody strongly inhibited RPE-mediated T-cell apoptosis. Retinal pigment epithelial cells...... induced apoptosis in several activated T-cell populations and T-cell lines, including T-cell antigen receptor (TCR)-CD3-negative T-cell lines. In contrast, RPE cells induced little or no apoptosis in resting peripheral T cells. Major histocompatibility complex (MHC) class II monoclonal antibodies, which...

Human retinal pigment epithelial cell-induced apoptosis in activated T cells

DEFF Research Database (Denmark)

Jørgensen, A; Wiencke, A K; la Cour, M

1998-01-01

PURPOSE: The immune privilege of the eye has been thought to be dependent on physical barriers and absence of lymphatic vessels. However, the immune privilege may also involve active immunologic processes, as recent studies have indicated. The purpose of the present study was to investigate whether...... human retinal pigment epithelial (RPE) cells can induce apoptosis in activated T cells. METHODS: Fas ligand (FasL) expression was detected by flow cytometry and immunohistochemistry. Cultured RPE cells were cocultured with T-cell lines and peripheral blood lymphocytes for 6 hours to 2 days. Induction...... of apoptosis was detected by 7-amino-actinomycin D and annexin V staining. RESULTS: Retinal pigment epithelial cells expressed FasL and induced apoptosis in activated Fas+ T cells. Blocking of Fas-FasL interaction with antibody strongly inhibited RPE-mediated T-cell apoptosis. Retinal pigment epithelial cells...

Nasal Wash Treatment

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... Medications Alternative Therapies Nasal Wash Treatment Nasal Wash Treatment Make an Appointment Ask a Question Refer Patient The Centers for Disease Control (CDC) guidelines for preparing water used in a nasal wash are listed below. Many ...

N-Myc Drives Neuroendocrine Prostate Cancer Initiated from Human Prostate Epithelial Cells

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Lee, John K.; Phillips, John W.; Smith, Bryan A.; Park, Jung Wook; Stoyanova, Tanya; McCaffrey, Erin F.; Baertsch, Robert; Sokolov, Artem; Meyerowitz, Justin G.; Mathis, Colleen; Cheng, Donghui; Stuart, Joshua M.; Shokat, Kevan M.; Gustafson, W. Clay; Huang, Jiaoti; Witte, Owen N.

2016-01-01

SUMMARY MYCN amplification and overexpression are common in neuroendocrine prostate cancer (NEPC). However, the impact of aberrant N-Myc expression in prostate tumorigenesis and the cellular origin of NEPC have not been established. We define N-Myc and activated AKT1 as oncogenic components sufficient to transform human prostate epithelial cells to prostate adenocarcinoma and NEPC with phenotypic and molecular features of aggressive, late-stage human disease. We directly show that prostate adenocarcinoma and NEPC can arise from a common epithelial clone. Further, N-Myc is required for tumor maintenance and destabilization of N-Myc through Aurora A kinase inhibition reduces tumor burden. Our findings establish N-Myc as a driver of NEPC and a target for therapeutic intervention. PMID:27050099

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

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

2014-01-01

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

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

Science.gov (United States)

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

2014-12-01

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

The nasal cavity microbiota of healthy adults

OpenAIRE

Bassis, Christine M; Tang, Alice L; Young, Vincent B; Pynnonen, Melissa A

2014-01-01

Background The microbiota of the nares has been widely studied. However, relatively few studies have investigated the microbiota of the nasal cavity posterior to the nares. This distinct environment has the potential to contain a distinct microbiota and play an important role in health. Results We obtained 35,142 high-quality bacterial 16S rRNA-encoding gene sequence reads from the nasal cavity and oral cavity (the dorsum of the tongue and the buccal mucosa) of 12 healthy adult humans and dep...

Vitamin D3 analog maxacalcitol (OCT) induces hCAP-18/LL-37 production in human oral epithelial cells.

Science.gov (United States)

Tada, Hiroyuki; Shimizu, Takamitsu; Nagaoka, Isao; Takada, Haruhiko

2016-01-01

Maxacalcitol (22-oxacalcitriol: OCT) is a synthetic vitamin D3 analog with a limited calcemic effect. In this study, we investigated whether OCT increases the production of LL-37/CAP-18, a human cathelicidin antimicrobial peptide, in human gingival/oral epithelial cells. A human gingival epithelial cell line (Ca9-22) and human oral epithelial cell lines (HSC-2, HSC-3, and HSC-4) exhibited the enhanced expression of LL-37 mRNA upon stimulation with OCT as well as active metabolites of vitamins D3 and D2. Among the human epithelial cell lines, Ca9-22 exhibited the strongest response to these vitamin D-related compounds. OCT induced the higher production of CAP-18 (ng/mL order) until 6 days time-dependently in Ca9-22 cells in culture. The periodontal pathogen Porphyromonas gingivalis was killed by treatment with the LL-37 peptide. These findings suggest that OCT induces the production of hCAP-18/LL-37 in a manner similar to that induced by the active metabolite of vitamin D3.

TGF-β1 induced epithelial to mesenchymal transition (EMT in human bronchial epithelial cells is enhanced by IL-1β but not abrogated by corticosteroids

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Zuraw Bruce L

2009-10-01

Full Text Available Abstract Background Chronic persistent asthma is characterized by ongoing airway inflammation and airway remodeling. The processes leading to airway remodeling are poorly understood, and there is increasing evidence that even aggressive anti-inflammatory therapy does not completely prevent this process. We sought to investigate whether TGFβ1 stimulates bronchial epithelial cells to undergo transition to a mesenchymal phenotype, and whether this transition can be abrogated by corticosteroid treatment or enhanced by the pro-inflammatory cytokine IL-1β. Methods BEAS-2B and primary normal human bronchial epithelial cells were stimulated with TGFβ1 and expression of epithelial and mesenchymal markers assessed by quantitative real-time PCR, immunoblotting, immunofluorescence microscopy and zymography. In some cases the epithelial cells were also incubated with corticosteroids or IL-1β. Results were analyzed using non-parametric statistical tests. Results Treatment of BEAS-2B or primary human bronchial epithelial cells with TGFβ1 significantly reduced the expression level of the epithelial adherence junction protein E-cadherin. TGFβ1 then markedly induced mesenchymal marker proteins such as collagen I, tenascin C, fibronectin and α-smooth muscle actin mRNA in a dose dependant manner. The process of mesenchymal transition was accompanied by a morphological change towards a more spindle shaped fibroblast cell type with a more motile and invasive phenotype. Corticosteroid pre-treatment did not significantly alter the TGFβ1 induced transition but IL-1β enhanced the transition. Conclusion Our results indicate, that TGFβ1 can induce mesenchymal transition in the bronchial epithelial cell line and primary cells. Since asthma has been strongly associated with increased expression of TGFβ1 in the airway, epithelial to mesenchymal transition may contribute to the contractile and fibrotic remodeling process that accompanies chronic asthma.

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

Science.gov (United States)

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

2010-04-01

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

IL-17 suppresses immune effector functions in human papillomavirus-associated epithelial hyperplasia.

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Gosmann, Christina; Mattarollo, Stephen R; Bridge, Jennifer A; Frazer, Ian H; Blumenthal, Antje

2014-09-01

Persistent infection with high-risk human papillomaviruses (HPV) causes epithelial hyperplasia that can progress to cancer and is thought to depend on immunosuppressive mechanisms that prevent viral clearance by the host. IL-17 is a cytokine with diverse functions in host defense and in the pathology of autoimmune disorders, chronic inflammatory diseases, and cancer. We analyzed biopsies from patients with HPV-associated cervical intraepithelial neoplasia grade 2/3 and murine skin displaying HPV16 E7 protein-induced epithelial hyperplasia, which closely models hyperplasia in chronic HPV lesions. Expression of IL-17 and IL-23, a major inducer of IL-17, was elevated in both human HPV-infected and murine E7-expressing lesions. Using a skin-grafting model, we demonstrated that IL-17 in HPV16 E7 transgenic skin grafts inhibited effective host immune responses against the graft. IL-17 was produced by CD3(+) T cells, predominantly CD4(+) T cells in human, and CD4(+) and γδ T cells in mouse hyperplastic lesions. IL-23 and IL-1β, but not IL-18, induced IL-17 production in E7 transgenic skin. Together, these findings demonstrate an immunosuppressive role for IL-17 in HPV-associated epithelial hyperplasia and suggest that blocking IL-17 in persistent viral infection may promote antiviral immunity and prevent progression to cancer. Copyright © 2014 by The American Association of Immunologists, Inc.

The fate of epithelial cells in the human large intestine.

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Barkla, D H; Gibson, P R

1999-08-01

One hundred and forty biopsies of the colon and rectum, collected during routine colonoscopies of 51 patients aged 19 to 74 years, were examined using light microscopy and transmission and scanning electron microscopy. The results indicated that surface epithelial cells undergo apoptosis, passing through fenestrations in the basement membrane to where they enter the lamina propria and are taken up by macrophages; and it is hypothesized that apoptotic cells are carried through the fenestrations on a current of fluid. The study also found that epithelial cells positioned over the crypts are better attached and more robust than those more distant from the crypt opening; and it is further hypothesized that, after reaching the top of the crypts, some goblet cells cease secreting mucus and pass onto the surface compartment of absorptive cells. An unexpected finding was that the lower regions of the crypts commonly contain isolated necrotic colonocytes. Apoptotic cells were rarely observed in the crypt epithelium. The findings of this study support the "recycling" model of epithelial cell death in the surface compartment of the human colon.

Nasal Carriage of Staphylococcus intermedius in Humans in Contact with Dogs

OpenAIRE

Harvey, R. G.; Marples, R. R.; Noble, W. C.

2011-01-01

A study of staphylococci isolated from the anterior nares of 16 owners of dogs with atopic dermatitis and 13 veterinary practice staff in constant contact with dogs was conducted. There was one persistent nasal carrier and four transient nasal carriers of Staphylococcus intermedius. This carriage rate is higher than previously reported and presumably contributes to the presence of antibodies to S. intermedius in about 20 per cent of the normal population. Thus transfer of S. intermedius from ...

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

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

2006-01-01

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

Effect of the nasal cycle on congestive response during bilateral nasal allergen provocation

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Tomasz Gotlib

2014-06-01

Full Text Available Background. Bilateral nasal allergen provocation usually produces more pronounced obstruction of one nasal passage. It was found that this could be related to the stage of the nasal cycle before the provocation. objective. To discover whether the stage of the nasal cycle is decisive for asymmetry in congestive response observed during bilateral allergen nasal provocation. methods. Two bilateral nasal allergen provocations were performed in a group of 26 pollen-sensitive volunteers. Acoustic rhinometry measurements were taken during the nasal cycle, and then after the provocation. A cross-sectional area at the level of the inferior turbinate (CSA-2 was measured. Consecutive challenges were performed in the opposite phase of the nasal cycle: the side which had been wide just before the first challenge, was narrow before the second provocation. results. Asymmetry in CSA-2 reduction between the nasal passages was observed in most cases. Significant difference was observed between mean CSA-2 reduction rate (reactivity of the side that responded with greater congestion, and the opposite side. No significant difference was found in mean CSA-2 reduction rate between the side which was narrow, and the side which was wide before provocation. conclusions. Asymmetry of congestive response during bilateral nasal allergen provocation is not dependent on the stage of the nasal cycle preceding the challenge.

Androgen-Sensitized Apoptosis of HPr-1AR Human Prostate Epithelial Cells.

Directory of Open Access Journals (Sweden)

Congcong Chen

Full Text Available Androgen receptor (AR signaling is crucial to the development and homeostasis of the prostate gland, and its dysregulation mediates common prostate pathologies. The mechanisms whereby AR regulates growth suppression and differentiation of luminal epithelial cells in the prostate gland and proliferation of malignant versions of these cells have been investigated in human and rodent adult prostate. However, the cellular stress response of human prostate epithelial cells is not well understood, though it is central to prostate health and pathology. Here, we report that androgen sensitizes HPr-1AR and RWPE-AR human prostate epithelial cells to cell stress agents and apoptotic cell death. Although 5α-dihydrotestosterone (DHT treatment alone did not induce cell death, co-treatment of HPr-1AR cells with DHT and an apoptosis inducer, such as staurosporine (STS, TNFt, or hydrogen peroxide, synergistically increased cell death in comparison to treatment with each apoptosis inducer by itself. We found that the synergy between DHT and apoptosis inducer led to activation of the intrinsic/mitochondrial apoptotic pathway, which is supported by robust cleavage activation of caspase-9 and caspase-3. Further, the dramatic depolarization of the mitochondrial membrane potential that we observed upon co-treatment with DHT and STS is consistent with increased mitochondrial outer membrane permeabilization (MOMP in the pro-apoptotic mechanism. Interestingly, the synergy between DHT and apoptosis inducer was abolished by AR antagonists and inhibitors of transcription and protein synthesis, suggesting that AR mediates pro-apoptotic synergy through transcriptional regulation of MOMP genes. Expression analysis revealed that pro-apoptotic genes (BCL2L11/BIM and AIFM2 were DHT-induced, whereas pro-survival genes (BCL2L1/BCL-XL and MCL1 were DHT-repressed. Hence, we propose that the net effect of these AR-mediated expression changes shifts the balance of BCL2-family proteins

Interleukin-13–induced MUC5AC Is Regulated by 15-Lipoxygenase 1 Pathway in Human Bronchial Epithelial Cells

Science.gov (United States)

Zhao, Jinming; Maskrey, Ben; Balzar, Silvana; Chibana, Kazuyuki; Mustovich, Anthony; Hu, Haizhen; Trudeau, John B.; O'Donnell, Valerie; Wenzel, Sally E.

2009-01-01

Rationale: 15-Lipoxygenase-1 (15LO1) and MUC5AC are highly expressed in asthmatic epithelial cells. IL-13 is known to induce 15LO1 and MUC5AC in human airway epithelial cells in vitro. Whether 15LO1 and/or its product 15-HETE modulate MUC5AC expression is unknown. Objectives: To determine the expression of 15LO1 in freshly harvested epithelial cells from subjects with asthma and normal control subjects and to determine whether IL-13–induced 15LO1 expression and activation regulate MUC5AC expression in human bronchial epithelial cells in vitro. Methods: Human airway epithelial cells from subjects with asthma and normal subjects were evaluated ex vivo for 15LO1 and MUC5AC expression. The impact of 15LO1 on MUC5AC expression in vitro was analyzed by inhibiting 15LO1 through pharmacologic (PD146176) and siRNA approaches in human bronchial epithelial cells cultured under air–liquid interface. We analyzed 15 hydroxyeicosatetraenoic acid (15-HETE) by liquid chromatography/UV/mass spectrometry. MUC5AC and 15LO1 were analyzed by real-time RT-PCR, immunofluoresence, and Western blot. Measurements and Main Results: Epithelial 15LO1 expression increased with asthma severity (P < 0.0001). 15LO1 significantly correlated with MUC5AC ex vivo and in vitro. IL-13 increased 15LO1 expression and stimulated formation of two molecular species of 15-HETE esterified to phosphotidylethanolamine (15-HETE-PE). Inhibition of 15LO1 suppressed 15-HETE-PE and decreased MUC5AC expression in the presence of IL-13 stimulation. The addition of exogenous 15-HETE partially restored MUC5AC expression. Conclusions: Epithelial 15LO1 expression increases with increasing asthma severity. IL-13 induction of 15-HETE-PE enhances MUC5AC expression in human airway epithelial cells. High levels of 15LO1 activity could contribute to the increases of MUC5AC observed in asthma. PMID:19218191

Treatment of chronic desquamative gingivitis using tissue-engineered human cultured gingival epithelial sheets: a case report.

Science.gov (United States)

Okuda, Kazuhiro; Momose, Manabu; Murata, Masashi; Saito, Yoshinori; lnoie, Masukazu; Shinohara, Chikara; Wolff, Larry F; Yoshie, Hiromasa

2004-04-01

Human cultured gingival epithelial sheets were used as an autologous grafting material for regenerating gingival tissue in the maxillary left and mandibular right quadrants of a patient with chronic desquamative gingivitis. Six months post-surgery in both treated areas, there were gains in keratinized gingiva and no signs of gingival inflammation compared to presurgery. In the maxillary left quadrant, preoperative histopathologic findings revealed the epithelium was separated from the connective tissue and inflammatory cells were extensive. After grafting with the gingival epithelial sheets, inflammatory cells were decreased and separation between epithelium and connective tissue was not observed. The human cultured gingival epithelial sheets fabricated using tissue engineering technology showed significant promise for gingival augmentation in periodontal therapy.

Comparison of radiosensitivities of human autologous normal and neoplastic thyroid epithelial cells

International Nuclear Information System (INIS)

Miller, R.C.; Kopecky, K.J.; Hiraoka, T.; Ezaki, H.; Clifton, K.H.

1986-01-01

Studies were conducted to examine differences between the radiosensitivities of normal and neoplastic epithelial cells of the human thyroid. Freshly excised thyroid tissues from the tumours of eight patients with papillary carcinoma (PC) and five with follicular adenoma (FA) were cultured in vitro separately from normal thyroid tissue obtained from the surgical margins of the same patients. Plating efficiency of unirradiated control tissue was lower, on average for tumour tissue compared with normal tissue. Radiosensitivity, measured by the 37% inactivation dose D 0 , was greater for carcinoma tissue than for normal tissue in seven out of eight PC cases. Adenomatous tissue was less radiosensitive than normal tissue in four out of five FA cases. This is the first report comparing the radiosensitivity of autologous normal and abnormal epithelial tissue from the human thyroid. (author)

Absolute humidity and the human nose: A reanalysis of climate zones and their influence on nasal form and function.

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Maddux, Scott D; Yokley, Todd R; Svoma, Bohumil M; Franciscus, Robert G

2016-10-01

Investigations into the selective role of climate on human nasal variation commonly divide climates into four broad adaptive zones (hot-dry, hot-wet, cold-dry, and cold-wet) based on temperature and relative humidity. Yet, absolute humidity-not relative humidity-is physiologically more important during respiration. Here, we investigate the global distribution of absolute humidity to better clarify ecogeographic demands on nasal physiology. We use monthly observations from the Climatic Research Unit Timeseries 3 (CRU TS3) database to construct global maps of average annual temperature, relative humidity and absolute humidity. Further, using data collected by Thomson and Buxton (1923) for over 15,000 globally-distributed individuals, we calculate the actual amount of heat and water that must be transferred to inspired air in different climatic regimes to maintain homeostasis, and investigate the influence of these factors on the nasal index. Our results show that absolute humidity, like temperature, generally decreases with latitude. Furthermore, our results demonstrate that environments typically characterized as "cold-wet" actually exhibit low absolute humidities, with values virtually identical to cold-dry environments and significantly lower than hot-wet and even hot-dry environments. Our results also indicate that strong associations between the nasal index and absolute humidity are, potentially erroneously, predicated on individuals from hot-dry environments possessing intermediate (mesorrhine) nasal indices. We suggest that differentially allocating populations to cold-dry or cold-wet climates is unlikely to reflect different selective pressures on respiratory physiology and nasal morphology-it is cold-dry, and to a lesser degree hot-dry environments, that stress respiratory function. Our study also supports assertions that demands for inspiratory modification are reduced in hot-wet environments, and that expiratory heat elimination for thermoregulation is a

Disposition of nasal, intravenous, and oral methadone in healthy volunteers.

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Dale, Ola; Hoffer, Christine; Sheffels, Pamela; Kharasch, Evan D

2002-11-01

Nasal administration of many opioids demonstrates rapid uptake and fast onset of action. Nasal administration may be an alternative to intravenous and oral administration of methadone and was therefore studied in human volunteers. The study was approved by the Institutional Review Board of the University of Washington, Seattle. Eight healthy volunteers (6 men and 2 women) aged 19 to 33 years were enrolled after informed written consent was obtained. Subjects received 10 mg methadone hydrochloride nasally, orally, or intravenously on 3 separate occasions in a crossover design. Nasal methadone (50 mg/mL in aqueous solution) was given as a 100-microL spray in each nostril (Pfeiffer BiDose sprayer). Blood samples for liquid chromatography-mass spectrometry analyses of methadone and the metabolite 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolinium were drawn for up to 96 hours. The methadone effect was measured by noninvasive infrared pupilometry coincident with blood sampling. Nasal uptake of methadone was rapid, with maximum plasma concentrations occurring within 7 minutes. The maximum effects of intravenous, nasal, and oral methadone, on the basis of dark-adapted pupil diameter, were reached in about 15 minutes, 30 minutes, and 2 hours, respectively. The respective durations were 24, 10, and 8 hours. Both nasal and oral bioavailabilities were 0.85. Subjects reported that nasal methadone caused a burning sensation. Nasal administration of methadone results in rapid absorption and onset of effect and high bioavailability, which was greater than that reported for other nasal opioids, with a similar duration of effect. Nasal administration may be an alternative route of methadone administration; however, improved formulations are desirable to reduce nasal irritation.

Is the human nasal cavity at risk from inhaled radionuclides?

International Nuclear Information System (INIS)

Boecker, B.B.; Hahn, F.F.; Cuddihy, R.G.; Snipes, M.B.; McClellan, R.O.

1986-01-01

In a series of three life-span studies in which beagle dogs inhaled relatively soluble forms of beta-emitting radionuclides, a number of cancers of the nasal cavity have arisen at long times after the inhalation exposure. No such cancers were observed in the control dogs. Data obtained in other studies involving serial sacrifice of dogs that received these radionuclides in similar forms have shown that high local concentrations of the radionuclides can persist in nasal turbinates for long periods of time, depending on the physical half-life of the radionuclide inhaled. Several nasal carcinomas have also been observed in dogs injected with 137 CsCl in which the relative concentrations of beta activity in the turbinate region were not as pronounced as in the above studies. Similar risks of sinonasal cancer were calculated for dogs in each of these studies regardless of differences in radionuclide, dosimetry, and route of administration. Since sinonasal cancers have occurred in people exposed to alpha-emitting radionuclides, it is reasonable to assume this could occur with beta emitters as well. Radiation protection guidelines should account for the sinonasal region being at risk. 23 refs., 1 fig., 6 tabs

Telomerase-immortalized non-malignant human prostate epithelial cells retain the properties of multipotent stem cells

International Nuclear Information System (INIS)

Li Hongzhen; Zhou Jianjun; Miki, Jun; Furusato, Bungo; Gu Yongpeng; Srivastava, Shiv; McLeod, David G.; Vogel, Jonathan C.; Rhim, Johng S.

2008-01-01

Understanding prostate stem cells may provide insight into the origin of prostate cancer. Primary cells have been cultured from human prostate tissue but they usually survive only 15-20 population doublings before undergoing senescence. We report here that RC-170N/h/clone 7 cells, a clonal cell line from hTERT-immortalized primary non-malignant tissue-derived human prostate epithelial cell line (RC170N/h), retain multipotent stem cell properties. The RC-170N/h/clone 7 cells expressed a human embryonic stem cell marker, Oct-4, and potential prostate epithelial stem cell markers, CD133, integrin α2β1 hi and CD44. The RC-170N/h/clone 7 cells proliferated in KGM and Dulbecco's Modified Eagle Medium with 10% fetal bovine serum and 5 μg/ml insulin (DMEM + 10% FBS + Ins.) medium, and differentiated into epithelial stem cells that expressed epithelial cell markers, including CK5/14, CD44, p63 and cytokeratin 18 (CK18); as well as the mesenchymal cell markers, vimentin, desmin; the neuron and neuroendocrine cell marker, chromogranin A. Furthermore the RC170 N/h/clone 7 cells differentiated into multi tissues when transplanted into the sub-renal capsule and subcutaneously of NOD-SCID mice. The results indicate that RC170N/h/clone 7 cells retain the properties of multipotent stem cells and will be useful as a novel cell model for studying the mechanisms of human prostate stem cell differentiation and transformation

Nasal Cancer

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... 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 ...

The parietal epithelial cell is crucially involved in human idiopathic focal segmental glomerulosclerosis.

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Dijkman, Henry; Smeets, Bart; van der Laak, Jeroen; Steenbergen, Eric; Wetzels, Jack

2005-10-01

Focal segmental glomerulosclerosis (FSGS) is one of the most common patterns of glomerular injury encountered in human renal biopsies. Epithelial hyperplasia, which can be prominent in FSGS, has been attributed to dedifferentiation and proliferation of podocytes. Based on observations in a mouse model of FSGS, we pointed to the role of parietal epithelial cells (PECs). In the present study we investigated the relative role of PECs and podocytes in human idiopathic FSGS. We performed a detailed study of lesions from a patient with recurrent idiopathic FSGS by serial sectioning, marker analysis and three-dimensional reconstruction of glomeruli. We have studied the expression of markers for podocytes, PECs, mesangial cells, endothelium, and myofibroblasts. We also looked at proliferation and composition of the deposited extracellular matrix (ECM). We found that proliferating epithelial cells in FSGS lesions are negative for podocyte and macrophage markers, but stain for PEC markers. The composition of the matrix deposited by these cells is identical to Bowman's capsule. Our study demonstrates that PECs are crucially involved in the pathogenesis of FSGS lesions.

Oral focal epithelial hyperplasia: report of 3 cases with human papillomavirus DNA sequencing analysis.

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Gültekin, S E; Tokman Yildirim, Benay; Sarisoy, S

2011-01-01

Focal epithelial hyperplasia (FEH), or Heck's disease, is a benign proliferative viral infection of the oral mucosa that is related to Human Papil-lomavirus (HPV), mainly subtypes 13 and 32. Although this condition is known to exist in numerous populations and ethnic groups, the reported cases among Caucasians are relatively rare. It presents as asymptomatic papules or nodules on the oral mucosa, gingiva, tongue, and lips. Histopathologically, it is characterized by parakeratosis, epithelial hyperplasia, focal acanthosis, fusion, and horizontal outgrowth of epithelial ridges and the cells named mitozoids. The purpose of this case report was to present 3 cases of focal epithelial hyperplasia in a pediatric age group. Histopathological and clinical features of cases are discussed and DNA sequencing analysis is reported in which HPV 13, HPV 32, and HPV 11 genomes are detected.

Is there any relationship between right and left hand dominance and right and left nasal airflow dominance?

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Price, A; Eccles, R

2017-10-01

Left- or right-handedness is a common human trait, and it has been previously reported that human nasal airflow dominance correlates with hand dominance. Any relationship between hand dominance and nasal airflow dominance would be unusual. This study aimed to measure nasal airflow and look for any relationship to handedness. The modified Glatzel mirror was used to record the dominant nasal passage at 15-minute intervals over a 6-hour period in 29 healthy participants consisting of 15 left-handers and 14 right-handers. In left-handers, the percentage of time that the left nasal passage was dominant ranged from 0 to 100 per cent. In right-handers, the percentage of time that the right nasal passage was dominant ranged from 4.2 to 95.8 per cent. No correlation between nasal airflow dominance and hand dominance was identified. The results do not support the hypothesis that nasal airflow and handedness are related.

Streptococcus pneumoniae Colonization Is Required To Alter the Nasal Microbiota in Cigarette Smoke-Exposed Mice.

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Shen, Pamela; Whelan, Fiona J; Schenck, L Patrick; McGrath, Joshua J C; Vanderstocken, Gilles; Bowdish, Dawn M E; Surette, Michael G; Stämpfli, Martin R

2017-10-01

Smokers have nasal microbiota dysbiosis, with an increased frequency of colonizing bacterial pathogens. It is possible that cigarette smoke increases pathogen acquisition by perturbing the microbiota and decreasing colonization resistance. However, it is difficult to disentangle microbiota dysbiosis due to cigarette smoke exposure from microbiota changes caused by increased pathogen acquisition in human smokers. Using an experimental mouse model, we investigated the impact of cigarette smoke on the nasal microbiota in the absence and presence of nasal pneumococcal colonization. We observed that cigarette smoke exposure alone did not alter the nasal microbiota composition. The microbiota composition was also unchanged at 12 h following low-dose nasal pneumococcal inoculation, suggesting that the ability of the microbiota to resist initial nasal pneumococcal acquisition was not impaired in smoke-exposed mice. However, nasal microbiota dysbiosis occurred as a consequence of established high-dose nasal pneumococcal colonization at day 3 in smoke-exposed mice. Similar to clinical reports on human smokers, an enrichment of potentially pathogenic bacterial genera such as Fusobacterium , Gemella , and Neisseria was observed. Our findings suggest that cigarette smoke exposure predisposes to pneumococcal colonization independent of changes to the nasal microbiota and that microbiota dysbiosis observed in smokers may occur as a consequence of established pathogen colonization. Copyright © 2017 American Society for Microbiology.

Comparative Morphology and Histology of the Nasal Fossa in Four Mammals: Gray Squirrel, Bobcat, Coyote, and White-Tailed Deer.

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Yee, Karen K; Craven, Brent A; Wysocki, Charles J; Van Valkenburgh, Blaire

2016-07-01

Although the anatomy of the nasal fossa is broadly similar among terrestrial mammals, differences are evident in the intricacies of nasal turbinal architecture, which varies from simple scroll-like to complex branching forms, and in the extent of nonsensory and olfactory epithelium covering the turbinals. In this study, detailed morphological and immunohistochemical examinations and quantitative measurements of the turbinals and epithelial lining of the nasal fossa were conducted in an array of species that include the gray squirrel, bobcat, coyote, and white-tailed deer. Results show that much more of the nose is lined with olfactory epithelium in the smallest species (gray squirrel) than in the larger species. In two species with similar body masses, bobcat and coyote, the foreshortened felid snout influences turbinal size and results in a decrease of olfactory epithelium on the ethmoturbinals relative to the longer canine snout. Ethmoturbinal surface area exceeds that of the maxilloturbinals in all four sampled animals, except the white-tailed deer, in which the two are similar in size. Combining our results with published data from a broader array of mammalian noses, it is apparent that olfactory epithelial surface area is influenced by body mass, but is also affected by aspects of life history, such as diet and habitat, as well as skull morphology, itself a product of multiple compromises between various functions, such as feeding, vision, and cognition. The results of this study warrant further examination of other mammalian noses to broaden our evolutionary understanding of nasal fossa anatomy. Anat Rec, 299:840-852, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Nasal Carriage of 200 Patients with Nasal Bone Fracture in Korea

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Jun Wook Lee

2013-09-01

Full Text Available BackgroundPathogens in the nasal cavity during nasal surgery could lead to a systemic infectious condition, such as bacteremia, nosocomial infection, or toxic shock syndrome. However, there is no research about the prevalence of nasal carriage in patients with nasal bone fracture.MethodsThis was a prospective, double-blind, randomized study about the rate of nasal carriage in 200 patients with nasal bone fracture in Korea. Nasal secretions were taken from both the middle nasal meatus and colonized. All analyses were carried out using SPSS software.ResultsPathogens were identified in 178 of the 200 cases. Coagulase-negative staphylococci (CNS were the most cultured bacteria in 127 (66.84% of the 190 total patients after excluding 10 cases of contaminated samples, and methicillin-resistant coagulase-negative staphylococci (MRCNS were found in 48 (25.26%. Staphylococcus aureus was the second most identified pathogen, found in 36 (18.95%, followed by 7 cases (3.68% of methicillin-resistant Staphylococcus aureus (MRSA. The prevalence rate of MRSA in the females was higher than that in the males (RR=4.70; 95% CI, 1.09-20.18, but other demographic factors had no effect on the prevalence rate of MRSA and MRCNS.ConclusionsThe prevalence rate of these pathogens in patients with nasal bone fracture in Korea was similar to other reports. However, few studies have addressed the prevalence rate of CNS and MRCNS in accordance with risk factors or the change in prevalence according to specific prophylaxis against infectious complications. Additional research is needed on the potential connections between clinical factors and microbiological data.

Development and Characterization of a Human and Mouse Intestinal Epithelial Cell Monolayer Platform

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Kenji Kozuka

2017-12-01

Full Text Available Summary: We describe the development and characterization of a mouse and human epithelial cell monolayer platform of the small and large intestines, with a broad range of potential applications including the discovery and development of minimally systemic drug candidates. Culture conditions for each intestinal segment were optimized by correlating monolayer global gene expression with the corresponding tissue segment. The monolayers polarized, formed tight junctions, and contained a diversity of intestinal epithelial cell lineages. Ion transport phenotypes of monolayers from the proximal and distal colon and small intestine matched the known and unique physiology of these intestinal segments. The cultures secreted serotonin, GLP-1, and FGF19 and upregulated the epithelial sodium channel in response to known biologically active agents, suggesting intact secretory and absorptive functions. A screen of over 2,000 pharmacologically active compounds for inhibition of potassium ion transport in the mouse distal colon cultures led to the identification of a tool compound. : Siegel and colleagues describe their development of a human and mouse intestinal epithelial cell monolayer platform that maintains the cellular, molecular, and functional characteristics of tissue for each intestinal segment. They demonstrate the platform's application to drug discovery by screening a library of over 2,000 compounds to identify an inhibitor of potassium ion transport in the mouse distal colon. Keywords: intestinal epithelium, organoids, monolayer, colon, small intestine, phenotype screening assays, enteroid, colonoid

Cigarette smoke modulates expression of human rhinovirus-induced airway epithelial host defense genes.

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David Proud

Full Text Available Human rhinovirus (HRV infections trigger acute exacerbations of chronic obstructive pulmonary disease (COPD and asthma. The human airway epithelial cell is the primary site of HRV infection and responds to infection with altered expression of multiple genes, the products of which could regulate the outcome to infection. Cigarette smoking aggravates asthma symptoms, and is also the predominant risk factor for the development and progression of COPD. We, therefore, examined whether cigarette smoke extract (CSE modulates viral responses by altering HRV-induced epithelial gene expression. Primary cultures of human bronchial epithelial cells were exposed to medium alone, CSE alone, purified HRV-16 alone or to HRV-16+ CSE. After 24 h, supernatants were collected and total cellular RNA was isolated. Gene array analysis was performed to examine mRNA expression. Additional experiments, using real-time RT-PCR, ELISA and/or western blotting, validated altered expression of selected gene products. CSE and HRV-16 each induced groups of genes that were largely independent of each other. When compared to gene expression in response to CSE alone, cells treated with HRV+CSE showed no obvious differences in CSE-induced gene expression. By contrast, compared to gene induction in response to HRV-16 alone, cells exposed to HRV+CSE showed marked suppression of expression of a number of HRV-induced genes associated with various functions, including antiviral defenses, inflammation, viral signaling and airway remodeling. These changes were not associated with altered expression of type I or type III interferons. Thus, CSE alters epithelial responses to HRV infection in a manner that may negatively impact antiviral and host defense outcomes.

Nasal Glioma: Case report

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Ozgur Surmelioglu

2011-02-01

Full Text Available Nasal gliomas are rare, benign, congenital tumors that are thought to be result of abnormality in embryonic development. Three types of clinical presentations have been recognized; extranasal, intranasal and combined. Clinically, these masses are non-pulsatile, gray or purple lesions that obstruct the nasal cavity and cause deformity extranasaly. Histologically, they are made up of astrocytic cells, fibrous and vascular connective tissue that is covered with nasal respiratory mucosa. Treatment of the nasal glioma requires a multidisciplinary approach including an radiologist, neurosurgeon and otorhinolaryngologist. Radiological investigation should be performed to describe intracranial extension. In this case, a 2 years old boy with nasal mass that was diagnosed as nasal glioma is reported. . [Cukurova Med J 2011; 36(1.000: 34-36

Nasal Glioma: Case report

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Ozgur Surmelioglu

2011-03-01

Full Text Available Nasal gliomas are rare, benign, congenital tumors that are thought to be result of abnormality in embryonic development. Three types of clinical presentations have been recognized; extranasal, intranasal and combined. Clinically, these masses are non-pulsatile, gray or purple lesions that obstruct the nasal cavity and cause deformity extranasaly. Histologically, they are made up of astrocytic cells, fibrous and vascular connective tissue that is covered with nasal respiratory mucosa. Treatment of the nasal glioma requires a multidisciplinary approach including an radiologist, neurosurgeon and otorhinolaryngologist. Radiological investigation should be performed to describe intracranial extension. In this case, a 2 years old boy with nasal mass that was diagnosed as nasal glioma is reported. . [Cukurova Med J 2011; 36(1: 34-36

Epigenetic influences of low-dose bisphenol A in primary human breast epithelial cells

International Nuclear Information System (INIS)

Weng, Yu-I; Hsu, Pei-Yin; Liyanarachchi, Sandya; Liu, Joseph; Deatherage, Daniel E.; Huang Yiwen; Zuo Tao; Rodriguez, Benjamin; Lin, Ching-Hung; Cheng, Ann-Lii; Huang, Tim H.-M.

2010-01-01

Substantial evidence indicates that exposure to bisphenol A (BPA) during early development may increase breast cancer risk later in life. The changes may persist into puberty and adulthood, suggesting an epigenetic process being imposed in differentiated breast epithelial cells. The molecular mechanisms by which early memory of BPA exposure is imprinted in breast progenitor cells and then passed onto their epithelial progeny are not well understood. The aim of this study was to examine epigenetic changes in breast epithelial cells treated with low-dose BPA. We also investigated the effect of BPA on the ERα signaling pathway and global gene expression profiles. Compared to control cells, nuclear internalization of ERα was observed in epithelial cells preexposed to BPA. We identified 170 genes with similar expression changes in response to BPA. Functional analysis confirms that gene suppression was mediated in part through an ERα-dependent pathway. As a result of exposure to BPA or other estrogen-like chemicals, the expression of lysosomal-associated membrane protein 3 (LAMP3) became epigenetically silenced in breast epithelial cells. Furthermore, increased DNA methylation in the LAMP3 CpG island was this repressive mark preferentially occurred in ERα-positive breast tumors. These results suggest that the in vitro system developed in our laboratory is a valuable tool for exposure studies of BPA and other xenoestrogens in human cells. Individual and geographical differences may contribute to altered patterns of gene expression and DNA methylation in susceptible loci. Combination of our exposure model with epigenetic analysis and other biochemical assays can give insight into the heritable effect of low-dose BPA in human cells.

Type 2 innate lymphoid cells disrupt bronchial epithelial barrier integrity by targeting tight junctions through IL-13 in asthmatic patients.

Science.gov (United States)

Sugita, Kazunari; Steer, Catherine A; Martinez-Gonzalez, Itziar; Altunbulakli, Can; Morita, Hideaki; Castro-Giner, Francesc; Kubo, Terufumi; Wawrzyniak, Paulina; Rückert, Beate; Sudo, Katsuko; Nakae, Susumu; Matsumoto, Kenji; O'Mahony, Liam; Akdis, Mübeccel; Takei, Fumio; Akdis, Cezmi A

2018-01-01

Bronchial epithelial barrier leakiness and type 2 innate lymphoid cells (ILC2s) have been separately linked to asthma pathogenesis; however, the influence of ILC2s on the bronchial epithelial barrier has not been investigated previously. We investigated the role of ILC2s in the regulation of bronchial epithelial tight junctions (TJs) and barrier function both in bronchial epithelial cells of asthmatic patients and healthy subjects and general innate lymphoid cell- and ILC2-deficient mice. Cocultures of human ILC2s and bronchial epithelial cells were used to determine transepithelial electrical resistance, paracellular flux, and TJ mRNA and protein expressions. The effect of ILC2s on TJs was examined by using a murine model of IL-33-induced airway inflammation in wild-type, recombination-activating gene 2 (Rag2) -/- , Rag2 -/- Il2rg -/- , and Rora sg/sg mice undergoing bone marrow transplantation to analyze the in vivo relevance of barrier disruption by ILC2s. ILC2s significantly impaired the epithelial barrier, as demonstrated by reduced transepithelial electrical resistance and increased fluorescein isothiocyanate-dextran permeability in air-liquid interface cultures of human bronchial epithelial cells. This was in parallel to decreased mRNAs and disrupted protein expression of TJ proteins and was restored by neutralization of IL-13. Intranasal administration of recombinant IL-33 to wild-type and Rag2 -/- mice lacking T and B cells triggered TJ disruption, whereas Rag2 -/- Il2rg -/- and Rora sg/sg mice undergoing bone marrow transplantation that lack ILC2s did not show any barrier leakiness. Direct nasal administration of IL-13 was sufficient to induce deficiency in the TJ barrier in the bronchial epithelium of mice in vivo. These data highlight an essential mechanism in asthma pathogenesis by demonstrating that ILC2s are responsible for bronchial epithelial TJ barrier leakiness through IL-13. Copyright © 2017 American Academy of Allergy, Asthma & Immunology

Generation of corneal epithelial cells from induced pluripotent stem cells derived from human dermal fibroblast and corneal limbal epithelium.

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Ryuhei Hayashi

Full Text Available Induced pluripotent stem (iPS cells can be established from somatic cells. However, there is currently no established strategy to generate corneal epithelial cells from iPS cells. In this study, we investigated whether corneal epithelial cells could be differentiated from iPS cells. We tested 2 distinct sources: human adult dermal fibroblast (HDF-derived iPS cells (253G1 and human adult corneal limbal epithelial cells (HLEC-derived iPS cells (L1B41. We first established iPS cells from HLEC by introducing the Yamanaka 4 factors. Corneal epithelial cells were successfully induced from the iPS cells by the stromal cell-derived inducing activity (SDIA differentiation method, as Pax6(+/K12(+ corneal epithelial colonies were observed after prolonged differentiation culture (12 weeks or later in both the L1B41 and 253G1 iPS cells following retinal pigment epithelial and lens cell induction. Interestingly, the corneal epithelial differentiation efficiency was higher in L1B41 than in 253G1. DNA methylation analysis revealed that a small proportion of differentially methylated regions still existed between L1B41 and 253G1 iPS cells even though no significant difference in methylation status was detected in the specific corneal epithelium-related genes such as K12, K3, and Pax6. The present study is the first to demonstrate a strategy for corneal epithelial cell differentiation from human iPS cells, and further suggests that the epigenomic status is associated with the propensity of iPS cells to differentiate into corneal epithelial cells.

Silencing of Kv4.1 potassium channels inhibits cell proliferation of tumorigenic human mammary epithelial cells

International Nuclear Information System (INIS)

Jang, Soo Hwa; Choi, Changsun; Hong, Seong-Geun; Yarishkin, Oleg V.; Bae, Young Min; Kim, Jae Gon; O'Grady, Scott M.; Yoon, Kyong-Ah; Kang, Kyung-Sun; Ryu, Pan Dong; Lee, So Yeong

2009-01-01

Potassium channel activity has been shown to facilitate cell proliferation in cancer cells. In the present study, the role of Kv4.1 channels in immortal and tumorigenic human mammary epithelial cells was investigated. Kv4.1 protein expression was positively correlated with tumorigenicity. Moreover, transfection with siRNAs targeting Kv4.1 mRNA suppressed proliferation of tumorigenic mammary epithelial cells. Experiments using mRNA isolated from human breast cancer tissues revealed that the level of Kv4.1 mRNA expression varied depending on the stage of the tumor. Kv4.1 protein expression increased during stages T2 and T3 compared to normal tissue. These results demonstrated that Kv4.1 plays a role in proliferation of tumorigenic human mammary epithelial cells. In addition, elevated Kv4.1 expression may be useful as a diagnostic marker for staging mammary tumors and selective blockers of Kv4.1 may serve to suppress tumor cell proliferation.

Interleukin-17A induces bicarbonate secretion in normal human bronchial epithelial cells

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Kreindler, James L.; Bertrand, Carol A.; Lee, Robert J.; Karasic, Thomas; Aujla, Shean; Pilewski, Joseph M.; Frizzell, Raymond A.; Kolls, Jay K.

2009-01-01

The innate immune functions of human airways include mucociliary clearance and antimicrobial peptide activity. Both functions may be affected by changes in epithelial ion transport. Interleukin-17A (IL-17A), which has a receptor at the basolateral membrane of airway epithelia, is a T cell cytokine that has been shown to increase mucus secretion and antimicrobial peptide production by human bronchial epithelial (HBE) cells. Furthermore, IL-17A levels are increased in sputum from patients during pulmonary exacerbations of cystic fibrosis. Therefore, we investigated the effects of IL-17A on basal, amiloride-sensitive, and forskolin-stimulated ion transport in mature, well-differentiated HBE cells. Exposure of HBE monolayers to IL-17A for 48 h induced a novel forskolin-stimulated bicarbonate secretion in addition to forskolin-stimulated chloride secretion and resulted in alkalinization of liquid on the mucosal surface of polarized cells. IL-17A-induced bicarbonate secretion was cystic fibrosis transmembrane conductance regulator (CFTR)-dependent, mucosal chloride-dependent, partially Na+-dependent, and sensitive to serosal, but not mucosal, stilbene inhibition. These data suggest that IL-17A modulates epithelial bicarbonate secretion and implicate a mechanism by which airway surface liquid pH changes may be abnormal in cystic fibrosis. PMID:19074559

Involvement of vascular endothelial growth factor in nasal obstruction in patients with nasal allergy

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Tetsuji Yamashita

2000-01-01

Full Text Available It has recently been shown that vascular endothelial growth factor (VEGF enhances vascular permeability and that mast cells produce VEGF, suggesting the involvement of VEGF in allergic diseases. In the present study we quantitatively analyzed VEGF in the nasal lavage fluid of patients with nasal allergy. We performed nasal antigen challenge with Japanese cedar pollen antigen in 10 healthy adult volunteers and in 10 cedar pollen IgE-positive patients with nasal allergy. In all patients with nasal allergy, VEGF and histamine levels in the nasal lavage fluid reached a peak 30 min after antigen challenge, then returned to prechallenge values 2 h after antigen challenge. In these patients, the histamine level increased three-fold, while the VEGF level increased 10-fold. However, in all healthy adult volunteers, VEGF and histamine levels did not increase. A stronger correlation was noted between the ratio of decreased nasal cavity volume and the ratio of increased VEGF levels (R = 0.823; P < 0.001 than between the ratio of nasal cavity volume and the ratio of increased histamine levels (R = 0.660; P < 0.01. These results suggest that VEGF may contribute to the pathogenesis of nasal obstruction in the early phase of nasal allergy as a new factor involved in increasing vascular permeability.

Effect of titanium dioxide nanoparticles (TiO2 NPs) on the expression of mucin genes in human airway epithelial cells.

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Kim, Gui Ok; Choi, Yoon Seok; Bae, Chang Hoon; Song, Si-Youn; Kim, Yong-Dae

2017-01-01

Titanium dioxide nanoparticles (TiO 2 NPs) are utilized with growing frequency for a wide variety of industrial applications. Recently, acute and chronic exposures to TiO 2 NPs have been found to induce inflammatory response in the human respiratory tract. However, the effect and mechanism underlying the induction of major airway mucins by TiO 2 NPs have not been elucidated. This study was conducted to characterize the effect of TiO 2 NPs, and the mechanism involved, on the expressions of airway mucins in human airway epithelial cells. In NCI-H292 cells and primary cultures of normal nasal epithelial cells, the effects of TiO 2 NPs and signaling pathway for airway mucin genes were investigated by reverse transcriptase-polymerase chain reaction (RT-PCR), real-time PCR, enzyme immunoassays and immunoblot analysis using several specific inhibitors and small interfering RNAs (siRNAs). TiO 2 NPs increased MUC5B expression and activated the phosphorylations of extracellular signal-related kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK). U0126 (an ERK1/2 MAPK inhibitor) and SB203580 (a p38 MAPK inhibitor) inhibited TiO 2 NPs-induced MUC5B expression. And knockdown of ERK1, ERK2 and p38 MAPK using siRNAs significantly blocked TiO 2 NPs-induced MUC5B mRNA expression. Furthermore, Toll-like receptor 4 (TLR4) mRNA expression was increased by TiO 2 NPs, and knockdown by TLR4 siRNA significantly attenuated TiO 2 NPs-induced MUC5B mRNA expression and the TiO 2 NPs-induced phosphorylations of ERK1/2 and p38 MAPK. These results demonstrate for the first time that TiO 2 NPs induce MUC5B expression via TLR4-dependent ERK1/2 and p38 MAPK signaling pathways in respiratory epithelium.

Nasal Lobular Capillary Hemangioma

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Prashant Patil

2013-01-01

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

New bioreactor vessel for tissue engineering of human nasal septal chondrocytes

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Princz Sascha

2016-09-01

Full Text Available Cultivation of human nasal septal chondrocytes in a self-established automated bioreactor system with a new designed reactor glass vessel and the results of a computational fluid dynamics model are presented. The first results show the effect of a homogeneous fluidic condition of the continuous medium flow and the resulting stresses on the scaffolds’ surface and their influence on the migration of the cells into the scaffold matrix under these conditions. For this purpose computational models, generated with the computational fluid dynamics software STAR-CCM+, and the results of alcian blue staining for newly synthesized sulphated glycosaminoglycans have been compared during cultivation in the new and a first version of the glass reactor vessel with inhomogeneous fluidic conditions, with the same automated bioreactor system and under similar cultivation conditions.

Distribution of aquaporins in the nasal passage of Octodon degus, a South-American desert rodent and its implications for water conservation Distribución de acuaporinas en los pasajes nasales de Octodon degus, un roedor de ambientes desérticos sudamericanos: implicaciones en la conservación de agua

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PEDRO GALLARDO

2008-03-01

Full Text Available Rodents from arid and semiarid environments live under conditions where the spatial and temporal availability of water is limited. Octodon degus is a South-American desert-dwelling rodent inhabiting arid and semiarid habitats of central and northern Chile. Its survival depends on morphological, physiological and behavioral adaptations that allow water conservation. This rodent has a high urine concentrating ability, high capacity of fecal dehydration and low evaporative water loss, related to the ability of the nasal passages to condense water from the exhaled air; this water must be absorbed in order to avoid its accumulation in the nasal passages and potential loss through the nostrils. We hypothesize that aquaporins (AQPs might be present in the nasal mucosa; therefore, we studied the distribution of AQP-1, AQP-2, AQP-3 and AQP-4 through immunocytochemistry. Intense AQP-1 labeling was observed throughout the subepithelial vascular network; no AQP-1 immunoreactivity was detected in olfactory and non-olfactory epithelial cells. No signal was detected for AQP-2 and 4. AQP-3 distribution was restricted to the surface non-olfactory epithelial cells lining the turbinates in narrow passages and blind spaces. Therefore, AQP-1 and AQP-3 coincided at the level of the turbinates, although in different cell types which suggest a pathway for water removal from the nasal surface first through AQP-3 in non-olfactory epithelial cells and then into the capillary lumen through AQP-1Los roedores de ambientes áridos y semiáridos viven bajo una disponibilidad limitada de agua tanto espacial como temporal. Octodon degus es un roedor sudamericano que habita ambientes áridos y semiáridos del norte y zona central de Chile. Su supervivencia depende de adaptaciones morfológicas, fisiológicas y conductuales que permiten optimizar la conservación de agua. Este tiene una alta capacidad de concentración urinaria y de deshidratación de la fecas además de una baja

Computational Modelling of Gas-Particle Flows with Different Particle Morphology in the Human Nasal Cavity

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Kiao Inthavong

2009-01-01

Full Text Available This paper summarises current studies related to numerical gas-particle flows in the human nasal cavity. Of interest are the numerical modelling requirements to consider the effects of particle morphology for a variety of particle shapes and sizes such as very small particles sizes (nanoparticles, elongated shapes (asbestos fibres, rough shapes (pollen, and porous light density particles (drug particles are considered. It was shown that important physical phenomena needed to be addressed for different particle characteristics. This included the Brownian diffusion for submicron particles. Computational results for the nasal capture efficiency for nano-particles and various breathing rates in the laminar regime were found to correlate well with the ratio of particle diffusivity to the breathing rate. For micron particles, particle inertia is the most significant property and the need to use sufficient drag laws is important. Drag correlations for fibrous and rough surfaced particles were investigated to enable particle tracking. Based on the simulated results, semi-empirical correlations for particle deposition were fitted in terms of Peclet number and inertial parameter for nanoparticles and micron particles respectively.

Normal Anatomy, Histology, and Spontaneous Pathology of the Nasal Cavity of the Cynomolgus Monkey (Macaca fascicularis).

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Chamanza, Ronnie; Taylor, Ian; Gregori, Michela; Hill, Colin; Swan, Mark; Goodchild, Joel; Goodchild, Kane; Schofield, Jane; Aldous, Mark; Mowat, Vasanthi

2016-07-01

The evaluation of inhalation studies in monkeys is often hampered by the scarcity of published information on the relevant nasal anatomy and pathology. We examined nasal cavities of 114 control cynomolgus monkeys from 11 inhalation studies evaluated 2008 to 2013, in order to characterize and document the anatomic features and spontaneous pathology. Compared to other laboratory animals, the cynomolgus monkey has a relatively simple nose with 2 unbranched, dorsoventrally stacked turbinates, large maxillary sinuses, and a nasal septum that continues into the nasopharynx. The vomeronasal organ is absent, but nasopalatine ducts are present. Microscopically, the nasal epithelium is thicker than that in rodents, and the respiratory (RE) and transitional epithelium (TE) rest on a thick basal lamina. Generally, squamous epithelia and TE line the vestibule, RE, the main chamber and nasopharynx, olfactory epithelium, a small caudodorsal region, while TE is observed intermittently along the passages. Relatively high incidences of spontaneous pathology findings, some resembling induced lesions, were observed and included inflammation, luminal exudate, scabs, squamous and respiratory metaplasia or hyperplasia, mucous cell hyperplasia/metaplasia, and olfactory degeneration. Regions of epithelial transition were the most affected. This information is considered helpful in the histopathology evaluation and interpretation of inhalation studies in monkeys. © The Author(s) 2016.

Cosmetic reconstruction of a nasal plane and rostral nasal skin defect using a modified nasal rotation flap in a dog

NARCIS (Netherlands)

ter Haar, G.; Buiks, S.C.; Kirpensteijn, J.

2013-01-01

Abstract OBJECTIVE: To report reconstruction of a defect of the nasal plane and the rostral dorsum of the nose in a dog using a nasal rotation flap with Burow's triangles. STUDY DESIGN: Clinical report. ANIMALS: Mixed-breed dog (1.5 years, 8.6 kg). METHODS: A nasal defect caused by chronic

Surgical management of nasal obstruction.

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Moche, Jason A; Palmer, Orville

2012-05-01

The proper evaluation of the patient with nasal obstruction relies on a comprehensive history and physical examination. Once the site of obstruction is accurately identified, the patient may benefit from a trial of medical management. At times however, the definitive treatment of nasal obstruction relies on surgical management. Recognizing the nasal septum, nasal valve, and turbinates as possible sites of obstruction and addressing them accordingly can dramatically improve a patient's nasal breathing. Conservative resection of septal cartilage, submucous reduction of the inferior turbinate, and structural grafting of the nasal valve when appropriate will provide the optimal improvement in nasal airflow and allow for the most stable results. Copyright © 2012. Published by Elsevier Inc.

Deep RNA-Seq analysis reveals unexpected features of human prostate basal epithelial cells

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Dingxiao Zhang

2016-03-01

Full Text Available Prostate cancer is the second leading cause of cancer-related deaths among American men [1]. The prostate gland mainly contains basal and luminal cells, which are constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here, for the first time, we describe a whole-genome transcriptome analysis of human benign prostatic basal and luminal populations by using deep RNA sequencing (GSE67070 [2]. Combined with comprehensive molecular and biological characterizations, we show that the differential gene expression profiles account for their distinct functional phenotypes. Strikingly, in contrast to luminal cells, basal cells preferentially express gene categories associated with stem cells, neural and neuronal development, and RNA processing. Of clinical relevance, the treatment failed castration-resistant and anaplastic prostate cancers molecularly resemble a basal-like phenotype. We also identified genes associated with patient clinical outcome. Therefore, we provide a gene expression resource for understanding human prostate epithelial lineages, and link the cell-type specific gene signatures to subtypes of prostate cancer development. Keywords: Prostate epithelial cells, Basal cells, Luminal cells, RNA-seq

Establishment of three-dimensional cultures of human pancreatic duct epithelial cells

International Nuclear Information System (INIS)

Gutierrez-Barrera, Angelica M.; Menter, David G.; Abbruzzese, James L.; Reddy, Shrikanth A.G.

2007-01-01

Three-dimensional (3D) cultures of epithelial cells offer singular advantages for studies of morphogenesis or the role of cancer genes in oncogenesis. In this study, as part of establishing a 3D culture system of pancreatic duct epithelial cells, we compared human pancreatic duct epithelial cells (HPDE-E6E7) with pancreatic cancer cell lines. Our results show, that in contrast to cancer cells, HPDE-E6E7 organized into spheroids with what appeared to be apical and basal membranes and a luminal space. Immunostaining experiments indicated that protein kinase Akt was phosphorylated (Ser473) and CTMP, a negative Akt regulator, was expressed in both HPDE-E6E7 and cancer cells. However, a nuclear pool of CTMP was detectable in HPDE-E6E7 cells that showed a dynamic concentrated expression pattern, a feature that further distinguished HPDE-E637 cells from cancer cells. Collectively, these data suggest that 3D cultures of HPDE-E6E7 cells are useful for investigating signaling and morphological abnormalities in pancreatic cancer cells

Normal Human Gingival Epithelial Cells Sense C. parapsilosis by Toll-Like Receptors and Module Its Pathogenesis through Antimicrobial Peptides and Proinflammatory Cytokines

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Raouf Bahri

2010-01-01

Full Text Available This study was designed to investigate the interaction between C. parapsilosis and human epithelial cells using monolayer cultures and an engineered human oral mucosa (EHOM. C. parapsilosis was able to adhere to gingival epithelial cells and to adopt the hyphal form in the presence of serum. Interestingly, when cultured onto the engineered human oral mucosa (EHOM, C. parapsilosis formed small biofilm and invaded the connective tissue. Following contact with C. parapsilosis, normal human gingival epithelial cells expressed high levels of Toll-like receptors (TLR-2, -4, and -6, but not TLR-9 mRNA. The upregulation of TLRs was paralleled by an increase of IL-1β, TNFα, and IFNγ mRNA expression, suggesting the involvement of these cytokines in the defense against infection with C. parapsilosis. The active role of epithelial cells in the innate immunity against C. parapsilosis infection was enhanced by their capacity to express high levels of human beta-defensin-1, -2, and -3. The upregulation of proinflammatory cytokines and antimicrobial peptide expression may explain the growth inhibition of C. parapsilosis by the gingival epithelial cells. Overall results provide additional evidence of the involvement of epithelial cells in the innate immunity against C. parapsilosis infections.

Automated method for structural segmentation of nasal airways based on cone beam computed tomography

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Tymkovych, Maksym Yu.; Avrunin, Oleg G.; Paliy, Victor G.; Filzow, Maksim; Gryshkov, Oleksandr; Glasmacher, Birgit; Omiotek, Zbigniew; DzierŻak, RóŻa; Smailova, Saule; Kozbekova, Ainur

2017-08-01

The work is dedicated to the segmentation problem of human nasal airways using Cone Beam Computed Tomography. During research, we propose a specialized approach of structured segmentation of nasal airways. That approach use spatial information, symmetrisation of the structures. The proposed stages can be used for construction a virtual three dimensional model of nasal airways and for production full-scale personalized atlases. During research we build the virtual model of nasal airways, which can be used for construction specialized medical atlases and aerodynamics researches.

Culture models of human mammary epithelial cell transformation

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Stampfer, Martha R.; Yaswen, Paul

2000-11-10

Human pre-malignant breast diseases, particularly ductal carcinoma in situ (DCIS)3 already display several of the aberrant phenotypes found in primary breast cancers, including chromosomal abnormalities, telomerase activity, inactivation of the p53 gene and overexpression of some oncogenes. Efforts to model early breast carcinogenesis in human cell cultures have largely involved studies in vitro transformation of normal finite lifespan human mammary epithelial cells (HMEC) to immortality and malignancy. We present a model of HMEC immortal transformation consistent with the know in vivo data. This model includes a recently described, presumably epigenetic process, termed conversion, which occurs in cells that have overcome stringent replicative senescence and are thus able to maintain proliferation with critically short telomeres. The conversion process involves reactivation of telomerase activity, and acquisition of good uniform growth in the absence and presence of TFGB. We propose th at overcoming the proliferative constraints set by senescence, and undergoing conversion, represent key rate-limiting steps in human breast carcinogenesis, and occur during early stage breast cancer progression.

Nasal myiasis: report of a case and literature review

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Reyes-Romero, Karen Eliana

2016-07-01

Full Text Available Myiasis is the infection of animal or human tissues or organs by larvae of Diptera. It may affect individuals of any age, but is more common in middle-aged and elderly patients. Nasal myiasis, an infection of the nasal and paranasal cavities by such larvae, is a common disease in tropical and developing countries. Reported cases of nasal myiasis have been caused by several different species, such as Lucilia sericata in Korea and Iran, Estro ovis in Algeria and France, Lucilia cuprina and Phaenicia sericata in Malaysia, Cochliomyia hominivorax in French Guiana, Drosophila melanogaster in Turkey, Eristalis tenax in Iran and Oestrus ovis in Israel. Signs and symptoms are related to the presence and movement of the larvae, and include foreign body sensation, bloody or muco-purulent nasal discharge. Prevention may be done with insect repellent. Treatment is based on antiparasitic drugs and techniques for removal of larvae, but may include the use of prophylactic topical or systemic antibiotics for possible secondary infections. We report a case of nasal and left maxillary sinus myiasis in an elderly woman, who responded favorably to treatment.

Acoustic rhinometry (AR): An Alternative Method to Image Nasal Airway Geometry

DEFF Research Database (Denmark)

Straszek, Sune; Pedersen, O.F.

  ACOUSTIC RHINOMETRY (AR): AN ALTERNATIVE METHOD TO IMAGE NASAL AIRWAY GEOMETRY.  INTRODUCTION AND BACKGROUND:  In human studies the acoustic reflection technique was first applied to describe the area-distance relationship of the lower airways, but later the acoustic reflection technique appeared...... to be of more use in the description of nasal cavity geometry. Applied to human subjects AR has been applied to monitor the effect of corrective surgery and mucosal effects of pharmacological interventions. In recent years, however, AR has found use also in pharmacological studies in animals ranging in size...

Immunohistochemical localisation of keratin and luminal epithelial antigen in myoepithelial and luminal epithelial cells of human mammary and salivary gland tumours.

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Nathrath, W B; Wilson, P D; Trejdosiewicz, L K

1982-01-01

Rabbit antisera to human 40-63 000 MW epidermal keratin, one batch with restricted distribution of reactivity from an initial (aK1) and one with "broad spectrum" distribution of reactivity from a late bleeding (aK), and to "luminal epithelial antigen" (aLEA) were applied to formalin fixed paraffin embedded sections of human normal and neoplastic mammary and salivary glands using an indirect immunoperoxidase method. aK1 reacted with myoepithelial cells, aLEA with luminal epithelial cells and aK with both cell types in normal mammary and salivary gland. In breast carcinomas the majority of intraluminal and infiltrating carcinoma cells reacted with aLEA but not with aK1 which reacted only with surrounding myoepithelial cells. aK reacted with both myoepithelial cells and with intraluminal and infiltrating tumour cells. In the salivary gland adenomas the majority of cells reacted with aK, and those cells arranged in a tubular fashion reacted with aLEA.

Nasalance norms in Greek adults.

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Okalidou, Areti; Karathanasi, Asimina; Grigoraki, Eleni

2011-08-01

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 sentences and four sets of oral sentences and (3) repetitions of each of 12 syllable types (8 oral and 4 nasal). The last two sets of material corpus were based on an adaptation of the Simplified Nasometric Assessment Procedures Test (SNAP test) test ( MacKay and Kummer, 1994 ) in Greek, called the G-SNAP test. Eighty monolingual healthy young adult speakers of Greek, 40 males (mean age = 21 years) and 40 females (mean age = 20.5 years), with normal hearing and speech characteristics and unremarkable history were included in the study. The Nasometer (model 6200-3) was used to derive nasalance scores. Mean normative nasalance for spoken Greek was 25.50%, based on the G-oronasal text (with 8.6% nasals). Nasalance scores did not differ significantly with respect to gender. Finally, spoken Greek consistently yielded lower nasalance scores than other languages examined in past work. The aforementioned normative data on nasalance of young adult speakers of Greek are valid across gender and have direct clinical utility as they provide valuable reference information for the diagnosis and management of Greek adults with resonance disorders caused by velar dysfunction.

Hypothiocyanite produced by human and rat respiratory epithelial cells inactivates extracellular H1N2 influenza A virus.

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Gingerich, Aaron; Pang, Lan; Hanson, Jarod; Dlugolenski, Daniel; Streich, Rebecca; Lafontaine, Eric R; Nagy, Tamás; Tripp, Ralph A; Rada, Balázs

2016-01-01

Our aim was to study whether an extracellular, oxidative antimicrobial mechanism inherent to tracheal epithelial cells is capable of inactivating influenza H1N2 virus. Epithelial cells were isolated from tracheas of male Sprague-Dawley rats. Both primary human and rat tracheobronchial epithelial cells were differentiated in air-liquid interface cultures. A/swine/Illinois/02860/09 (swH1N2) influenza A virions were added to the apical side of airway cells for 1 h in the presence or absence of lactoperoxidase or thiocyanate. Characterization of rat epithelial cells (morphology, Duox expression) occurred via western blotting, PCR, hydrogen peroxide production measurement and histology. The number of viable virions was determined by plaque assays. Statistical difference of the results was analyzed by ANOVA and Tukey's test. Our data show that rat tracheobronchial epithelial cells develop a differentiated, polarized monolayer with high transepithelial electrical resistance, mucin production and expression of dual oxidases. Influenza A virions are inactivated by human and rat epithelial cells via a dual oxidase-, lactoperoxidase- and thiocyanate-dependent mechanism. Differentiated air-liquid interface cultures of rat tracheal epithelial cells provide a novel model to study airway epithelium-influenza interactions. The dual oxidase/lactoperoxidase/thiocyanate extracellular oxidative system producing hypothiocyanite is a fast and potent anti-influenza mechanism inactivating H1N2 viruses prior to infection of the epithelium.

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

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Kai Zhao

Full Text Available 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.

Small-Molecule Induction Promotes Corneal Epithelial Cell Differentiation from Human Induced Pluripotent Stem Cells

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Alexandra Mikhailova

2014-02-01

Full Text Available Human induced pluripotent stem cells (hiPSCs offer unique opportunities for developing novel cell-based therapies and disease modeling. In this study, we developed a directed differentiation method for hiPSCs toward corneal epithelial progenitor cells capable of terminal differentiation toward mature corneal epithelial-like cells. In order to improve the efficiency and reproducibility of our method, we replicated signaling cues active during ocular surface ectoderm development with the help of two small-molecule inhibitors in combination with basic fibroblast growth factor (bFGF in serum-free and feeder-free conditions. First, small-molecule induction downregulated the expression of pluripotency markers while upregulating several transcription factors essential for normal eye development. Second, protein expression of the corneal epithelial progenitor marker p63 was greatly enhanced, with up to 95% of cells being p63 positive after 5 weeks of differentiation. Third, corneal epithelial-like cells were obtained upon further maturation.

Stanniocalcin-1 regulates re-epithelialization in human keratinocytes.

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Bonnie H Y Yeung

Full Text Available Stanniocalcin-1 (STC1, a glycoprotein hormone, is believed to be involved in various biological processes such as inflammation, oxidative responses and cell migration. Riding on these emerging evidences, we hypothesized that STC1 may participate in the re-epithelialization during wound healing. Re-epithelialization is a critical step that involves keratinocyte lamellipodia (e-lam formation, followed by cell migration. In this study, staurosporine (STS treatment induced human keratinocyte (HaCaT e-lam formation on fibronectin matrix and migration via the activation of focal adhesion kinase (FAK, the surge of intracellular calcium level [Ca²⁺]i and the inactivation of Akt. In accompanied with these migratory features, a time- and dose-dependent increase in STC1 expression was detected. STC1 gene expression was found not the downstream target of FAK-signaling as illustrated by FAK inhibition using PF573228. The reduction of [Ca²⁺]i by BAPTA/AM blocked the STS-mediated keratinocyte migration and STC1 gene expression. Alternatively the increase of [Ca²⁺]i by ionomycin exerted promotional effect on STS-induced STC1 gene expression. The inhibition of Akt by SH6 and GSK3β by lithium chloride (LiCl could respectively induce and inhibit the STS-mediated e-lam formation, cell migration and STC1 gene expression. The STS-mediated e-lam formation and cell migration were notably hindered or induced respectively by STC1 knockdown or overexpression. This notion was further supported by the scratched wound assay. Collectively the findings provide the first evidence that STC1 promotes re-epithelialization in wound healing.

Stanniocalcin-1 regulates re-epithelialization in human keratinocytes.

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Yeung, Bonnie H Y; Wong, Chris K C

2011-01-01

Stanniocalcin-1 (STC1), a glycoprotein hormone, is believed to be involved in various biological processes such as inflammation, oxidative responses and cell migration. Riding on these emerging evidences, we hypothesized that STC1 may participate in the re-epithelialization during wound healing. Re-epithelialization is a critical step that involves keratinocyte lamellipodia (e-lam) formation, followed by cell migration. In this study, staurosporine (STS) treatment induced human keratinocyte (HaCaT) e-lam formation on fibronectin matrix and migration via the activation of focal adhesion kinase (FAK), the surge of intracellular calcium level [Ca²⁺]i and the inactivation of Akt. In accompanied with these migratory features, a time- and dose-dependent increase in STC1 expression was detected. STC1 gene expression was found not the downstream target of FAK-signaling as illustrated by FAK inhibition using PF573228. The reduction of [Ca²⁺]i by BAPTA/AM blocked the STS-mediated keratinocyte migration and STC1 gene expression. Alternatively the increase of [Ca²⁺]i by ionomycin exerted promotional effect on STS-induced STC1 gene expression. The inhibition of Akt by SH6 and GSK3β by lithium chloride (LiCl) could respectively induce and inhibit the STS-mediated e-lam formation, cell migration and STC1 gene expression. The STS-mediated e-lam formation and cell migration were notably hindered or induced respectively by STC1 knockdown or overexpression. This notion was further supported by the scratched wound assay. Collectively the findings provide the first evidence that STC1 promotes re-epithelialization in wound healing.

Nasal obstruction and sleep-disordered breathing: the effect of supine body position on nasal measurements in snorers.

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Virkkula, Paula; Maasilta, Paula; Hytönen, Maija; Salmi, Tapani; Malmberg, Henrik

2003-06-01

Nasal obstruction is considered to be a potential etiological factor in sleep-disordered breathing. However, a significant correlation between nasal measurements and obstructive sleep apnea has not been demonstrated so far. The aim of this study was to investigate the relationships between nasal resistance, nasal volumes and selected sleep parameters using nasal measurements performed in both seated and supine positions. We also investigated whether snoring patients in our clinical sample showed increased positional or decongestive nasal mucosal changes. Forty-one snoring men on a waiting list for correction of nasal obstruction underwent polysomnography, anterior rhinomanometry and acoustic rhinometry. Nineteen non-snoring control subjects were also recruited. Nasal measurements were performed in a seated position, after lying down in a supine position and, after decongestion of nasal mucosa, in a seated position again. In the overall patient group, nasal volume at a distance 2-4 cm from the nares in the supine position correlated inversely with apnea-hypopnea index (AHI) (r = -0.32, p patients, total nasal resistance measured in a supine position correlated with AHI (r = 0.50, p position and sleep parameters. Postural or decongestive changes in nasal measurements were not increased in snoring patients compared with control subjects. The relationship found between nasal measurements and sleep parameters suggests that nasal obstruction does augment airway collapse.

Nasal Carriage of 200 Patients with Nasal Bone Fracture in Korea

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Jun Wook Lee

2013-09-01

Full Text Available Background Pathogens in the nasal cavity during nasal surgery could lead to a systemicinfectious condition, such as bacteremia, nosocomial infection, or toxic shock syndrome.However, there is no research about the prevalence of nasal carriage in patients with nasalbone fracture.Methods This was a prospective, double-blind, randomized study about the rate of nasalcarriage in 200 patients with nasal bone fracture in Korea. Nasal secretions were taken fromboth the middle nasal meatus and colonized. All analyses were carried out using SPSS software.Results Pathogens were identified in 178 of the 200 cases. Coagulase-negative staphylococci(CNS were the most cultured bacteria in 127 (66.84% of the 190 total patients after excluding10 cases of contaminated samples, and methicillin-resistant coagulase-negative staphylococci(MRCNS were found in 48 (25.26%. Staphylococcus aureus was the second mostidentified pathogen, found in 36 (18.95%, followed by 7 cases (3.68% of methicillin-resistantStaphylococcus aureus (MRSA. The prevalence rate of MRSA in the females was higher thanthat in the males (RR=4.70; 95% CI, 1.09-20.18, but other demographic factors had no effecton the prevalence rate of MRSA and MRCNS.Conclusions The prevalence rate of these pathogens in patients with nasal bone fracture inKorea was similar to other reports. However, few studies have addressed the prevalence rateof CNS and MRCNS in accordance with risk factors or the change in prevalence according tospecific prophylaxis against infectious complications. Additional research is needed on thepotential connections between clinical factors and microbiological data.

Comparison of Early-period Results of Nasal Splint and Merocel Nasal Packs in Septoplasty

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Bingöl, Fatih; Budak, Ali; Şimşek, Eda; Kılıç, Korhan; Bingöl, Buket Özel

2017-01-01

Objective Several types of nasal packs are used postoperatively in septoplasty. In this study, we compared two commonly used nasal packing materials, the intranasal septal splint with airway and Merocel tampon, in terms of pain, bleeding, nasal obstruction, eating difficulties, discomfort in sleep, and pain and bleeding during removal of packing in the early period. Methods The study group included 60 patients undergoing septoplasty. Patients were divided into two groups (n=30 in each group). An intranasal splint with airway was used for the patients in the first group after septoplasty, while Merocel nasal packing was used for the second group. Patients were investigated in terms of seven different factors - pain, bleeding while the tampon was in place, nasal obstruction, eating difficulties, night sleep, pain during removal of the nasal packing, and bleeding after removal of packing. Results There was no statistically significant difference between the groups in terms of pain 24 hours after operation (p=0.05), while visual analog scale (VAS) scores for nasal obstruction, night sleep, eating difficulties, and pain during packing removal were lower in the nasal splint group with a statistically significant difference (p<0.05). There was no statistically significant difference between the groups in terms of postoperative bleeding (p=0.23). Significantly less bleeding occurred during removal of the packing in the nasal splint group (p<0.05). Conclusion Our study indicates that the nasal splint was more comfortable and effective in terms of causing lesser bleeding and pain during removal of packing. PMID:29392071

Detonation Nanodiamond Toxicity in Human Airway Epithelial Cells Is Modulated by Air Oxidation

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Detonational nanodiamonds (DND), a nanomaterial with an increasing range of industrial and biomedical applications, have previously been shown to induce a pro-inflammatory response in cultured human airway epithelial cells (HAEC). We now show that surface modifications induced by...

Nasal septal hematoma

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... medlineplus.gov/ency/article/001292.htm Nasal septal hematoma To use the sharing features on this page, please enable JavaScript. A nasal septal hematoma is a collection of blood within the septum ...

Assessment of nasal spray deposition pattern in a silicone human nose model using a color-based method.

Science.gov (United States)

Kundoor, Vipra; Dalby, Richard N

2010-01-01

To develop a simple and inexpensive method to visualize and quantify droplet deposition patterns. Deposition pattern was determined by uniformly coating the nose model with Sar-Gel (a paste that changes from white to purple on contact with water) and subsequently discharging sprays into the nose model. The color change was captured using a digital camera and analyzed using Adobe Photoshop. Several tests were conducted to validate the method. Deposition patterns of different nasal sprays (Ayr, Afrin, and Zicam) and different nasal drug delivery devices (Afrin nasal spray and PARI Sinustar nasal nebulizer) were compared. We also used the method to evaluate the effect of inhaled flow rate on nasal spray deposition. There was a significant difference in the deposition area for Ayr, Afrin, and Zicam. The deposition areas of Afrin nasal spray and PARI Sinustar nasal nebulizer (2 min and 5 min) were significantly different. Inhaled flow rate did not have a significant effect on the deposition pattern. Lower viscosity formulations (Ayr, Afrin) provided greater coverage than the higher viscosity formulation (Zicam). The nebulizer covered a greater surface area than the spray pump we evaluated. Aerosol deposition in the nose model was not affected by air flow conditions.

Human Primary Intestinal Epithelial Cells as an Improved In Vitro Model for Cryptosporidium parvum Infection

Science.gov (United States)

Cabada, Miguel M.; Nichols, Joan; Gomez, Guillermo; White, A. Clinton

2013-01-01

The study of human intestinal pathogens has been limited by the lack of methods for the long-term culture of primary human intestinal epithelial cells (PECs). The development of infection models with PECs would allow a better understanding of host-parasite interactions. The objective of this study was to develop a novel method for prolonged in vitro cultivation of PECs that can be used to study Cryptosporidium infection. We isolated intact crypts from human intestines removed during weight loss surgery. The fragments of intestinal layers were cultivated with culture medium supplemented with growth factors and antiapoptotic molecules. After 7 days, the PECs formed self-regenerating cell clusters, forming villi that resemble intestinal epithelium. The PECs proliferated and remained viable for at least 60 days. The cells expressed markers for intestinal stem cells, epithelial cells, and mature enterocytes. The PECs were infected with Cryptosporidium. In contrast to older models in which parasite numbers decay, the burden of parasites increased for >120 h. In summary, we describe here a novel method for the cultivation of self-regenerating human epithelial cells from small intestinal crypts, which contain both intestinal stem cells and mature villus cells. We present data that suggest these cells support Cryptosporidium better than existing cell lines. PECs should provide an improved tool for studying host-parasite interactions involving Cryptosporidium and other intestinal pathogens. PMID:23509153

Internal nasal floor configuration in Homo with special reference to the evolution of Neandertal facial form.

Science.gov (United States)

Franciscus, Robert G

2003-06-01

The presence of a steeply sloping or depressed nasal floor within the nasal cavity of Neandertals is frequently mentioned as a likely specialization or autapomorphy. The depressed nasal floor has also been seen as contributing to a relatively more capacious nasal cavity in Neandertals, which is tied to cold-climate respiratory adaptation and energetics. These observations have been limited largely to a relatively few intact crania, and the character states associated with this trait have not been as precisely codified or analyzed as those published for Plio-Pleistocene hominins (McCollum et al., 1993, J. Hum. Evol. 24, 87; McCollum, 2000, Am. J. Phys. Anthrop. 112, 275). This study examines the internal nasal floor topography in complete crania and isolated maxillae in European, west Asian, and African fossil Homo (n=158) including 25 Neandertals, and a wide range of recent humans from Europe, the Near East, and Africa (n=522). The configuration of the internal nasal floor relative to the nasal cavity entrance is codified as: 1) level, forming a smooth continuous plane; 2) sloped or mildly stepped; or 3) bilevel with a pronounced vertical depression. The frequency of these nasal floor configurations, and their relationship to both nasal margin cresting patterning and a comprehensive set of nasofacial metrics is examined. Neandertals show a high frequency of the bilevel (depressed) configuration in both adults and subadults (80%), but this configuration is also present in lower frequencies in Middle Pleistocene African, Late Pleistocene non-Neandertal (Skhul, Qafzeh), and European Later Upper Paleolithic samples (15%-50%). The bilevel configuration is also present in lower frequencies (ca. 10%) in all recent human samples, but attains nearly 20% in some sub-Saharan African samples. Across extinct and extant Homo (excluding Neandertals), internal nasal floor configuration is not associated with piriform aperture nasal margin patterning, but the two are strongly

Nasal capillariasis in a dog

International Nuclear Information System (INIS)

King, R.R.; Greiner, E.C.; Ackerman, N.; Woodard, J.C.

1990-01-01

A five-year-old dog was evaluated for chronic nasal discharge. Nasal infection caused by Capillaria aerophila was diagnosed by identification of adult nematodes and eggs in the nasal flush sediment and by nasal biopsy samples and eggs in faecal flotations. Reinfection occurred following treatment with fenbendazole and ivermectin, probably because of a contaminated housing area

Disrupted epithelial/macrophage crosstalk via Spinster homologue 2-mediated S1P signaling may drive defective macrophage phagocytic function in COPD.

Directory of Open Access Journals (Sweden)

Hai B Tran

Full Text Available We have previously established a link between impaired phagocytic capacity and deregulated S1P signaling in alveolar macrophages from COPD subjects. We hypothesize that this defect may include a disruption of epithelial-macrophage crosstalk via Spns2-mediated intercellular S1P signaling.Primary alveolar macrophages and bronchial epithelial cells from COPD subjects and controls, cell lines, and a mouse model of chronic cigarette smoke exposure were studied. Cells were exposed to 10% cigarette smoke extract, or vehicle control. Spns2 expression and subcellular localization was studied by immunofluorescence, confocal microscopy and RT-PCR. Phagocytosis was assessed by flow-cytometry. Levels of intra- and extracellular S1P were measured by S1P [3H]-labeling.Spns2 expression was significantly increased (p<0.05 in alveolar macrophages from current-smokers/COPD patients (n = 5 compared to healthy nonsmokers (n = 8 and non-smoker lung transplant patients (n = 4. Consistent with this finding, cigarette smoke induced a significant increase in Spns2 expression in both human alveolar and THP-1 macrophages. In contrast, a remarkable Spns2 down-regulation was noted in response to cigarette smoke in 16HBE14o- cell line (p<0.001 in 3 experiments, primary nasal epithelial cells (p<0.01 in 2 experiments, and in smoke-exposed mice (p<0.001, n = 6 animals per group. Spns2 was localized to cilia in primary bronchial epithelial cells. In both macrophage and epithelial cell types, Spns2 was also found localized to cytoplasm and the nucleus, in line with a predicted bipartile Nuclear Localization Signal at the position aa282 of the human Spns2 sequence. In smoke-exposed mice, alveolar macrophage phagocytic function positively correlated with Spns2 protein expression in bronchial epithelial cells.Our data suggest that the epithelium may be the major source for extracellular S1P in the airway and that there is a possible disruption of epithelial/macrophage cross talk via

Measurement with nasal scintigraphy of nasal mucociliary clearance in normal man

International Nuclear Information System (INIS)

Murai, Sumiko

1989-01-01

Nasal mucociliary function was evaluated by nasal scintigraphy in normal subjects. A microdrop of HSA or saline labelled with 99m Tc was dripped into the middle part of each middle meatus in the nasal cavity and its clearance was observed by scinticamera. The accumulated concentration of RI was determined every 30 seconds for 10 minutes. The changes of accumulated concentration were studied, and a curve of decreasing RI-counts was obtained, with the 'clearance rate' defined as 100% for the count at the initial 30 seconds and 'half time' as the time when radioactivity was reduced to one half the initial count. Nasal resistance was measured by rhinomanometry with the oscillation method. In nonsmokers, 10μl of saline was cleared (78.0±10.4%) significantly faster than 10μl of HSA (59.9±24.6%), and there was no significant difference in the clearance between 10μl and 5μl of HSA (55.9±27.7%). In smakers, the mucociliary clearance of 10μl of HSA and saline was significantly lower than in nonsmokers. The clearance of 10μl of HSA reflects a pathological state much better than that of 5μl. In nonsmokers, there is a significant negative correlation between nasal resistance and clearance rate, suggesting that the more patent the nose, the faster the mucociliary clearance. When both nostrils were closed, the clearance rate was significantly depressed. When one nostril was closed, there was no significant effect on clearance. Nasal resistance was decreased by exercise with a bicycle ergometer. Nasal mucociliary clearance was slightly decreased after exercise but not significantly so. (J.P.N.)

Inflammatory Cytokine Tumor Necrosis Factor α Confers Precancerous Phenotype in an Organoid Model of Normal Human Ovarian Surface Epithelial Cells

Directory of Open Access Journals (Sweden)

Joseph Kwong

2009-06-01

Full Text Available In this study, we established an in vitro organoid model of normal human ovarian surface epithelial (HOSE cells. The spheroids of these normal HOSE cells resembled epithelial inclusion cysts in human ovarian cortex, which are the cells of origin of ovarian epithelial tumor. Because there are strong correlations between chronic inflammation and the incidence of ovarian cancer, we used the organoid model to test whether protumor inflammatory cytokine tumor necrosis factor α would induce malignant phenotype in normal HOSE cells. Prolonged treatment of tumor necrosis factor α induced phenotypic changes of the HOSE spheroids, which exhibited the characteristics of precancerous lesions of ovarian epithelial tumors, including reinitiation of cell proliferation, structural disorganization, epithelial stratification, loss of epithelial polarity, degradation of basement membrane, cell invasion, and overexpression of ovarian cancer markers. The result of this study provides not only an evidence supporting the link between chronic inflammation and ovarian cancer formation but also a relevant and novel in vitro model for studying of early events of ovarian cancer.

Image diagnosis of nasal bone fracture

International Nuclear Information System (INIS)

Hirota, Yoshiharu; Shimizu, Yayoi; Iinuma, Toshitaka.

1988-01-01

Twenty cases of nasal bone fractures were evaluated as to the types of fractures based upon HRCT findings. Conventional X-Ray films for nasal bones were analyzed and compared with HRCT findings. Nasal bone fractures were classified into lateral and frontal fractures. HRCT images were evaluated in three planes including upper, middle and lower portions of the nasal bone. Fractures favored males of teens. Lateral fracture gave rise to the fractures of the nasal bone opposite to the external force, loosening of the ipsilateral nasomaxillary sutures and fractures of the frontal process of the maxilla. Conventional X-Ray films were reevaluated after HRCT evaluation and indications of nasal bone fractures were determined. In addition to the discontinuity of the nasal dorsum, fracture lines parallel to and beneath the nasal dorsum and indistinct fracture lines along the nasomaxillary sutures are the indication of nasal bone fractures by conventional X-Ray films. (author)

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

Science.gov (United States)

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.

Differentiation and molecular profiling of human embryonic stem cell-derived corneal epithelial cells.

Science.gov (United States)

Brzeszczynska, J; Samuel, K; Greenhough, S; Ramaesh, K; Dhillon, B; Hay, D C; Ross, J A

2014-06-01

It has been suggested that the isolation of scalable populations of limbal stem cells may lead to radical changes in ocular therapy. In particular, the derivation and transplantation of corneal stem cells from these populations may result in therapies providing clinical normality of the diseased or damaged cornea. Although feasible in theory, the lack of donor material in sufficient quantity and quality currently limits such a strategy. A potential scalable source of corneal cells could be derived from pluripotent stem cells (PSCs). We developed an in vitro and serum-free corneal differentiation model which displays significant promise. Our stepwise differentiation model was designed with reference to development and gave rise to cells which displayed similarities to epithelial progenitor cells which can be specified to cells displaying a corneal epithelial phenotype. We believe our approach is novel, provides a robust model of human development and in the future, may facilitate the generation of corneal epithelial cells that are suitable for clinical use. Additionally, we demonstrate that following continued cell culture, stem cell-derived corneal epithelial cells undergo transdifferentiation and exhibit squamous metaplasia and therefore, also offer an in vitro model of disease.

Velocity Measurements in Nasal Cavities by Means of Stereoscopic Piv - Preliminary Tests

Science.gov (United States)

Cozzi, Fabio; Felisati, Giovanni; Quadrio, Maurizio

2017-08-01

The prediction of detailed flow patterns in human nasal cavities using computational fluid dynamics (CFD) can provide essential information on the potential relationship between patient-specific geometrical characteristics of the nasal anatomy and health problems, and ultimately led to improved surgery. The complex flow structure and the intricate geometry of the nasal cavities make achieving such goals a challenge for CFD specialists. The need for experimental data to validate and improve the numerical simulations is particularly crucial. To this aim an experimental set-up based on Stereo PIV and a silicon phantom of nasal cavities have been designed and realized at Politecnico di Milano. This work describes the main features and challenges of the set-up along with some preliminary results.

[Expression of thioredoxin-2 in human lens epithelial cells with oxidative damage and its significance].

Science.gov (United States)

Che, Xuanyi; Zhao, Qingxia; Li, Di

2018-03-28

To explore whether thioredoin-2 (Trx-2) is involved in the development of cataract and to study the effect of Trx-2 on hydrogen peroxide (H2O2)-induced injury in human lens epithelial cells.
 Methods: A total of 10 volunteers (removing the lens due totraumatism) and 30 patients received phacoemulsification (age more than 60 years) were selected. The expression of Trx-2 protein in lens epithelial cells from cataract patients and volunteers were detected by the immunohistochemical streptavidin-peroxidase (SP) method. SRA01/04 cells were cultured and were divided into six groups according to different treatment: a control group, H2O2-treated groups at 20, 50 or 
100 μmol/L, a negative control group (transfected with pCMV6 plasmid plus 100 μmol/L H2O2), and a Trx-2 overexpression group (transfected with pCMV6-Trx-2 plasmid plus 100 μmol/L H2O2). Methyl thiazolyltetrazolium (MTT) assay and flow cytometry was performed to measure the cell viability and apoptosis for SRA01/04 cells, respectively. The activities of superoxide dismutase (SOD) and catalase (CAT), the content of glutathione (GSH) and malondialdehyde (MDA) in human lens epithelial cells were measured via chemical chromatometry. Western blot was used to measure the protein levels of Trx-2, B-cell lymphoma 2 protein (Bcl-2), Bcl-2 associated X protein (Bax) and caspase-3.
 Results: Compared with the volunteers, the expression of Trx-2 was significantly decreased in lens epithelial cells in patients with cataract (PTrx-2 protein in the 20, 50 or 100 μmol/L H2O2 groups was decreased (all PTrx-2 and Bcl-2 expression and up-regulated Bax and caspase-3 expression (all PTrx-2 overexpression group (PTrx-2 and Bcl-2 expression and down-regulated Bax and caspase-3 expression (PTrx-2 might be involved in the apoptosis of lens epithelial cells in patients with cataract. The overexpression of Trx-2 obviously attenuated H2O2-induced injury of human lens epithelial cells, which might be associated with the

Effect of Local Nasal Immunotherapy on Nasal Blockage in Pollen-Induced Allergic Rhinitis of Guinea Pigs

Directory of Open Access Journals (Sweden)

Takeshi Nabe

2008-01-01

Conclusions: Local nasal immunotherapy may be clinically useful for allergic nasal blockage associated with nasal hyperresponsiveness. The mechanisms responsible for this effectiveness might not be related to IgE production. Additionally, the effectiveness for nasal tissue was dissociated from that seen for the ocular tissue.

Rhinoplasty via the midface degloving approach for nasal deformity due to nasal polyps: A case report of Woakes’ syndrome

Directory of Open Access Journals (Sweden)

Misato Ueda, MD

2017-09-01

Full Text Available Nasal polyps are inflammatory proliferative tumors arising from the mucosa of the nasal cavity and paranasal sinuses. Although many cases concerning nasal polyps have been reported, those involving external nasal deformities are rare. We report a case of nasal polyposis filling the nasal cavity and paranasal sinuses, leading to external nasal and facial deformities. The condition above is known as Woakes’ syndrome, which is characterized by severe recurrent nasal polyps with deformity of the nasal pyramid, leading to broadening of the nose. We performed nasal osteotomy and facial bone-shaving via the midface degloving approach, which improved the patient’s facial appearance.

Transplantation of human amniotic epithelial cells repairs brachial plexus injury:pathological and biomechanical analyses

Institute of Scientific and Technical Information of China (English)

Qi Yang; Min Luo; Peng Li; Hai Jin

2014-01-01

A brachial plexus injury model was established in rabbits by stretching the C6 nerve root. Imme-diately after the stretching, a suspension of human amniotic epithelial cells was injected into the injured brachial plexus. The results of tensile mechanical testing of the brachial plexus showed that the tensile elastic limit strain, elastic limit stress, maximum stress, and maximum strain of the injured brachial plexuses were signiifcantly increased at 24 weeks after the injection. The treat-ment clearly improved the pathological morphology of the injured brachial plexus nerve, as seen by hematoxylin eosin staining, and the functions of the rabbit forepaw were restored. These data indicate that the injection of human amniotic epithelial cells contributed to the repair of brachial plexus injury, and that this technique may transform into current clinical treatment strategies.

Effect of N-acetylcysteine on the human nasal ciliary activity in vitro

DEFF Research Database (Denmark)

Stafanger, G; Bisgaard, H; Pedersen, M

1987-01-01

N-acetylcysteine (NAC) is widely used as a mucolytic agent, but the clinical and pharmacological effects of NAC are still unclear. It has recently been claimed in animal studies that NAC will stimulate ciliary beating frequency at low concentrations, while inhibiting beating at higher concentrati......N-acetylcysteine (NAC) is widely used as a mucolytic agent, but the clinical and pharmacological effects of NAC are still unclear. It has recently been claimed in animal studies that NAC will stimulate ciliary beating frequency at low concentrations, while inhibiting beating at higher...... concentrations. Using a microphoto-oscillographic method combined with microperfusion technique, we studied the direct effect of NAC on human nasal cilia. NAC caused a direct dose- and time-related decrease in ciliary beating frequency, which was detectable at 2 mg/ml and reached statistically significant levels...

Chronic inorganic arsenic exposure in vitro induces a cancer cell phenotype in human peripheral lung epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Person, Rachel J.; Olive Ngalame, Ntube N.; Makia, Ngome L.; Bell, Matthew W.; Waalkes, Michael P.; Tokar, Erik J., E-mail: tokare@niehs.nih.gov

2015-07-01

Inorganic arsenic is a human lung carcinogen. We studied the ability of chronic inorganic arsenic (2 μM; as sodium arsenite) exposure to induce a cancer phenotype in the immortalized, non-tumorigenic human lung peripheral epithelial cell line, HPL-1D. After 38 weeks of continuous arsenic exposure, secreted matrix metalloproteinase-2 (MMP2) activity increased to over 200% of control, levels linked to arsenic-induced cancer phenotypes in other cell lines. The invasive capacity of these chronic arsenic-treated lung epithelial (CATLE) cells increased to 320% of control and colony formation increased to 280% of control. CATLE cells showed enhanced proliferation in serum-free media indicative of autonomous growth. Compared to control cells, CATLE cells showed reduced protein expression of the tumor suppressor gene PTEN (decreased to 26% of control) and the putative tumor suppressor gene SLC38A3 (14% of control). Morphological evidence of epithelial-to-mesenchymal transition (EMT) occurred in CATLE cells together with appropriate changes in expression of the EMT markers vimentin (VIM; increased to 300% of control) and e-cadherin (CDH1; decreased to 16% of control). EMT is common in carcinogenic transformation of epithelial cells. CATLE cells showed increased KRAS (291%), ERK1/2 (274%), phosphorylated ERK (p-ERK; 152%), and phosphorylated AKT1 (p-AKT1; 170%) protein expression. Increased transcript expression of metallothioneins, MT1A and MT2A and the stress response genes HMOX1 (690%) and HIF1A (247%) occurred in CATLE cells possibly in adaptation to chronic arsenic exposure. Thus, arsenic induced multiple cancer cell characteristics in human peripheral lung epithelial cells. This model may be useful to assess mechanisms of arsenic-induced lung cancer. - Highlights: • Chronic arsenic exposure transforms a human peripheral lung epithelia cell line. • Cells acquire characteristics in common with human lung adenocarcinoma cells. • These transformed cells provide a

Three-dimensional epithelial tissues generated from human embryonic stem cells.

Science.gov (United States)

Hewitt, Kyle J; Shamis, Yulia; Carlson, Mark W; Aberdam, Edith; Aberdam, Daniel; Garlick, Jonathan A

2009-11-01

The use of pluripotent human embryonic stem (hES) cells for tissue engineering may provide advantages over traditional sources of progenitor cells because of their ability to give rise to multiple cell types and their unlimited expansion potential. We derived cell populations with properties of ectodermal and mesenchymal cells in two-dimensional culture and incorporated these divergent cell populations into three-dimensional (3D) epithelial tissues. When grown in specific media and substrate conditions, two-dimensional cultures were enriched in cells (EDK1) with mesenchymal morphology and surface markers. Cells with a distinct epithelial morphology (HDE1) that expressed cytokeratin 12 and beta-catenin at cell junctions became the predominant cell type when EDK1 were grown on surfaces enriched in keratinocyte-derived extracellular matrix proteins. When these cells were incorporated into the stromal and epithelial tissue compartments of 3D tissues, they generated multilayer epithelia similar to those generated with foreskin-derived epithelium and fibroblasts. Three-dimensional tissues demonstrated stromal cells with morphologic features of mature fibroblasts, type IV collagen deposition in the basement membrane, and a stratified epithelium that expressed cytokeratin 12. By deriving two distinct cell lineages from a common hES cell source to fabricate complex tissues, it is possible to explore environmental cues that will direct hES-derived cells toward optimal tissue form and function.

Determining adaptive and adverse oxidative stress responses in human bronical epithelial cells exposed to zinc

Science.gov (United States)

Determining adaptive and adverse oxidative stress responses in human bronchial epithelial cells exposed to zincJenna M. Currier1,2, Wan-Yun Cheng1, Rory Conolly1, Brian N. Chorley1Zinc is a ubiquitous contaminant of ambient air that presents an oxidant challenge to the human lung...

EPITHELIAL MYOEPITHELIAL CARCINOMA OF MAXILLARY SINUS —A DIAGNOSTIC DILEMMA

OpenAIRE

Rajeev Sen; Sumiti Gupta; Kanika Taneja; Nisha Marwah; Sonia Chhabra; Sonia Hasija

2015-01-01

Epithelial – Myoepithelial Carcinoma (EMC) is a rare malignant salivary gland neoplasm that most commonly occurs in the Parotid gland, but can also arise in the Minor Salivary Glands. EMC of the maxillary sinus extremely rare. We describe here a case of a 74-year-old patient who presented with maxillary swelling for 4months and nasal discharge for 3 months. Computed Tomography Scan revealed an expansile soft tissue mass in the left maxillary sinus eroding all its walls. In View of high sus...

Kinetics of naphthalene metabolism in target and non-target tissues of rodents and in nasal and airway microsomes from the Rhesus monkey

Energy Technology Data Exchange (ETDEWEB)

Buckpitt, Alan, E-mail: arbuckpitt@ucdavis.edu [Department of Molecular Biosciences, School of Veterinary Medicine, UC Davis, Davis, CA 95616 (United States); Morin, Dexter [Department of Molecular Biosciences, School of Veterinary Medicine, UC Davis, Davis, CA 95616 (United States); Murphy, Shannon; Edwards, Patricia; Van Winkle, Laura [Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, UC Davis, Davis, CA 95616 (United States); Center for Health and the Environment, UC Davis, Davis, CA 95616 United States (United States)

2013-07-15

Naphthalene produces species and cell selective injury to respiratory tract epithelial cells of rodents. In these studies we determined the apparent K{sub m}, V{sub max}, and catalytic efficiency (V{sub max}/K{sub m}) for naphthalene metabolism in microsomal preparations from subcompartments of the respiratory tract of rodents and non-human primates. In tissues with high substrate turnover, major metabolites were derived directly from naphthalene oxide with smaller amounts from conjugates of diol epoxide, diepoxide, and 1,2- and 1,4-naphthoquinones. In some tissues, different enzymes with dissimilar K{sub m} and V{sub max} appeared to metabolize naphthalene. The rank order of V{sub max} (rat olfactory epithelium > mouse olfactory epithelium > murine airways ≫ rat airways) correlated well with tissue susceptibility to naphthalene. The V{sub max} in monkey alveolar subcompartment was 2% that in rat nasal olfactory epithelium. Rates of metabolism in nasal compartments of the monkey were low. The catalytic efficiencies of microsomes from known susceptible tissues/subcompartments are 10 and 250 fold higher than in rat airway and monkey alveolar subcompartments, respectively. Although the strong correlations between catalytic efficiencies and tissue susceptibility suggest that non-human primate tissues are unlikely to generate metabolites at a rate sufficient to produce cellular injury, other studies showing high levels of formation of protein adducts support the need for additional studies. - Highlights: • Naphthalene is metabolized with high catalytic efficiency in susceptible tissue. • Naphthalene is metabolized at low catalytic efficiency in non-susceptible tissue. • Respiratory tissues of the non human primate metabolize naphthalene slowly.

Entrance and Survival of Brucella pinnipedialis Hooded Seal Strain in Human Macrophages and Epithelial Cells

Science.gov (United States)

Briquemont, Benjamin; Sørensen, Karen K.; Godfroid, Jacques

2013-01-01

Marine mammal Brucella spp. have been isolated from pinnipeds (B. pinnipedialis) and cetaceans (B. ceti) from around the world. Although the zoonotic potential of marine mammal brucellae is largely unknown, reports of human disease exist. There are few studies of the mechanisms of bacterial intracellular invasion and multiplication involving the marine mammal Brucella spp. We examined the infective capacity of two genetically different B. pinnipedialis strains (reference strain; NTCT 12890 and a hooded seal isolate; B17) by measuring the ability of the bacteria to enter and replicate in cultured phagocytes and epithelial cells. Human macrophage-like cells (THP-1), two murine macrophage cell lines (RAW264.7 and J774A.1), and a human malignant epithelial cell line (HeLa S3) were challenged with bacteria in a gentamicin protection assay. Our results show that B. pinnipedialis is internalized, but is then gradually eliminated during the next 72 – 96 hours. Confocal microscopy revealed that intracellular B. pinnipedialis hooded seal strain colocalized with lysosomal compartments at 1.5 and 24 hours after infection. Intracellular presence of B. pinnipedialis hooded seal strain was verified by transmission electron microscopy. By using a cholesterol-scavenging lipid inhibitor, entrance of B. pinnipedialis hooded seal strain in human macrophages was significantly reduced by 65.8 % (± 17.3), suggesting involvement of lipid-rafts in intracellular entry. Murine macrophages invaded by B. pinnipedialis do not release nitric oxide (NO) and intracellular bacterial presence does not induce cell death. In summary, B. pinnipedialis hooded seal strain can enter human and murine macrophages, as well as human epithelial cells. Intracellular entry of B. pinnipedialis hooded seal strain involves, but seems not to be limited to, lipid-rafts in human macrophages. Brucella pinnipedialis does not multiply or survive for prolonged periods intracellulary. PMID:24376851

Human lactoferrin stimulates skin keratinocyte function and wound re-epithelialization.

Science.gov (United States)

Tang, L; Wu, J J; Ma, Q; Cui, T; Andreopoulos, F M; Gil, J; Valdes, J; Davis, S C; Li, J

2010-07-01

Human lactoferrin (hLF), a member of the transferrin family, is known for its antimicrobial and anti-inflammatory effects. Recent studies on various nonskin cell lines indicate that hLF may have a stimulatory effect on cell proliferation. To study the potential role of hLF in wound re-epithelialization. The effects of hLF on cell growth, migration, attachment and survival were assessed, with a rice-derived recombinant hLF (holo-rhLF), using proliferation analysis, scratch migration assay, calcein-AM/propidium iodide staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) method, respectively. The mechanisms of hLF on cell proliferation and migration were explored using specific pathway inhibitors. The involvement of lactoferrin receptor low-density lipoprotein receptor-related protein 1 (LRP1) was examined with RNA interference technique. An in vivo swine second-degree burn wound model was also used to assess wound re-epithelialization. Studies revealed that holo-rhLF significantly stimulated keratinocyte proliferation which could be blocked by mitogen-activated protein kinase (MAPK) kinase 1 inhibitor. Holo-rhLF also showed strong promoting effects on keratinocyte migration, which could be blocked by either inhibition of the MAPK, Src and Rho/ROCK pathways, or downregulation of the LRP1 receptor. With cells under starving or 12-O-tetradecanoylphorbol-13-acetate exposure, the addition of holo-rhLF was found greatly to increase cell viability and inhibit cell apoptosis. Additionally, holo-rhLF significantly increased the rate of wound re-epithelialization in swine second-degree burn wounds. Our studies demonstrate the direct effects of holo-rhLF on wound re-epithelialization including the enhancement of keratinocyte proliferation and migration as well as the protection of cells from apoptosis. The data strongly indicate its potential therapeutic applications in wound healing.

Cosmetic and Functional Nasal Deformities

Science.gov (United States)

... nasal complaints. Nasal deformity can be categorized as “cosmetic” or “functional.” Cosmetic deformity of the nose results in a less ... taste , nose bleeds and/or recurrent sinusitis . A cosmetic or functional nasal deformity may occur secondary to ...

Smart Polymers in Nasal Drug Delivery.

Science.gov (United States)

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.

Recovery from radiation-induced damage in primary cultures of human epithelial thyroid cells

International Nuclear Information System (INIS)

Miller, R.C.; Hiraoka, Toshio; Enno, Masumi; Takeichi, Nobuo.

1985-01-01

Human thyroid epithelial tissues from 23 individuals were obtained from surgical tissue, and cultured in vitro. Dose response survival curves showed thyroid cells, when compared to mammary epithelial and skin fibroblast cells of human origin, to be only slightly more radiosensitive to X-rays. Cell survival curves from the cell strains showed wide variability in radiation sensitivity. Of the 23 cell strains tested, 21 strains displayed significant shoulders (nonzero quasi-threshold (D q ) values and extrapolation number (n) values greater than 1) at low dose exposures. The ability of human cells to recover from radiation damage was further studied by dose fractionation. Two cell strains were given a total X-ray dose of 304 cGy in two equal fractions separated by varying time intervals. Maximal cell survival was observed when the time interval exceeded two hours. When the two cell strains were exposed to 152 cGy of X-rays followed four hours later by second graded doses, cell survival was enhanced as compared to survival after single dose exposures. However, no benefit of dose splitting was observed when cells were exposed to low second doses. These results support previous studies showing that human cells are capable of repair but require relatively large doses to elicit a repair response. (author)

Recovery from radiation-induced damage in primary cultures of human epithelial thyroid cells

International Nuclear Information System (INIS)

Miller, R.C.; Hiraoka, Toshio; Enno, Masumi; Takeichi, Nobuo.

1985-09-01

Human thyroid epithelial tissue from 23 individuals was obtained from surgical tissue, and cultured in vitro. Dose-response survival curves showed thyroid cells, when compared to mammary epithelial and skin fibroblast cells of human origin, to be only slightly more radiosensitive to X rays. Cell survival curves from the cell strains showed wide variability in radiation sensitivity. Of the 23 cell strains tested, 21 strains displayed significant shoulders (nonzero quasi-threshold (Dsub(q)) values and extrapolation number (n) values greater than 1)* at low dose exposures. The ability of human cells to recover from radiation damage was further studied by dose fractionation. Two cell strains were given a total X-ray dose of 304 cGy in two equal fractions separated by varying time intervals. Maximal cell survival was observed when the time interval exceeded two hours. When the two cell strains were exposed to 152 cGy of X rays followed four hours later by second graded doses, cell survival was enhanced as compared to survival after single dose exposures. However, no benefit of dose splitting was observed when cells were exposed to low second doses. These results support previous studies showing that human cells are capable of repair but require relatively large doses to elicit a repair response. (author)

Ghrelin ameliorates the human alveolar epithelial A549 cell apoptosis induced by lipopolysaccharide

International Nuclear Information System (INIS)

Huang, Chunrong; Zheng, Haichong; He, Wanmei; Lu, Guifang; Li, Xia; Deng, Yubin; Zeng, Mian

2016-01-01

Ghrelin is a gastric acyl-peptide that plays an inhibitory role in cell apoptosis. Herein we investigate the protective effects of ghrelin in LPS-induced apoptosis of human alveolar epithelial A549 cells, along with the possible molecular mechanisms. LPS exposure impaired cell viability and increased apoptosis of A549 cells significantly in concentration- and time-dependent manners embodied in increased Bax and cleaved caspase-3 production, coupled with decreased Bcl-2 levels. Simultaneously, LPS remarkably decreased the expression of phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) and extracellular signal-regulated kinas (ERK) in A549 cells. However, ghrelin'pretreatment ameliorated LPS-caused alterations in the ratio of Bax/Bcl-2 and cleaved caspase-3 expression, whereas activated the PI3K/Akt and ERK signaling. These results demonstrate that ghrelin lightens LPS-induced apoptosis of human alveolar epithelial cells partly through activating the PI3K/Akt and ERK pathway and thereby might benefit alleviating septic ALI. -- Graphical abstract: Ghrelin ameliorates the human alveolar epithelial A549 cells apoptosis induced by lipopolysaccharide partly through activating the PI3K/Akt and ERK pathway. Display Omitted -- Highlights: •It has been observed that LPS insult significantly increased apoptosis in A549 cells. •Both Akt and ERK signaling are critical adapter molecules to mediate the ghrelin-mediated proliferative effect. •Ghrelin may have a therapeutic effect in the prevention of LPS-induced apoptosis.

Ghrelin ameliorates the human alveolar epithelial A549 cell apoptosis induced by lipopolysaccharide

Energy Technology Data Exchange (ETDEWEB)

Huang, Chunrong; Zheng, Haichong; He, Wanmei; Lu, Guifang; Li, Xia [Department of Medical Intensive Care Unit, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080 (China); Deng, Yubin, E-mail: dengyub@mail.sysu.edu.cn [Research Center of Translational Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080 (China); Zeng, Mian, E-mail: zengmian2004@163.com [Department of Medical Intensive Care Unit, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080 (China)

2016-05-20

Ghrelin is a gastric acyl-peptide that plays an inhibitory role in cell apoptosis. Herein we investigate the protective effects of ghrelin in LPS-induced apoptosis of human alveolar epithelial A549 cells, along with the possible molecular mechanisms. LPS exposure impaired cell viability and increased apoptosis of A549 cells significantly in concentration- and time-dependent manners embodied in increased Bax and cleaved caspase-3 production, coupled with decreased Bcl-2 levels. Simultaneously, LPS remarkably decreased the expression of phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) and extracellular signal-regulated kinas (ERK) in A549 cells. However, ghrelin'pretreatment ameliorated LPS-caused alterations in the ratio of Bax/Bcl-2 and cleaved caspase-3 expression, whereas activated the PI3K/Akt and ERK signaling. These results demonstrate that ghrelin lightens LPS-induced apoptosis of human alveolar epithelial cells partly through activating the PI3K/Akt and ERK pathway and thereby might benefit alleviating septic ALI. -- Graphical abstract: Ghrelin ameliorates the human alveolar epithelial A549 cells apoptosis induced by lipopolysaccharide partly through activating the PI3K/Akt and ERK pathway. Display Omitted -- Highlights: •It has been observed that LPS insult significantly increased apoptosis in A549 cells. •Both Akt and ERK signaling are critical adapter molecules to mediate the ghrelin-mediated proliferative effect. •Ghrelin may have a therapeutic effect in the prevention of LPS-induced apoptosis.

Risk factors for nasal malignancies in German men: the South-German Nasal cancer study.

Science.gov (United States)

Greiser, Eberhard M; Greiser, Karin Halina; Ahrens, Wolfgang; Hagen, Rudolf; Lazszig, Roland; Maier, Heinz; Schick, Bernhard; Zenner, Hans Peter

2012-11-06

There are few studies of the effects of nasal snuff and environmental factors on the risk of nasal cancer. This study aimed to investigate the impact of using nasal snuff and of other risk factors on the risk of nasal cancer in German men. A population-based case-control study was conducted in the German Federal States of Bavaria and Baden-Württemberg. Tumor registries and ear, nose and throat departments provided access to patients born in 1926 or later. Telephone interviews were conducted with 427 cases (mean age 62.1 years) and 2.401 population-based controls (mean age 60.8 years). Ever-use of nasal snuff was associated with an odds ratio (OR) for nasal cancer of 1.45 (95% confidence interval [CI] 0.88-2.38) in the total study population, whereas OR in smokers was 2.01 (95% CI 1.00-4.02) and in never smokers was 1.10 (95% CI 0.43-2.80). The OR in ever-smokers vs. never-smokers was 1.60 (95% CI 1.24-2.07), with an OR of 1.06 (95% CI 1.05-1.07) per pack-year smoked, and the risk was significantly decreased after quitting smoking. Exposure to hardwood dust for at least 1 year resulted in an OR of 2.33 (95% CI 1.40-3.91) in the total population, which was further increased in never-smokers (OR 4.89, 95% CI 1.92-12.49) in analyses stratified by smoking status. The OR for nasal cancer after exposure to organic solvents for at least 1 year was 1.53 (1.17-2.01). Ever-use of nasal sprays/nasal lavage for at least 1 month rendered an OR of 1.59 (1.04-2.44). The OR after use of insecticides in homes was 1.48 (95% CI 1.04-2.11). Smoking and exposure to hardwood dust were confirmed as risk factors for nasal carcinoma. There is evidence that exposure to organic solvents, and in-house use of insecticides could represent novel risk factors. Exposure to asbestos and use of nasal snuff were risk factors in smokers only.

Enhanced chondrogenesis of human nasal septum derived progenitors on nanofibrous scaffolds

Energy Technology Data Exchange (ETDEWEB)

Shafiee, Abbas [Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Stem Cell biology and Tissue Engineering Departments, Stem Cell Technology Research Center, Tehran (Iran, Islamic Republic of); Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, QLD (Australia); Seyedjafari, Ehsan [Department of Biotechnology, College of Science, University of Tehran, Tehran (Iran, Islamic Republic of); Sadat Taherzadeh, Elham [Stem Cell biology and Tissue Engineering Departments, Stem Cell Technology Research Center, Tehran (Iran, Islamic Republic of); Dinarvand, Peyman [Stem Cell biology and Tissue Engineering Departments, Stem Cell Technology Research Center, Tehran (Iran, Islamic Republic of); The Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, Saint Louis, MO (United States); Soleimani, Masoud [Hematology Department, Faculty of Medical Science, Tarbiat Modares University, Tehran (Iran, Islamic Republic of); Ai, Jafar, E-mail: jafar_ai@tums.ac.ir [Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Brain and Spinal Injury Research Center, Imam Hospital, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

2014-07-01

Topographical cues can be exploited to regulate stem cell attachment, proliferation, differentiation and function in vitro and in vivo. In this study, we aimed to investigate the influence of different nanofibrous topographies on the chondrogenic differentiation potential of nasal septum derived progenitors (NSP) in vitro. Aligned and randomly oriented Ploy (L-lactide) (PLLA)/Polycaprolactone (PCL) hybrid scaffolds were fabricated via electrospinning. First, scaffolds were fully characterized, and then NSP were seeded on them to study their capacity to support stem cell attachment, proliferation and chondrogenic differentiation. Compared to randomly oriented nanofibers, aligned scaffolds showed a high degree of nanofiber alignment with much better tensile strength properties. Both scaffolds supported NSP adhesion, proliferation and chondrogenic differentiation. Despite the higher rate of cell proliferation on random scaffolds, a better chondrogenic differentiation was observed on aligned nanofibers as deduced from higher expression of chondrogenic markers such as collagen type II and aggrecan on aligned scaffolds. These findings demonstrate that electrospun constructs maintain NSP proliferation and differentiation, and that the aligned nanofibrous scaffolds can significantly enhance chondrogenic differentiation of nasal septum derived progenitors. - Highlights: • Electrospun nanofiber scaffolds with different topographies were fabricated. • Aligned nanofiber scaffolds had better tensile strength properties. • Nasal septum derived progenitors were cultured on nanofibrous scaffolds. • Both topographies support proliferation and chondrogenic differentiation. • Better chondrogenic differentiation was observed on aligned nanofibers.

Enhanced chondrogenesis of human nasal septum derived progenitors on nanofibrous scaffolds

International Nuclear Information System (INIS)

Shafiee, Abbas; Seyedjafari, Ehsan; Sadat Taherzadeh, Elham; Dinarvand, Peyman; Soleimani, Masoud; Ai, Jafar

2014-01-01

Topographical cues can be exploited to regulate stem cell attachment, proliferation, differentiation and function in vitro and in vivo. In this study, we aimed to investigate the influence of different nanofibrous topographies on the chondrogenic differentiation potential of nasal septum derived progenitors (NSP) in vitro. Aligned and randomly oriented Ploy (L-lactide) (PLLA)/Polycaprolactone (PCL) hybrid scaffolds were fabricated via electrospinning. First, scaffolds were fully characterized, and then NSP were seeded on them to study their capacity to support stem cell attachment, proliferation and chondrogenic differentiation. Compared to randomly oriented nanofibers, aligned scaffolds showed a high degree of nanofiber alignment with much better tensile strength properties. Both scaffolds supported NSP adhesion, proliferation and chondrogenic differentiation. Despite the higher rate of cell proliferation on random scaffolds, a better chondrogenic differentiation was observed on aligned nanofibers as deduced from higher expression of chondrogenic markers such as collagen type II and aggrecan on aligned scaffolds. These findings demonstrate that electrospun constructs maintain NSP proliferation and differentiation, and that the aligned nanofibrous scaffolds can significantly enhance chondrogenic differentiation of nasal septum derived progenitors. - Highlights: • Electrospun nanofiber scaffolds with different topographies were fabricated. • Aligned nanofiber scaffolds had better tensile strength properties. • Nasal septum derived progenitors were cultured on nanofibrous scaffolds. • Both topographies support proliferation and chondrogenic differentiation. • Better chondrogenic differentiation was observed on aligned nanofibers

Nasal Delivery of High Molecular Weight Drugs

Directory of Open Access Journals (Sweden)

Erdal Cevher

2009-09-01

Full Text Available Nasal drug delivery may be used for either local or systemic effects. Low molecular weight drugs with are rapidly absorbed through nasal mucosa. The main reasons for this are the high permeability, fairly wide absorption area, porous and thin endothelial basement membrane of the nasal epithelium. Despite the many advantages of the nasal route, limitations such as the high molecular weight (HMW of drugs may impede drug absorption through the nasal mucosa. Recent studies have focused particularly on the nasal application of HMW therapeutic agents such as peptide-protein drugs and vaccines intended for systemic effects. Due to their hydrophilic structure, the nasal bioavailability of peptide and protein drugs is normally less than 1%. Besides their weak mucosal membrane permeability and enzymatic degradation in nasal mucosa, these drugs are rapidly cleared from the nasal cavity after administration because of mucociliary clearance. There are many approaches for increasing the residence time of drug formulations in the nasal cavity resulting in enhanced drug absorption. In this review article, nasal route and transport mechanisms across the nasal mucosa will be briefly presented. In the second part, current studies regarding the nasal application of macromolecular drugs and vaccines with nanoand micro-particulate carrier systems will be summarised.

Stromal-epithelial interactions in aging and cancer: Senescent fibroblasts alter epithelial cell differentiation

Energy Technology Data Exchange (ETDEWEB)

Parrinello, Simona; Coppe, Jean-Philippe; Krtolica, Ana; Campisi, Judith

2004-07-14

Cellular senescence suppresses cancer by arresting cells at risk for malignant tumorigenesis. However, senescent cells also secrete molecules that can stimulate premalignant cells to proliferate and form tumors, suggesting the senescence response is antagonistically pleiotropic. We show that premalignant mammary epithelial cells exposed to senescent human fibroblasts in mice irreversibly lose differentiated properties, become invasive and undergo full malignant transformation. Moreover, using cultured mouse or human fibroblasts and non-malignant breast epithelial cells, we show that senescent fibroblasts disrupt epithelial alveolar morphogenesis, functional differentiation, and branching morphogenesis. Further, we identify MMP-3 as the major factor responsible for the effects of senescent fibroblasts on branching morphogenesis. Our findings support the idea that senescent cells contribute to age-related pathology, including cancer, and describe a new property of senescent fibroblasts--the ability to alter epithelial differentiation--that might also explain the loss of tissue function and organization that is a hallmark of aging.

Apoptosis induction of human endometriotic epithelial and stromal cells by noscapine

Directory of Open Access Journals (Sweden)

Mohammad Rasoul Khazaei

2016-09-01

Full Text Available Objective(s: Endometriosis is a complex gynecologic disease with unknown etiology. Noscapine has been introduced as a cancer cell suppressor. Endometriosis was considered as a cancer like disorder, The aim of present study was to investigate noscapine apoptotic effect on human endometriotic epithelial and stromal cells in vitro. Materials and Methods:In this in vitro study, endometrial biopsies from endometriosis patients (n=9 were prepared and digested by an enzymatic method (collagenase I, 2 mg/ml. Stromal and epithelial cells were separated by sequential filtration through a cell strainer and ficoll layering. The cells of each sample were divided into five groups: control (0, 10, 25, 50 and 100 micromole/liter (µM concentration of noscapine and were cultured for three different periods of times; 24, 48 and 72 hr. Cell viability was assessed by colorimetric assay. Nitric oxide (NO concentration was measured by Griess reagent. Cell death was analyzed by Acridine Orange (AO–Ethidium Bromide (EB double staining and Terminal deoxynucleotidyl transferase (TdT dUTP Nick-End Labeling (TUNEL assay. Data were analyzed by one-way ANOVA. Results: Viability of endometrial epithelial and stromal cells significantly decreased in 10, 25, 50 and 100 µM noscapine concentration in 24, 48, 72 hr (P

High level expression of human epithelial β-defensins (hBD-1, 2 and 3 in papillomavirus induced lesions

Directory of Open Access Journals (Sweden)

Chong Kong T

2006-09-01

Full Text Available Abstract Background Epithelial defensins including human β-defensins (hBDs and α-defensins (HDs are antimicrobial peptides that play important roles in the mucosal defense system. However, the role of defensins in papillomavirus induced epithelial lesions is unknown. Results Papilloma tissues were prospectively collected from 15 patients with recurrent respiratory papillomatosis (RRP and analyzed for defensins and chemokine IL-8 expression by quantitative, reverse-transcriptase polymerase chain reaction (RT-PCR assays. HBD-1, -2 and -3 mRNAs were detectable in papilloma samples from all RRP patients and the levels were higher than in normal oral mucosal tissues from healthy individuals. Immunohistochemical analysis showed that both hBD-1 and 2 were localized in the upper epithelial layers of papilloma tissues. Expression of hBD-2 and hBD-3 appeared to be correlated as indicated by scatter plot analysis (r = 0.837, p Conclusion Human β-defensins are upregulated in respiratory papillomas. This novel finding suggests that hBDs might contribute to innate and adaptive immune responses targeted against papillomavirus-induced epithelial lesions.

Inhibiting glycogen synthase kinase-3 and transforming growth factor-β signaling to promote epithelial transition of human adipose mesenchymal stem cells.

Science.gov (United States)

Setiawan, Melina; Tan, Xiao-Wei; Goh, Tze-Wei; Hin-Fai Yam, Gary; Mehta, Jodhbir S

2017-09-02

This study was aimed to investigate the epithelial differentiation of human adipose-derived mesenchymal stem cells (ADSCs) by inhibiting glycogen synthase kinase-3 (GSK3) and transforming growth factor β (TGFβ) signaling. STEMPRO human ADSCs at passage 2 were treated with CHIR99021 (GSK3 inhibitor), E-616452 (TGFβ1 receptor kinase inhibitor), A-83-01 (TGFβ type 1 receptor inhibitor), valproic acid (histone deacetylase inhibitor), tranylcypromine (monoamine oxidase inhibitor) and all-trans retinoic acid for 72 h. The mesenchymal-epithelial transition was shown by down-regulation of mesenchymal genes (Slug, Zinc Finger E-box Binding Homeobox 1 ZEB1, integrin α5 ITGA5 and vimentin VIM) and up-regulation of epithelial genes (E-cadherin, Epithelial Cell Adhesion Molecule EpCAM, Zonula Occludens-1 ZO-1, occludin, deltaN p63 δNp63, Transcription Factor 4 TCF4 and Twist Family bHLH Transcription Factor TWIST), compared to untreated ADSCs. Cell morphology and stress fiber pattern were examined and the treated cells became less migratory in scratch wound closure assay. The formation of cell junction complexes was observed under transmission electron microscopy. Global gene expression using GeneChip ® Human Genome U133 Array (Affymetrix) showed that the treatment up-regulated 540 genes (containing genes for cell cycle, cytoskeleton reorganization, chemotaxis, epithelium development and regulation of cell migration) and down-regulated 483 genes. Human ADSCs were transited to epithelial lineage by inhibiting GSK3 and TGFβ signaling. It can be an adult stem cell source for epithelial cell-based therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

Alteration of canonical and non-canonical WNT-signaling by crystalline silica in human lung epithelial cells

International Nuclear Information System (INIS)

Perkins, Timothy N.; Dentener, Mieke A.; Stassen, Frank R.; Rohde, Gernot G.; Mossman, Brooke T.; Wouters, Emiel F.M.; Reynaert, Niki L.

2016-01-01

Growth and development of the mature lung is a complex process orchestrated by a number of intricate developmental signaling pathways. Wingless-type MMTV-integration site (WNT) signaling plays critical roles in controlling branching morphogenesis cell differentiation, and formation of the conducting and respiratory airways. In addition, WNT pathways are often re-activated in mature lungs during repair and regeneration. WNT- signaling has been elucidated as a crucial contributor to the development of idiopathic pulmonary fibrosis as well as other hyper-proliferative lung diseases. Silicosis, a detrimental occupational lung disease caused by excessive inhalation of crystalline silica dust, is hallmarked by repeated cycles of damaging inflammation, epithelial hyperplasia, and formation of dense, hyalinized nodules of whorled collagen. However, mechanisms of epithelial cell hyperplasia and matrix deposition are not well understood, as most research efforts have focused on the pronounced inflammatory response. Microarray data from our previous studies has revealed a number of WNT-signaling and WNT-target genes altered by crystalline silica in human lung epithelial cells. In the present study, we utilize pathway analysis to designate connections between genes altered by silica in WNT-signaling networks. Furthermore, we confirm microarray findings by QRT-PCR and demonstrate both activation of canonical (β-catenin) and down-regulation of non-canonical (WNT5A) signaling in immortalized (BEAS-2B) and primary (PBEC) human bronchial epithelial cells. These findings suggest that WNT-signaling and cross-talk with other pathways (e.g. Notch), may contribute to proliferative, fibrogenic and inflammatory responses to silica in lung epithelial cells. - Highlights: • Pathway analysis reveals silica-induced WNT-signaling in lung epithelial cells. • Silica-induced canonical WNT-signaling is mediated by autocrine/paracrine signals. • Crystalline silica decreases non-canonical WNT

Alteration of canonical and non-canonical WNT-signaling by crystalline silica in human lung epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Perkins, Timothy N.; Dentener, Mieke A. [Department of Respiratory Medicine, Maastricht University Medical Centre +, Maastricht University Maastricht (Netherlands); Stassen, Frank R. [Department of Medical Microbiology, Maastricht University Medical Centre +, Maastricht University Maastricht (Netherlands); Rohde, Gernot G. [Department of Respiratory Medicine, Maastricht University Medical Centre +, Maastricht University Maastricht (Netherlands); Mossman, Brooke T. [Department of Pathology, University of Vermont College of Medicine, Burlington, VT (United States); Wouters, Emiel F.M. [Department of Respiratory Medicine, Maastricht University Medical Centre +, Maastricht University Maastricht (Netherlands); Reynaert, Niki L., E-mail: n.reynaert@maastrichtuniversity.nl [Department of Respiratory Medicine, Maastricht University Medical Centre +, Maastricht University Maastricht (Netherlands)

2016-06-15

Growth and development of the mature lung is a complex process orchestrated by a number of intricate developmental signaling pathways. Wingless-type MMTV-integration site (WNT) signaling plays critical roles in controlling branching morphogenesis cell differentiation, and formation of the conducting and respiratory airways. In addition, WNT pathways are often re-activated in mature lungs during repair and regeneration. WNT- signaling has been elucidated as a crucial contributor to the development of idiopathic pulmonary fibrosis as well as other hyper-proliferative lung diseases. Silicosis, a detrimental occupational lung disease caused by excessive inhalation of crystalline silica dust, is hallmarked by repeated cycles of damaging inflammation, epithelial hyperplasia, and formation of dense, hyalinized nodules of whorled collagen. However, mechanisms of epithelial cell hyperplasia and matrix deposition are not well understood, as most research efforts have focused on the pronounced inflammatory response. Microarray data from our previous studies has revealed a number of WNT-signaling and WNT-target genes altered by crystalline silica in human lung epithelial cells. In the present study, we utilize pathway analysis to designate connections between genes altered by silica in WNT-signaling networks. Furthermore, we confirm microarray findings by QRT-PCR and demonstrate both activation of canonical (β-catenin) and down-regulation of non-canonical (WNT5A) signaling in immortalized (BEAS-2B) and primary (PBEC) human bronchial epithelial cells. These findings suggest that WNT-signaling and cross-talk with other pathways (e.g. Notch), may contribute to proliferative, fibrogenic and inflammatory responses to silica in lung epithelial cells. - Highlights: • Pathway analysis reveals silica-induced WNT-signaling in lung epithelial cells. • Silica-induced canonical WNT-signaling is mediated by autocrine/paracrine signals. • Crystalline silica decreases non-canonical WNT

Nasal solitary chemoreceptor cell responses to bitter and trigeminal stimulants in vitro.

Science.gov (United States)

Gulbransen, Brian D; Clapp, Tod R; Finger, Thomas E; Kinnamon, Sue C

2008-06-01

Nasal trigeminal chemosensitivity in mice and rats is mediated in part by epithelial solitary chemoreceptor (chemosensory) cells (SCCs), but the exact role of these cells in chemoreception is unclear. Histological evidence suggests that SCCs express elements of the bitter taste transduction pathway including T2R (bitter taste) receptors, the G protein alpha-gustducin, PLCbeta2, and TRPM5, leading to speculation that SCCs are the receptor cells that mediate trigeminal nerve responses to bitter taste receptor ligands. To test this hypothesis, we used calcium imaging to determine whether SCCs respond to classic bitter-tasting or trigeminal stimulants. SCCs from the anterior nasal cavity were isolated from transgenic mice in which green fluorescent protein (GFP) expression was driven by either TRPM5 or gustducin. Isolated cells were exposed to a variety of test stimuli to determine which substances caused an increase in intracellular Ca2+ ([Ca2+]i). GFP-positive cells respond with increased [Ca2+]i to the bitter receptor ligand denatonium and this response is blocked by the PLC inhibitor U73122. In addition, GFP+ cells respond to the neuromodulators adenosine 5'-triphosphate and acetylcholine but only very rarely to other bitter-tasting or trigeminal stimuli. Our results demonstrate that TRPM5- and gustducin-expressing nasal SCCs respond to the T2R agonist denatonium via a PLC-coupled transduction cascade typical of T2Rs in the taste system.

[Nasal septal abscess].

Science.gov (United States)

Barril, María F; Ferolla, Fausto M; José, Pablo; Echave, Cecilia; Tomezzoli, Silvana; Fiorini, Sandra; López, Eduardo Luis

2008-12-01

A nasal septal abscess (NA) is defined as a collection of pus between the cartilage or bony septum and its normally applied mucoperichondrium or mucoperiostium. It is an uncommon disease which should be suspected in a patient with acute onset of nasal obstruction and recent history of nasal trauma, periodontal infection or an inflammatory process of the rhinosinusal region. We report a case of an 8-year-old boy with bilateral NA caused by community-acquired methicillin-resistant Staphylococcus aureus(MR-CO) in order to emphasize the importance of prompt diagnosis and adequate treatment to prevent the potentially dangerous spread of infection and the development of severe functional and cosmetic sequelae.

Cyanocobalamin Nasal Gel

Science.gov (United States)

... to supply extra vitamin B12 to people who need unusually large amounts of this vitamin because they are pregnant or have certain diseases. ... Cyanocobalamin nasal gel will supply you with enough vitamin B12 only as ... it regularly. You may need to use cyanocobalamin nasal gel every week for ...

Response of cultured human airway epithelial cells to X-rays and energetic α-particles

International Nuclear Information System (INIS)

Yang, T.C.; Holley, W.R.; Curtis, S.B.; Gruenert, D.C.; California Univ., San Francisco, CA

1990-01-01

Radon and its progeny, which emit α-particles during decay, may play an important role in inducing human lung cancer. To gain a better understanding of the biological effects of α-particles in human lung we studied the response of cultured human airway epithelial cells to X-rays and monoenergetic helium ions. Experimental results indicated that the radiation response of primary cultures was similar to that for airway epithelial cells that were transformed with a plasmid containing an origin-defective SV40 virus. The RBE for cell inactivation determined by the ratio of D 0 for X-rays to that for 8 MeV helium ions was 1.8-2.2. The cross-section for helium ions, calculated from the D 0 value, was about 24 μm 2 for cells of the primary culture. This cross-section is significantly smaller than the average geometric nuclear area (∼ 180 μm 2 ), suggesting that an average of 7.5 α-particles (8 MeV helium ions) per cell nucleus are needed to induce a lethal lesion. (author)

Histamine and tryptase in nasal lavage fluid after allergen challenge

DEFF Research Database (Denmark)

Jacobi, H H; Skov, P S; Poulsen, L K

1999-01-01

BACKGROUND: Antihistamines (H1-receptor antagonists) act by competitive antagonism of histamine at H1-receptors. In addition, high concentrations of some antihistamines inhibit allergen-induced histamine release from mast cells in vitro. OBJECTIVE: The purpose of this study was to determine...... the effect of intranasal azelastine or systemic cetirizine (both potent antihistamines) on the allergen-induced release of mast-cell mediators from the human nasal mucosa in vivo. METHODS: Patients allergic to birch pollen (n = 11) and control subjects not allergic to birch pollen (n = 5) were included......, nasal allergen challenges were performed, and the number of sneezes were counted. In addition, nasal lavage fluid was collected, and the levels of mast-cell mediators (histamine and tryptase) were measured. RESULTS: The allergen challenge of patients allergic to pollen produced sneezing...

Gene expression analysis uncovers novel Hedgehog interacting protein (HHIP) effects in human bronchial epithelial cells

Science.gov (United States)

Zhou, Xiaobo; Qiu, Weiliang; Sathirapongsasuti, J. Fah.; Cho, Michael H.; Mancini, John D.; Lao, Taotao; Thibault, Derek M.; Litonjua, Gus; Bakke, Per S.; Gulsvik, Amund; Lomas, David A.; Beaty, Terri H.; Hersh, Craig P.; Anderson, Christopher; Geigenmuller, Ute; Raby, Benjamin A.; Rennard, Stephen I.; Perrella, Mark A.; Choi, Augustine M.K.; Quackenbush, John; Silverman, Edwin K.

2013-01-01

Hedgehog Interacting Protein (HHIP) was implicated in chronic obstructive pulmonary disease (COPD) by genome-wide association studies (GWAS). However, it remains unclear how HHIP contributes to COPD pathogenesis. To identify genes regulated by HHIP, we performed gene expression microarray analysis in a human bronchial epithelial cell line (Beas-2B) stably infected with HHIP shRNAs. HHIP silencing led to differential expression of 296 genes; enrichment for variants nominally associated with COPD was found. Eighteen of the differentially expressed genes were validated by real-time PCR in Beas-2B cells. Seven of 11 validated genes tested in human COPD and control lung tissues demonstrated significant gene expression differences. Functional annotation indicated enrichment for extracellular matrix and cell growth genes. Network modeling demonstrated that the extracellular matrix and cell proliferation genes influenced by HHIP tended to be interconnected. Thus, we identified potential HHIP targets in human bronchial epithelial cells that may contribute to COPD pathogenesis. PMID:23459001

Nasal colonization of humans with methicillin-resistant Staphylococcus aureus (MRSA CC398 with and without exposure to pigs.

Directory of Open Access Journals (Sweden)

Christiane Cuny

Full Text Available BACKGROUND: Studies in several European countries and in North America revealed a frequent nasal colonization of livestock with MRSA CC398 and also in humans with direct professional exposure to colonized animals. The study presented here addresses the question of further transmission to non exposed humans. METHODS: After selecting 47 farms with colonized pigs in different regions of Germany we sampled the nares of 113 humans working daily with pigs and of their 116 non exposed family members. The same was performed in 18 veterinarians attending pig farms and in 44 of their non exposed family members. For investigating transmission beyond families we samples the nares of 462 pupils attending a secondary school in a high density pig farming area. MRSA were detected by direct culture on selective agar. The isolates were typed by means of spa-sequence typing and classification of SCCmec elements. For attribution of spa sequence types to clonal lineages as defined by multi locus sequence typing we used the BURP algorithm. Antibiotic susceptibility testing was performed by microbroth dilution assay. RESULTS: At the farms investigated 86% of humans exposed and only 4.3% of their family members were found to carry MRSA exhibiting spa-types corresponding to clonal complex CC398. Nasal colonization was also found in 45% of veterinarians caring for pig farms and in 9% of their non exposed family members. Multivariate analysis revealed that antibiotic usage prior to sampling beard no risk with respect to colonization. From 462 pupils only 3 were found colonized, all 3 were living on pig farms. CONCLUSION: These results indicate that so far the dissemination of MRSA CC398 to non exposed humans is infrequent and probably does not reach beyond familial communities.

Nasal Glial Heterotopia with Cleft Palate.

Science.gov (United States)

Chandna, Sudhir; Mehta, Milind A; Kulkarni, Abhishek Kishore

2018-01-01

Congenital midline nasal masses are rare anomalies of which nasal glial heterotopia represents an even rarer subset. We report a case of a 25-day-old male child with nasal glial heterotopia along with cleft palate suggesting embryonic fusion anomaly which was treated with excision and primary closure for nasal mass followed by palatal repair at later date.

Mycobacterium tuberculosis infection causes different levels of apoptosis and necrosis in human macrophages and alveolar epithelial cells.

Science.gov (United States)

Danelishvili, Lia; McGarvey, Jeffery; Li, Yong-Jun; Bermudez, Luiz E

2003-09-01

Mycobacterium tuberculosis interacts with macrophages and epithelial cells in the alveolar space of the lung, where it is able to invade and replicate in both cell types. M. tuberculosis-associated cytotoxicity to these cells has been well documented, but the mechanisms of host cell death are not well understood. We examined the induction of apoptosis and necrosis of human macrophages (U937) and type II alveolar epithelial cells (A549) by virulent (H37Rv) and attenuated (H37Ra) M. tuberculosis strains. Apoptosis was determined by both enzyme-linked immunosorbent assay (ELISA) and TdT-mediated dUTP nick end labelling (TUNEL) assay, whereas necrosis was evaluated by the release of lactate dehydrogenase (LDH). Both virulent and attenuated M. tuberculosis induced apoptosis in macrophages; however, the attenuated strain resulted in significantly more apoptosis than the virulent strain after 5 days of infection. In contrast, cytotoxicity of alveolar cells was the result of necrosis, but not apoptosis. Although infection with M. tuberculosis strains resulted in apoptosis of 14% of the cells on the monolayer, cell death associated with necrosis was observed in 59% of alveolar epithelial cells after 5 days of infection. Infection with M. tuberculosis suppressed apoptosis of alveolar epithelial cells induced by the kinase inhibitor, staurosporine. Because our findings suggest that M. tuberculosis can modulate the apoptotic response of macrophages and epithelial cells, we carried out an apoptosis pathway-specific cDNA microarray analysis of human macrophages and alveolar epithelial cells. Whereas the inhibitors of apoptosis, bcl-2 and Rb, were upregulated over 2.5-fold in infected (48 h) alveolar epithelial cells, the proapoptotic genes, bad and bax, were downregulated. The opposite was observed when U937 macrophages were infected with M. tuberculosis. Upon infection of alveolar epithelial cells with M. tuberculosis, the generation of apoptosis, as determined by the

Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett's epithelium.

Science.gov (United States)

Sato, Toshiro; Stange, Daniel E; Ferrante, Marc; Vries, Robert G J; Van Es, Johan H; Van den Brink, Stieneke; Van Houdt, Winan J; Pronk, Apollo; Van Gorp, Joost; Siersema, Peter D; Clevers, Hans

2011-11-01

We previously established long-term culture conditions under which single crypts or stem cells derived from mouse small intestine expand over long periods. The expanding crypts undergo multiple crypt fission events, simultaneously generating villus-like epithelial domains that contain all differentiated types of cells. We have adapted the culture conditions to grow similar epithelial organoids from mouse colon and human small intestine and colon. Based on the mouse small intestinal culture system, we optimized the mouse and human colon culture systems. Addition of Wnt3A to the combination of growth factors applied to mouse colon crypts allowed them to expand indefinitely. Addition of nicotinamide, along with a small molecule inhibitor of Alk and an inhibitor of p38, were required for long-term culture of human small intestine and colon tissues. The culture system also allowed growth of mouse Apc-deficient adenomas, human colorectal cancer cells, and human metaplastic epithelia from regions of Barrett's esophagus. We developed a technology that can be used to study infected, inflammatory, or neoplastic tissues from the human gastrointestinal tract. These tools might have applications in regenerative biology through ex vivo expansion of the intestinal epithelia. Studies of these cultures indicate that there is no inherent restriction in the replicative potential of adult stem cells (or a Hayflick limit) ex vivo. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

Downregulation of tight junction-associated MARVEL protein marvelD3 during epithelial-mesenchymal transition in human pancreatic cancer cells.

Science.gov (United States)

Kojima, Takashi; Takasawa, Akira; Kyuno, Daisuke; Ito, Tatsuya; Yamaguchi, Hiroshi; Hirata, Koichi; Tsujiwaki, Mitsuhiro; Murata, Masaki; Tanaka, Satoshi; Sawada, Norimasa

2011-10-01

The novel tight junction protein marvelD3 contains a conserved MARVEL (MAL and related proteins for vesicle trafficking and membrane link) domain like occludin and tricellulin. However, little is yet known about the detailed role and regulation of marvelD3 in normal epithelial cells and cancer cells, including pancreatic cancer. In the present study, we investigated marvelD3 expression in well and poorly differentiated human pancreatic cancer cell lines and normal pancreatic duct epithelial cells in which the hTERT gene was introduced into human pancreatic duct epithelial cells in primary culture, and the changes of marvelD3 during Snail-induced epithelial-mesenchymal transition (EMT) under hypoxia, TGF-β treatment and knockdown of FOXA2 in well differentiated pancreatic cancer HPAC cells. MarvelD3 was transcriptionally downregulated in poorly differentiated pancreatic cancer cells and during Snail-induced EMT of pancreatic cancer cells in which Snail was highly expressed and the fence function downregulated, whereas it was maintained in well differentiated human pancreatic cancer cells and normal pancreatic duct epithelial cells. Depletion of marvelD3 by siRNAs in HPAC cells resulted in downregulation of barrier functions indicated as a decrease in transepithelial electric resistance and an increase of permeability to fluorescent dextran tracers, whereas it did not affect fence function of tight junctions. In conclusion, marvelD3 is transcriptionally downregulated in Snail-induced EMT during the progression for the pancreatic cancer. Copyright © 2011 Elsevier Inc. All rights reserved.

Heat shock protein-27 protects human bronchial epithelial cells against oxidative stress–mediated apoptosis: possible implication in asthma

Science.gov (United States)

Merendino, Anna M.; Paul, Catherine; Vignola, Antonio M.; Costa, Maria A.; Melis, Mario; Chiappara, Giuseppina; Izzo, V.; Bousquet, J.; Arrigo, André-Patrick

2002-01-01

Inflammation of the human bronchial epithelium, as observed in asthmatics, is characterized by the selective death of the columnar epithelial cells, which desquamate from the basal cells. Tissue repair initiates from basal cells that resist inflammation. Here, we have evaluated the extent of apoptosis as well as the Hsp27 level of expression in epithelial cells from bronchial biopsy samples taken from normal and asthmatic subjects. Hsp27 is a chaperone whose expression protects against oxidative stress. We report that in asthmatic subjects the basal epithelium cells express a high level of Hsp27 but no apoptotic morphology. In contrast, apoptotic columnar cells are devoid of Hsp27 expression. Moreover, we observed a decreased resistance to hydrogen peroxide–induced apoptosis in human bronchial epithelial 16–HBE cells when they were genetically modified to express reduced levels of Hsp27. PMID:12482203

Measurement of secretion in nasal lavage

DEFF Research Database (Denmark)

Bisgaard, H; Krogsgaard, O W; Mygind, N

1987-01-01

1. The amount of admixture in nasal lavage fluids was determined by addition of 99mTc labelled albumin, providing a correction factor for measurements of cellular material and humoral substances in nasal lavage return as well as a quantitative measure of nasal secretions. 2. Albumin was chosen...... secretion to be carried out on the whole sample of lavage fluid, thereby avoiding the necessity of complete admixture between marker and lavage fluid which would be pertinent to marker molecules measured chemically. The radiation from a nasal lavage is minimal and the procedure is fully acceptable...... of the nose, yet not the oropharynx. 5. A dose related increase in nasal secretion harvested by the nasal lavage in 10 persons challenged with histamine chloride could be demonstrated by this technique. 6. It is concluded that the use of 99mTc-albumin in a nasal washing provides a safe, simple and quick...

Differential transcriptional regulation of IL-8 expression by human airway epithelial cells exposed to diesel exhaust particles

International Nuclear Information System (INIS)

Tal, Tamara L.; Simmons, Steven O.; Silbajoris, Robert; Dailey, Lisa; Cho, Seung-Hyun; Ramabhadran, Ram; Linak, William; Reed, William; Bromberg, Philip A.; Samet, James M.

2010-01-01

Exposure to diesel exhaust particles (DEP) induces inflammatory signaling characterized by MAP kinase-mediated activation of NFkB and AP-1 in vitro and in bronchial biopsies obtained from human subjects exposed to DEP. NFkB and AP-1 activation results in the upregulation of genes involved in promoting inflammation in airway epithelial cells, a principal target of inhaled DEP. IL-8 is a proinflammatory chemokine expressed by the airway epithelium in response to environmental pollutants. The mechanism by which DEP exposure induces IL-8 expression is not well understood. In the current study, we sought to determine whether DEP with varying organic content induces IL-8 expression in lung epithelial cells, as well as, to develop a method to rapidly evaluate the upstream mechanism(s) by which DEP induces IL-8 expression. Exposure to DEP with varying organic content differentially induced IL-8 expression and IL-8 promoter activity human airway epithelial cells. Mutational analysis of the IL-8 promoter was also performed using recombinant human cell lines expressing reporters linked to the mutated promoters. Treatment with a low organic-containing DEP stimulated IL-8 expression by a mechanism that is predominantly NFkB-dependent. In contrast, exposure to high organic-containing DEP induced IL-8 expression independently of NFkB through a mechanism that requires AP-1 activity. Our study reveals that exposure to DEP of varying organic content induces proinflammatory gene expression through multiple specific mechanisms in human airway epithelial cells. The approaches used in the present study demonstrate the utility of a promoter-reporter assay ensemble for identifying transcriptional pathways activated by pollutant exposure.

Ex vivo 2D and 3D HSV-2 infection model using human normal vaginal epithelial cells.

Science.gov (United States)

Zhu, Yaqi; Yang, Yan; Guo, Juanjuan; Dai, Ying; Ye, Lina; Qiu, Jianbin; Zeng, Zhihong; Wu, Xiaoting; Xing, Yanmei; Long, Xiang; Wu, Xufeng; Ye, Lin; Wang, Shubin; Li, Hui

2017-02-28

Herpes simplex virus type 2 (HSV-2) infects human genital mucosa and establishes life-long latent infection. It is unmet need to establish a human cell-based microphysiological system for virus biology and anti-viral drug discovery. One of barriers is lacking of culture system of normal epithelial cells in vitro over decades. In this study, we established human normal vaginal epithelial cell (HNVEC) culture using co-culture system. HNVEC cells were then propagated rapidly and stably in a defined culture condition. HNVEC cells exhibited a normal diploid karyotype and formed the well-defined and polarized spheres in matrigel three-dimension (3D) culture, while malignant cells (HeLa) formed disorganized and nonpolar solid spheres. HNVEC cells had a normal cellular response to DNA damage and had no transforming property using soft agar assays. HNVEC expressed epithelial marker cytokeratin 14 (CK14) and p63, but not cytokeratin 18 (CK18). Next, we reconstructed HNVEC-derived 3D vaginal epithelium using air-liquid interface (ALI) culture. This 3D vaginal epithelium has the basal and apical layers with expression of epithelial markers as its originated human vaginal tissue. Finally, we established an HSV-2 infection model based on the reconstructed 3D vaginal epithelium. After inoculation of HSV-2 (G strain) at apical layer of the reconstructed 3D vaginal epithelium, we observed obvious pathological effects gradually spreading from the apical layer to basal layer with expression of a viral protein. Thus, we established an ex vivo 2D and 3D HSV-2 infection model that can be used for HSV-2 virology and anti-viral drug discovery.

Objective measurements for grading the nasal esthetics on Basal view in individuals with secondary cleft nasal deformity.

Science.gov (United States)

He, Xing; Li, Hua; Shao, Yan; Shi, Bing

2015-01-01

The purpose of this study is to ascertain objective nasal measurements from the basal view that are predictive of nasal esthetics in individuals with secondary cleft nasal deformity. Thirty-three patients who had undergone unilateral cleft lip repair were retrospectively reviewed in this study. The degree of nasal deformity was subjectively ranked by seven surgeons using standardized basal-view measurements. Nine physical objective parameters including angles and ratios were measured. Correlations and regressions between these objective and subjective measurements were then analyzed. There was high concordance in subjective measurements by different surgeons (Kendall's harmonious coefficient = W = .825, P = .006). The strongest predictive factors for nasal aesthetics were the ratio of length of nasal alar (r = .370, P = .034) and the degree of deviation of the columnar axis (r = .451, P = .008). The columellar angle had a more powerful effect in rating nasal esthetics. There was reliable concordance in subjective ranking of nasal esthetics by surgeons. Measurement of the columnar angle may serve as an independent, objective predictor of esthetics of the nose.

Staphylococcus aureus induces IL-8 expression through its lipoproteins in the human intestinal epithelial cell, Caco-2.

Science.gov (United States)

Kang, Seok-Seong; Noh, Su Young; Park, Ok-Jin; Yun, Cheol-Heui; Han, Seung Hyun

2015-09-01

Staphylococcus aureus can cause the intestinal inflammatory diseases. However, little is known about the molecular mechanism of S. aureus infection in the intestine. In the present study, we investigated whether S. aureus could stimulate human intestinal epithelial cells triggering inflammation. When the human intestinal epithelial cell-line, Caco-2, and the primary colon cells were stimulated with ethanol-inactivated S. aureus, IL-8 expression was induced in a dose-dependent manner. The inactivated S. aureus preferentially stimulated Toll-like receptor (TLR) 2 rather than TLR4. Lipoproteins, lipoteichoic acid (LTA), and peptidoglycan (PGN) are considered as potential TLR2 ligands of S. aureus. Interestingly, S aureus lipoproteins and Pam2CSK4 mimicking Gram-positive bacterial lipoproteins, but not LTA and PGN of S. aureus, significantly induced IL-8 expression in Caco-2 cells. Furthermore, lipoprotein-deficient S. aureus mutant strain failed to induce IL-8 production. Collectively, these results suggest that S. aureus stimulates the human intestinal epithelial cells to induce the chemokine IL-8 production through its lipoproteins, potentially contributing the development of intestinal inflammation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Relative position and extent of the nasal and orbital openings in Gorilla, Pan and the human species from the study of their areas and centres of area.

Science.gov (United States)

Schmittbuhl, M; Le Minor, J M; Schaaf, A

1996-01-01

In order to quantify the relative position and extent of the nasal and orbital openings in hominoid primates, a new methodology based on image analysis was developed and applied to a series of 134 hominoid skulls (52 Gorilla gorilla; 30 Pan troglodytes; 44 Homo sapiens, and, as comparison material, 8 Pongo pygmaeus). The areas and the centres of area of the orbital and nasal openings were determined automatically. The orbitonasal triangle connecting these three centres of area was then constructed. This triangle was used to quantify the elongation of the face. It was most elongated in gorilla, shortest in the human species and intermediate in Pan; the elongation in Pongo was close to that in Gorilla. The proportions of the areas of the orbital and nasal openings in the face were related to the extent of the bony structures of the midface and were thus used to quantify the facial robustness. A robust face was demonstrated in Gorilla, but a gracile face in the human species. Robusticity in Pan was intermediate.

High Frequency and Diversity of Antimicrobial Activities Produced by Nasal Staphylococcus Strains against Bacterial Competitors.

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Daniela Janek

2016-08-01

Full Text Available The human nasal microbiota is highly variable and dynamic often enclosing major pathogens such as Staphylococcus aureus. The potential roles of bacteriocins or other mechanisms allowing certain bacterial clones to prevail in this nutrient-poor habitat have hardly been studied. Of 89 nasal Staphylococcus isolates, unexpectedly, the vast majority (84% was found to produce antimicrobial substances in particular under habitat-specific stress conditions, such as iron limitation or exposure to hydrogen peroxide. Activity spectra were generally narrow but highly variable with activities against certain nasal members of the Actinobacteria, Proteobacteria, Firmicutes, or several groups of bacteria. Staphylococcus species and many other Firmicutes were insusceptible to most of the compounds. A representative bacteriocin was identified as a nukacin-related peptide whose inactivation reduced the capacity of the producer Staphylococcus epidermidis IVK45 to limit growth of other nasal bacteria. Of note, the bacteriocin genes were found on mobile genetic elements exhibiting signs of extensive horizontal gene transfer and rearrangements. Thus, continuously evolving bacteriocins appear to govern bacterial competition in the human nose and specific bacteriocins may become important agents for eradication of notorious opportunistic pathogens from human microbiota.

Peroxisome proliferator-activated receptor-γ agonists inhibit the replication of respiratory syncytial virus (RSV) in human lung epithelial cells

International Nuclear Information System (INIS)

Arnold, Ralf; Koenig, Wolfgang

2006-01-01

We have previously shown that peroxisome proliferator-activated receptor-γ (PPARγ) agonists inhibited the inflammatory response of RSV-infected human lung epithelial cells. In this study, we supply evidence that specific PPARγ agonists (15d-PGJ 2 , ciglitazone, troglitazone, Fmoc-Leu) efficiently blocked the RSV-induced cytotoxicity and development of syncytia in tissue culture (A549, HEp-2). All PPARγ agonists under study markedly inhibited the cell surface expression of the viral G and F protein on RSV-infected A549 cells. This was paralleled by a reduced cellular amount of N protein-encoding mRNA determined by real-time RT-PCR. Concomitantly, a reduced release of infectious progeny virus into the cell supernatants of human lung epithelial cells (A549, normal human bronchial epithelial cells (NHBE)) was observed. Similar results were obtained regardless whether PPARγ agonists were added prior to RSV infection or thereafter, suggesting that the agonists inhibited viral gene expression and not the primary adhesion or fusion process

Human papillomavirus-32-associated focal epithelial hyperplasia accompanying HPV-16-positive papilloma-like lesions in oral mucosa.

Science.gov (United States)

Liu, Na; Wang, Jiayi; Lei, Lei; Li, Yanzhong; Zhou, Min; Dan, Hongxia; Zeng, Xin; Chen, Qianming

2013-05-01

Human papillomavirus infection can cause a variety of benign or malignant oral lesions, and the various genotypes can cause distinct types of lesions. To our best knowledge, there has been no report of 2 different human papillomavirus-related oral lesions in different oral sites in the same patient before. This paper reported a patient with 2 different oral lesions which were clinically and histologically in accord with focal epithelial hyperplasia and oral papilloma, respectively. Using DNA extracted from these 2 different lesions, tissue blocks were tested for presence of human papillomavirus followed by specific polymerase chain reaction testing for 6, 11, 13, 16, 18, and 32 subtypes in order to confirm the clinical diagnosis. Finally, human papillomavirus-32-positive focal epithelial hyperplasia accompanying human papillomavirus-16-positive oral papilloma-like lesions were detected in different sites of the oral mucosa. Nucleotide sequence sequencing further confirmed the results. So in our clinical work, if the simultaneous occurrences of different human papillomavirus associated lesions are suspected, the multiple biopsies from different lesions and detection of human papillomavirus genotype are needed to confirm the diagnosis.

Nasal glial heterotopia with cleft palate

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Sudhir Chandna

2018-01-01

Full Text Available Congenital midline nasal masses are rare anomalies of which nasal glial heterotopia represents an even rarer subset. We report a case of a 25-day-old male child with nasal glial heterotopia along with cleft palate suggesting embryonic fusion anomaly which was treated with excision and primary closure for nasal mass followed by palatal repair at later date.

Prevalence of human papillomavirus, Epstein-Barr virus, p21, and p53 expression in sinonasal inverted papilloma, nasal polyp, and hypertrophied turbinate in Hong Kong patients.

Science.gov (United States)

Sham, C L; To, K F; Chan, Paul K S; Lee, Dennis L Y; Tong, Michael C F; van Hasselt, C Andrew

2012-04-01

The purpose of this study of human papillomavirus (HPV), Epstein-Barr virus (EBV), p21, and p53 in sinonasal inverted papilloma (IP) was to help elucidate its pathogenesis. Seventy-three IPs, 48 nasal polyps, and 85 hypertrophied turbinates were subjected to HPV polymerase chain reaction (PCR) study. Seventy-three IPs, 30 nasal polyps, and 32 hypertrophied turbinates were subjected to EBV in situ hybridization (ISH), p21, and p53 immunohistochemical (IHC) studies. HPV was positive in 3 of 73 IPs (4.1%). All specimens were EBV negative. In all, 99% of IPs showed strong and diffuse p21 nuclear reactivity. Most nasal polyps and hypertrophied turbinates showed weak to moderate immunoreactivity of the basal and parabasal cells. Only focal p53 immunoreactivity of the basal and parabasal cells was found in 19% of IPs and 40% of nasal polyps. HPV prevalence of our IP is low. EBV is not present in IP. High p21 and low p53 expression in IP suggests a non-p53-dependent regulation pathway. Copyright © 2011 Wiley Periodicals, Inc.

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

Science.gov (United States)

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 ...

Nasal endotracheal intubation in a premature infant with a nasal encephalocele.

Science.gov (United States)

Bannister, C M; Kashab, M; Dagestani, H; Placzek, M

1993-01-01

After a difficult nasal intubation a premature infant leaked cerebrospinal fluid (CSF) from one nostril. After developing bacterial meningitis, the baby was referred for neurosurgical management of the CSF fistula. Transaxial computed tomograms demonstrated a nasal encephalocele, but coronal scans were needed to show the defect in the cribriform plate. Images PMID:8346963

Anti-apoptotic effects of Z alpha1-antitrypsin in human bronchial epithelial cells.

LENUS (Irish Health Repository)

Greene, C M

2010-05-01

alpha(1)-antitrypsin (alpha(1)-AT) deficiency is a genetic disease which manifests as early-onset emphysema or liver disease. Although the majority of alpha(1)-AT is produced by the liver, it is also produced by bronchial epithelial cells, amongst others, in the lung. Herein, we investigate the effects of mutant Z alpha(1)-AT (ZAAT) expression on apoptosis in a human bronchial epithelial cell line (16HBE14o-) and delineate the mechanisms involved. Control, M variant alpha(1)-AT (MAAT)- or ZAAT-expressing cells were assessed for apoptosis, caspase-3 activity, cell viability, phosphorylation of Bad, nuclear factor (NF)-kappaB activation and induced expression of a selection of pro- and anti-apoptotic genes. Expression of ZAAT in 16HBE14o- cells, like MAAT, inhibited basal and agonist-induced apoptosis. ZAAT expression also inhibited caspase-3 activity by 57% compared with control cells (p = 0.05) and was a more potent inhibitor than MAAT. Whilst ZAAT had no effect on the activity of Bad, its expression activated NF-kappaB-dependent gene expression above control or MAAT-expressing cells. In 16HBE14o- cells but not HEK293 cells, ZAAT upregulated expression of cIAP-1, an upstream regulator of NF-kappaB. cIAP1 expression was increased in ZAAT versus MAAT bronchial biopsies. The data suggest a novel mechanism by which ZAAT may promote human bronchial epithelial cell survival.

Effects of conditioned media from human amniotic epithelial cells on corneal alkali injuries in rabbits

Science.gov (United States)

Kim, Tae-Hyun; Park, Young-Woo; Ahn, Jae-Sang; Ahn, Jeong-Taek; Kim, Se-Eun; Jeong, Man-Bok; Seo, Min-Su; Kang, Kyung-Sun

2013-01-01

This study was performed to evaluate the effects of conditioned media (CM) from human amniotic epithelial cells (HAECs) on the corneal wound healing process. Eighteen rabbits (36 eyes) were used and randomly assigned to three groups according treatment: CM from HAECs (group 1), vehicle alone (group 2), and saline (group 3). Corneal alkali injuries were induced with 1 N sodium hydroxide. Each reagent used for treatment evaluation was injected into the dorsal bulbar subconjunctiva and the area of the corneal epithelial defect was measured every other day. Two animals from each group were euthanized at a time on days 3, 7, and 15, and the cornea was removed for histological examination. The sum of the epithelial defect areas measured on day 0 to day 6 as well as day 0 to day 14 in group 1 was significantly smaller than those of other groups. Histological examination revealed that the group 1 corneas had less inflammatory cell infiltration and showed more intact epithelial features compared to the other groups. These results suggest that CM from HAECs promote corneal wound healing in rabbits. PMID:23388445

Measurement of secretion in nasal lavage

DEFF Research Database (Denmark)

Bisgaard, H; Krogsgaard, O W; Mygind, N

1987-01-01

1. The amount of admixture in nasal lavage fluids was determined by addition of 99mTc labelled albumin, providing a correction factor for measurements of cellular material and humoral substances in nasal lavage return as well as a quantitative measure of nasal secretions. 2. Albumin was chosen...... as marker molecule, since only negligible amounts were absorbed or adsorbed to the mucosa during the nasal lavage. 3. Labelling of the albumin with 99mTc ensured an accuracy of measurements only limited by the precision of the weighing. The isotope allowed for the determination of the amount of admixed...... of the nose, yet not the oropharynx. 5. A dose related increase in nasal secretion harvested by the nasal lavage in 10 persons challenged with histamine chloride could be demonstrated by this technique. 6. It is concluded that the use of 99mTc-albumin in a nasal washing provides a safe, simple and quick...

Appraisal of transverse nasal groove: a study.

Science.gov (United States)

Sathyanarayana, Belagola D; Basavaraj, Halevoor B; Nischal, Kuchangi C; Swaroop, Mukunda R; Umashankar, Puttagangu N; Agrawal, Dhruv P; Swamy, Suchetha S; Okram, Sarda

2012-01-01

Transverse nasal groove is a condition of cosmetic concern which awaits due recognition and has been widely described as a shallow groove that extends transversely over the dorsum of nose. However, we observed variations in the clinical presentations of this entity, hitherto undescribed in literature. We conducted a clinicoepidemiological study of transverse nasal lesions in patients attending our outpatient department. We conducted a prospective observational study. We screened all patients attending our out-patient department for presence of transverse nasal lesions, signs of any dermatosis and associated other skin conditions. One hundred patients were recruited in the study. Females (80%) predominated over males. Most patients were of 15-45 years age group (70%). Majority of the transverse nasal lesions were classical transverse nasal groove (39%) and others included transverse nasal line (28%), strip (28%), ridge (4%) and loop (1%). Seborrhoeic diathesis was the most common condition associated with transverse nasal lesion. Occurrence of transverse nasal line, strip, ridge and loop, in addition to classical transverse nasal groove implies that latter is actually a subset of transverse nasal lesions. Common association of this entity with seborrheic dermatitis, seborrhea and dandruff raises a possibility of whether transverse nasal lesion is a manifestation of seborrheic diathesis.

Transcriptional profiling of putative human epithelial stem cells

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Koçer Salih S

2008-07-01

may be enriched for stem cells. This study is the first comprehensive gene expression profile of putative human epithelial stem cells and their progeny that were isolated directly from neonatal foreskin tissue. Our study is important for understanding self renewal and differentiation of epidermal stem cells, and for elucidating signaling pathways involved in those processes. The generated data base may serve those working with other human epithelial tissue progenitors.

Staphylococcus aureus nasal carriage could be a risk for development of clinical infections in rabbits

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Laura Selva Martínez

2015-09-01

Full Text Available Although nasal carriage has been described as a risk factor for Staphylococcus aureus infections in humans, there is a scarcity of studies about S. aureus nasal carriers in animals. In rabbits, S. aureus is one of the most important pathogens responsible for a number of different types of infections. This study was designed to determine the extent of staphylococcal nasal carriage and to establish whether a relationship exists between nasal carriage and development of lesions. One hundred and sixteen rabbits with and without chronic signs of staphylococcosis from 6 industrial rabbitries were monitored. Nasal swabs for microbiological assessments were obtained from all animals. Microbiological results showed that 56% of the animals carried S. aureus in their nasal cavities with significantly higher incidence in animals with staphylococcal-related lesions (84.2% compared to apparently healthy animals (28.8%. Additionally, the S. aureus strains isolated from the nasal cavity and lesions were clonally related in 91.7% of animals. This suggests that nasal carriage of S. aureus in rabbits could be a risk for development of clinical infections.

Characterizing adult human nasal airway dimensions

International Nuclear Information System (INIS)

Guilmette, R.A.; Griffith, W.C.

1994-01-01

Respiratory tract models used in calculating radiation dose from exposure to inhaled radioactive aerosols have only recently focused attention on the importance of the nasal airways (NAs). Because the NAs are the first tissues of the respiratory tract available for aerosol deposition in normally nose-breathing people, any deposition of aerosol in this anatomical structure will reduce the amounts available to be deposited in the remainder of the respiratory tract. Thus, uncertainties in estimating the deposition fractions in the NAs will propagate throughout the remainder of the respiratory tract, creating errors in the calculated dose estimates. Additionally, there is evidence that the NAs are also at risk for induction of cancer from exposure to certain occupational aerosols such as wood dust, leather dust, chromium, and nickel. The purpose of this investigation was to conduct an anatomical study to assess the variabilities in NA dimensions

Lifespan Extension and Sustained Expression of Stem Cell Phenotype of Human Breast Epithelial Stem Cells in a Medium with Antioxidants

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Kai-Hung Wang

2016-01-01

Full Text Available We have previously reported the isolation and culture of a human breast epithelial cell type with stem cell characteristics (Type I HBEC from reduction mammoplasty using the MSU-1 medium. Subsequently, we have developed several different normal human adult stem cell types from different tissues using the K-NAC medium. In this study, we determined whether this low calcium K-NAC medium with antioxidants (N-acetyl-L-cysteine and L-ascorbic acid-2-phosphate is a better medium to grow human breast epithelial cells. The results clearly show that the K-NAC medium is a superior medium for prolonged growth (cumulative population doubling levels ranged from 30 to 40 of normal breast epithelial cells that expressed stem cell phenotypes. The characteristics of these mammary stem cells include deficiency in gap junctional intercellular communication, expression of Oct-4, and the ability to differentiate into basal epithelial cells and to form organoid showing mammary ductal and terminal end bud-like structures. Thus, this new method of growing Type I HBECs will be very useful in future studies of mammary development, breast carcinogenesis, chemoprevention, and cancer therapy.

Nasal budesonide offers superior symptom relief in perennial allergic rhinitis in comparison to nasal azelastine.

Science.gov (United States)

Stern, M A; Wade, A G; Ridout, S M; Cambell, L M

1998-10-01

Allergic rhinitis is usually treated with oral antihistamines or nasal steroids. Topically active nasal antihistamine is a new treatment modality for allergic rhinitis. The efficacy in comparison to well established topical treatment alternatives is not fully known. To compare the efficacy of intranasally administered azelastine to budesonide, at their respectively recommended dosage, on the symptoms of perennial rhinitis patients. A placebo-controlled, randomized, parallel group study was conducted to compare the efficacy and tolerability of intranasal budesonide aqueous suspension (256 microg once daily) with azelastine hydrochloride nasal spray (280 microg twice daily (560 microg/day)) and with placebo in the treatment of perennial allergic rhinitis. The 195 patients (with at least a 2-year history of perennial allergic rhinitis) recorded individual nasal symptom scores, the degree of symptom control achieved and any adverse events experienced over a 2-week baseline period and a 6-week treatment period. Following treatment, the reductions in mean combined and individual nasal symptom scores from baseline values were significantly greater in the budesonide group compared with the placebo group (P < .0001 for all variables except runny nose P = .01). In patients treated with budesonide, there were also significantly larger reductions from baseline values in combined nasal symptom scores (P < .01) and in scores for all individual nasal symptoms (P < or = .05) compared with those treated with azelastine. The reductions from baseline in both combined and individual nasal symptom scores did not differ between azelastine and placebo. The study medications were well tolerated, producing no unexpected or serious treatment-related adverse events. A once-daily dose of 256 microg of intranasal budesonide aqueous suspension is significantly more effective at relieving the symptoms of perennial allergic rhinitis compared with a twice daily dose of 280 microg of azelastine

Variations in the ultrastructure of human nasal cilia including abnormalities found in retinitis pigmentosa.

OpenAIRE

Fox, B; Bull, T B; Arden, G B

1980-01-01

The electron microscopic structure of cilia from the inferior turbinate of the nose was studied in 12 adults, four with chronic sinusitis, one with allergic rhinitis, two with bronchiectasis, three with deviated nasal septum, and two normals. The changes are compared with those found in nasal cilia in 14 patients with retinitis pigmentosa. There were compound cilia in the seven cases with chronic sinusitis, allergic rhinitis, and bronchiectasis but, apart from this, the structure of the cilia...

The Bacterial Species Campylobacter jejuni Induce Diverse Innate Immune Responses in Human and Avian Intestinal Epithelial Cells

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Daniel A. John

2017-09-01

Full Text Available Campylobacter remain the major cause of human gastroenteritis in the Developed World causing a significant burden to health services. Campylobacter are pathogens in humans and chickens, although differences in mechanistic understanding are incomplete, in part because phenotypic strain diversity creates inconsistent findings. Here, we took Campylobacter jejuni isolates (n = 100 from multi-locus sequence typed collections to assess their pathogenic diversity, through their inflammatory, cytotoxicity, adhesion, invasion and signaling responses in a high-throughput model using avian and human intestinal epithelial cells. C. jejuni induced IL-8 and CXCLi1/2 in human and avian epithelial cells, respectively, in a MAP kinase-dependent manner. In contrast, IL-10 responses in both cell types were PI 3-kinase/Akt-dependent. C. jejuni strains showed diverse levels of invasion with high invasion dependent on MAP kinase signaling in both cell lines. C. jejuni induced diverse cytotoxic responses in both cell lines with cdt-positive isolates showing significantly higher toxicity. Blockade of endocytic pathways suggested that invasion by C. jejuni was clathrin- and dynamin-dependent but caveolae- independent in both cells. In contrast, IL-8 (and CXCLi1/2 production was dependent on clathrin, dynamin, and caveolae. This study is important because of its scale, and the data produced, suggesting that avian and human epithelial cells use similar innate immune pathways where the magnitude of the response is determined by the phenotypic diversity of the Campylobacter species.

Neural differentiation of choroid plexus epithelial cells: role of human traumatic cerebrospinal fluid

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Elham Hashemi

2017-01-01

Full Text Available As the key producer of cerebrospinal fluid (CSF, the choroid plexus (CP provides a unique protective system in the central nervous system. CSF components are not invariable and they can change based on the pathological conditions of the central nervous system. The purpose of the present study was to assess the effects of non-traumatic and traumatic CSF on the differentiation of multipotent stem-like cells of CP into the neural and/or glial cells. CP epithelial cells were isolated from adult male rats and treated with human non-traumatic and traumatic CSF. Alterations in mRNA expression of Nestin and microtubule-associated protein (MAP2, as the specific markers of neurogenesis, and astrocyte marker glial fibrillary acidic protein (GFAP in cultured CP epithelial cells were evaluated using quantitative real-time PCR. The data revealed that treatment with CSF (non-traumatic and traumatic led to increase in mRNA expression levels of MAP2 and GFAP. Moreover, the expression of Nestin decreased in CP epithelial cells treated with non-traumatic CSF, while treatment with traumatic CSF significantly increased its mRNA level compared to the cells cultured only in DMEM/F12 as control. It seems that CP epithelial cells contain multipotent stem-like cells which are inducible under pathological conditions including exposure to traumatic CSF because of its compositions.

PKC activation induces inflammatory response and cell death in human bronchial epithelial cells.

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Hyunhee Kim

Full Text Available A variety of airborne pathogens can induce inflammatory responses in airway epithelial cells, which is a crucial component of host defence. However, excessive inflammatory responses and chronic inflammation also contribute to different diseases of the respiratory system. We hypothesized that the activation of protein kinase C (PKC is one of the essential mechanisms of inflammatory response in airway epithelial cells. In the present study, we stimulated human bronchial lung epithelial (BEAS-2B cells with the phorbol ester Phorbol 12, 13-dibutyrate (PDBu, and examined gene expression profile using microarrays. Microarray analysis suggests that PKC activation induced dramatic changes in gene expression related to multiple cellular functions. The top two interaction networks generated from these changes were centered on NFκB and TNF-α, which are two commonly known pathways for cell death and inflammation. Subsequent tests confirmed the decrease in cell viability and an increase in the production of various cytokines. Interestingly, each of the increased cytokines was differentially regulated at mRNA and/or protein levels by different sub-classes of PKC isozymes. We conclude that pathological cell death and cytokine production in airway epithelial cells in various situations may be mediated through PKC related signaling pathways. These findings suggest that PKCs can be new targets for treatment of lung diseases.

Efeito do exercício físico sobre o volume nasal Effects of physical exercise in nasal volume

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Marconi Teixeira Fonseca

2006-04-01

Full Text Available A variação da permeabilidade nasal tem sido demonstrada usando-se várias técnicas de exame. As estruturas nasais geram uma resistência que representa cerca de 50% da resistência respiratória total. O exercício físico é um dos fatores que pode causar um efeito vasoconstritor sobre a mucosa nasal. OBJETIVO: O objetivo deste estudo é avaliar o grau de mudança do volume nasal após exercício físico e o tempo de retorno aos níveis basais. MATERIAIS E MÉTODOS: Dezenove indivíduos foram submetidos à realização de teste físico em bicicleta ergométrica. O volume nasal foi obtido através da rinometria acústica, realizada em repouso, após o fim do exercício físico, e nos minutos décimo e vigésimo de seu final. RESULTADOS: Os resultados rinométricos mostram um aumento estatisticamente significativo do volume nasal (p The nasal permeability has been demonstrated using several exams. Nasal structures produces a resistance to the nasal air flux that represents over 50% of the total respiratory resistance. Physical exercises is a factor that brings a vasoconstrictor effect over nasal mucosa. AINS: Evaluate the improvement degree of nasal volume after aerobic physical exercises and time to return to previous levels. SUBJECTS AND METHODS: Nineteen heathly subjects were submitted to aerobic exercise in ergometric bike. The nasal volume was obtained by Acoustic Rhinometry perfomed in rest, after aerobic exercise, 10o and 20o minutes after the aerobic exercise. RESULTS: Rhynometrics results shows a statically and significant increase of nasal volume (p<0,001. The nasal volume, in twenty minutes, returns nearby the rest levels. CONCLUSIONS: Aerobic exercises, generally, increases the nasal volume. However, the increase of nasal volume was transitory, and occurs a major reduction of increase in the first ten minutes after the exercises ends, and perform a greater vasoconstrictor effect over nasal mucosa, Twenty minutes after the physical

Climatic effects on the nasal complex: a CT imaging, comparative anatomical, and morphometric investigation of Macaca mulatta and Macaca fascicularis.

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Márquez, Samuel; Laitman, Jeffrey T

2008-11-01

Previous studies exploring the effects of climate on the nasal region have largely focused on external craniofacial linear parameters, using dry crania of modern human populations. This investigation augments traditional craniofacial morphometrics with internal linear and volumetric measures of the anatomic units comprising the nasal complex (i.e., internal nasal cavity depth, maxillary sinus volumes). The study focuses on macaques (i.e., Macaca mulatta and Macaca fascicularis) living at high and low altitudes, rather than on humans, since the short residency of migratory human populations may preclude using them as reliable models to test the long-term relationship of climate to nasal morphology. It is hypothesized that there will be significant differences in nasal complex morphology among macaques inhabiting different climates. This study integrated three different approaches: CT imaging, comparative anatomy, and morphometrics-in an effort to better understand the morphological structure and adaptive nature of the nasal complex. Results showed statistically significant differences when subsets of splanchnocranial and neurocranial variables were regressed against total maxillary sinus volume for particular taxa. For example, basion-hormion was significant for M. fascicularis, whereas choanal dimensions were significant only for M. mulatta. Both taxa revealed strong correlation between sinus volume and prosthion to staphylion distance, which essentially represents the length of the nasal cavity floor-and is by extension an indicator of the air conditioning capacity of the nasal region. These results clearly show that climatic effects play a major role in shaping the anatomy of the nasal complex in closely related species. The major influence upon these differing structures appears to be related to respiratory-related adaptations subserving differing climatic factors. In addition, the interdependence of the paranasal sinuses with other parts of the complex strongly

Niclosamide inhibits epithelial-mesenchymal transition and tumor growth in lapatinib-resistant human epidermal growth factor receptor 2-positive breast cancer.

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Liu, Junjun; Chen, Xiaosong; Ward, Toby; Mao, Yan; Bockhorn, Jessica; Liu, Xiaofei; Wang, Gen; Pegram, Mark; Shen, Kunwei

2016-02-01

Acquired resistance to lapatinib, a human epidermal growth factor receptor 2 kinase inhibitor, remains a clinical problem for women with human epidermal growth factor receptor 2-positive advanced breast cancer, as metastasis is commonly observed in these patients. Niclosamide, an anti-helminthic agent, has recently been shown to exhibit cytotoxicity to tumor cells with stem-like characteristics. This study was designed to identify the mechanisms underlying lapatinib resistance and to determine whether niclosamide inhibits lapatinib resistance by reversing epithelial-mesenchymal transition. Here, two human epidermal growth factor receptor 2-positive breast cancer cell lines, SKBR3 and BT474, were exposed to increasing concentrations of lapatinib to establish lapatinib-resistant cultures. Lapatinib-resistant SKBR3 and BT474 cells exhibited up-regulation of the phenotypic epithelial-mesenchymal transition markers Snail, vimentin and α-smooth muscle actin, accompanied by activation of nuclear factor-кB and Src and a concomitant increase in stem cell marker expression (CD44(high)/CD24(low)), compared to naive lapatinib-sensitive SKBR3 and BT474 cells, respectively. Interestingly, niclosamide reversed epithelial-mesenchymal transition, induced apoptosis and inhibited cell growth by perturbing aberrant signaling pathway activation in lapatinib-resistant human epidermal growth factor receptor 2-positive cells. The ability of niclosamide to alleviate stem-like phenotype development and invasion was confirmed. Collectively, our results demonstrate that lapatinib resistance correlates with epithelial-mesenchymal transition and that niclosamide inhibits lapatinib-resistant cell viability and epithelial-mesenchymal transition. These findings suggest a role of niclosamide or derivatives optimized for more favorable bioavailability not only in reversing lapatinib resistance but also in reducing metastatic potential during the treatment of human epidermal growth factor receptor

Loss of prostasin (PRSS8) in human bladder transitional cell carcinoma cell lines is associated with epithelial-mesenchymal transition (EMT)

International Nuclear Information System (INIS)

Chen, Li-Mei; Verity, Nicole J; Chai, Karl X

2009-01-01

The glycosylphosphatidylinositol (GPI)-anchored epithelial extracellular membrane serine protease prostasin (PRSS8) is expressed abundantly in normal epithelia and essential for terminal epithelial differentiation, but down-regulated in human prostate, breast, and gastric cancers and invasive cancer cell lines. Prostasin is involved in the extracellular proteolytic modulation of the epidermal growth factor receptor (EGFR) and is an invasion suppressor. The aim of this study was to evaluate prostasin expression states in the transitional cell carcinomas (TCC) of the human bladder and in human TCC cell lines. Normal human bladder tissues and TCC on a bladder cancer tissue microarray (TMA) were evaluated for prostasin expression by means of immunohistochemistry. A panel of 16 urothelial and TCC cell lines were evaluated for prostasin and E-cadherin expression by western blot and quantitative PCR, and for prostasin gene promoter region CpG methylation by methylation-specific PCR (MSP). Prostasin is expressed in the normal human urothelium and in a normal human urothelial cell line, but is significantly down-regulated in high-grade TCC and lost in 9 (of 15) TCC cell lines. Loss of prostasin expression in the TCC cell lines correlated with loss of or reduced E-cadherin expression, loss of epithelial morphology, and promoter DNA hypermethylation. Prostasin expression could be reactivated by demethylation or inhibition of histone deacetylase. Re-expression of prostasin or a serine protease-inactive variant resulted in transcriptional up-regulation of E-cadherin. Loss of prostasin expression in bladder transitional cell carcinomas is associated with epithelial-mesenchymal transition (EMT), and may have functional implications in tumor invasion and resistance to chemotherapy

Does Post Septoplasty Nasal Packing Reduce Complications?

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Bijan Naghibzadeh

2011-01-01

Full Text Available 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.

Prevalence of human papillomavirus in epithelial ovarian cancer tissue. A meta-analysis of observational studies

DEFF Research Database (Denmark)

Svahn, Malene F; Faber, Mette Tuxen; Christensen, Jane

2014-01-01

The role of human papillomavirus (HPV) in the pathogenesis of ovarian cancer is controversial, and conflicting results have been published. We conducted a systematic review and meta-analysis to estimate the prevalence of HPV in epithelial ovarian cancer tissue....

Nasal drug delivery: Design of a novel mucoadhesive and in situ gelling polymer.

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Menzel, Claudia; Jelkmann, Max; Laffleur, Flavia; Bernkop-Schnürch, Andreas

2017-01-30

The aim of the present study was to establish a novel polymeric excipient for liquid nasal dosage forms exhibiting viscosity increasing properties, improved mucoadhesion and stability towards oxidation in solution. In order to achieve this goal, 2-mercaptonicotinic acid was first coupled to l-cysteine by disulfide exchange reaction and after purification directly attached to the polymeric backbone of xanthan gum by carbodiimide mediated amide bond formation. The resulting conjugate was characterized with respect to the amount of coupled ligand, the in situ gelling behavior, mucoadhesive properties and stability towards oxidation. Furthermore, the influence of preactivated polymers on ciliary beat frequency (CBF) of porcine nasal epithelial cells was investigated. Results showed, that 252.52±20.54μmol of the ligand was attached per gram polymer. No free thiol groups could be detected on the polymeric backbone indicating entire preactivation. Rheological investigations of polymer mucus mixtures revealed a 1.7-fold and 2.5-fold enhanced mucoadhesion of entirely preactivated xanthan (Xan-Cys-MNA) compared to thiolated xanthan (Xan-Cys) and unmodified xanthan (Xan). Tensile force evaluation reported a 2.87 and 5.11-fold higher total work of adhesion (TWA) as well as a 1.63 and 2.41-fold higher maximum detachement force of Xan-Cys-MNA compared to Xan-Cys and Xan. In the presence of H 2 O 2 as an oxidizing agent Xan-Cys-MNA showed unlike Xan-Cys no increase in viscosity, indicating high stability towards oxidation. Addition of CaCl 2 to Xan-Cys-MNA solutions caused a decrease in viscosity at nevertheless higher total viscosity. Results from CBF studies proved nasal safety for the novel conjugate. According to these results, entirely preactivated thiolated xanthan gum seems to be a promising excipient for nasal dosage forms in order to improve drug bioavailability. Copyright © 2016 Elsevier B.V. All rights reserved.

MAPK Activation Is Essential for Waddlia chondrophila Induced CXCL8 Expression in Human Epithelial Cells.

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Skye Storrie

Full Text Available Waddlia chondrophila (W. chondrophila is an emerging agent of respiratory and reproductive disease in humans and cattle. The organism is a member of the order Chlamydiales, and shares many similarities at the genome level and in growth studies with other well-characterised zoonotic chlamydial agents, such as Chlamydia abortus (C. abortus. The current study investigated the growth characteristics and innate immune responses of human and ruminant epithelial cells in response to infection with W. chondrophila.Human epithelial cells (HEp2 were infected with W. chondrophila for 24h. CXCL8 release was significantly elevated in each of the cell lines by active-infection with live W. chondrophila, but not by exposure to UV-killed organisms. Inhibition of either p38 or p42/44 MAPK significantly inhibited the stimulation of CXCL8 release in each of the cell lines. To determine the pattern recognition receptor through which CXCL8 release was stimulated, wild-type HEK293 cells which express no TLR2, TLR4, NOD2 and only negligible NOD1 were infected with live organisms. A significant increase in CXCL8 was observed.W. chondrophila actively infects and replicates within both human and ruminant epithelial cells stimulating CXCL8 release. Release of CXCL8 is significantly inhibited by inhibition of either p38 or p42/44 MAPK indicating a role for this pathway in the innate immune response to W. chondrophila infection. W. chondrophila stimulation of CXCL8 secretion in HEK293 cells indicates that TLR2, TLR4, NOD2 and NOD1 receptors are not essential to the innate immune response to infection.

Nasal morphological characteristics of the Serbian population

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Jovanović J.

2014-01-01

Full Text Available The aim of this study was to determine the nasal parameters in the population of central Serbia and to compare them with those determined in earlier studies in different populations. The research was conducted on 496 randomly selected persons (262 males and 234 females, aged 18-65 years. The measured parameters were nasal height and nasal breadth and the standard spreading caliper with scale was used for measurements. There were significant differences in the nasal parameters between male and female subjects. The nasal breadth was 34.72 mm in females, and in the male population it was 36.7 mm. The mean values of nasal height were 52.6 mm and 54.32 mm in females and males, respectively. The nasal index in females and males was 66.01 and 67.56, respectively, and the mean value of the nasal index of all respondents was 66.78. After conducting the research it was concluded that the dominant nasal type in the population of the central part of Serbia is leptorrhine. The present study showed the existence of sexual dimorphism in nasal morphology. The data obtained in our study may be useful in anthropological and forensic research, as well as in cosmetic planning and reconstructive surgery.

IL-33-responsive innate lymphoid cells are an important source of IL-13 in chronic rhinosinusitis with nasal polyps.

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Shaw, Joanne L; Fakhri, Samer; Citardi, Martin J; Porter, Paul C; Corry, David B; Kheradmand, Farrah; Liu, Yong-Jun; Luong, Amber

2013-08-15

Chronic rhinosinusitis (CRS) without nasal polyps (CRSsNP) and CRS with nasal polyps (CRSwNP) are associated with Th1 and Th2 cytokine polarization, respectively; however, the pathophysiology of CRS remains unclear. The importance of innate lymphoid cells in Th2-mediated inflammatory disease has not been clearly defined. The objective of this study was to investigate the role of the epithelial cell-derived cytokine IL-33 and IL-33-responsive innate lymphoid cells in the pathophysiology of CRS. Relative gene expression was evaluated using quantitative real-time polymerase chain reaction. Innate lymphoid cells in inflamed ethmoid sinus mucosa from patients with CRSsNP and CRSwNP were characterized using flow cytometry. Cytokine production from lymphoid cells isolated from inflamed mucosa of patients with CRS was examined using ELISA and intracellular cytokine staining. Elevated expression of ST2, the ligand-binding chain of the IL-33 receptor, was observed in inflamed sinonasal mucosa from CRSwNP compared with CRSsNP and healthy control subjects. An increased percentage of innate lymphoid cells was observed in inflamed sinonasal mucosa from CRSwNP compared with CRSsNP. ST2(+) innate lymphoid cells are a consistent source of IL-13 in response to IL-33 stimulation. Significant induction of IL-33 was observed in epithelial cells derived from patients with CRSwNP compared with patients with CRSsNP in response to stimulation with Aspergillus fumigatus extract. These data suggest a role for sinonasal epithelial cell-derived IL-33 and an IL-33-responsive innate lymphoid cell population in the pathophysiology of CRSwNP demonstrating the functional importance of innate lymphoid cells in Th2-mediated inflammatory disease.

Presurgical Nasal Molding With a Nasal Spring in Patients With Mild-to-Moderate Nasal Deformity With Incomplete Unilateral Cleft Lip With or Without Cleft Palate.

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Peanchitlertkajorn, Supakit

2018-01-01

Traditional nasoalveolar molding (NAM) requires steep learning curve for clinicians and significant compliance from parents. Nasal springs have been developed by the author to simplify presurgical nasal molding. This article presents the design, construction, and application of the spring. The treatment goal is to improve nasal deformity prior to primary repair in infants born with incomplete unilateral cleft lip with or without cleft palate. The design, fabrication, and utility of the nasal spring are described. The spring has a simpler design and construction compared to a traditional NAM appliance. Two patients with incomplete unilateral cleft lip with and without cleft palate are presented. The spring is constructed and delivered. The active arm of the spring can be 3-dimensionally (3-D) adjusted to mold the alar cartilage of the affected nostril. The spring does not require an oral plate for adherence as a traditional NAM appliance does, hence an oral impression is not needed. The spring is easy for clinicians to adjust. It also requires less compliance by parents. Main Outcome Measures/Results: The presurgical molding achieved by the use of a nasal spring improved surgical nasolabial aesthetic outcomes. The nasal springs are effective in reducing the initial cleft nasal deformity. This facilitates primary surgical cleft lip and nose correction and improves surgical outcomes in patients with incomplete unilateral cleft lip with or without cleft palate.

Primary human polarized small intestinal epithelial barriers respond differently to a hazardous and an innocuous protein.

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Eaton, A D; Zimmermann, C; Delaney, B; Hurley, B P

2017-08-01

An experimental platform employing human derived intestinal epithelial cell (IEC) line monolayers grown on permeable Transwell ® filters was previously investigated to differentiate between hazardous and innocuous proteins. This approach was effective at distinguishing these types of proteins and perturbation of monolayer integrity, particularly transepithelial electrical resistance (TEER), was the most sensitive indicator. In the current report, in vitro indicators of monolayer integrity, cytotoxicity, and inflammation were evaluated using primary (non-transformed) human polarized small intestinal epithelial barriers cultured on Transwell ® filters to compare effects of a hazardous protein (Clostridium difficile Toxin A [ToxA]) and an innocuous protein (bovine serum albumin [BSA]). ToxA exerted a reproducible decrease on barrier integrity at doses comparable to those producing effects observed from cell line-derived IEC monolayers, with TEER being the most sensitive indicator. In contrast, BSA, tested at concentrations substantially higher than ToxA, did not cause changes in any of the tested variables. These results demonstrate a similarity in response to certain proteins between cell line-derived polarized IEC models and a primary human polarized small intestinal epithelial barrier model, thereby reinforcing the potential usefulness of cell line-derived polarized IECs as a valid experimental platform to differentiate between hazardous and non-hazardous proteins. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Nasal chondrocyte-based engineered autologous cartilage tissue for repair of articular cartilage defects: an observational first-in-human trial.

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Mumme, Marcus; Barbero, Andrea; Miot, Sylvie; Wixmerten, Anke; Feliciano, Sandra; Wolf, Francine; Asnaghi, Adelaide M; Baumhoer, Daniel; Bieri, Oliver; Kretzschmar, Martin; Pagenstert, Geert; Haug, Martin; Schaefer, Dirk J; Martin, Ivan; Jakob, Marcel

2016-10-22

Articular cartilage injuries have poor repair capacity, leading to progressive joint damage, and cannot be restored predictably by either conventional treatments or advanced therapies based on implantation of articular chondrocytes. Compared with articular chondrocytes, chondrocytes derived from the nasal septum have superior and more reproducible capacity to generate hyaline-like cartilage tissues, with the plasticity to adapt to a joint environment. We aimed to assess whether engineered autologous nasal chondrocyte-based cartilage grafts allow safe and functional restoration of knee cartilage defects. In a first-in-human trial, ten patients with symptomatic, post-traumatic, full-thickness cartilage lesions (2-6 cm 2 ) on the femoral condyle or trochlea were treated at University Hospital Basel in Switzerland. Chondrocytes isolated from a 6 mm nasal septum biopsy specimen were expanded and cultured onto collagen membranes to engineer cartilage grafts (30 × 40 × 2 mm). The engineered tissues were implanted into the femoral defects via mini-arthrotomy and assessed up to 24 months after surgery. Primary outcomes were feasibility and safety of the procedure. Secondary outcomes included self-assessed clinical scores and MRI-based estimation of morphological and compositional quality of the repair tissue. This study is registered with ClinicalTrials.gov, number NCT01605201. The study is ongoing, with an approved extension to 25 patients. For every patient, it was feasible to manufacture cartilaginous grafts with nasal chondrocytes embedded in an extracellular matrix rich in glycosaminoglycan and type II collagen. Engineered tissues were stable through handling with forceps and could be secured in the injured joints. No adverse reactions were recorded and self-assessed clinical scores for pain, knee function, and quality of life were improved significantly from before surgery to 24 months after surgery. Radiological assessments indicated variable degrees of

Correlation analysis on alpha attenuation and nasal skin temperature

International Nuclear Information System (INIS)

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

Sulfation of chlorotyrosine and nitrotyrosine by human lung endothelial and epithelial cells: Role of the human SULT1A3

International Nuclear Information System (INIS)

Yasuda, Shin; Yasuda, Tomoko; Liu, Ming-Yih; Shetty, Sreerama; Idell, Steven; Boggaram, Vijayakumar; Suiko, Masahito; Sakakibara, Yoichi; Fu Jian; Liu, Ming-Cheh

2011-01-01

During inflammation, potent reactive oxidants formed may cause chlorination and nitration of both free and protein-bound tyrosine. In addition to serving as biomarkers of inflammation-mediated oxidative stress, elevated levels of chlorotyrosine and nitrotyrosine have been linked to the pathogenesis of lung and vascular disorders. The current study was designed to investigate whether the lung cells are equipped with mechanisms for counteracting these tyrosine derivatives. By metabolic labeling, chlorotyrosine O-[ 35 S]sulfate and nitrotyrosine O-[ 35 S]sulfate were found to be generated and released into the labeling media of human lung endothelial and epithelial cells labeled with [ 35 S]sulfate in the presence of added chlorotyrosine and nitrotyrosine. Enzymatic assays using the eleven known human cytosolic sulfotransferases (SULTs) revealed SULT1A3 as the enzyme responsible for catalyzing the sulfation of chlorotyrosine and nitrotyrosine. Reverse transcription-polymerase chain reaction (RT-PCR) analysis demonstrated the expression of SULT1A3 in the lung endothelial and epithelial cells used in this study. Kinetic constants of the sulfation of chlorotyrosine and nitrotyrosine by SULT1A3 were determined. Collectively, these results suggest that sulfation by SULT1A3 in lung endothelial and epithelial cells may play a role in the inactivation and/or disposal of excess chlorotyrosine and nitrotyrosine generated during inflammation.

Effects of alpha-particles on survival and chromosomal aberrations in human mammary epithelial cells

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Durante, M.; Grossi, G. F.; Gialanella, G.; Pugliese, M.; Nappo, M.; Yang, T. C.

1995-01-01

We have studied the radiation responses of a human mammary epithelial cell line, H184B5 F5-1 M/10. This cell line was derived from primary mammary cells after treatment with chemicals and heavy ions. The F5-1 M/10 cells are immortal, density-inhibited in growth, and non-tumorigenic in athymic nude mice and represent an in vitro model of the human epithelium for radiation studies. Because epithelial cells are the target of alpha-particles emitted from radon daughters, we concentrated our studies on the efficiency of alpha-particles. Confluent cultures of M/10 cells were exposed to accelerated alpha-particles [beam energy incident at the cell monolayer = 3.85 MeV, incident linear energy transfer (LET) in cell = 109 keV/microns] and, for comparison, to 80 kVp x-rays. The following endpoints were studied: (1) survival, (2) chromosome aberrations at the first postirradiation mitosis, and (3) chromosome alterations at later passages following irradiation. The survival curve was exponential for alpha-particles (D0 = 0.73 +/- 0.04 Gy), while a shoulder was observed for x-rays (alpha/beta = 2.9 Gy; D0 = 2.5 Gy, extrapolation number 1.6). The relative biological effectiveness (RBE) of high-LET alpha-particles for human epithelial cell killing was 3.3 at 37% survival. Dose-response curves for the induction of chromosome aberrations were linear for alpha-particles and linearquadratic for x-rays. The RBE for the induction of chromosome aberrations varied with the type of aberration scored and was high (about 5) for chromosome breaks and low (about 2) for chromosome exchanges.(ABSTRACT TRUNCATED AT 250 WORDS).

Depleted uranium induces neoplastic transformation in human lung epithelial cells.

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Xie, Hong; LaCerte, Carolyne; Thompson, W Douglas; Wise, John Pierce

2010-02-15

Depleted uranium (DU) is commonly used in military armor and munitions, and thus, exposure of soldiers and noncombatants is frequent and widespread. Previous studies have shown that DU has both chemical and radiological toxicity and that the primary route of exposure of DU to humans is through inhalation and ingestion. However, there is limited research information on the potential carcinogenicity of DU in human bronchial cells. Accordingly, we determined the neoplastic transforming ability of particulate DU to human bronchial epithelial cells (BEP2D). We observed the loss of contact inhibition and anchorage independent growth in cells exposed to DU after 24 h. We also characterized these DU-induced transformed cell lines and found that 40% of the cell lines exhibit alterations in plating efficiency and no significant changes in the cytotoxic response to DU. Cytogenetic analyses showed that 53% of the DU-transformed cell lines possess a hypodiploid phenotype. These data indicate that human bronchial cells are transformed by DU and exhibit significant chromosome instability consistent with a neoplastic phenotype.

Transcriptional program of ciliated epithelial cells reveals new cilium and centrosome components and links to human disease.

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Ramona A Hoh

Full Text Available Defects in the centrosome and cilium are associated with a set of human diseases having diverse phenotypes. To further characterize the components that define the function of these organelles we determined the transcriptional profile of multiciliated tracheal epithelial cells. Cultures of mouse tracheal epithelial cells undergoing differentiation in vitro were derived from mice expressing GFP from the ciliated-cell specific FOXJ1 promoter (FOXJ1:GFP. The transcriptional profile of ciliating GFP+ cells from these cultures was defined at an early and a late time point during differentiation and was refined by subtraction of the profile of the non-ciliated GFP- cells. We identified 649 genes upregulated early, when most cells were forming basal bodies, and 73 genes genes upregulated late, when most cells were fully ciliated. Most, but not all, of known centrosome proteins are transcriptionally upregulated early, particularly Plk4, a master regulator of centriole formation. We found that three genes associated with human disease states, Mdm1, Mlf1, and Dyx1c1, are upregulated during ciliogenesis and localize to centrioles and cilia. This transcriptome for mammalian multiciliated epithelial cells identifies new candidate centrosome and cilia proteins, highlights similarities between components of motile and primary cilia, and identifies new links between cilia proteins and human disease.

Nasal mass removal in the koala (Phascolarctos cinereus).

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Bercier, Marjorie; Wynne, Janna; Klause, Stephen; Stadler, Cynthia K; Gorow, April; Pye, Geoffrey W

2012-12-01

Nasal masses in the koala (Phascolarctos cinereus) are not uncommon and can be challenging to diagnose and treat. Differential diagnoses for nasal masses in the koala are cryptococcal granulomas, nasal polyps, nasal adenocarcinoma, and osteochondromatosis. This report describes successful surgical approaches for two adult koalas with nasal masses and includes photodocumentation and description of the anatomy of the koala nasal passages from the postmortem transverse sectioning of a normal koala head. Surgical removal of the nasal masses in these koalas resulted in a rapid resolution of clinical signs.

The V protein of canine distemper virus is required for virus replication in human epithelial cells.

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Noriyuki Otsuki

Full Text Available Canine distemper virus (CDV becomes able to use human receptors through a single amino acid substitution in the H protein. In addition, CDV strains possessing an intact C protein replicate well in human epithelial H358 cells. The present study showed that CDV strain 007Lm, which was isolated from lymph node tissue of a dog with distemper, failed to replicate in H358 cells, although it possessed an intact C protein. Sequence analyses suggested that a cysteine-to-tyrosine substitution at position 267 of the V protein caused this growth defect. Analyses using H358 cells constitutively expressing the CDV V protein showed that the V protein with a cysteine, but not that with a tyrosine, at this position effectively blocked the interferon-stimulated signal transduction pathway, and supported virus replication of 007Lm in H358 cells. Thus, the V protein as well as the C protein appears to be functional and essential for CDV replication in human epithelial cells.

Nasal Foreign Bodies: A Sweet Experiment.

Science.gov (United States)

Leopard, D C; Williams, R G

2015-10-01

It is generally accepted that paediatric intranasal foreign bodies should be removed in the emergency setting. In the case of a difficult to access dissolvable foreign body in an uncooperative child, the question must be raised regarding whether or not a watch and wait strategy is more appropriate. We ask: How long does it take for popular sweets (candy) to dissolve in the human nose? Five popular UK sweets were placed in the right nasal cavity of a 29-year-old male (the author) with no sino-nasal disease. Time taken to dissolve was recorded. All five sweets were completely dissolved in under one hour. A watch and wait strategy in favour of examination under anaesthetic may be a viable option in some cases. Limitations of the study include the age of the participant and size of the sweets. It is also important in practice that the clinician is able to elicit an accurate history regarding the exact nature of the foreign body. It remains prudent to perform an examination under anaesthetic of an uncooperative child with a solid or unknown nasal foreign body. However, if the clinician can be certain the foreign body is a small sugar or chocolate based sweet only, a watch and wait strategy may be a reasonable choice. © 2015 John Wiley & Sons Ltd.

Antigen presentation and MHC class II expression by human esophageal epithelial cells: role in eosinophilic esophagitis.

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Mulder, Daniel J; Pooni, Aman; Mak, Nanette; Hurlbut, David J; Basta, Sameh; Justinich, Christopher J

2011-02-01

Professional antigen-presenting cells (APCs) play a crucial role in initiating immune responses. Under pathological conditions, epithelial cells at mucosal surfaces act as nonprofessional APCs, thereby regulating immune responses at the site of exposure. Epithelial cells in the esophagus may contribute to the pathogenesis of eosinophilic esophagitis (EoE) by presenting antigens on the major histocompatibility complex (MHC) class II. Our goal was to demonstrate the ability of esophageal epithelial cells to process and present antigens on the MHC class II system and to investigate the contribution of epithelial cell antigen presentation to EoE. Immunohistochemistry detected HLA-DR, CD80, and CD86 expression and enzyme-linked immunosorbent assay detected interferon-γ (IFNγ) in esophageal biopsies. Antigen presentation was studied using the human esophageal epithelial cell line HET-1A by reverse transcriptase-PCR, flow cytometry, and confocal microscopy. T helper cell lymphocyte proliferation was assessed by flow cytometry and IL-2 secretion. IFNγ and MHC class II were increased in mucosa of patients with EoE. IFNγ increased mRNA of HLA-DP, HLA-DQ, HLA-DR, and CIITA in HET-1A cells. HET-1A engulfed cell debris and processed ovalbumin. HET-1A cells expressed HLA-DR after IFNγ treatment. HET-1A stimulated T helper cell activation. In this study, we demonstrated the ability of esophageal epithelial cells to act as nonprofessional APCs in the presence of IFNγ. Esophageal epithelial cell antigen presentation may contribute to the pathophysiology of eosinophilic esophagitis. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Influence of deposition and spray pattern of nasal powders on insulin bioavailability.

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Pringels, E; Callens, C; Vervaet, C; Dumont, F; Slegers, G; Foreman, P; Remon, J P

2006-03-09

The influence of the deposition pattern and spray characteristics of nasal powder formulations on the insulin bioavailability was investigated in rabbits. The formulations were prepared by freeze drying a dispersion containing a physical mixture of drum dried waxy maize starch (DDWM)/Carbopol 974P (90/10, w/w) or a spray-dried mixture of Amioca starch/Carbopol 974P (25/75, w/w). The deposition in the nasal cavity of rabbits and in a silicone human nose model after actuation of three nasal delivery devices (Monopowder, Pfeiffer and experimental system) was compared and related to the insulin bioavailability. Posterior deposition of the powder formulation in the nasal cavity lowered the insulin bioavailability. To study the spray pattern, the shape and cross-section of the emitted powder cloud were analysed. It was concluded that the powder bulk density of the formulation influenced the spray pattern. Consequently, powders of different bulk density were prepared by changing the solid fraction of the freeze dried dispersion and by changing the freezing rate during freeze drying. After nasal delivery of these powder formulations no influence of the powder bulk density and of the spray pattern on the insulin bioavailability was observed.

Nasal septum extramedullary plasmacytoma

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Belić Branislav

2013-01-01

Full Text Available Introduction. Plasmacytomas are malignant tumors characterized by abnormal monoclonal proliferation of plasma cells. They originate in either bone - solitary osseous plasmacytoma, or in soft tissue - extramedullary plasmacytoma (EMP. EMP represents less than 1% of all head and neck malignancies. Case report. We presented a case of EMP of the nasal septum in a 44-year-old male who had progressive difficulty in breathing through the nose and frequent heavy epistaxis on the right side. Nasal endoscopy showed dark red, soft, polypoid tumor in the last third of the right nasal cavity arising from the nasal septum. The biopsy showed that it was plasmacytoma. Bence Jones protein in the urine, serum electrophoresis, bone marrow biopsy, skeletal survey and other screening tests failed to detect multiple myeloma. This confirmed the diagnosis of EMP. The mass was completely removed via an endoscopic approach, and then, 4 week later, radiotherapy was conducted with a radiation dose of 50 Gray. No recurrence was noted in a 3-year follow- up period. Conclusion. EMP of the nasal cavity, being rare and having long natural history, represents a diagnostic and therapeutic challenge for any ear, nose and throat surgeon. Depending on the resectability of the lesion, a combined therapy is the accepted treatment.

Nasal symptoms following endoscopic transsphenoidal pituitary surgery: assessment using the General Nasal Patient Inventory.

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Wang, Yi Yuen; Srirathan, Vinothan; Tirr, Erica; Kearney, Tara; Gnanalingham, Kanna K

2011-04-01

The endoscopic approach for pituitary tumors is a recent innovation and is said to reduce the nasal trauma associated with transnasal transsphenoidal surgery. The authors assessed the temporal changes in the rhinological symptoms following endoscopic transsphenoidal surgery for pituitary lesions, using the General Nasal Patient Inventory (GNPI). The GNPI was administered to 88 consecutive patients undergoing endoscopic transsphenoidal surgery at 3 time points (presurgery, 3-6 months postsurgery, and at final follow-up). The total GNPI score and the scores for the individual GNPI questions were calculated and differences between groups were assessed once before surgery, several months after surgery, and at final follow-up. Of a maximum possible score of 135, the mean GNPI score at 3-6 months postsurgery was only 12.9 ± 12 and was not significantly different from the preoperative score (10.4 ± 13) or final follow-up score (10.3 ± 10). Patients with functioning tumors had higher GNPI scores than those with nonfunctioning tumors for each of these time points (p surgery, with partial recovery (nasal sores and bleeding) or complete recovery (nasal blockage, painful sinuses, and unpleasant nasal smell) by final follow-up (p transsphenoidal surgery is a well-tolerated minimally invasive procedure for pituitary fossa lesions. Overall patient-assessed nasal symptoms do not change, but some individual symptoms may show a mild worsening or overall improvement.

The effect of nasalization on /a/ vowel formants before and after nasal consonant in 4-9-year old normal Persian speaking children

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Kowsar Baghban

2014-01-01

Full Text Available Background and Aim : Nasalization of a vowel refers to the addition of nasal resonance to the vocal tract transfer function. Also, vowel nasalization occurs because of coarticulation. Coupling of the nasal resonating space to the oropharyngeal cavity alters the vocal tract formants in complex ways. The purpose of this study was to investigate the effect of nasalization on /a/ vowel formants in before and after nasal consonant.Methods: In current cross-sectional study, voice samples of 60 normal children ranging the age of four-nine years were investigated. Participants were asked to repeat / ʔ ama/ three times and vowel /a/ after presentation of an auditory model. Then, obtained samples were analyzed using Praat 5.3.13 . Average of F0, F1, F2 and F3 were calculated for /a/ comes before and after /m/ in production of / ʔ ama/ over three trials.Results: There were statistically significant differences of F1, F2 and F3 between / a/ which proceeds nasal consonant and /a/ follows nasal consonant , the before nasal consonant /a/ versus single /a/ and the after nasal consonant /a/ versus single /a/ (p=0.001 for all.Conclusion : F1, F2 and F3 in /a/ before nasal consonant affected by anticipatory nasal coarticulation and in /a/ after nasal consonant affected by carry-over nasal coarticulation . This study showed nasal coarticulation and nasalization result in decreasing F1, F2 and F3 in /a/ vowel.

Loss of prostasin (PRSS8 in human bladder transitional cell carcinoma cell lines is associated with epithelial-mesenchymal transition (EMT

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Chai Karl X

2009-10-01

Full Text Available Abstract Background The glycosylphosphatidylinositol (GPI-anchored epithelial extracellular membrane serine protease prostasin (PRSS8 is expressed abundantly in normal epithelia and essential for terminal epithelial differentiation, but down-regulated in human prostate, breast, and gastric cancers and invasive cancer cell lines. Prostasin is involved in the extracellular proteolytic modulation of the epidermal growth factor receptor (EGFR and is an invasion suppressor. The aim of this study was to evaluate prostasin expression states in the transitional cell carcinomas (TCC of the human bladder and in human TCC cell lines. Methods Normal human bladder tissues and TCC on a bladder cancer tissue microarray (TMA were evaluated for prostasin expression by means of immunohistochemistry. A panel of 16 urothelial and TCC cell lines were evaluated for prostasin and E-cadherin expression by western blot and quantitative PCR, and for prostasin gene promoter region CpG methylation by methylation-specific PCR (MSP. Results Prostasin is expressed in the normal human urothelium and in a normal human urothelial cell line, but is significantly down-regulated in high-grade TCC and lost in 9 (of 15 TCC cell lines. Loss of prostasin expression in the TCC cell lines correlated with loss of or reduced E-cadherin expression, loss of epithelial morphology, and promoter DNA hypermethylation. Prostasin expression could be reactivated by demethylation or inhibition of histone deacetylase. Re-expression of prostasin or a serine protease-inactive variant resulted in transcriptional up-regulation of E-cadherin. Conclusion Loss of prostasin expression in bladder transitional cell carcinomas is associated with epithelial-mesenchymal transition (EMT, and may have functional implications in tumor invasion and resistance to chemotherapy.

FoxO3a Serves as a Biomarker of Oxidative Stress in Human Lens Epithelial Cells under Conditions of Hyperglycemia.

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Ilangovan Raju

Full Text Available Forkhead box 'O' transcription factors (FoxOs are implicated in the pathogenesis of type2 diabetes and other metabolic diseases. Abnormal activity of FoxOs was reported in the glucose and insulin metabolism. Expression of FoxO proteins was reported in ocular tissues; however their function under hyperglycemic conditions was not examined.Human lens epithelial cell line was used to study the function of FoxO proteins. Immunofluorescence, flow cytometry and Western blotting were employed to detect the FoxO proteins under the conditions of hyperglycemia.In this study we examined the role of FoxO3a in hyperglycemia-induced oxidative stress in human lens epithelial cells. FoxO3a protein expression was elevated in a dose- and time-dependent fashion after high glucose treatment. Anti-oxidant defense mechanisms of the lens epithelial cells were diminished as evidenced from loss of mitochondrial membrane integrity and lowered MnSOD after 72 h treatment with high glucose. Taken together, FoxO3a acts as a sensitive indicator of oxidative stress and cell homeostasis in human lens epithelial cells during diabetic conditions.FoxO3a is an early stress response protein to glucose toxicity in diabetic conditions.

Expression of nestin, mesothelin and epithelial membrane antigen (EMA) in developing and adult human meninges and meningiomas.

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Petricevic, Josko; Forempoher, Gea; Ostojic, Ljerka; Mardesic-Brakus, Snjezana; Andjelinovic, Simun; Vukojevic, Katarina; Saraga-Babic, Mirna

2011-11-01

The spatial and temporal pattern of appearance of nestin, epithelial membrane antigen (EMA) and mesothelin proteins was immunohistochemically determined in the cells of normal developing and adult human meninges and meningiomas. Human meninges developed as two mesenchymal condensations in the head region. The simple squamous epithelium on the surface of leptomeninges developed during mesenchymal to epithelial transformation. Nestin appeared for the first time in week 7, EMA in week 8, while mesothelin appeared in week 22 of development. In the late fetal period and after birth, nestin expression decreased, whereas expression of EMA and mesothelin increased. EMA appeared in all surface epithelial cells and nodules, while mesothelin was found only in some of them. In adult meninges, all three proteins were predominantly localized in the surface epithelium and meningeal nodules. In meningothelial meningiomas (WHO grade I), EMA was detected in all tumor cells except in the endothelial cells, mesothelin characterized nests of tumor cells, while nestin was found predominantly in the walls of blood vessels. The distribution pattern of those proteins in normal meningeal and tumor cells indicates that nestin might characterize immature cells, while EMA and mesothelin appeared in maturing epithelial cells. Neoplastic transformation of these specific cell lineages contributes to the cell population in meningiomas. Copyright © 2010 Elsevier GmbH. All rights reserved.

Nasal dermoid sinus cyst.

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Cauchois, R; Laccourreye, O; Bremond, D; Testud, R; Küffer, R; Monteil, J P

1994-08-01

Nasal dermoid sinus cyst is one of the diagnoses of midline nasal masses in children. This retrospective study analyzes the various theories regarding the origin of this congenital abnormality, the differential diagnosis, and the value of magnetic resonance imaging, as well as the various surgical options available.

Human adipose tissue from normal and tumoral breast regulates the behavior of mammary epithelial cells.

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Pistone Creydt, Virginia; Fletcher, Sabrina Johanna; Giudice, Jimena; Bruzzone, Ariana; Chasseing, Norma Alejandra; Gonzalez, Eduardo Gustavo; Sacca, Paula Alejandra; Calvo, Juan Carlos

2013-02-01

Stromal-epithelial interactions mediate both breast development and breast cancer progression. In the present work, we evaluated the effects of conditioned media (CMs) of human adipose tissue explants from normal (hATN) and tumor (hATT) breast on proliferation, adhesion, migration and metalloproteases activity on tumor (MCF-7 and IBH-7) and non-tumor (MCF-10A) human breast epithelial cell lines. Human adipose tissues were obtained from patients and the conditioned medium from hATN and hATT collected after 24 h of incubation. MCF-10A, MCF-7 and IBH-7 cells were grown and incubated with CMs and proliferation and adhesion, as well as migration ability and metalloprotease activity, of epithelial cells after exposing cell cultures to hATN- or hATT-CMs were quantified. The statistical significance between different experimental conditions was evaluated by one-way ANOVA. Tukey's post hoc tests were performed. Tumor and non-tumor breast epithelial cells significantly increased their proliferation activity after 24 h of treatment with hATT-CMs compared to control-CMs. Furthermore, cellular adhesion of these two tumor cell lines was significantly lower with hATT-CMs than with hATN-CMs. Therefore, hATT-CMs seem to induce significantly lower expression or less activity of the components involved in cellular adhesion than hATN-CMs. In addition, hATT-CMs induced pro-MMP-9 and MMP-9 activity and increased the migration of MCF-7 and IBH-7 cells compared to hATN-CMs. We conclude that the microenvironment of the tumor interacts in a dynamic way with the mutated epithelium. This evidence leads to the possibility to modify the tumor behavior/phenotype through the regulation or modification of its microenvironment. We developed a model in which we obtained CMs from adipose tissue explants completely, either from normal or tumor breast. In this way, we studied the contribution of soluble factors independently of the possible effects of direct cell contact.

Characterization of primary human mammary epithelial cells isolated and propagated by conditional reprogrammed cell culture.

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Jin, Liting; Qu, Ying; Gomez, Liliana J; Chung, Stacey; Han, Bingchen; Gao, Bowen; Yue, Yong; Gong, Yiping; Liu, Xuefeng; Amersi, Farin; Dang, Catherine; Giuliano, Armando E; Cui, Xiaojiang

2018-02-20

Conditional reprogramming methods allow for the inexhaustible in vitro proliferation of primary epithelial cells from human tissue specimens. This methodology has the potential to enhance the utility of primary cell culture as a model for mammary gland research. However, few studies have systematically characterized this method in generating in vitro normal human mammary epithelial cell models. We show that cells derived from fresh normal breast tissues can be propagated and exhibit heterogeneous morphologic features. The cultures are composed of CK18, desmoglein 3, and CK19-positive luminal cells and vimentin, p63, and CK14-positive myoepithelial cells, suggesting the maintenance of in vivo heterogeneity. In addition, the cultures contain subpopulations with different CD49f and EpCAM expression profiles. When grown in 3D conditions, cells self-organize into distinct structures that express either luminal or basal cell markers. Among these structures, CK8-positive cells enclosing a lumen are capable of differentiation into milk-producing cells in the presence of lactogenic stimulus. Furthermore, our short-term cultures retain the expression of ERα, as well as its ability to respond to estrogen stimulation. We have investigated conditionally reprogrammed normal epithelial cells in terms of cell type heterogeneity, cellular marker expression, and structural arrangement in two-dimensional (2D) and three-dimensional (3D) systems. The conditional reprogramming methodology allows generation of a heterogeneous culture from normal human mammary tissue in vitro . We believe that this cell culture model will provide a valuable tool to study mammary cell function and malignant transformation.

Modulation of Kingella kingae adherence to human epithelial cells by type IV Pili, capsule, and a novel trimeric autotransporter.

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Porsch, Eric A; Kehl-Fie, Thomas E; St Geme, Joseph W

2012-10-23

Kingella kingae is an emerging bacterial pathogen that is being recognized increasingly as an important etiology of septic arthritis, osteomyelitis, and bacteremia, especially in young children. Colonization of the posterior pharynx is a key step in the pathogenesis of K. kingae disease. Previous work established that type IV pili are necessary for K. kingae adherence to the respiratory epithelium. In this study, we set out to identify additional factors that influence K. kingae interactions with human epithelial cells. We found that genetic disruption of the gene encoding a predicted trimeric autotransporter protein called Knh (Kingella NhhA homolog) resulted in reduced adherence to human epithelial cells. In addition, we established that K. kingae elaborates a surface-associated polysaccharide capsule that requires a predicted ABC-type transporter export operon called ctrABCD for surface presentation. Furthermore, we discovered that the presence of a surface capsule interferes with Knh-mediated adherence to human epithelial cells by nonpiliated organisms and that maximal adherence in the presence of a capsule requires the predicted type IV pilus retraction machinery, PilT/PilU. On the basis of the data presented here, we propose a novel adherence mechanism that allows K. kingae to adhere efficiently to human epithelial cells while remaining encapsulated and more resistant to immune clearance. Kingella kingae is a Gram-negative bacterium that is being recognized increasingly as a cause of joint and bone infections in young children. The pathogenesis of disease due to K. kingae begins with bacterial colonization of the upper respiratory tract, and previous work established that surface hair-like fibers called type IV pili are necessary for K. kingae adherence to respiratory epithelial cells. In this study, we set out to identify additional factors that influence K. kingae interactions with respiratory epithelial cells. We discovered a novel surface protein called

Radiation-induced transformation of SV40-immortalized human thyroid epithelial cells by single and fractionated exposure to γ-irradiation in vitro

International Nuclear Information System (INIS)

Riches, A.C.; Herceg, Z.; Bryant, P.E.; Wynford-Thomas, D.

1994-01-01

Radiation-induced transformation of a human thyroid epithelial cell line (HTori-3) has been investigated following exposure to single and fractionated doses of γ-irradiation. The human epithelial cells were irradiated in vitro and following passaging, transplanted to the athymic nude mouse. Following a single exposure to γ-irradiation in the range 0.5-4Gy, 22 tumours were observed in 45 recipients and following three equal fractions in the range 0.5-4Gy per fraction, 18 tumours were observed in 31 recipients. Tumours were undifferentiated carcinomas and were observed from 7 to 20 weeks after transplantation. They occurred after similar radiation doses to those received by the children in the Belarus region of Ukraine, who developed thyroid tumours. The number of tumours observed, in each group receiving cells irradiated with a single dose of γ-irradiation in the range 0.5-4 Gy, was similar. Cell lines were established from some tumours and the tumorigenicity confirmed by retransplantation. These tumour cell lines were more radiosensitive than the human thyroid epithelial cell line they were derived from. This indicates that transformed cells were not being selected from a subpopulation within the parent cell line but that radiation-induced transformants were being induced de novo. The human origin of the tumours was established by karyotyping, immunocytochemical demonstration of human epithelial cytokeratins and p53 analysis. DNA fingerprinting confirmed that the tumours were derived from the original cell line. (author)

Lung fibroblasts accelerate wound closure in human alveolar epithelial cells through hepatocyte growth factor/c-Met signaling.

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Ito, Yoko; Correll, Kelly; Schiel, John A; Finigan, Jay H; Prekeris, Rytis; Mason, Robert J

2014-07-01

There are 190,600 cases of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) each year in the United States, and the incidence and mortality of ALI/ARDS increase dramatically with age. Patients with ALI/ARDS have alveolar epithelial injury, which may be worsened by high-pressure mechanical ventilation. Alveolar type II (ATII) cells are the progenitor cells for the alveolar epithelium and are required to reestablish the alveolar epithelium during the recovery process from ALI/ARDS. Lung fibroblasts (FBs) migrate and proliferate early after lung injury and likely are an important source of growth factors for epithelial repair. However, how lung FBs affect epithelial wound healing in the human adult lung has not been investigated in detail. Hepatocyte growth factor (HGF) is known to be released mainly from FBs and to stimulate both migration and proliferation of primary rat ATII cells. HGF is also increased in lung tissue, bronchoalveolar lavage fluid, and serum in patients with ALI/ARDS. Therefore, we hypothesized that HGF secreted by FBs would enhance wound closure in alveolar epithelial cells (AECs). Wound closure was measured using a scratch wound-healing assay in primary human AEC monolayers and in a coculture system with FBs. We found that wound closure was accelerated by FBs mainly through HGF/c-Met signaling. HGF also restored impaired wound healing in AECs from the elderly subjects and after exposure to cyclic stretch. We conclude that HGF is the critical factor released from FBs to close wounds in human AEC monolayers and suggest that HGF is a potential strategy for hastening alveolar repair in patients with ALI/ARDS. Copyright © 2014 the American Physiological Society.

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

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Claire M. Smith

2016-08-01

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

Ultrastructural Comparison of the Nasal Epithelia of Healthy and Naturally Affected Rabbits with Pasteurella multocida A

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Paula Esquinas

2013-01-01

Full Text Available An ultrastructural comparison between the nasal cavities of healthy rabbits and those suffering from two forms of spontaneous infection with Pasteurella multocida was undertaken. Twelve commercially produced rabbits of different ages and respiratory health status were divided into four groups: healthy from 0 to 21 days (G1, n=2; healthy from 23 to 49 days (G2, n=2; healthy from 51 to 69 days (G3, n=2; diseased rabbits with septicemia and the rhinitic form of P. multocida infection (G4, n=3. The main ultrastructural changes observed were a widening of the interepithelial spaces, increased activity and number of goblet cells, the formation of two types of vacuoles in epithelial cells, the degranulation and migration of heterophils between the epithelial cells, and the association of this migration with some of the other changes. No bacteria were observed adhering to the epithelium, and very few were observed free in the mucus. Scant inter-epithelial spaces were found in healthy rabbits, but they were not as large and numerous as those found in diseased animals. We discuss the origin and meaning of these changes but, we focus on the significance of the inter-epithelial spaces and goblet cells for the defense of the upper respiratory airways against the bacterium and its lipopolysaccharide.

IL-29 Enhances CXCL10 Production in TNF-α-stimulated Human Oral Epithelial Cells.

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Hosokawa, Yoshitaka; Hosokawa, Ikuko; Shindo, Satoru; Ozaki, Kazumi; Matsuo, Takashi

2017-08-01

Interleukin-29 (IL-29) is a cytokine belonging to the Type III interferon family. It was recently detected in the gingival crevicular fluid of periodontitis patients. However, the role of IL-29 in the pathogenesis of periodontal disease remains unknown. The aim of this study was to examine the effects of IL-29 on C-X-C motif chemokine ligand 10 (CXCL10) production in human oral epithelial cells. We measured CXCL10 production in TR146 cells, which is a human oral epithelial cell line, using an enzyme-linked immunosorbent assay. We used a Western blot analysis to detect IL-29 receptor expression and the phosphorylation levels of signal transduction molecules, including p38 mitogen-activated protein kinases (MAPK), signal transducer and activator of transcription 3 (STAT3), and nuclear factor (NF)- κB p65, in the TR146 cells. The TR146 cells expressed the IL-29 receptor. IL-29 induced CXCL10 production in the TR146 cells. IL-29 significantly enhanced CXCL10 production in tumor necrosis factor (TNF)-α-stimulated TR146 cells. The p38 MAPK, STAT3, and NF-κB pathways were found to be related to the IL-29-induced enhancement of CXCL10 production in TNF-α-stimulated TR146 cells. IL-29 promotes T helper 1-cell accumulation in periodontal lesions by inducing CXCL10 production in oral epithelial cells.

Distilled water nasal provocation in hyperreactive patients.

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Baudoin, T; Anzic, S A; Kalogjera, L

1999-01-01

Nonisotonic aerosol may act as a provocation agent in the upper and lower airways of hyperreactive individuals. The purpose of the study was to compare the results of nasal challenge with distilled water in patients with allergic rhinitis to those with noninfective nonallergic rhinitis (NINAR), with respect to the potential clinical use of the obtained data. A group of 68 ambulatory patients with allergic rhinitis or NINAR (39 perennial allergic, 6 seasonal, 23 NINAR) were challenged with 10 mL of distilled water aerosol after the baseline active anterior rhinomanometry. Patients with nasal polyposis at endoscopy, significant unilateral septal deviation, positive bacteriologic swab, recent nasal surgery, and uncertain anamnestic data about the medication taken 6 weeks before the provocation were excluded from the study. After 10 minutes of nasal provocation, rhinomanometry was repeated to assess the response. In 15 patients of the perennial allergic group, the same measurements were performed after a 2-week oral antihistamine and topical steroid therapy. Nasal resistance was significantly increased on the more patent side of the nose after nasal provocation with distilled water aerosol in allergic patients in comparison to the nasal resistance before provocation. In the patients with NINAR, the provocation resulted in a significant rise on the more patent side, but the total nasal airway resistance (NAR) levels were also significantly increased. The systemic antihistamine and topical steroid 2-week therapy in patients with perennial allergic rhinitis significantly reduced the response to nasal distilled water provocation. Nasal provocation with distilled water aerosol is a cheap, simple, and acceptable method that provides useful clinical data on the level of nonspecific nasal hyperreactivity and the therapy success.

Relevance of histamine and tryptase concentrations in nasal secretions after nasal challenges with phosphate buffered saline and allergen

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D. Wang

1995-01-01

Full Text Available In this prospective study, a quantitative determination of histamine and tryptase in nasal secretions after nasal phosphate buffered saline (PBS and allergen challenge was performed in 18 atopic patients who were compared with ten non-allergic healthy volunteers. The aim of the study was to determine the normal and pathological concentrations of these important mediators in nasal secretions. The second objective was to test the relevance of these two mast cell secreted mediators after nasal challenge. Results showed that the concentrations of tryptase in almost all samples were under the minimal detection limit (< 0.5 μU/g and only a sigrtificant increase of tryptase (median, 28 μU/g occurred immediately after nasal allergen challenge in the patient group. Histamine concentration significantly increased after every nasal PBS challenge (median, 69 ng/g after first PBS challenge and 165 ng/g after second PBS challenge in the control group, as well as in the patient group after both PBS (median, 69 ng/g and allergen (median, 214 ng/g challenge. On the other hand, a rapid onset of sneezing and increase in nasal airway resistance was experienced only in the patient group after nasal allergen challenge, but did not occur after PBS challenge even though the histamine concentrations significantly increased in both groups. This study suggests that tryptase is a more preferable marker than histamine in quantitative monitoring of mast cell activation especially during the early phase nasal allergic reaction.

Andrographolide suppresses epithelial mesenchymal transition by ...

Indian Academy of Sciences (India)

Epithelial mesenchymal transition (EMT) of lens epithelial cells (LECs) may contribute to the development of posterior capsular opacification (PCO), which leads to visual impairment. Andrographolide has been shown to have therapeutic potential against various cancers. However, its effect on human LECs is still unknown.

Chlorobenzene induces oxidative stress in human lung epithelial cells in vitro

International Nuclear Information System (INIS)

Feltens, Ralph; Moegel, Iljana; Roeder-Stolinski, Carmen; Simon, Jan-Christoph; Herberth, Gunda; Lehmann, Irina

2010-01-01

Chlorobenzene is a volatile organic compound (VOC) that is widely used as a solvent, degreasing agent and chemical intermediate in many industrial settings. Occupational studies have shown that acute and chronic exposure to chlorobenzene can cause irritation of the mucosa of the upper respiratory tract and eyes. Using in vitro assays, we have shown in a previous study that human bronchial epithelial cells release inflammatory mediators such as the cytokine monocyte chemoattractant protein-1 (MCP-1) in response to chlorobenzene. This response is mediated through the NF-κB signaling pathway. Here, we investigated the effects of monochlorobenzene on human lung cells, with emphasis on potential alterations of the redox equilibrium to clarify whether the chlorobenzene-induced inflammatory response in lung epithelial cells is caused via an oxidative stress-dependent mechanism. We found that expression of cellular markers for oxidative stress, such as heme oxygenase 1 (HO-1), glutathione S-transferase π1 (GSTP1), superoxide dismutase 1 (SOD1), prostaglandin-endoperoxide synthase 2 (PTGS2) and dual specificity phosphatase 1 (DUSP1), were elevated in the presence of monochlorobenzene. Likewise, intracellular reactive oxygen species (ROS) were increased in response to exposure. However, in the presence of the antioxidants N-(2-mercaptopropionyl)-glycine (MPG) or bucillamine, chlorobenzene-induced upregulation of marker proteins and release of the inflammatory mediator MCP-1 are suppressed. These results complement our previous findings and point to an oxidative stress-mediated inflammatory response following chlorobenzene exposure.

Primary nasal tuberculosis following blunt trauma nose

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Kaushik Saha

2014-01-01

Full Text Available Primary nasal tuberculosis is a rare disease with nearly 40 cases reported. Our patient was a young male presented with left sided nasal obstruction, anosmia and occasional epistaxis for last 7 weeks after 6 months of blunt trauma nose. Contrast enhanced computed tomography of the para nasal sinuses showed increased soft-tissue density with contrast enhancement in the left maxillary antrum with extension through left osteomeatal foramen to the left nasal cavity along with further extension through choana to nasopharynx resulting in partial obliteration of the nasopharyngeal airway. Nasal endoscopy revealed a sessile polypoidal pinkish mass arising from the left osteomeatal foramen. Histopathological examination of excisional biopsy of that area showed caseating granuloma. Our patient diagnosed as primary nasal tuberculosis following trauma and treated with anti-tubercular chemotherapy.

Epigenetic Reprogramming of Lineage-Committed Human Mammary Epithelial Cells Requires DNMT3A and Loss of DOT1L

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Jerrica L. Breindel

2017-09-01

Full Text Available Organogenesis and tissue development occur through sequential stepwise processes leading to increased lineage restriction and loss of pluripotency. An exception to this appears in the adult human breast, where rare variant epithelial cells exhibit pluripotency and multilineage differentiation potential when removed from the signals of their native microenvironment. This phenomenon provides a unique opportunity to study mechanisms that lead to cellular reprogramming and lineage plasticity in real time. Here, we show that primary human mammary epithelial cells (HMECs lose expression of differentiated mammary epithelial markers in a manner dependent on paracrine factors and epigenetic regulation. Furthermore, we demonstrate that HMEC reprogramming is dependent on gene silencing by the DNA methyltransferase DNMT3A and loss of histone transcriptional marks following downregulation of the methyltransferase DOT1L. These results demonstrate that lineage commitment in adult tissues is context dependent and highlight the plasticity of somatic cells when removed from their native tissue microenvironment.

Influenza H5N1 virus infection of polarized human alveolar epithelial cells and lung microvascular endothelial cells

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Yuen Kit M

2009-10-01

Full Text Available Abstract Background Highly pathogenic avian influenza (HPAI H5N1 virus is entrenched in poultry in Asia and Africa and continues to infect humans zoonotically causing acute respiratory disease syndrome and death. There is evidence that the virus may sometimes spread beyond respiratory tract to cause disseminated infection. The primary target cell for HPAI H5N1 virus in human lung is the alveolar epithelial cell. Alveolar epithelium and its adjacent lung microvascular endothelium form host barriers to the initiation of infection and dissemination of influenza H5N1 infection in humans. These are polarized cells and the polarity of influenza virus entry and egress as well as the secretion of cytokines and chemokines from the virus infected cells are likely to be central to the pathogenesis of human H5N1 disease. Aim To study influenza A (H5N1 virus replication and host innate immune responses in polarized primary human alveolar epithelial cells and lung microvascular endothelial cells and its relevance to the pathogenesis of human H5N1 disease. Methods We use an in vitro model of polarized primary human alveolar epithelial cells and lung microvascular endothelial cells grown in transwell culture inserts to compare infection with influenza A subtype H1N1 and H5N1 viruses via the apical or basolateral surfaces. Results We demonstrate that both influenza H1N1 and H5N1 viruses efficiently infect alveolar epithelial cells from both apical and basolateral surface of the epithelium but release of newly formed virus is mainly from the apical side of the epithelium. In contrast, influenza H5N1 virus, but not H1N1 virus, efficiently infected polarized microvascular endothelial cells from both apical and basolateral aspects. This provides a mechanistic explanation for how H5N1 virus may infect the lung from systemic circulation. Epidemiological evidence has implicated ingestion of virus-contaminated foods as the source of infection in some instances and our

Composition of nasal airway surface liquid in cystic fibrosis and other airway diseases determined by X-ray microanalysis.

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Vanthanouvong, V; Kozlova, I; Johannesson, M; Nääs, E; Nordvall, S L; Dragomir, A; Roomans, G M

2006-04-01

The ionic composition of the airway surface liquid (ASL) in healthy individuals and in patients with cystic fibrosis (CF) has been debated. Ion transport properties of the upper airway epithelium are similar to those of the lower airways and it is easier to collect nasal ASL from the nose. ASL was collected with ion exchange beads, and the elemental composition of nasal fluid was determined by X-ray microanalysis in healthy subjects, CF patients, CF heterozygotes, patients with rhinitis, and with primary ciliary dyskinesia (PCD). In healthy subjects, the ionic concentrations were approximately isotonic. In CF patients, CF heterozygotes, rhinitis, and PCD patients, [Na] and [Cl] were significantly higher compared when compared with those in controls. [K] was significantly higher in CF and PCD patients compared with that in controls. Severely affected CF patients had higher ionic concentrations in their nasal ASL than in patients with mild or moderate symptoms. Female CF patients had higher levels of Na, Cl, and K than male patients. As higher salt concentrations in the ASL are also found in other patients with airway diseases involving chronic inflammation, it appears likely that inflammation-induced epithelial damage is important in determining the ionic composition of the ASL. Copyright (c) 2006 Wiley-Liss, Inc.

Overexpression of Notch3 and pS6 Is Associated with Poor Prognosis in Human Ovarian Epithelial Cancer

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Zhaoxia Liu

2016-01-01

Full Text Available Notch3 and pS6 play important roles in tumor angiogenesis. To assess the expression of Notch3 and pS6 in Chinese ovarian epithelial cancer patients, a ten-year follow-up study was performed in ovarian epithelial cancer tissues from 120 specimens of human ovarian epithelial cancer, 30 specimens from benign ovarian tumors, and 30 samples from healthy ovaries by immunohistochemistry. The results indicate that the expression of Notch3 and pS6 was higher in ovarian epithelial cancer than in normal ovary tissues and in benign ovarian tumor tissues (p0.05 but positively associated with clinical stage, pathological grading, histologic type, lymph node metastasis, and ascites (p<0.05 or p<0.01. A follow-up survey of 64 patients with ovarian epithelial cancer showed that patients with high Notch3 and pS6 expression had a shorter survival time (p<0.01, in which the clinical stage (p<0.05 and Notch3 expression (p<0.01 played important roles. In conclusion, Notch3 and pS6 are significantly related to ovarian epithelial cancer development and prognosis, and their combination represents a potential biomarker and therapeutic target in ovarian tumor angiogenesis.

Phototoxicity and cytotoxicity of fullerol in human lens epithelial cells

International Nuclear Information System (INIS)

Roberts, Joan E.; Wielgus, Albert R.; Boyes, William K.; Andley, Usha; Chignell, Colin F.

2008-01-01

The water-soluble, hydroxylated fullerene [fullerol, nano-C 60 (OH) 22-26 ] has several clinical applications including use as a drug carrier to bypass the blood ocular barriers. We have assessed fullerol's potential ocular toxicity by measuring its cytotoxicity and phototoxicity induced by UVA and visible light in vitro with human lens epithelial cells (HLE B-3). Accumulation of nano-C 60 (OH) 22-26 in the cells was confirmed spectrophotometrically at 405 nm and cell viability estimated using MTS and LDH assays. Fullerol was cytotoxic to HLE B-3 cells maintained in the dark at concentrations higher than 20 μM. Exposure to either UVA or visible light in the presence of > 5 μM fullerol-induced phototoxic damage. When cells were pretreated with non-toxic antioxidants: 20 μM lutein, 1 mM N-acetyl cysteine, or 1 mM L-ascorbic acid prior to irradiation, only the singlet oxygen quencher-lutein significantly protected against fullerol photodamage. Apoptosis was observed in lens cells treated with fullerol whether or not the cells were irradiated, in the order UVA > visible light > dark. Dynamic light scattering (DLS) showed that in the presence of the endogenous lens protein α-crystallin, large aggregates of fullerol were reduced. In conclusion, fullerol is both cytotoxic and phototoxic to human lens epithelial cells. Although the acute toxicity of water-soluble nano-C 60 (OH) 22-26 is low, these compounds are retained in the body for long periods, raising concern for their chronic toxic effect. Before fullerols are used to deliver drugs to the eye, they should be tested for photo- and cytotoxicity in vivo

Nasal Drug Delivery in Traditional Persian Medicine

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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

Spectral features of nasals in Standard Latvian

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Jana Taperte

2015-12-01

Full Text Available In the article, the acoustic features of nasals in Standard Latvian are investigated. The aim of the study is to examine whether some of the spectral properties of nasal murmur (namely anti-formant frequency, as well as frequency and bandwidth of the first nasal formant can be considered as efficient cues for distinguishing between nasal places of articulation.Speech recordings from 10 native speakers of Standard Latvian, five male and five female, aged 19–39, without any disorders or dialectal traces in their pronunciation, were used for the analysis. Prevocalic nasals [m; n; ɲ] were analyzed in isolated CVC syllables, where C is one of the nasals and V is one of the vowels [i(ː; e(ː; æ(ː; ɑ(ː; ɔ(ː; u(ː]. The velar [ŋ] — the allophone of the phoneme /n/ — was recorded in postvocalic position in [k]V[ŋks] structure units. 1260 items were analyzed in total.According to the results, the nasals of Standard Latvian can be distinguished by anti-formant frequencies rather efficiently, and the results generally agree with those obtained in previous research of Latvian as well as data reported for other languages. The frequencies and the bandwidths of the first nasal formant are less informative regarding nasal place of articulation and can be used only for distinguishing between [ŋ] and [m; n; ɲ]. Conducting perception tests to assess the auditory relevance of these acoustic features is necessary.

A Triple Co-Culture Model of the Human Respiratory Tract to Study Immune-Modulatory Effects of Liposomes and Virosomes.

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Rebecca A M Blom

Full Text Available The respiratory tract with its ease of access, vast surface area and dense network of antigen-presenting cells (APCs represents an ideal target for immune-modulation. Bio-mimetic nanocarriers such as virosomes may provide immunomodulatory properties to treat diseases such as allergic asthma. In our study we employed a triple co-culture model of epithelial cells, macrophages and dendritic cells to simulate the human airway barrier. The epithelial cell line 16HBE was grown on inserts and supplemented with human blood monocyte-derived macrophages (MDMs and dendritic cells (MDDCs for exposure to influenza virosomes and liposomes. Additionally, primary human nasal epithelial cells (PHNEC and EpCAM+ epithelial progenitor cell mono-cultures were utilized to simulate epithelium from large and smaller airways, respectively. To assess particle uptake and phenotype change, cell cultures were analyzed by flow cytometry and pro-inflammatory cytokine concentrations were measured by ELISA. All cell types internalized virosomes more efficiently than liposomes in both mono- and co-cultures. APCs like MDMs and MDDCs showed the highest uptake capacity. Virosome and liposome treatment caused a moderate degree of activation in MDDCs from mono-cultures and induced an increased cytokine production in co-cultures. In epithelial cells, virosome uptake was increased compared to liposomes in both mono- and co-cultures with EpCAM+ epithelial progenitor cells showing highest uptake capacity. In conclusion, all cell types successfully internalized both nanocarriers with virosomes being taken up by a higher proportion of cells and at a higher rate inducing limited activation of MDDCs. Thus virosomes may represent ideal carrier antigen systems to modulate mucosal immune responses in the respiratory tract without causing excessive inflammatory changes.

Using organotypic (raft) epithelial tissue cultures for the biosynthesis and isolation of infectious human papillomaviruses.

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Ozbun, Michelle A; Patterson, Nicole A

2014-08-01

Papillomaviruses have a strict tropism for epithelial cells, and they are fully reliant on cellular differentiation for completion of their life cycles, resulting in the production of progeny virions. Thus, a permissive environment for full viral replication in vitro-wherein virion morphogenesis occurs under cooperative viral and cellular cues-requires the cultivation of epithelium. Presented in the first section of this unit is a protocol to grow differentiating epithelial tissues that mimic many important morphological and biochemical aspects of normal skin. The technique involves growing epidermal cells atop a dermal equivalent consisting of live fibroblasts and a collagen lattice. Epithelial stratification and differentiation ensues when the keratinocyte-dermal equivalent is placed at the air-liquid interface. The apparent floating nature of the cell-matrix in this method led to the nickname "raft" cultures. The general technique can be applied to normal low passage keratinocytes, to cells stably transfected with papillomavirus genes or genomes, or keratinocytes established from neoplastic lesions. However, infectious papillomavirus particles have only been isolated from organotypic epithelial cultures initiated with cells that maintain oncogenic human papillomavirus genomes in an extrachomosomal replicative form. The second section of this unit is dedicated to a virion isolation method that minimizes aerosol and skin exposure to these human carcinogens. Although the focus of the protocols is on the growth of tissues that yields infectious papillomavirus progeny, this culture system facilitates the investigation of these fastidious viruses during their complex replicative cycles, and raft tissues can be manipulated and harvested at any point during the process. Importantly, a single-step virus growth cycle is achieved in this process, as it is unlikely that progeny virions are released to initiate subsequent rounds of infection. Copyright © 2014 John Wiley

Nasal Septum Perforation due to Methamphetamine abuse

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Mehdi Bakhshaee

2012-07-01

Full Text Available Introduction: Spontaneous Perforation of the nasal septum is an uncommon condition. Nasal inhalation of substances such as cocaine has long been linked to this Perforation. Case Report: This report describes the case of a 46-year-old woman who was addicted to methamphetamine and who presented with perforation of the nasal septum.This is the first reported case of nasal septal necrosis linked to nasal inhalation of methamphetamine. Conclusions: Patient history and assurance regardingillegal drug consumption and abuse is a key point for fast and accurate diagnosis. The pathophysiology of drug-induced sinunasal disease and a review of the literature are also presented.

Evaluation of existing and development of new human epithelial cell transformation systems and determination of their potential in radiation protection studies

International Nuclear Information System (INIS)

Seymour, C.B.; Riches, A.C.; Pertusa, J.

1993-01-01

The aims of the project are to collaborate on a systematic study of radiation induced oncogenic transformation using different human epithelial cell lines and to study initiation of carcinogenesis by radiation by examining changes which occur in molecular, genetic and morphological features of normal human cells after exposure to radiation. This more longterm aim is at present being approached at a mainly qualitative level. This approach provides the next logical step in developing a full understanding of radiation-induced transformation of human epithelial cells. Objectives and results of five contributions to the project for the reporting period are presented. (R.P.) 20 refs., 4 figs

Delivery of antigen to nasal-associated lymphoid tissue microfold cells through secretory IgA targeting local dendritic cells confers protective immunity.

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Rochereau, Nicolas; Pavot, Vincent; Verrier, Bernard; Jospin, Fabienne; Ensinas, Agathe; Genin, Christian; Corthésy, Blaise; Paul, Stéphane

2016-01-01

Transmission of mucosal pathogens relies on their ability to bind to the surfaces of epithelial cells, to cross this thin barrier, and to gain access to target cells and tissues, leading to systemic infection. This implies that pathogen-specific immunity at mucosal sites is critical for the control of infectious agents using these routes to enter the body. Although mucosal delivery would ensure the best onset of protective immunity, most of the candidate vaccines are administered through the parenteral route. The present study evaluates the feasibility of delivering the chemically bound p24gag (referred to as p24 in the text) HIV antigen through secretory IgA (SIgA) in nasal mucosae in mice. We show that SIgA interacts specifically with mucosal microfold cells present in the nasal-associated lymphoid tissue. p24-SIgA complexes are quickly taken up in the nasal cavity and selectively engulfed by mucosal dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin-positive dendritic cells. Nasal immunization with p24-SIgA elicits both a strong humoral and cellular immune response against p24 at the systemic and mucosal levels. This ensures effective protection against intranasal challenge with recombinant vaccinia virus encoding p24. This study represents the first example that underscores the remarkable potential of SIgA to serve as a carrier for a protein antigen in a mucosal vaccine approach targeting the nasal environment. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Nasal birth trauma: a review of appropriate treatment.

LENUS (Irish Health Repository)

Cashman, E C

2012-02-01

The aetiology of nasal deformity has frequently included birth trauma. There is no consensus in the literature as to whether nasal surgery, in the form of closed reduction, is indicated in neonates. The majority of studies in the literature that advocate intervention have inadequate followup periods and there is a paucity of evidence for the adverse effects of conservative management. This case highlights the therapeutic dilemma posed by such nasal injuries in the neonate and, to the best of the authors\\' knowledge, at the time of writing, represents the earliest reported case in the literature of nasal deformity in the neonate. The term nasal deformity is used to denote deformity of the nasal pyramid, soft tissue, and septum. Three main aspects of neonatal nasal deformity are addressed including, firstly, if nasal deformity at birth needs to be addressed, secondly, if left unaltered, what the long-term effects are and, finally, if intervention alters the normal course of midfacial development.

Human amniotic epithelial cell transplantation for the repair of injured brachial plexus nerve: evaluation of nerve viscoelastic properties

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Hua Jin

2015-01-01

Full Text Available The transplantation of embryonic stem cells can effectively improve the creeping strength of nerves near an injury site in animals. Amniotic epithelial cells have similar biological properties as embryonic stem cells; therefore, we hypothesized that transplantation of amniotic epithelial cells can repair peripheral nerve injury and recover the creeping strength of the brachial plexus nerve. In the present study, a brachial plexus injury model was established in rabbits using the C 6 root avulsion method. A suspension of human amniotic epithelial cells was repeatedly injected over an area 4.0 mm lateral to the cephal and caudal ends of the C 6 brachial plexus injury site (1 × 10 6 cells/mL, 3 μL/injection, 25 injections immediately after the injury. The results showed that the decrease in stress and increase in strain at 7,200 seconds in the injured rabbit C 6 brachial plexus nerve were mitigated by the cell transplantation, restoring the viscoelastic stress relaxation and creep properties of the brachial plexus nerve. The forepaw functions were also significantly improved at 26 weeks after injury. These data indicate that transplantation of human amniotic epithelial cells can effectively restore the mechanical properties of the brachial plexus nerve after injury in rabbits and that viscoelasticity may be an important index for the evaluation of brachial plexus injury in animals.

Regulation of potassium transport in human lens epithelial cells.

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Lauf, Peter K; Warwar, Ronald; Brown, Thomas L; Adragna, Norma C

2006-01-01

The major K influx pathways and their response to thiol modification by N-ethylmaleimide (NEM) and protein kinase and phosphatase inhibitors were characterized in human lens epithelial B3 (HLE-B3) cells with Rb as K congener. Ouabain (0.1 mM) and bumetanide (5 microM) discriminated between the Na/K pump ( approximately 35% of total Rb influx) and Na-K-2Cl cotransport (NKCC) ( approximately 50%). Cl-replacement with nitrate or sulfamate revealed 100 microM, activated the Na/K pump and abolished NKCC but did not affect KCC. The data suggest at least partial inverse regulation of KCC and NKCC in HLE-B3 cells by signaling cascades involving serine, threonine and tyrosine phosphorylation/dephosphorylation equilibria.

Superoxide production and expression of NAD(P)H oxidases by transformed and primary human colonic epithelial cells

DEFF Research Database (Denmark)

Perner, A; Andresen, Lars; Pedersen, G

2003-01-01

Superoxide (O(2)(-)) generation through the activity of reduced nicotinamide dinucleotide (NADH) or reduced nicotinamide dinucleotide phosphate (NADPH) oxidases has been demonstrated in a variety of cell types, but not in human colonic epithelial cells....

Bile acids deoxycholic acid and ursodeoxycholic acid differentially regulate human β-defensin-1 and -2 secretion by colonic epithelial cells.

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Lajczak, Natalia K; Saint-Criq, Vinciane; O'Dwyer, Aoife M; Perino, Alessia; Adorini, Luciano; Schoonjans, Kristina; Keely, Stephen J

2017-09-01

Bile acids and epithelial-derived human β-defensins (HβDs) are known to be important factors in the regulation of colonic mucosal barrier function and inflammation. We hypothesized that bile acids regulate colonic HβD expression and aimed to test this by investigating the effects of deoxycholic acid (DCA) and ursodeoxycholic acid on the expression and release of HβD1 and HβD2 from colonic epithelial cells and mucosal tissues. DCA (10-150 µM) stimulated the release of both HβD1 and HβD2 from epithelial cell monolayers and human colonic mucosal tissue in vitro In contrast, ursodeoxycholic acid (50-200 µM) inhibited both basal and DCA-induced defensin release. Effects of DCA were mimicked by the Takeda GPCR 5 agonist, INT-777 (50 μM), but not by the farnesoid X receptor agonist, GW4064 (10 μM). INT-777 also stimulated colonic HβD1 and HβD2 release from wild-type, but not Takeda GPCR 5 -/- , mice. DCA stimulated phosphorylation of the p65 subunit of NF-κB, an effect that was attenuated by ursodeoxycholic acid, whereas an NF-κB inhibitor, BMS-345541 (25 μM), inhibited DCA-induced HβD2, but not HβD1, release. We conclude that bile acids can differentially regulate colonic epithelial HβD expression and secretion and discuss the implications of our findings for intestinal health and disease.-Lajczak, N. K., Saint-Criq, V., O'Dwyer, A. M., Perino, A., Adorini, L., Schoonjans, K., Keely, S. J. Bile acids deoxycholic acid and ursodeoxycholic acid differentially regulate human β-defensin-1 and -2 secretion by colonic epithelial cells. © FASEB.

Tungsten-induced carcinogenesis in human bronchial epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Laulicht, Freda; Brocato, Jason; Cartularo, Laura; Vaughan, Joshua; Wu, Feng; Kluz, Thomas; Sun, Hong [Department of Environmental Medicine, New York University Langone Medical Center, Tuxedo, NY 10987 (United States); Oksuz, Betul Akgol [Genome Technology Center, New York University Langone Medical Center, New York, NY 10016 (United States); Shen, Steven [Center for Health Informatics and Bioinformatics, New York University Langone Medical Center, New York, NY 10016 (United States); Peana, Massimiliano; Medici, Serenella; Zoroddu, Maria Antonietta [Department of Chemistry and Pharmacy, University of Sassari, Sassari (Italy); Costa, Max, E-mail: Max.Costa@nyumc.org [Department of Environmental Medicine, New York University Langone Medical Center, Tuxedo, NY 10987 (United States)

2015-10-01

Metals such as arsenic, cadmium, beryllium, and nickel are known human carcinogens; however, other transition metals, such as tungsten (W), remain relatively uninvestigated with regard to their potential carcinogenic activity. Tungsten production for industrial and military applications has almost doubled over the past decade and continues to increase. Here, for the first time, we demonstrate tungsten's ability to induce carcinogenic related endpoints including cell transformation, increased migration, xenograft growth in nude mice, and the activation of multiple cancer-related pathways in transformed clones as determined by RNA sequencing. Human bronchial epithelial cell line (Beas-2B) exposed to tungsten developed carcinogenic properties. In a soft agar assay, tungsten-treated cells formed more colonies than controls and the tungsten-transformed clones formed tumors in nude mice. RNA-sequencing data revealed that the tungsten-transformed clones altered the expression of many cancer-associated genes when compared to control clones. Genes involved in lung cancer, leukemia, and general cancer genes were deregulated by tungsten. Taken together, our data show the carcinogenic potential of tungsten. Further tests are needed, including in vivo and human studies, in order to validate tungsten as a carcinogen to humans. - Highlights: • Tungsten (W) induces cell transformation and increases migration in vitro. • W increases xenograft growth in nude mice. • W altered the expression of cancer-related genes such as those involved in leukemia. • Some of the dysregulated leukemia genes include, CD74, CTGF, MST4, and HOXB5. • For the first time, data is presented that demonstrates tungsten's carcinogenic potential.

Avaliação da aeração nasal pré e pós a realização de manobras de massagem e limpeza nasal Evaluation of nasal aeration before and after the accomplishment of massage and nasal cleanness

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Fabíola Maria Gomes de Melo

2007-09-01

Full Text Available OBJETIVO: identificar a modificação da aeração nasal após a realização de manobras de massagem e limpeza nasal. MÉTODOS: vinte crianças na faixa etária de quatro a onze anos com diagnóstico de rinite alérgica foram submetidas à avaliação da aeração nasal com o auxílio do espelho milimetrado de Altmann. Inicialmente houve a marcação do ar expirado na placa metálica, posteriormente foram realizadas manobras de massagem e limpeza nasal para retirada da secreção, havendo uma nova marcação para a comparação dos resultados. Foi aplicado o teste Kolmogorov-Smirnov para observar a suposição de normalidade dos dados e o teste t-student para amostras pareadas, sendo todas as conclusões tomadas ao nível de significância de 5%. RESULTADOS: pode-se observar que as médias obtidas da quantificação da aeração nasal após as manipulações e limpeza na região foram significativas pPURPOSE: to identify the modification of nasal aeration after the accomplishment of maneuvers of massage and nasal cleanness. METHODS: twenty children aging from four to eleven years with diagnosis of allergic rhinitis have been submitted to evaluation of nasal aeration with the Altmann's milimetric mirror. Initially, we was marked the air exhaled on the metallic plate, afterwards we made a massage and nasal cleanness for removing of the secretion, having a new benchmark to compare the results. Kolmogorov-Smirnov test was applied to test the assumption of normality for the data and t-student test for paired samples. All conclusions were taken under 5% significance. RESULTS: it was observed that the obtained averages of the nasal aeration after the manipulations and cleanness in the region were significant: p<0,001. CONCLUSION: from the results obtained in this research it was possible to observe a significant increase in the nasal aeration after the massage and nasal cleanness.

Epstein–Barr virus (EBV-associated epithelial and non-epithelial lesions of the oral cavity

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Kentaro Kikuchi

2017-08-01

Full Text Available Epstein–Barr virus (EBV is known to be associated with the development of malignant lymphoma and lymphoproliferative disorders (LPDs in immunocompromised patients. EBV, a B-lymphotropic gamma-herpesvirus, causes infectious mononucleosis and oral hairy leukoplakia, as well as various pathological types of lymphoid malignancy. Furthermore, EBV is associated with epithelial malignancies such as nasopharyngeal carcinoma (NPC, salivary gland tumor, gastric carcinoma and breast carcinoma. In terms of oral disease, there have been several reports of EBV-related oral squamous cell carcinoma (OSCC worldwide. However, the role of EBV in tumorigenesis of human oral epithelial or lymphoid tissue is unclear. This review summarizes EBV-related epithelial and non-epithelial tumors or tumor-like lesions of the oral cavity. In addition, we describe EBV latent genes and their expression in normal epithelium, inflamed gingiva, epithelial dysplasia and SCC, as well as considering LPDs (MTX- and age-related and DLBCLs of the oral cavity.

Chondrosarcoma of the nasal septum

International Nuclear Information System (INIS)

Yamamoto, Seiji; Motoori, Ken; Ueda, Takuya; Osaka, Iwao; Takano, Hideyuki; Nagata, Hiroshi

2002-01-01

The nasal septum is a particularly rare site of origin of chondrosarcoma. Cranial base invasion may be at hand, with such lesions making complete tumor removal difficult. MRI techniques allow precise definition of tumor extent. In the described case, CT and Dynamic MR imaging were performed in a case of chondrosarcoma of the nasal septum. Imaging clearly illustrated size and extent of the mass with central regions of internal calcification. Dynamic MRI was additionally performed, which helped to define the presumed origin of the lesion from the nasal septum. (orig.)

Protection against radiation-induced oxidative stress in cultured human epithelial cells by treatment with antioxidant agents

International Nuclear Information System (INIS)

Wan, X. Steven; Ware, Jeffrey H.; Zhou, Zhaozong; Donahue, Jeremiah J.; Guan, Jun; Kennedy, Ann R.

2006-01-01

Purpose: To evaluate the protective effects of antioxidant agents against space radiation-induced oxidative stress in cultured human epithelial cells. Methods and Materials: The effects of selected concentrations of N-acetylcysteine, ascorbic acid, sodium ascorbate, co-enzyme Q10, α-lipoic acid, L-selenomethionine, and vitamin E succinate on radiation-induced oxidative stress were evaluated in MCF10 human breast epithelial cells exposed to radiation with X-rays, γ-rays, protons, or high mass, high atomic number, and high energy particles using a dichlorofluorescein assay. Results: The results demonstrated that these antioxidants are effective in protecting against radiation-induced oxidative stress and complete or nearly complete protection was achieved by treating the cells with a combination of these agents before and during the radiation exposure. Conclusion: The combination of antioxidants evaluated in this study is likely be a promising countermeasure for protection against space radiation-induced adverse biologic effects

A method for high purity intestinal epithelial cell culture from adult human and murine tissues for the investigation of innate immune function.

Science.gov (United States)

Graves, Christina L; Harden, Scott W; LaPato, Melissa; Nelson, Michael; Amador, Byron; Sorenson, Heather; Frazier, Charles J; Wallet, Shannon M

2014-12-01

Intestinal epithelial cells (IECs) serve as an important physiologic barrier between environmental antigens and the host intestinal immune system. Thus, IECs serve as a first line of defense and may act as sentinel cells during inflammatory insults. Despite recent renewed interest in IEC contributions to host immune function, the study of primary IEC has been hindered by lack of a robust culture technique, particularly for small intestinal and adult tissues. Here, a novel adaptation for culture of primary IEC is described for human duodenal organ donor tissue as well as duodenum and colon of adult mice. These epithelial cell cultures display characteristic phenotypes and are of high purity. In addition, the innate immune function of human primary IEC, specifically with regard to Toll-like receptor (TLR) expression and microbial ligand responsiveness, is contrasted with a commonly used intestinal epithelial cell line (HT-29). Specifically, TLR expression at the mRNA level and production of cytokine (IFNγ and TNFα) in response to TLR agonist stimulation is assessed. Differential expression of TLRs as well as innate immune responses to ligand stimulation is observed in human-derived cultures compared to that of HT-29. Thus, use of this adapted method to culture primary epithelial cells from adult human donors and from adult mice will allow for more appropriate studies of IECs as innate immune effectors. Published by Elsevier B.V.

[Pyodermatitis-pyostomatitis vegetans with nasal involvement].