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Sample records for bronchial epithelium induced

  1. Measurement of the thickness of the bronchial epithelium

    International Nuclear Information System (INIS)

    Cancer of the lung in uranium miners is thought to be related to the inhalation of gaseous radon daughters which become attached to molecules of water vapour or to dust particles. Since, the depth of tissue penetration by alpha particles is short, the thickness of the epithelium that lines the bronchial tree may be a critical factor in the development of cancers at specific sites in the lung. The objectives of the present study were: 1) to measure the thickness of human bronchial epithelium; 2) to determine the distribution and depth of the nuclei of basal cells in the bronchial epithelium; and 3) to compare these parameters in groups of smokers and non-smokers. Twenty-nine surgically removed specimens of the lung were examined (26 smokers, 3 non-smokers). The specimens were fixed and prepared for examination by light and electron microscopy. Blocks of tissue were oriented so that the maximum number of bronchi were cut in cross-section; measurements included bronchi of all sizes from bronchial generations (1≥ 9.01 mm) diameter to the smallest bronchioles, generations 7 - 16 (0.26 - 2.0 mm). Comparison of measurements in smokers and non-smokers show no significant differences, so that the 29 cases are considered to represent a homogeneous group. With progressive divisions of the bronchi, the epithelium decreases in thickness. Of more importance are the figures relating to the distance from the cell surface to the underlying nucleus. Here too, with the exception of goblet cells, the measurements are significantly smaller in generations 7 - 16 than in generation 1

  2. Lack of Dystrophin Affects Bronchial Epithelium in mdx Mice.

    Science.gov (United States)

    Morici, Giuseppe; Rappa, Francesca; Cappello, Francesco; Pace, Elisabetta; Pace, Andrea; Mudò, Giuseppa; Crescimanno, Grazia; Belluardo, Natale; Bonsignore, Maria R

    2016-10-01

    Mild exercise training may positively affect the course of Duchenne Muscular Dystrophy (DMD). Training causes mild bronchial epithelial injury in both humans and mice, but no study assessed the effects of exercise in mdx mice, a well known model of DMD. The airway epithelium was examined in mdx (C57BL/10ScSn-Dmdmdx) mice, and in wild type (WT, C57BL/10ScSc) mice either under sedentary conditions (mdx-SD, WT-SD) or during mild exercise training (mdx-EX, WT-EX). At baseline, and after 30 and 45 days of training (5 d/wk for 6 weeks), epithelial morphology and markers of regeneration, apoptosis, and cellular stress were assessed. The number of goblet cells in bronchial epithelium was much lower in mdx than in WT mice under all conditions. At 30 days, epithelial regeneration (PCNA positive cells) was higher in EX than SD animals in both groups; however, at 45 days, epithelial regeneration decreased in mdx mice irrespective of training, and the percentage of apoptotic (TUNEL positive) cells was higher in mdx-EX than in WT-EX mice. Epithelial expression of HSP60 (marker of stress) progressively decreased, and inversely correlated with epithelial apoptosis (r = -0.66, P = 0.01) only in mdx mice. Lack of dystrophin in mdx mice appears associated with defective epithelial differentiation, and transient epithelial regeneration during mild exercise training. Hence, lack of dystrophin might impair repair in bronchial epithelium, with potential clinical consequences in DMD patients. J. Cell. Physiol. 231: 2218-2223, 2016. © 2016 Wiley Periodicals, Inc. PMID:26868633

  3. Cavitary Lung Cancer Lined with Normal Bronchial Epithelium and Cancer Cells

    OpenAIRE

    Goto, Taichiro; Maeshima, Arafumi; Oyamada, Yoshitaka; Kato, Ryoichi

    2011-01-01

    Reports of cavitary lung cancer are not uncommon, and the cavity generally contains either dilated bronchi or cancer cells. Recently, we encountered a surgical case of cavitary lung cancer whose cavity tended to enlarge during long-term follow-up, and was found to be lined with normal bronchial epithelium and adenocarcinoma cells.

  4. Effects of Poly(I:C, LPS and PGN stimulation on the innate immune function of human bronchial epithelium

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    Jing-xi ZHANG

    2013-07-01

    Full Text Available Objective To study the effect of polyinosinic:polycytidylic acid (poly(I:C, lipolysaccharide (LPS, peptidoglycan (PGN on the barrier function and inflammatory mediators release of bronchial epithelium, and explore the impact of different specific Toll-like receptor (TLR 2, 3, 4 ligands on airway mucosal innate immune responses. Methods Polarized human bronchial epithelial cells (16HBEs were cultured using transwell system to establish human bronchial epithelium model in vitro. The stimulation of Poly(I:C, LPS and PGN, respectively, was given on 16HBEs apically. The permeabilities of micromolecule and macromolecule between cells were measured by detecting trans-epithelial electrical resistance (TER and basolateral medium FITC¬dextran concentrations after 24h stimulation. IL-8, GM-CSF and TNF-α protein content of apical and basal supernatants released by 16HBEs were measured by ELISA after 24h stimulation. Results 10μg/ml Poly(I:C resulted in decrease of TER and reduction of increase of FITC-dextran permeability significantly (P<0.001, while 10μg/ml LPS and 100μg/ml PGN showed no obvious effects on TER and FITC-dextran permeability. Poly(I:C, LPS and PGN induced an increase in apical and basolateral IL-8, TNF-α release and apical GM-CSF release of the cells. There was no change in basal expression of GM-CSF after being stimulated by LPS and PGN. The apical increase in IL-8 and GM-CSF was higher in Poly(I:C, LPS and PGN groups than their basal increase, thus forming the concentration gradient between two sides of the polarized cells. Conclusions Poly (I:C can damage the barrier integrity of the bronchial epithelium, leading to an increase in micromolecular and macromolecular permeability, and induce the secretion of inflammatory mediators towards the top side at the same time. LPS and PGN can only induce the secretion of inflammatory mediators towards the top side mildly, without affecting the barrier function. It is suggested that

  5. Rhinovirus infection induces cytotoxicity and delays wound healing in bronchial epithelial cells

    OpenAIRE

    Constantopoulos Andreas G; Skevaki Chrysanthi L; Gourgiotis Dimitrios; Psarras Stelios; Bossios Apostolos; Saxoni-Papageorgiou Photini; Papadopoulos Nikolaos G

    2005-01-01

    Abstract Background Human rhinoviruses (RV), the most common triggers of acute asthma exacerbations, are considered not cytotoxic to the bronchial epithelium. Recent observations, however, have questioned this knowledge. The aim of this study was to evaluate the ability of RV to induce epithelial cytotoxicity and affect epithelial repair in-vitro. Methods Monolayers of BEAS-2B bronchial epithelial cells, seeded at different densities were exposed to RV serotypes 1b, 5, 7, 9, 14, 16. Cytotoxic...

  6. Role of aberrant metalloproteinase activity in the pro-inflammatory phenotype of bronchial epithelium in COPD

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    Postma Dirkje S

    2011-08-01

    Full Text Available Abstract Background Cigarette smoke, the major risk factor for COPD, is known to activate matrix metalloproteinases in airway epithelium. We investigated whether metalloproteinases, particularly A Disintegrin and Metalloproteinase (ADAM17, contribute to increased pro-inflammatory epithelial responses with respect to the release of IL-8 and TGF-α, cytokines implicated in COPD pathogenesis. Methods We studied the effects of cigarette smoke extract (CSE and metalloproteinase inhibitors on TGF-α and IL-8 release in primary bronchial epithelial cells (PBECs from COPD patients, healthy smokers and non-smokers. Results We observed that TGF-α was mainly shed by ADAM17 in PBECs from all groups. Interestingly, IL-8 production occurred independently from ADAM17 and TGF-α shedding, but was significantly inhibited by broad-spectrum metalloproteinase inhibitor TAPI-2. CSE did not induce ADAM17-dependent TGF-α shedding, while it slightly augmented the production of IL-8. This was accompanied by reduced endogenous inhibitor of metalloproteinase (TIMP-3 levels, suggesting that CSE does not directly but rather indirectly alter activity of ADAM17 through the regulation of its endogenous inhibitor. Furthermore, whereas baseline TGF-α shedding was lower in COPD PBECs, the early release of IL-8 (likely due to its shedding was higher in PBECs from COPD than healthy smokers. Importantly, this was accompanied by lower TIMP-2 levels in COPD PBECs, while baseline TIMP-3 levels were similar between groups. Conclusions Our data indicate that IL-8 secretion is regulated independently from ADAM17 activity and TGF-α shedding and that particularly its early release is differentially regulated in PBECs from COPD and healthy smokers. Since TIMP-2-sensitive metalloproteinases could potentially contribute to IL-8 release, these may be interesting targets to further investigate novel therapeutic strategies in COPD.

  7. Increased polysomy of chromosome 7 in bronchial epithelium from patients at high risk for lung cancer

    International Nuclear Information System (INIS)

    Current models of carcinogenesis suggest that tissues progress through multiple genetic and epigenetic changes which ultimately lead to development of invasive cancer. Epidemiologic studies of Peto, R.R. and J.A. Doll indicate that the accumulation of these genetic changes over time, rather than any single unique genetic change, is probably responsible for development of the malignant phenotype. The bronchial epithelium of cigarette smokers is diffusely exposed to a broad spectrum of carcinogens, toxicants, and tumor promoters contained in tobacco smoke. This exposure increases the risk of developing multiple, independent premalignant foci throughout the lower respiratory tract that may contain independent gene aberrations. This open-quotes field cancerizationclose quotes theory is supported by studies that have demonstrated progressive histologic changes distributed throughout the lower respiratory tract of smokers. A series of autopsy studies demonstrated that cigarette smokers exhibit premalignant histologic changes ranging from hyperplasia and metaplasia to severe dysplasia and carcinoma in situ diffusely throughout the bronchial mucosa. The proximal bronchi appear to exhibit the greatest number of changes, particularly at bifurcations. The results described are the first to quantitate the frequency for a chromosome aberration in open-quotes normalclose quotes bronchial epithelial cells

  8. Increased polysomy of chromosome 7 in bronchial epithelium from patients at high risk for lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Belinsky, S.A.; Neft, R.E.; Lechner, J.F. [and others

    1995-12-01

    Current models of carcinogenesis suggest that tissues progress through multiple genetic and epigenetic changes which ultimately lead to development of invasive cancer. Epidemiologic studies of Peto, R.R. and J.A. Doll indicate that the accumulation of these genetic changes over time, rather than any single unique genetic change, is probably responsible for development of the malignant phenotype. The bronchial epithelium of cigarette smokers is diffusely exposed to a broad spectrum of carcinogens, toxicants, and tumor promoters contained in tobacco smoke. This exposure increases the risk of developing multiple, independent premalignant foci throughout the lower respiratory tract that may contain independent gene aberrations. This {open_quotes}field cancerization{close_quotes} theory is supported by studies that have demonstrated progressive histologic changes distributed throughout the lower respiratory tract of smokers. A series of autopsy studies demonstrated that cigarette smokers exhibit premalignant histologic changes ranging from hyperplasia and metaplasia to severe dysplasia and carcinoma in situ diffusely throughout the bronchial mucosa. The proximal bronchi appear to exhibit the greatest number of changes, particularly at bifurcations. The results described are the first to quantitate the frequency for a chromosome aberration in {open_quotes}normal{close_quotes} bronchial epithelial cells.

  9. Correspondence regarding "Effect of active smoking on the human bronchial epithelium transcriptome"

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    Zuyderduyn Scott D

    2009-02-01

    Full Text Available Abstract Background In the work of Chari et al. entitled "Effect of active smoking on the human bronchial epithelium transcriptome" the authors use SAGE to identify candidate gene expression changes in bronchial brushings from never, former, and current smokers. These gene expression changes are categorized into those that are reversible or irreversible upon smoking cessation. A subset of these identified genes is validated on an independent cohort using RT-PCR. The authors conclude that their results support the notion of gene expression changes in the lungs of smokers which persist even after an individual has quit. Results This correspondence raises questions about the validity of the approach used by the authors to analyze their data. The majority of the reported results suffer deficiencies due to the methods used. The most fundamental of these are explained in detail: biases introduced during data processing, lack of correction for multiple testing, and an incorrect use of clustering for gene discovery. A randomly generated "null" dataset is used to show the consequences of these shortcomings. Conclusion Most of Chari et al.'s findings are consistent with what would be expected by chance alone. Although there is clear evidence of reversible changes in gene expression, the majority of those identified appear to be false positives. However, contrary to the authors' claims, no irreversible changes were identified. There is a broad consensus that genetic change due to smoking persists once an individual has quit smoking; unfortunately, this study lacks sufficient scientific rigour to support or refute this hypothesis or identify any specific candidate genes. The pitfalls of large-scale analysis, as exemplified here, may not be unique to Chari et al.

  10. In vitro bioelectric properties of bronchial epithelium from transplanted lungs in recipients with cystic fibrosis.

    OpenAIRE

    Tsang, V. T.; Alton, E. W.; Hodson, M E; Yacoub, M

    1993-01-01

    BACKGROUND--Bronchial epithelial function after heart-lung transplantation (HLT) for cystic fibrosis (CF) may be affected by the original disease as well as other factors such as prolonged organ ischaemic time, the interruption of bronchial arterial and lymphatic supply, infection, rejection, and cyclosporin. In vitro measurement of the bioelectric properties of the bronchial mucosal lining may be an effective means of characterising the mucosal function of the lung allografts in response to ...

  11. Rhinovirus infection induces cytotoxicity and delays wound healing in bronchial epithelial cells

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    Constantopoulos Andreas G

    2005-10-01

    Full Text Available Abstract Background Human rhinoviruses (RV, the most common triggers of acute asthma exacerbations, are considered not cytotoxic to the bronchial epithelium. Recent observations, however, have questioned this knowledge. The aim of this study was to evaluate the ability of RV to induce epithelial cytotoxicity and affect epithelial repair in-vitro. Methods Monolayers of BEAS-2B bronchial epithelial cells, seeded at different densities were exposed to RV serotypes 1b, 5, 7, 9, 14, 16. Cytotoxicity was assessed chromatometrically. Epithelial monolayers were mechanically wounded, exposed or not to RV and the repopulation of the damaged area was assessed by image analysis. Finally epithelial cell proliferation was assessed by quantitation of proliferating cell nuclear antigen (PCNA by flow cytometry. Results RV1b, RV5, RV7, RV14 and RV16 were able to induce considerable epithelial cytotoxicity, more pronounced in less dense cultures, in a cell-density and dose-dependent manner. RV9 was not cytotoxic. Furthermore, RV infection diminished the self-repair capacity of bronchial epithelial cells and reduced cell proliferation. Conclusion RV-induced epithelial cytotoxicity may become considerable in already compromised epithelium, such as in the case of asthma. The RV-induced impairment on epithelial proliferation and self-repair capacity may contribute to the development of airway remodeling.

  12. Virus Infection-Induced Bronchial Asthma Exacerbation

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    Mutsuo Yamaya

    2012-01-01

    Full Text Available Infection with respiratory viruses, including rhinoviruses, influenza virus, and respiratory syncytial virus, exacerbates asthma, which is associated with processes such as airway inflammation, airway hyperresponsiveness, and mucus hypersecretion. In patients with viral infections and with infection-induced asthma exacerbation, inflammatory mediators and substances, including interleukins (ILs, leukotrienes and histamine, have been identified in the airway secretions, serum, plasma, and urine. Viral infections induce an accumulation of inflammatory cells in the airway mucosa and submucosa, including neutrophils, lymphocytes and eosinophils. Viral infections also enhance the production of inflammatory mediators and substances in airway epithelial cells, mast cells, and other inflammatory cells, such as IL-1, IL-6, IL-8, GM-CSF, RANTES, histamine, and intercellular adhesion molecule-1. Viral infections affect the barrier function of the airway epithelial cells and vascular endothelial cells. Recent reports have demonstrated augmented viral production mediated by an impaired interferon response in the airway epithelial cells of asthma patients. Several drugs used for the treatment of bronchial asthma reduce viral and pro-inflammatory cytokine release from airway epithelial cells infected with viruses. Here, I review the literature on the pathogenesis of the viral infection-induced exacerbation of asthma and on the modulation of viral infection-induced airway inflammation.

  13. A normal and biotransforming model of the human bronchial epithelium for the toxicity testing of aerosols and solubilised substances.

    Science.gov (United States)

    Prytherch, Zoë C; BéruBé, Kelly A

    2014-12-01

    In this article, we provide an overview of the experimental workflow by the Lung and Particle Research Group at Cardiff University, that led to the development of the two in vitro lung models - the normal human bronchial epithelium (NHBE) model and the lung-liver model, Metabo-Lung™. This work was jointly awarded the 2013 Lush Science Prize. The NHBE model is a three-dimensional, in vitro, human tissue-based model of the normal human bronchial epithelium, and Metabo-Lung involves the co-culture of the NHBE model with primary human hepatocytes, thus permitting the biotransformation of inhaled toxicants in an in vivo-like manner. Both models can be used as alternative test systems that could replace the use of animals in research and development for safety and toxicity testing in a variety of industries (e.g. the pharmaceutical, environmental, cosmetics, and food industries). Metabo-Lung itself is a unique tool for the in vitro detection of toxins produced by reactive metabolites. This 21st century animal replacement model could yield representative in vitro predictions for in vivo toxicity. This advancement in in vitro toxicology relies on filter-well technology that will enable a wide-spectrum of researchers to create viable and economic alternatives for respiratory safety assessment and disease-focused research. PMID:25635646

  14. Comparison of proteomic and transcriptomic profiles in the bronchial airway epithelium of current and never smokers.

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    Katrina Steiling

    Full Text Available BACKGROUND: Although prior studies have demonstrated a smoking-induced field of molecular injury throughout the lung and airway, the impact of smoking on the airway epithelial proteome and its relationship to smoking-related changes in the airway transcriptome are unclear. METHODOLOGY/PRINCIPAL FINDINGS: Airway epithelial cells were obtained from never (n = 5 and current (n = 5 smokers by brushing the mainstem bronchus. Proteins were separated by one dimensional polyacrylamide gel electrophoresis (1D-PAGE. After in-gel digestion, tryptic peptides were processed via liquid chromatography/ tandem mass spectrometry (LC-MS/MS and proteins identified. RNA from the same samples was hybridized to HG-U133A microarrays. Protein detection was compared to RNA expression in the current study and a previously published airway dataset. The functional properties of many of the 197 proteins detected in a majority of never smokers were similar to those observed in the never smoker airway transcriptome. LC-MS/MS identified 23 proteins that differed between never and current smokers. Western blotting confirmed the smoking-related changes of PLUNC, P4HB1, and uteroglobin protein levels. Many of the proteins differentially detected between never and current smokers were also altered at the level of gene expression in this cohort and the prior airway transcriptome study. There was a strong association between protein detection and expression of its corresponding transcript within the same sample, with 86% of the proteins detected by LC-MS/MS having a detectable corresponding probeset by microarray in the same sample. Forty-one proteins identified by LC-MS/MS lacked detectable expression of a corresponding transcript and were detected in epithelium proteome and identified proteins expressed at different levels as a

  15. Benzalkonium Chloride Induced Bronchoconstriction in Patients with Stable Bronchial Asthma

    OpenAIRE

    Lee, Byoung Hoon; Kim, Sang-Hoon

    2007-01-01

    Background Although benzalkonium chloride (BAC)-induced bronchoconstriction occurs in patients with bronchial asthma, BAC-containing nebulizer solutions are still being used in daily practice in Korea. The aim of this study was to evaluate the effects of inhaled aqueous solutions containing BAC. Methods Thirty subjects with bronchial asthma and 10 normal controls inhaled up to three 600 µg nebulized doses of BAC using a jet nebulizer. FEV1 (forced expiratory volume at one second) was measured...

  16. Epidemiologic approach to determining the REM dose to bronchial epithelium from radon daughter exposures in man

    International Nuclear Information System (INIS)

    Dosimetric evaluation of exposures to the bronchial epithelial stem cells from inhalation of alpha emitters is complex and the number of assumptions required leads to substantial uncertainty. Moreover, it is evident that many factors such as variable breathing patterns will modify the results. An empirical approach to determining the rem dose biologically effective in producing bronchial cancer by inhalation of radon daughters is possible by comparison of cumulative exposure in terms of Working Level Months with the dose of penetrating low-LET radiation to produce the same bronchial cancer risk in other groups investigated. This method is possible when the dosimetry of the comparison groups is well known and lung cancer risks are reasonably well-defined. A number of epidemiologic considerations must be taken into account in such comparisons, however. These include age at exposure, length of following, age at expression of or death from cancer, and for underground miners exposed to radon daughters the lung cancer-latent period model applied to long-term exposures. Use of these methods gives results consistent with dosimetry derived from models of bronchial deposition and clearance, as well as reasonable values for the quality factor for alpha radiation. This comparison gives an average equivalent dose for a working population exposed to short-lived isotopes

  17. Ultraviolet induced lysosome activity in corneal epithelium

    International Nuclear Information System (INIS)

    A 5.000 W Xe-Hg high pressure lamp and a double monochromator were used to produce a 3.3 nm half-bandpass ultraviolet radiation at 295 nm. Pigmented rabbit eyes were irradiated with radiant exposures from 140 Jm-2 to 10.000 Jm-2 and evaluated by slit-lamp biomicroscopy, light and electron microscopy. Corneal threshold (Hsub(c) was 200 Jm-2 and lens threshold (Hsub(L)) was 7.500 Jm-2. The most repeatable and reliable corneal response to these levels of UV was the development of corneal epithelial granules. Histological changes included a loss of superficial epithelial cells and selective UV induced autolysis of the wing cells. It is suggested that the biomicroscopically observed granules are the clinical manifestation of the secondary lysosomes revealed by light and electron microscopy. It is proposed that UV breaks down the primary lysosome membranes to release hydrolytic enzymes which in turn form the secondary lysosomes during autolysis. Extreme levels of radiant exposure at 295 nm result in indiscriminate destruction of all layers of the corneal epithelium, but the posterior cornea was spared. (orig.)

  18. Interferon response of the cystic fibrosis bronchial epithelium to major and minor group rhinovirus infection.

    Science.gov (United States)

    Schögler, Aline; Stokes, Andrea B; Casaulta, Carmen; Regamey, Nicolas; Edwards, Michael R; Johnston, Sebastian L; Jung, Andreas; Moeller, Alexander; Geiser, Thomas; Alves, Marco P

    2016-05-01

    Rhinoviruses (RVs) are associated with exacerbations of cystic fibrosis (CF), asthma and COPD. There is growing evidence suggesting the involvement of the interferon (IFN) pathway in RV-associated morbidity in asthma and COPD. The mechanisms of RV-triggered exacerbations in CF are poorly understood. In a pilot study, we assessed the antiviral response of CF and healthy bronchial epithelial cells (BECs) to RV infection, we measured the levels of IFNs, pattern recognition receptors (PRRs) and IFN-stimulated genes (ISGs) upon infection with major and minor group RVs and poly(IC) stimulation. Major group RV infection of CF BECs resulted in a trend towards a diminished IFN response at the level of IFNs, PRRs and ISGs in comparison to healthy BECs. Contrary to major group RV, the IFN pathway induction upon minor group RV infection was significantly increased at the level of IFNs and PRRs in CF BECs compared to healthy BECs. PMID:26613982

  19. Plasma catecholamines during exercise-induced bronchoconstriction in bronchial asthma.

    OpenAIRE

    Zieliński, J; Chodosowska, E; Radomyski, A; Araszkiewicz, Z; Kozlowski, S

    1980-01-01

    Plasma levels of adrenaline and noradrenaline during and after submaximal exercise in patients with bronchial asthma were investigated. Three groups were studied comprising 10 patients with exercise-induced bronchoconstriction (EIB), 10 asthmatic patients without EIB and four normal control subjects. Plasma catecholamines were measured at rest, at the end of exercise, and five and 15 minutes after exercise. Changes in airway resistance were assessed by measuring peak expiratory flow rate. Sig...

  20. Regeneration of tracheal epithelium using mouse induced pluripotent stem cells.

    Science.gov (United States)

    Ikeda, Masakazu; Imaizumi, Mitsuyoshi; Yoshie, Susumu; Otsuki, Koshi; Miyake, Masao; Hazama, Akihiro; Wada, Ikuo; Omori, Koichi

    2016-04-01

    Conclusion The findings demonstrated the potential use of induced pluripotent stem cells for regeneration of tracheal epithelium. Objective Autologous tissue implantation techniques using skin or cartilage are often applied in cases of tracheal defects with laryngeal inflammatory lesions and malignant tumor invasion. However, these techniques are invasive with an unstable clinical outcome. The purpose of this study was to investigate regeneration in a tracheal defect site of nude rats after implantation of ciliated epithelium that was differentiated from induced pluripotent stem cells. Method Embryoid bodies were formed from mouse induced pluripotent stem cells. They were cultured with growth factors for 5 days, and then cultured at the air-liquid interface. The degree of differentiation achieved prior to implantation was determined by histological findings and the results of real-time polymerase chain reaction. Embryoid bodies including ciliated epithelium were embedded into collagen gel that served as an artificial scaffold, and then implanted into nude rats, creating an 'air-liquid interface model'. Histological evaluation was performed 7 days after implantation. Results The ciliated epithelial structure survived on the lumen side of regenerated tissue. It was demonstrated histologically that the structure was composed of ciliated epithelial cells. PMID:26755348

  1. Gelsolin Restores Aβ-Induced Alterations in Choroid Plexus Epithelium

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    Teo Vargas

    2010-01-01

    Full Text Available Histologically, Alzheimer's disease (AD is characterized by senile plaques and cerebrovascular amyloid deposits. In previous studies we demonstrated that in AD patients, amyloid-β (Aβ peptide also accumulates in choroid plexus, and that this process is associated with mitochondrial dysfunction and epithelial cell death. However, the molecular mechanisms underlying Aβ accumulation at the choroid plexus epithelium remain unclear. Aβ clearance, from the brain to the blood, involves Aβ carrier proteins that bind to megalin, including gelsolin, a protein produced specifically by the choroid plexus epithelial cells. In this study, we show that treatment with gelsolin reduces Aβ-induced cytoskeletal disruption of blood-cerebrospinal fluid (CSF barrier at the choroid plexus. Additionally, our results demonstrate that gelsolin plays an important role in decreasing Aβ-induced cytotoxicity by inhibiting nitric oxide production and apoptotic mitochondrial changes. Taken together, these findings make gelsolin an appealing tool for the prophylactic treatment of AD.

  2. Captopril augments acetylcholine-induced bronchial smooth muscle contractions in vitro via kinin-dependent mechanisms.

    Science.gov (United States)

    Agrawal, Naman; Akella, Aparna; Deshpande, Shripad B

    2016-06-01

    Angiotensin converting enzyme (ACE) inhibitors therapy is aassociated with bothersome dry cough as an adverse effect. The mechanisms underlying this adverse effect are not clear. Therefore, influence of captopril (an ACE inhibitor) on acetylcholine (ACh)-induced bronchial smooth muscle contractions was investigated. Further, the mechanisms underlying the captopril-induced changes were also explored. In vitro contractions of rat bronchial smooth muscle to cumulative concentrations of ACh were recorded before and after exposure to captopril. Further, the involvement of kinin and inositol triphosphate (IP₃) pathways for captopril-induced alterations were explored. ACh produced concentration-dependent (5-500 µM) increase in bronchial smooth muscle contractions. Pre-treatment with captopril augmented the ACh-induced contractions at each concentration significantly. Pre-treatment with aprotinin (kinin synthesis inhibitor) or heparin (inositol triphosphate, IP₃-inhibitor), blocked the captopril-induced augmentation of bronchial smooth muscle contractions evoked by ACh. Further, captopril-induced augmentation was absent in calcium-free medium. These results suggest that captopril sensitizes bronchial smooth muscles to ACh-induced contractions. This sensitization may be responsible for dry cough associated with captopril therapy. PMID:27468462

  3. Enhancement of Methacholine-Evoked Tracheal Contraction Induced by Bacterial Lipopolysaccharides Depends on Epithelium and Tumor Necrosis Factor

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    T. Secher

    2012-01-01

    Full Text Available Inhaled bacterial lipopolysaccharides (LPSs induce an acute tumour necrosis factor-alpha (TNF-α- dependent inflammatory response in the murine airways mediated by Toll-like receptor 4 (TLR4 via the myeloid differentiation MyD88 adaptor protein pathway. However, the contractile response of the bronchial smooth muscle and the role of endogenous TNFα in this process have been elusive. We determined the in vivo respiratory pattern of C57BL/6 mice after intranasal LPS administration with or without the presence of increasing doses of methacholine (MCh. We found that LPS administration altered the basal and MCh-evoked respiratory pattern that peaked at 90 min and decreased thereafter in the next 48 h, reaching basal levels 7 days later. We investigated in controlled ex vivo condition the isometric contraction of isolated tracheal rings in response to MCh cholinergic stimulation. We observed that preincubation of the tracheal rings with LPS for 90 min enhanced the subsequent MCh-induced contractile response (hyperreactivity, which was prevented by prior neutralization of TNFα with a specific antibody. Furthermore, hyperreactivity induced by LPS depended on an intact epithelium, whereas hyperreactivity induced by TNFα was well maintained in the absence of epithelium. Finally, the enhanced contractile response to MCh induced by LPS when compared with control mice was not observed in tracheal rings from TLR4- or TNF- or TNF-receptor-deficient mice. We conclude that bacterial endotoxin-mediated hyperreactivity of isolated tracheal rings to MCh depends upon TLR4 integrity that signals the activation of epithelium, which release endogenous TNFα.

  4. The Effect of Therapeutic Blockades of Dust Particles-Induced Ca2+ Signaling and Proinflammatory Cytokine IL-8 in Human Bronchial Epithelial Cells

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    Ju Hee Yoon

    2015-01-01

    Full Text Available Bronchial epithelial cells are the first barrier of defense against respiratory pathogens. Dust particles as extracellular stimuli are associated with inflammatory reactions after inhalation. It has been reported that dust particles induce intracellular Ca2+ signal, which subsequently increases cytokines production such as interleukin- (IL- 8. However, the study of therapeutic blockades of Ca2+ signaling induced by dust particles in human bronchial epithelial cells is poorly understood. We investigated how to modulate dust particles-induced Ca2+ signaling and proinflammatory cytokine IL-8 expression. Bronchial epithelial BEAS-2B cells were exposed to PM10 dust particles and subsequent mediated intracellular Ca2+ signaling and reactive oxygen species signal. Our results show that exposure to several inhibitors of Ca2+ pathway attenuated the PM10-induced Ca2+ response and subsequent IL-8 mRNA expression. PM10-mediated Ca2+ signal and IL-8 expression were attenuated by several pharmacological blockades such as antioxidants, IP3-PLC blockers, and TRPM2 inhibitors. Our results show that blockades of PLC or TRPM2 reduced both of PM10-mediated Ca2+ signal and IL-8 expression, suggesting that treatment with these blockades should be considered for potential therapeutic trials in pulmonary epithelium for inflammation caused by environmental events such as seasonal dust storm.

  5. Lithium Attenuates TGF-β 1-Induced Fibroblasts to Myofibroblasts Transition in Bronchial Fibroblasts Derived from Asthmatic Patients

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    Marta Michalik; Katarzyna Anna Wójcik; Bogdan Jakieła; Katarzyna Szpak; Małgorzata Pierzchalska; Marek Sanak; Zbigniew Madeja; Jarosław Czyż

    2012-01-01

    Bronchial asthma is a chronic disorder accompanied by phenotypic transitions of bronchial epithelial cells, smooth muscle cells, and fibroblasts. Human bronchial fibroblasts (HBFs) derived from patients with diagnosed asthma display predestination towards TGF- β -induced phenotypic switches. Since the interference between TGF- β and GSK-3 β signaling contributes to pathophysiology of chronic lung diseases, we investigated the effect of lithium, a nonspecific GSK-3 β inhibitor, on TGF- β 1-ind...

  6. Oxidative stress induced Interleukin-32 mRNA expression in human bronchial epithelial cells

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    Kudo Megumi

    2012-03-01

    Full Text Available Abstract Background Chronic obstructive pulmonary disease (COPD is characterized by airflow obstruction and persistent inflammation in the airways and lung parenchyma. Oxidative stress contributes to the pathogenesis of COPD. Interleukin (IL-32 expression has been reported to increase in the lung tissue of patients with COPD. Here, we show that IFNγ upregulated IL-32 expression and that oxidative stress augmented IFNγ-induced-IL-32 expression in airway epithelial cells. We further investigated transcriptional regulation responsible for IFNγ induced IL-32 expression in human airway epithelial cells. Methods Human bronchial epithelial (HBE cells were stimulated with H2O2 and IFNγ, and IL-32 expression was evaluated. The cell viability was confirmed by MTT assay. The intracellular signaling pathways regulating IL-32 expression were investigated by examining the regulatory effects of MAPK inhibitors and JAK inhibitor after treatment with H2O2 and IFNγ, and by using a ChIP assay to identify transcription factors (i.e. c-Jun, CREB binding to the IL-32 promoter. Promoter activity assays were conducted after mutations were introduced into binding sites of c-Jun and CREB in the IL-32 promoter. IL-32 expression was also examined in HBE cells in which the expression of either c-Jun or CREB was knocked out by siRNA of indicated transcription factors. Results There were no significant differences of cell viability among groups. After stimulation with H2O2 or IFNγ for 48 hours, IL-32 expression in HBE cells was increased by IFNγ and synergistically upregulated by the addition of H2O2. The H2O2 augmented IFNγ induced IL-32 mRNA expression was suppressed by a JNK inhibitor, but not by MEK inhibitor, p38 inhibitor, and JAK inhibitor I. Significant binding of c-Jun and CREB to the IL-32 promoter was observed in the IFNγ + H2O2 stimulated HBE cells. Introducing mutations into the c-Jun/CREB binding sites in the IL-32 promoter prominently suppressed its

  7. Intestinal ischemia/reperfusion induces bronchial hyperreactivity and increases serum TNF-alpha in rats

    Directory of Open Access Journals (Sweden)

    Arruda Marcio Jose Cristiano de

    2006-01-01

    Full Text Available INTRODUCTION: Intestinal or hepatic ischemia/reperfusion induces acute lung injury in animal models of multiple organ failure. Tumor necrosis factor (TNF- alpha is involved in the underlying inflammatory mechanism of acute respiratory distress syndrome. Although the inflammatory cascade leading to acute respiratory distress syndrome has been extensively investigated, the mechanical components of acute respiratory distress syndrome are not fully understood. Our hypothesis is that splanchnic ischemia/reperfusion increases airway reactivity and serum TNF-alpha levels. OBJECTIVE: To assess bronchial smooth muscle reactivity under methacholine stimulation, and to measure serum TNF-alpha levels following intestinal and/or hepatic ischemia/reperfusion in rats. METHOD: Rats were subjected to 45 minutes of intestinal ischemia, or 20 minutes of hepatic ischemia, or to both (double ischemia, or sham procedures (control, followed by 120 minutes of reperfusion. The animals were then sacrificed, and the bronchial response to increasing methacholine molar concentrations (10-7 to 3 x 10-4 was evaluated in an ex-vivo bronchial muscle preparation. Serum TNF-alpha was determined by the L929-cell bioassay. RESULTS: Bronchial response (g/100 mg tissue showed increased reactivity to increasing methacholine concentrations in the intestinal ischemia and double ischemia groups, but not in the hepatic ischemia group. Similarly, serum TNF-alpha (pg/mL concentration was increased in the intestinal ischemia and double ischemia groups, but not in the hepatic ischemia group. CONCLUSION: Intestinal ischemia, either isolated or associated with hepatic ischemia, increased bronchial smooth muscle reactivity, suggesting a possible role for bronchial constriction in respiratory dysfunction following splanchnic ischemia/reperfusion. This increase occurred in concomitance with serum TNF-alpha increase, but whether the increase in TNF-alpha caused this bronchial contractility remains

  8. Effects of swimming training on aerobic capacity and exercise induced bronchoconstriction in children with bronchial asthma

    OpenAIRE

    Matsumoto, I.; Araki, H; Tsuda, K; Odajima, H; Nishima, S; Higaki, Y.; Tanaka, H.; Tanaka, M.; Shindo, M

    1999-01-01

    BACKGROUND—A study was undertaken to determine whether swimming training improved aerobic capacity, exercise induced bronchoconstriction (EIB), and bronchial responsiveness to inhaled histamine in children with asthma.
METHODS—Eight children with mild or moderate asthma participated in swimming training every day for six weeks. The intensity of training was individually determined and set at 125% of the child's lactate threshold (LT), measured using a swimming ergometer. ...

  9. Rhinovirus-induced modulation of gene expression in bronchial epithelial cells from subjects with asthma

    OpenAIRE

    Bochkov, YA; Hanson, KM; Keles, S.; Brockman-Schneider, RA; Jarjour, NN; Gern, JE

    2009-01-01

    Rhinovirus (RV) infections trigger asthma exacerbations. Genome-wide expression analysis of RV1A-infected primary bronchial epithelial cells from normal and asthmatic donors was performed to determine whether asthma is associated with a unique pattern of RV-induced gene expression. Virus replication rates were similar in cells from normal and asthmatic donors. Overall, RV downregulated 975 and upregulated 69 genes. Comparisons of transcriptional profiles generated from microarrays and confirm...

  10. Fetal-juvenile origins of point mutations in the adult human tracheal-bronchial epithelium: Absence of detectable effects of age, gender or smoking status

    International Nuclear Information System (INIS)

    Allele-specific mismatch amplification mutation assays (MAMA) of anatomically distinct sectors of the upper bronchial tracts of nine nonsmokers revealed many numerically dispersed clusters of the point mutations C742T, G746T, G747T of the TP53 gene, G35T of the KRAS gene and G508A of the HPRT1 gene. Assays of these five mutations in six smokers have yielded quantitatively similar results. One hundred and eighty four micro-anatomical sectors of 0.5-6 x 106 tracheal-bronchial epithelial cells represented en toto the equivalent of approximately 1.7 human smokers' bronchial trees to the fifth bifurcation. Statistically significant mutant copy numbers above the 95% upper confidence limits of historical background controls were found in 198 of 425 sector assays. No significant differences (P = 0.1) for negative sector fractions, mutant fractions, distributions of mutant cluster size or anatomical positions were observed for smoking status, gender or age (38-76 year). Based on the modal cluster size of mitochondrial point mutants, the size of the adult bronchial epithelial maintenance turnover unit was estimated to be about 32 cells. When data from all 15 lungs were combined the log 2 of nuclear mutant cluster size plotted against log 2 of the number of clusters of a given cluster size displayed a slope of ∼1.1 over a range of cluster sizes from ∼26 to 215 mutant copies. A parsimonious interpretation of these nuclear and previously reported data for lung epithelial mitochondrial point mutant clusters is that they arose from mutations in stem cells at a high but constant rate per stem cell doubling during at least ten stem cell doublings of the later fetal-juvenile period. The upper and lower decile range of summed point mutant fractions among lungs was about 7.5-fold, suggesting an important source of stratification in the population with regard to risk of tumor initiation

  11. Fetal-juvenile origins of point mutations in the adult human tracheal-bronchial epithelium: Absence of detectable effects of age, gender or smoking status

    Energy Technology Data Exchange (ETDEWEB)

    Sudo, Hiroko [Massachusetts Institute of Technology, Department of Biological Engineering, 21 Ames St., 16-743 Cambridge, MA 02139 (United States); Toray Industries, Inc., New Frontiers Research Laboratories 10-1, Tebiro 6-chome, Kamakura, Kanagawa 248-8555 (Japan); Li-Sucholeiki, Xiao-Cheng [Massachusetts Institute of Technology, Department of Biological Engineering, 21 Ames St., 16-743 Cambridge, MA 02139 (United States); Agencourt Bioscience Corp., 500 Cummings Center, Suite 2450, Beverly, MA 01915 (United States); Marcelino, Luisa A. [Massachusetts Institute of Technology, Department of Biological Engineering, 21 Ames St., 16-743 Cambridge, MA 02139 (United States); Biomedical Engineering Department, Northwestern University, 633 Clark Street, Evanston, IL 60208 (United States); Gruhl, Amanda N. [Massachusetts Institute of Technology, Department of Biological Engineering, 21 Ames St., 16-743 Cambridge, MA 02139 (United States); Herrero-Jimenez, Pablo [Massachusetts Institute of Technology, Department of Biological Engineering, 21 Ames St., 16-743 Cambridge, MA 02139 (United States); SLC Ontario, 690 Dorval Drive, Suite 200, Oakville, Ontario L6K 3W7 Canada (Canada); Zarbl, Helmut [UMDNJ-Robert Wood Johnson Medical School, Environmental and Occupational Health Sciences Institute, 170 Freylinghuysen Road, Room 426, Piscataway, NJ 08854 (United States); Willey, James C. [Medical College of Ohio, 3120 Glendale Avenue, Room 12, Toledo, OH 43614 (United States); Furth, Emma E. [University of Pennsylvania Medical Center, Department of Pathology, 3400 Spruce Street, 6 Founders Building, Philadelphia, PA 19104 (United States); Morgenthaler, Stephan [Institute of Applied Mathematics, Swiss Federal Institute of Technology (EPFL), SB/IMA, 1015 Lausanne (Switzerland)] (and others)

    2008-11-10

    Allele-specific mismatch amplification mutation assays (MAMA) of anatomically distinct sectors of the upper bronchial tracts of nine nonsmokers revealed many numerically dispersed clusters of the point mutations C742T, G746T, G747T of the TP53 gene, G35T of the KRAS gene and G508A of the HPRT1 gene. Assays of these five mutations in six smokers have yielded quantitatively similar results. One hundred and eighty four micro-anatomical sectors of 0.5-6 x 10{sup 6} tracheal-bronchial epithelial cells represented en toto the equivalent of approximately 1.7 human smokers' bronchial trees to the fifth bifurcation. Statistically significant mutant copy numbers above the 95% upper confidence limits of historical background controls were found in 198 of 425 sector assays. No significant differences (P = 0.1) for negative sector fractions, mutant fractions, distributions of mutant cluster size or anatomical positions were observed for smoking status, gender or age (38-76 year). Based on the modal cluster size of mitochondrial point mutants, the size of the adult bronchial epithelial maintenance turnover unit was estimated to be about 32 cells. When data from all 15 lungs were combined the log 2 of nuclear mutant cluster size plotted against log 2 of the number of clusters of a given cluster size displayed a slope of {approx}1.1 over a range of cluster sizes from {approx}2{sup 6} to 2{sup 15} mutant copies. A parsimonious interpretation of these nuclear and previously reported data for lung epithelial mitochondrial point mutant clusters is that they arose from mutations in stem cells at a high but constant rate per stem cell doubling during at least ten stem cell doublings of the later fetal-juvenile period. The upper and lower decile range of summed point mutant fractions among lungs was about 7.5-fold, suggesting an important source of stratification in the population with regard to risk of tumor initiation.

  12. Dietary antioxidants and ozone-induced bronchial hyperresponsiveness in adults with asthma.

    Science.gov (United States)

    Trenga, C A; Koenig, J Q; Williams, P V

    2001-01-01

    Ozone exposure aggravates asthma, as has been demonstrated in both controlled exposures and epidemiologic studies. In the current double-blind crossover study, the authors evaluated the effects of dietary antioxidants (i.e., 400 IU vitamin E/500 mg vitamin C) on ozone-induced bronchial hyperresponsiveness in adult subjects with asthma. Seventeen subjects were exposed to 0.12 ppm of ozone or to air for 45 min during intermittent moderate exercise. Bronchial hyperresponsiveness was assessed with 10-min sulfur dioxide (i.e., 0.10 ppm and 0.25 ppm) inhalation challenges. Subjects who were given dietary antioxidants responded less severely to sulfur dioxide challenge than subjects given a placebo (i.e., forced expiratory volume in the 1st sec: -1.2% vs. 4.4%, respectively; peak flow: +2.2% vs. -3.0%, respectively; and mid-forced expiratory flow: +2.0% vs. -4.3%, respectively). Effects were more pronounced when subjects were grouped by response to sulfur dioxide at the screening visit. The results suggest that dietary supplementation with vitamins E and C benefits asthmatic adults who are exposed to air pollutants. PMID:11480500

  13. Indomethacin does not inhibit the ozone-induced increase in bronchial responsiveness in human subjects

    Energy Technology Data Exchange (ETDEWEB)

    Ying, R.L.; Gross, K.B.; Terzo, T.S.; Eschenbacher, W.L. (Univ. of Michigan Medical Center, Ann Arbor (USA))

    1990-10-01

    Exposure of human subjects to sufficiently high levels of ozone can result in reversible changes in lung function (restrictive in nature) and increases in nonspecific airway responsiveness. Several studies have implicated products of cyclooxygenase metabolism in the mediation of these changes. The purpose of this study was to determine if indomethacin (a cyclooxygenase inhibitor) would alter the changes in the ozone-induced increase in responsiveness to methacholine or the ozone-induced decrease in lung function. Thirteen male subjects underwent three randomly assigned 2-h exposure to 0.4 ppm ozone with alternating 15-min periods of rest and exercise on a cycle ergometer (30 L/min/m2, body surface area). For the 4 days before each of the exposures, the subjects received either indomethacin (150 mg/day) or placebo, or no modification. Of the 13 subjects, only seven had both detectable indomethacin serum levels on the indomethacin Study Day and a significant increase in bronchial responsiveness to methacholine on the No Medication Day. For this group of seven subjects, we found that indomethacin did not alter the ozone-induced increase in bronchial responsiveness to methacholine (decrease in PC100SRaw for the different study days: no medication, -78.4 +/- 5.3% (mean +/- SEM); placebo, -48.9 +/- 12.2%; indomethacin, -64.5 +/- 6.3%; p greater than 0.2), although indomethacin did attenuate the ozone-induced decrease in lung function. The decrease in the FEV1 for the different study days was as follows: no medication, -20.7 +/- 5.0% (mean +/- SEM); placebo, -19.2 +/- 6.3%; indomethacin, -4.8 +/- 3.7% (p less than 0.001).

  14. A cost-effective system for differentiation of intestinal epithelium from human induced pluripotent stem cells

    OpenAIRE

    Soichiro Ogaki; Mayu Morooka; Kaito Otera; Shoen Kume

    2015-01-01

    The human intestinal epithelium is a useful model for pharmacological studies of absorption, metabolism, drug interactions, and toxicology, as well as for studies of developmental biology. We established a rapid and cost effective system for differentiation of human induced pluripotent stem (iPS) cells into definitive endoderm (DE) cells. In the presence of dimethyl sulfoxide (DMSO), a low concentration of Activin at 6.25 ng/ml is sufficient to give a similar differentiation efficiency with t...

  15. Epithelium-generated neuropeptide Y induces smooth muscle contraction to promote airway hyperresponsiveness.

    Science.gov (United States)

    Li, Shanru; Koziol-White, Cynthia; Jude, Joseph; Jiang, Meiqi; Zhao, Hengjiang; Cao, Gaoyuan; Yoo, Edwin; Jester, William; Morley, Michael P; Zhou, Su; Wang, Yi; Lu, Min Min; Panettieri, Reynold A; Morrisey, Edward E

    2016-05-01

    Asthma is one of the most common chronic diseases globally and can be divided into presenting with or without an immune response. Current therapies have little effect on nonimmune disease, and the mechanisms that drive this type of asthma are poorly understood. Here, we have shown that loss of the transcription factors forkhead box P1 (Foxp1) and Foxp4, which are critical for lung epithelial development, in the adult airway epithelium evokes a non-Th2 asthma phenotype that is characterized by airway hyperresponsiveness (AHR) without eosinophilic inflammation. Transcriptome analysis revealed that loss of Foxp1 and Foxp4 expression induces ectopic expression of neuropeptide Y (Npy), which has been reported to be present in the airways of asthma patients, but whose importance in disease pathogenesis remains unclear. Treatment of human lung airway explants with recombinant NPY increased airway contractility. Conversely, loss of Npy in Foxp1- and Foxp4-mutant airway epithelium rescued the AHR phenotype. We determined that NPY promotes AHR through the induction of Rho kinase activity and phosphorylation of myosin light chain, which induces airway smooth muscle contraction. Together, these studies highlight the importance of paracrine signals from the airway epithelium to the underlying smooth muscle to induce AHR and suggest that therapies targeting epithelial induction of this phenotype may prove useful in treatment of noneosinophilic asthma. PMID:27088802

  16. Garlic ameliorates histological changes in the uterine epithelium of lead induced mice

    International Nuclear Information System (INIS)

    To evaluate the protective role of garlic extract on the histology of the uterine epithelium exposed to lead acetate in an animal model. Study Design: Laboratory based randomized control trial. Place and Duration of Study: Department of Anatomy, Army Medical College in collaboration with National Institute of health from April to June 2013. Material and Methods: Thirty female BALBc mice were selected. Ten animals were placed in each group. Group A being the control was given normal diet. Group B was given lead acetate at a dose of 30 mg/kg/day. Group C was given lead acetate 30 mg/kg/day and garlic extract 500 mg/kg/day through oral gavage tube for 60 days. Animals were sacrificed and dissected at the end of 60 days. Right uterine horn was processed, embedded and stained for histological study. Height of epithelium was measured. It was taken from apical to basal end of the cells. Results: There was increase in height of the lining epithelium of uterus in group B, mean value 19.70 ± 4.81 meu m when compared to Group A, with mean value 13.25 ± 2.37 meu m. The height of the epithelium was relatively reduced in group C, with mean value 14.50 ± 2.30 meu m when compared with group B. In group C results were same as Group A. The p values were 0.001 when group A was compared to group B, 0.688 when group A was compared to group C and 0.005 when group B was compared to group C. Conclusion: The height of epithelium was markedly increased in lead acetate treated group which returned to normal when co treated with garlic extract. Hence garlic ameliorated the changes induced by lead. (author)

  17. Papain-induced asthma: diagnosis by skin test, RAST and bronchial provocation test

    International Nuclear Information System (INIS)

    Seven out of eleven workers occupationally exposed to airborne papain developed immediate hypersensitive reactions, predominantly asthma and rhinitis. Skin tests and RAST with papain were positive in all symptomatic workers, but not in the four asymptomatic workers. Furthermore, out of forty non-exposed asthmatics, thirty-eight had negative RAST results and all had negative skin test results. Bronchial provocation tests with 0.15-0.5 mg papain performed in five patients with a positive case history showed in each case an immediate asthmatic reaction; in addition to that, one patient developed signs of a dual asthmatic reaction. These results suggest that airborne papain is a highly immunogenic agent in humans, which induces type I allergic reactions in a large percentage of the exposed subjects. (author)

  18. Antioxidant effect of minocycline in gingival epithelium induced by Actinobacillus actinomycetemcomitans serotype B toxin

    Directory of Open Access Journals (Sweden)

    Ernie Maduratna Setiawati

    2009-03-01

    Full Text Available Background: Actinobacillus actinomycetemcomitans (Aa serotype B has been associated with aggressive periodontitis. Gingival epithelial cell is exquisitely sensitive to the toxin and may lead to the epithel protective barrier disruption. Experimental models show that minocycline is not related to it’s antimicrobial effect and protection against neuron cell apoptosis of a number experimental models of brain injury and Parkinson’s disease. Purpose: This study, examined antioxidant effect of minocycline to inhibit apoptosis of gingival epithelium induced crude toxin bacteria Aa serotype B in mice. Methods: Thirty adult mice strain Swiss Webster (balb C were divided randomly into three groups: control group (group A, toxin group (group B and toxin and minocycline group (group C. The mice were taken at 24 hours after application, and then the tissue sections of gingival epithelium were stained with tunnel assay and immunohistochemistry. Result: Treatment with these toxin induced apoptosis of gingival epithelium and was associated with DNA fragmentation and reduced gluthatione (GSH. Minocycline 100 nM significantly increased GSH and reduced apoptosis (p < 0.05. Minocycline provides antioxidant effect against citotoxicity of bacteria Aa serotipe B. Conclusion: Nanomolar concentration of minocycline potential as new therapeutic agent to prevent progressivity of aggressiveness of periodontitis.

  19. Serosal zinc attenuate serotonin and vasoactive intestinal peptide induced secretion in piglet small intestinal epithelium in vitro

    DEFF Research Database (Denmark)

    Carlson, Dorthe; Sehested, Jakob; Feng, Z;

    2008-01-01

    This study addressed the mechanisms by which dietary zinc affects diarrhoea and aimed to study possible interactions between zinc status and the presence of zinc in vitro on secretagogue-induced secretion from piglet intestinal epithelium in Ussing chambers.......This study addressed the mechanisms by which dietary zinc affects diarrhoea and aimed to study possible interactions between zinc status and the presence of zinc in vitro on secretagogue-induced secretion from piglet intestinal epithelium in Ussing chambers....

  20. HAIR CELL-LIKE CELL GENERATION INDUCED BY NATURE CULTURE OF ADULT RAT AUDITORY EPITHELIUM

    Institute of Scientific and Technical Information of China (English)

    Liu Hui; Zhu Hongliang; Li Shengli; Yao Xiaobao; Wang Xiaoxia

    2006-01-01

    Objective To establish adult rat auditory epithelial cell culture and try to find precursor cells of auditory hair cells in vitro. Methods With refinement of culture media and techniques, cochlear sensory epithelial cells of adult rat were cultured. Immunocytochemistry and Bromodeoxyuridine (BrdU)labeling were used to detect properties and mitotic status of cultured cells. Results The cultured auditory epithelial cells showed a large, flat epithelial morphotype and expressed F-actin and cytokeratin, a subset of cells generated from auditory epithelium were labeled by calretinin, a specific marker of early hair cell. Conclusion Adult rat auditory epithelium can be induced to generate hair cell-like cells by nature culture, this phenomenon suggests that progenitor cells may exist in rat cochlea and they may give birth to new hair cells. Whether these progenitor cells are tissue specific stem cells is still need more study.

  1. Severe Reduction in Number and Function of Peripheral T Cells Does Not Afford Protection toward Emphysema and Bronchial Remodeling Induced in Mice by Cigarette Smoke.

    Science.gov (United States)

    De Cunto, Giovanna; Lunghi, Benedetta; Bartalesi, Barbara; Cavarra, Eleonora; Fineschi, Silvia; Ulivieri, Cristina; Lungarella, Giuseppe; Lucattelli, Monica

    2016-07-01

    The protein Lck (p56(Lck)) is a Src family tyrosine kinase expressed at all stages of thymocyte development and is required for maturation of T cells. The targeted disruption of Lck gene in mice results in severe block in thymocyte maturation with substantial reduction in the development of CD4(+)CD8(+) thymocytes, severe reduction of peripheral T cells, and disruption of T-cell receptor signaling with defective function of T-cell responses. To investigate the role of T lymphocyte in the development of cigarette smoke-induced pulmonary changes, Lck(-/-) mice and corresponding congenic wild-type mice were chronically exposed to cigarette smoke, and their lungs were analyzed by biochemical, immunologic, and morphometric methods. Smoking mice from both genotypes showed disseminated foci of emphysema and large areas of goblet cell metaplasia in bronchial and bronchiolar epithelium. Morphometric evaluation of lung changes and lung elastin determination confirmed that mice from both genotypes showed the same degree of emphysematous lesions. Thus, cigarette smoke exposure in the presence of severe reduction in number and function of peripheral T cells does not influence the development of pulmonary changes induced by cigarette smoke. The data obtained suggest that innate immunity is a leading actor in the early development of pulmonary changes in smoking mice and that the adaptive immune response may play a role at later stages. PMID:27157991

  2. TGFβ signaling in lung epithelium regulates bleomycin-induced alveolar injury and fibroblast recruitment.

    Science.gov (United States)

    Degryse, Amber L; Tanjore, Harikrishna; Xu, Xiaochuan C; Polosukhin, Vasiliy V; Jones, Brittany R; Boomershine, Chad S; Ortiz, Camila; Sherrill, Taylor P; McMahon, Frank B; Gleaves, Linda A; Blackwell, Timothy S; Lawson, William E

    2011-06-01

    The response of alveolar epithelial cells (AECs) to lung injury plays a central role in the pathogenesis of pulmonary fibrosis, but the mechanisms by which AECs regulate fibrotic processes are not well defined. We aimed to elucidate how transforming growth factor-β (TGFβ) signaling in lung epithelium impacts lung fibrosis in the intratracheal bleomycin model. Mice with selective deficiency of TGFβ receptor 2 (TGFβR2) in lung epithelium were generated and crossed to cell fate reporter mice that express β-galactosidase (β-gal) in cells of lung epithelial lineage. Mice were given intratracheal bleomycin (0.08 U), and the following parameters were assessed: AEC death by terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling assay, inflammation by total and differential cell counts from bronchoalveolar lavage, fibrosis by scoring of trichrome-stained lung sections, and total lung collagen content. Mice with lung epithelial deficiency of TGFβR2 had improved AEC survival, despite greater lung inflammation, after bleomycin administration. At 3 wk after bleomycin administration, mice with epithelial TGFβR2 deficiency showed a significantly attenuated fibrotic response in the lungs, as determined by semiquantitatve scoring and total collagen content. The reduction in lung fibrosis in these mice was associated with a marked decrease in the lung fibroblast population, both total lung fibroblasts and epithelial-to-mesenchymal transition-derived (S100A4(+)/β-gal(+)) fibroblasts. Attenuation of TGFβ signaling in lung epithelium provides protection from bleomycin-induced fibrosis, indicating a critical role for the epithelium in transducing the profibrotic effects of this cytokine. PMID:21441353

  3. TGFβ signaling in lung epithelium regulates bleomycin-induced alveolar injury and fibroblast recruitment

    Science.gov (United States)

    Degryse, Amber L.; Tanjore, Harikrishna; Xu, Xiaochuan C.; Polosukhin, Vasiliy V.; Jones, Brittany R.; Boomershine, Chad S.; Ortiz, Camila; Sherrill, Taylor P.; McMahon, Frank B.; Gleaves, Linda A.; Blackwell, Timothy S.

    2011-01-01

    The response of alveolar epithelial cells (AECs) to lung injury plays a central role in the pathogenesis of pulmonary fibrosis, but the mechanisms by which AECs regulate fibrotic processes are not well defined. We aimed to elucidate how transforming growth factor-β (TGFβ) signaling in lung epithelium impacts lung fibrosis in the intratracheal bleomycin model. Mice with selective deficiency of TGFβ receptor 2 (TGFβR2) in lung epithelium were generated and crossed to cell fate reporter mice that express β-galactosidase (β-gal) in cells of lung epithelial lineage. Mice were given intratracheal bleomycin (0.08 U), and the following parameters were assessed: AEC death by terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling assay, inflammation by total and differential cell counts from bronchoalveolar lavage, fibrosis by scoring of trichrome-stained lung sections, and total lung collagen content. Mice with lung epithelial deficiency of TGFβR2 had improved AEC survival, despite greater lung inflammation, after bleomycin administration. At 3 wk after bleomycin administration, mice with epithelial TGFβR2 deficiency showed a significantly attenuated fibrotic response in the lungs, as determined by semiquantitatve scoring and total collagen content. The reduction in lung fibrosis in these mice was associated with a marked decrease in the lung fibroblast population, both total lung fibroblasts and epithelial-to-mesenchymal transition-derived (S100A4+/β-gal+) fibroblasts. Attenuation of TGFβ signaling in lung epithelium provides protection from bleomycin-induced fibrosis, indicating a critical role for the epithelium in transducing the profibrotic effects of this cytokine. PMID:21441353

  4. Sesame Oil Attenuates Ovalbumin-Induced Pulmonary Edema and Bronchial Neutrophilic Inflammation in Mice

    Directory of Open Access Journals (Sweden)

    Dur-Zong Hsu

    2013-01-01

    Full Text Available Background. Allergic asthma is one of the most common chronic inflammatory diseases of airways. Severe asthma may lead to hospitalization and death. Sesame oil is a natural product with anti-inflammatory property. However, the effect of sesame oil on allergic asthma has never been studied. Objective. We investigate the effect of sesame oil on pulmonary inflammation in allergic asthma model. Methods. Allergic airway inflammation was induced by sensitizing with two doses of 10 mg ovalbumin (OVA and then challenged with 1% OVA nebulizer exposure (1 h/day for 3 days. Sesame oil (0.25, 0.5, or 1 mL/kg/day was given orally 30 min before each challenge. Samples were collected 24 h after the last challenge. Results. Data showed that sesame oil inhibited pulmonary edema and decreased interleukin (IL-1β and IL-6 levels in bronchoalveolar lavage fluid in OVA-treated mice. Sesame oil also decreased pulmonary nitrite level, inducible nitric oxide synthase expression, and neutrophil infiltration induced by OVA. Further, sesame oil decreased serum IgE level in OVA-treated mice. Conclusion. Sesame oil may attenuate pulmonary edema and bronchial neutrophilic inflammation by inhibiting systemic IgE level in allergic asthma.

  5. Bronchial responsiveness in an elastase-induced mouse model of emphysema.

    Science.gov (United States)

    Santos, Luiz Marcelo Oliveira; de Brito Cervilha, Daniela Aparecida; Cabral, Layla Dutra Marinho; Garcia, Érika Kristina Incerpi; Teixeira, Vanessa Pereira; Brito, Jôse Mára; Moriya, Henrique Takachi; Soncini, Roseli

    2014-04-01

    Bronchial responsiveness during methacholine (MCh) challenge was analysed in an elastase-induced mouse model of emphysema to explore the magnitude of the response in this model. Swiss mice were intratracheally instilled with saline or elastase (0.3 or 0.6 U). Twenty days afterward, mechanical ventilation data were collected from the closed and opened thorax of baseline and MCh (vehicle, 50 and 100 mg/mL) challenged mice. The lungs were prepared for morphometric analysis. In the 0.6 U group, airway resistance (Raw) and tissue elastance (H) were decreased, and hysteresivity (η) was increased (closed thorax). MCh increased Raw, G and H in all groups, but this increase was attenuated in the elastase-induced emphysema groups, the largest attenuation was observed in the 0.6 U (closed thorax condition). Elastase increased hyperinflation of the alveoli, alveolar collapse and the Lm and reduced the normal area. MCh reduced respiratory mechanics in elastase-induced emphysema, and this reduction was modulated by the collapsed and/or hyperinflated areas, which increased the heterogeneity of the lungs. PMID:24463010

  6. The Secretome of Human Bronchial Epithelial Cells Exposed to Fine Atmospheric Particles Induces Fibroblast Proliferation

    Directory of Open Access Journals (Sweden)

    Laurent Martinon

    2013-08-01

    Full Text Available Chronic exposure to particulate pollution is suspected to exacerbate inflammatory respiratory diseases such as asthma characterized by an airway remodelling involving fibrosis. Our study aims to investigate whether the secretome from human bronchial epithelial (HBE cells exposed to fine particulate matter (PM induces fibroblast proliferation. Primary HBE cells grown on air liquid interface were repeatedly exposed to fine PM at 5 and 10 µg/cm² (four treatments, 48 hours apart and maintained in culture for five weeks. Collected basolateral culture medium was used as a conditioned medium for the subsequent treatment of fibroblasts. We observed that the conditioned medium collected from HBE cells treated with fine PM increased the growth rate of fibroblasts compared to the conditioned medium collected from control HBE cells. Fibroblast phenotype assessed by the observation of the vimentin network was well preserved. The mitogenic effect of conditioned medium was reduced in the presence of anti-epidermal growth factor receptor (EGFR, anti-amphiregulin or anti-TGFa, underlining the role of EGFR ligands in fibroblast proliferation. When fibroblasts were co-cultured with HBE cells treated once with fine PM, they exhibited a higher growth rate than fibroblasts co-cultured with non-treated HBE cells. Altogether these data show that the exposure of HBE cells to fine PM induced the production of EGFR ligands in sufficient amount to stimulate fibroblast proliferation providing insight into the role of PM in airway remodelling.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Genetic damage induced by organic extract of coke oven emissions on human bronchial epithelial cells.

    Science.gov (United States)

    Zhai, Qingfeng; Duan, Huawei; Wang, Yadong; Huang, Chuanfeng; Niu, Yong; Dai, Yufei; Bin, Ping; Liu, Qingjun; Chen, Wen; Ma, Junxiang; Zheng, Yuxin

    2012-08-01

    Coke oven emissions are known as human carcinogen, which is a complex mixture of polycyclic aromatic hydrocarbon. In this study, we aimed to clarify the mechanism of action of coke oven emissions induced carcinogenesis and to identify biomarkers of early biological effects in a human bronchial epithelial cell line with CYP1A1 activity (HBE-CYP1A1). Particulate matter was collected in the oven area on glass filter, extracted and analyzed by GC/MS. DNA breaks and oxidative damage were evaluated by alkaline and endonucleases (FPG, hOGG1 and ENDO III)-modified comet assays. Cytotoxicity and chromosomal damage were assessed by the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay. The cells were treated with organic extract of coke oven emissions (OE-COE) representing 5, 10, 20, 40μg/mL extract for 24h. We found that there was a dose-effect relationship between the OE-COE and the direct DNA damage presented by tail length, tail intensity and Olive tail moment in the comet assay. The presence of lesion-specific endonucleases in the assays increased DNA migration after OE-COE treatment when compared to those without enzymes, which indicated that OE-COE produced oxidative damage at the level of pyrimidine and purine bases. The dose-dependent increase of micronuclei, nucleoplasmic bridges and nuclear buds in exposed cells was significant, indicating chromosomal and genomic damage induced by OE-COE. Based on the cytotoxic biomarkers in CBMN-Cyt assay, OE-COE may inhibit nuclear division, interfere with apoptosis, or induce cell necrosis. This study indicates that OE-COE exposure can induce DNA breaks/oxidative damage and genomic instability in HBE-CYP1A1 cells. The FPG-comet assay appears more specific for detecting oxidative DNA damage induced by complex mixtures of genotoxic substances. PMID:22522113

  9. Lithium Attenuates TGF-β1-Induced Fibroblasts to Myofibroblasts Transition in Bronchial Fibroblasts Derived from Asthmatic Patients

    Directory of Open Access Journals (Sweden)

    Marta Michalik

    2012-01-01

    Full Text Available Bronchial asthma is a chronic disorder accompanied by phenotypic transitions of bronchial epithelial cells, smooth muscle cells, and fibroblasts. Human bronchial fibroblasts (HBFs derived from patients with diagnosed asthma display predestination towards TGF-β-induced phenotypic switches. Since the interference between TGF-β and GSK-3β signaling contributes to pathophysiology of chronic lung diseases, we investigated the effect of lithium, a nonspecific GSK-3β inhibitor, on TGF-β1-induced fibroblast to myofibroblast transition (FMT in HBF and found that the inhibition of GSK-3β attenuates TGF-β1-induced FMT in HBF populations derived from asthmatic but not healthy donors. Cytoplasmically sequestrated β-catenin, abundant in TGF-β1/LiCl-stimulated asthmatic HBFs, most likely interacts with and inhibits the nuclear accumulation and signal transduction of Smad proteins. These data indicate that the specific cellular context determines FMT-related responses of HBFs to factors interfering with the TGF-β signaling pathway. They may also provide a mechanistic explanation for epidemiological data revealing coincidental remission of asthmatic syndromes and their recurrence upon the discontinuation of lithium therapy in certain psychiatric diseases.

  10. Activation of lymphocytes induced by bronchial epithelial cells with prolonged RSV infection.

    Directory of Open Access Journals (Sweden)

    Ling Qin

    Full Text Available Respiratory syncytial virus (RSV preferentially infects airway epithelial cells,which might be responsible for susceptibility to asthma; however, the underlying mechanism is not clear. This study determined the activation of lymphocytes and drift of helper T (Th subsets induced by RSV-infected human bronchial epithelial cells (HBECs in vitro. HBECs had prolonged infection with RSV, and lymphocytes isolated from human peripheral blood were co-cultured with RSV-infected HBECs. Four groups were established, as follows: lymphocytes (group L; lymphocytes infected with RSV (group RL; co-culture of lymphocytes with non-infected HBECs (group HL; and co-culture of lymphocytes with infected HBECs (group HRL. After co-culture with HBECs for 24 hours, lymphocytes were collected and the following were determined in the 4 groups: cell cycle status; apoptosis rate; and concentrations of IL-4, IFN-γ, and IL-17 in the supernatants. Cell cycle analysis for lymphocytes showed a significant increase in S phase cells, a decrease in G1 phase cells, and a higher apoptosis rate in group HRL compared with the other three groups. In group HRL, the levels of IL-4, IFN-γ, and IL-17 in supernatants were also higher than the other three groups. For further study, lymphocytes were individually treated with supernatants from non-infected and RSV-infected HBECs for 24 h. We showed that supernatants from RSV-infected HBECs induced the differentiation of Th2 and Th17 subsets, and suppressed the differentiation of Treg subsets. Our results showed that HBECs with prolonged RSV infection can induce lymphocyte proliferation and apoptosis, and enhance the release of cytokines by lymphocytes. Moreover, subset drift might be caused by RSV-infected HBECs.

  11. Formaldehyde-induced gene expression in F344 rat nasal respiratory epithelium

    International Nuclear Information System (INIS)

    Formaldehyde (FA), an occupational and environmental toxicant used extensively in the manufacturing of many household and personal use products, is known to induce squamous cell carcinomas in the nasal turbinates of rats and mice and squamous metaplasia in monkey noses. Tissue responses to FA include a dose dependent epithelial degeneration, respiratory cell hypertrophy, and squamous metaplasia. The primary target for FA-induced toxicity in both rodents and monkeys is the respiratory nasal epithelium. FA increases nasal epithelial cell proliferation and DNA-protein crosslinks (DPX) that are associated with subsequent nasal cancer development. To address the acute effects of FA exposure that might contribute to known pathological changes, cDNA gene expression analysis was used. Two groups of male F344 rats received either 40 ul of distilled water or FA (400 mM) instilled into each nostril. Twenty-four hours following treatment, nasal epithelium was recovered from which total RNA was used to generate cDNA probes. Significance analysis of microarrays (SAM) hybridization data using ClontechTM Rat Atlas 1.2 arrays revealed that 24 of the 1185 genes queried were significantly up-regulated and 22 genes were significantly downregulated. Results for ten of the differentially expressed genes were confirmed by quantitative real time RT PCR. The identified genes with FA-induced change in expression belong to the functional gene categories xenobiotic metabolism, cell cycle, apoptosis, and DNA repair. These data suggest that multiple pathways are dysregulated by FA exposure, including those involved in DNA synthesis/repair and regulation of cell proliferation. Differential gene expression profiles may provide clues that could be used to define mechanisms involved in FA-induced nasal cancer

  12. A cost-effective system for differentiation of intestinal epithelium from human induced pluripotent stem cells.

    Science.gov (United States)

    Ogaki, Soichiro; Morooka, Mayu; Otera, Kaito; Kume, Shoen

    2015-01-01

    The human intestinal epithelium is a useful model for pharmacological studies of absorption, metabolism, drug interactions, and toxicology, as well as for studies of developmental biology. We established a rapid and cost effective system for differentiation of human induced pluripotent stem (iPS) cells into definitive endoderm (DE) cells. In the presence of dimethyl sulfoxide (DMSO), a low concentration of Activin at 6.25 ng/ml is sufficient to give a similar differentiation efficiency with that using Activin at 100 ng/ml at the presence of Wnt activator. In the presence of DMSO, Activin at low concentration triggered hiPS cells to undergo differentiation through G1 arrest, reduce apoptosis, and potentiate activation of downstream targets, such as SMAD2 phosphorylation and SOX17 expression. This increased differentiation into CDX2 + SOX17 + DE cells. The present differentiation procedure therefore permits rapid and efficient derivation of DE cells, capable of differentiating into intestinal epithelium upon BIO and DAPT treatment and of giving rise to functional cells, such as enterocytes. PMID:26616277

  13. Mechanism of cigarette smoke condensate-induced acute inflammatory response in human bronchial epithelial cells

    Directory of Open Access Journals (Sweden)

    Mohapatra Shyam S

    2002-07-01

    Full Text Available Abstract Background To demonstrate the involvement of tobacco smoking in the pathophysiology of lung disease, the responses of pulmonary epithelial cells to cigarette smoke condensate (CSC — the particulate fraction of tobacco smoke — were examined. Methods The human alveolar epithelial cell line A549 and normal human bronchial epithelial cells (NHBEs were exposed to 0.4 μg/ml CSC, a concentration that resulted in >90% cell survival and Results NHBEs exposed to CSC showed increased expression of the inflammatory mediators sICAM-1, IL-1β, IL-8 and GM-CSF, as determined by RT-PCR. CSC-induced IL-1β expression was reduced by PD98059, a blocker of mitogen-actived protein kinase (MAPK kinase (MEK, and by PDTC, a NFκB inhibitor. Analysis of intracellular signaling pathways, using antibodies specific for phosphorylated MAPKs (extracellular signal-regulated kinase [ERK]-1/2, demonstrated an increased level of phosphorylated ERK1/2 with increasing CSC concentration. Nuclear localization of phosphorylated ERK1/2 was seen within 30 min of CSC exposure and was inhibited by PD98059. Increased phosphorylation and nuclear translocation of IκB was also seen after CSC exposure. A549 cells transfected with a luciferase reporter plasmid containing a NFκB-inducible promoter sequence and exposed to CSC (0.4 μg/ml or TNF-α (50 ng/ml had an increased reporter activity of approximately 2-fold for CSC and 3.5-fold for TNF-α relative to untreated controls. Conclusion The acute phase response of NHBEs to cigarette smoke involves activation of both MAPK and NFκB.

  14. Pulmonary proteases in the cystic fibrosis lung induce interleukin 8 expression from bronchial epithelial cells via a heme/meprin/epidermal growth factor receptor/Toll-like receptor pathway.

    LENUS (Irish Health Repository)

    Cosgrove, Sonya

    2012-02-01

    A high intrapulmonary protease burden is characteristic of cystic fibrosis (CF), and the resulting dysregulation of the protease\\/anti-protease balance has serious implications for inflammation in the CF lung. Because of this inflammation, micro-bleeds can occur releasing hemoglobin into the lung. The aim of this study was to investigate the effect of the protease-rich environment of the CF lung on human hemoglobin and to assess the proinflammatory effect of heme on CF bronchial epithelium. Here, we show that the Pseudomonas proteases (Pseudomonas elastase and alkaline protease) and the neutrophil proteases (neutrophil elastase (NE) and proteinase-3) are capable of almost complete degradation of hemoglobin in vitro but that NE is the predominant protease that cleaves hemoglobin in vivo in CF bronchoalveolar lavage fluid. One of the effects of this is the release of heme, and in this study we show that heme stimulates IL-8 and IL-10 protein production from DeltaF508 CFBE41o(-) bronchial epithelial cells. In addition, heme-induced IL-8 expression utilizes a novel pathway involving meprin, EGF receptor, and MyD88. Meprin levels are elevated in CF cell lines and bronchial brushings, thus adding to the proinflammatory milieu. Interestingly, alpha(1)-antitrypsin, in addition to its ability to neutralize NE and protease-3, can also bind heme and neutralize heme-induced IL-8 from CFBE41o(-) cells. This study illustrates the proinflammatory effects of micro-bleeds in the CF lung, the process by which this occurs, and a potential therapeutic intervention.

  15. Pulmonary Proteases in the Cystic Fibrosis Lung Induce Interleukin 8 Expression from Bronchial Epithelial Cells via a Heme/Meprin/Epidermal Growth Factor Receptor/Toll-like Receptor Pathway.

    LENUS (Irish Health Repository)

    Cosgrove, Sonya

    2011-03-04

    A high intrapulmonary protease burden is characteristic of cystic fibrosis (CF), and the resulting dysregulation of the protease\\/anti-protease balance has serious implications for inflammation in the CF lung. Because of this inflammation, micro-bleeds can occur releasing hemoglobin into the lung. The aim of this study was to investigate the effect of the protease-rich environment of the CF lung on human hemoglobin and to assess the proinflammatory effect of heme on CF bronchial epithelium. Here, we show that the Pseudomonas proteases (Pseudomonas elastase and alkaline protease) and the neutrophil proteases (neutrophil elastase (NE) and proteinase-3) are capable of almost complete degradation of hemoglobin in vitro but that NE is the predominant protease that cleaves hemoglobin in vivo in CF bronchoalveolar lavage fluid. One of the effects of this is the release of heme, and in this study we show that heme stimulates IL-8 and IL-10 protein production from ΔF508 CFBE41o(-) bronchial epithelial cells. In addition, heme-induced IL-8 expression utilizes a novel pathway involving meprin, EGF receptor, and MyD88. Meprin levels are elevated in CF cell lines and bronchial brushings, thus adding to the proinflammatory milieu. Interestingly, α(1)-antitrypsin, in addition to its ability to neutralize NE and protease-3, can also bind heme and neutralize heme-induced IL-8 from CFBE41o(-) cells. This study illustrates the proinflammatory effects of micro-bleeds in the CF lung, the process by which this occurs, and a potential therapeutic intervention.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-02-01

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

  17. NiO nanoparticles induce apoptosis through repressing SIRT1 in human bronchial epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Duan, Wei-Xia; He, Min-Di; Mao, Lin [Department of Occupational Health, Third Military Medical University, Chongqing 400038 (China); Qian, Feng-Hua [Department of Hematology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Li, Yu-Ming [Institute of Hepatobiliary Surgery, XinQiao Hospital, Third Military Medical University, Chongqing 400038 (China); Pi, Hui-Feng; Liu, Chuan; Chen, Chun-Hai; Lu, Yong-Hui; Cao, Zheng-Wang; Zhang, Lei; Yu, Zheng-Ping [Department of Occupational Health, Third Military Medical University, Chongqing 400038 (China); Zhou, Zhou, E-mail: lunazhou00@163.com [Department of Occupational Health, Third Military Medical University, Chongqing 400038 (China)

    2015-07-15

    With application of nano-sized nickel-containing particles (Nano-Ni) expanding, the health concerns about their adverse effects on the pulmonary system are increasing. However, the mechanisms for the pulmonary toxicity of these materials remain unclear. In the present study, we focused on the impacts of NiO nanoparticles (NiONPs) on sirtuin1 (SIRT1), a NAD-dependent deacetylase, and investigated whether SIRT1 was involved in NiONPs-induced apoptosis. Although the NiONPs tended to agglomerate in fluid medium, they still entered into the human bronchial epithelial cells (BEAS-2B) and released Ni{sup 2+} inside the cells. NiONPs at doses of 5, 10, and 20 μg/cm{sup 2} inhibited the cell viability. NiONPs' produced cytotoxicity was demonstrated through an apoptotic process, indicated by increased numbers of Annexin V positive cells and caspase-3 activation. The expression of SIRT1 was markedly down-regulated by the NiONPs, accompanied by the hyperacetylation of p53 (tumor protein 53) and overexpression of Bax (Bcl-2-associated X protein). However, overexpression of SIRT1 through resveratrol treatment or transfection clearly attenuated the NiONPs-induced apoptosis and activation of p53 and Bax. Our results suggest that the repression of SIRT1 may underlie the NiONPs-induced apoptosis via p53 hyperacetylation and subsequent Bax activation. Because SIRT1 participates in multiple biologic processes by deacetylation of dozens of substrates, this knowledge of the impact of NiONPs on SIRT1 may lead to an improved understanding of the toxic mechanisms of Nano-Ni and provide a molecular target to antagonize Nano-Ni toxicity. - Highlights: • NiONPs were taken up by BEAS-2B cells and released Ni{sup 2+}. • NiONPs produced cytotoxicity was demonstrated through an apoptotic process. • NiONPs repressed SIRT1 expression and activated p53 and Bax. • Overexpression of SIRT1 attenuated NiONPs-induced apoptosis via deacetylation p53.

  18. The inhibitory mechanism of Cordyceps sinensis on cigarette smoke extract-induced senescence in human bronchial epithelial cells

    Directory of Open Access Journals (Sweden)

    Liu AL

    2016-07-01

    Full Text Available Ailing Liu,1,2,* Jinxiang Wu,1,* Aijun Li,2 Wenxiang Bi,3 Tian Liu,1 Liuzhao Cao,1 Yahui Liu,1 Liang Dong1 1Department of Pulmonary Diseases, Qilu Hospital, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Pulmonary Diseases, Weihai Municipal Hospital, Weihai, Shandong, People’s Republic of China; 3Institute of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China *These authors contributed equally to this work Objectives: Cellular senescence is a state of irreversible growth arrest induced either by telomere shortening (replicative senescence or stress. The bronchial epithelial cell is often injured by inhaled toxic substances, such as cigarette smoke. In the present study, we investigated whether exposure to cigarette smoke extract (CSE induces senescence of bronchial epithelial cells; and Cordyceps sinensis mechanism of inhibition of CSE-induced cellular senescence.Methods: Human bronchial epithelial cells (16HBE cells cultured in vitro were treated with CSE and/or C. sinensis. p16, p21, and senescence-associated-galactosidase activity were used to detect cellular senescence with immunofluorescence, quantitative polymerase chain reaction, and Western blotting. Reactive oxygen species (ROS, PI3K/AKT/mTOR and their phosphorylated proteins were examined to testify the activation of signaling pathway by ROS fluorescent staining and Western blotting. Then, inhibitors of ROS and PI3K were used to further confirm the function of this pathway.Results: Cellular senescence was upregulated by CSE treatment, and C. sinensis can decrease CSE-induced cellular senescence. Activation of ROS/PI3K/AKT/mTOR signaling pathway was enhanced by CSE treatment, and decreased when C. sinensis was added. Blocking ROS/PI3K/AKT/mTOR signaling pathway can attenuate CSE-induced cellular senescence.Conclusion: CSE can induce cellular senescence in human bronchial

  19. Mechanism for radiation-induced damage via TLR3 on the intestinal epithelium

    International Nuclear Information System (INIS)

    When the small-intestinal epithelium is injured due to high-dose radiation exposure, radiation-induced gastrointestinal syndrome (GIS) such as absorption inhibition and intestinal bacterial infection occurs, and lead to subacute death. The authors immunologically analyzed the disease onset mechanism of GIS. In the small-intestinal mucosal epithelium, the intestinal epithelial stem cells of crypt structure and their daughter cells are renewed through proliferation and differentiation in the cycle of 3 or 4 days. When DNA is damaged by radiation, although p53 gene stops cell cycle and repairs DNA, cell death is induced if the repair is impossible. When stem cells perish, cell supply stops resulting in epithelial breakdown and fatal GIS. The authors analyzed the involvement in GIS of toll-like receptor (TLR) with the function of natural immunity, based on lethal γ-ray irradiation on KO mice and other methods. The authors found the mechanism, in which RNA that was leaked due to cell death caused by p53 gene elicits inflammation by activating TLR3, and leads to GIS through a wide range of cell death induction and stem cell extinction. The administration of a TLR3/RNA binding inhibitor before the irradiation of mice decreased crypt cell death and greatly improved survival rate. The administration one hour after the irradiation also showed improvement. The administration of the TLR3 specific inhibitor within a fixed time after the exposure is hopeful for the prevention of GIS, without affecting the DNA repair function of p53 gene. (A.O.)

  20. The function and significance of SELENBP1 downregulation in human bronchial epithelial carcinogenic process.

    Directory of Open Access Journals (Sweden)

    Gu-Qing Zeng

    Full Text Available BACKGROUND: Our quantitative proteomic study showed that selenium-binding protein 1 (SELENBP1 was progressively decreased in human bronchial epithelial carcinogenic process. However, there is little information on expression and function of SELENBP1 during human lung squamous cell cancer (LSCC carcinogenesis. METHODS: iTRAQ-tagging combined with 2D LC-MS/MS analysis was used to identify differentially expressed proteins in the human bronchial epithelial carcinogenic process. SELENBP1, member of selenoproteins family and progressively downregulated in this process, was selected to further study. Both Western blotting and immunohistochemistry were performed to detect SELENBP1 expression in independent sets of tissues of bronchial epithelial carcinogenesis, and ability of SELENBP1 for discriminating NBE (normal bronchial epithelium from preneoplastic lesions from invasive LSCC was evaluated. The effects of SELENBP1 downregulation on the susceptibility of benzo(apyrene (B[a]P-induced human bronchial epithelial cell transformation were determined. RESULTS: 102 differentially expressed proteins were identified by quantitative proteomics, and SELENBP1 was found and confirmed being progressively decreased in the human bronchial epithelial carcinogenic process. The sensitivity and specificity of SELENBP1 were 80% and 79% in discriminating NBE from preneoplastic lesions, 79% and 82% in discriminating NBE from invasive LSCC, and 77% and 71% in discriminating preneoplastic lesions from invasive LSCC, respectively. Furthermore, knockdown of SELENBP1 in immortalized human bronchial epithelial cell line 16HBE cells significantly increased the efficiency of B[a]P-induced cell transformation. CONCLUSIONS: The present data shows for the first time that decreased SELENBP1 is an early event in LSCC, increases B[a]P-induced human bronchial epithelial cell transformation, and might serve as a novel potential biomarker for early detection of LSCC.

  1. Activation of VPAC1 receptors by VIP and PACAP-27 in human bronchial epithelial cells induces CFTR-dependent chloride secretion

    OpenAIRE

    Dérand, Renaud; Montoni, Alicia; Bulteau-Pignoux, Laurence; Janet, Thierry; Moreau, Bertrand; Muller, Jean-Marc; Becq, Frédéric

    2004-01-01

    In the human airway epithelium, VIP/PACAP receptors are distributed in nerve fibers and in epithelial cells but their role in transepithelial ion transport have not been reported. Here, we show that human bronchial epithelial Calu-3 cells expressed the VPAC1 receptor subtype which shares similar high affinity for VIP and PACAP-27.The stoichiometric binding parameters characterizing the 125I-VIP and 125I-PACAP-27 binding to these receptors were determined.We found that VIP (EC50≈7.6 nM) and PA...

  2. Bronchial, alveolar, and vascular-induced anaphylaxis and irritant-induced cardiovascular and pulmonary responses.

    OpenAIRE

    Yeates, D B; Mussatto, D J; Hameister, W M; Daza, A.; Chandra, T; Wong, L B

    2001-01-01

    We examine the respiratory, bronchomotor, cardiac, and vascular responses to histamine and ragweed allergen delivered to the bronchi or alveoli compartments and the potential role of sensory nerves and reflexes mediating the histamine-induced responses. The masses of aerosols deposited in the bronchi and alveoli were quantitated using radioaerosol techniques. Activation of sensory nerves and/or histamine-induced mediator release were characterized by depositing nedocromil sodium aerosol prior...

  3. Objective quantitative analysis of eosinophils and bronchial epithelial cells in induced sputum by laser scanning cytometry

    OpenAIRE

    Woltmann, G; Ward, R.; Symon, F; Rew, D.; Pavord, I.; Wardlaw, A

    1999-01-01

    BACKGROUND—Sputum induction is an important non-invasive technique for measuring airway inflammation in asthma. Cell numbers are often too low for flow cytometric analysis. Laser scanning cytometry (LSC) is a novel technique that allows objective multicolour fluorescence analysis of cells on a microscope slide.
METHODS—LSC was used to determine sputum eosinophil and bronchial epithelial cell counts. We first confirmed that we could measure eosinophil counts accurately in ...

  4. Human mesenchymal stem cells suppress the stretch-induced inflammatory miR-155 and cytokines in bronchial epithelial cells.

    Science.gov (United States)

    Kuo, Yi-Chun; Li, Yi-Shuan Julie; Zhou, Jing; Shih, Yu-Ru Vernon; Miller, Marina; Broide, David; Lee, Oscar Kuang-Sheng; Chien, Shu

    2013-01-01

    Current research in pulmonary pathology has focused on inflammatory reactions initiated by immunological responses to allergens and irritants. In addition to these biochemical stimuli, physical forces also play an important role in regulating the structure, function, and metabolism of the lung. Hyperstretch of lung tissues can contribute to the inflammatory responses in asthma, but the mechanisms of mechanically induced inflammation in the lung remain unclear. Our results demonstrate that excessive stretch increased the secretion of inflammatory cytokines by human bronchial epithelial cells (hBECs), including IL-8. This increase of IL-8 secretion was due to an elevated microRNA-155 (miR-155) expression, which caused the suppression of Src homology 2 domain-containing inositol 5-phosphatase 1 (SHIP1) production and the subsequent activation of JNK signaling. In vivo studies in our asthmatic mouse model also showed such changes in miR-155, IL-8, and SHIP1 expressions that reflect inflammatory responses. Co-culture with human mesenchymal stem cells (hMSCs) reversed the stretch-induced hBEC inflammatory responses as a result of IL-10 secretion by hMSCs to down-regulate miR-155 expression in hBECs. In summary, we have demonstrated that mechanical stretch modulates the homeostasis of the hBEC secretome involving miR-155 and that hMSCs can be used as a potential therapeutic approach to reverse bronchial epithelial inflammation in asthma. PMID:23967196

  5. Human mesenchymal stem cells suppress the stretch-induced inflammatory miR-155 and cytokines in bronchial epithelial cells.

    Directory of Open Access Journals (Sweden)

    Yi-Chun Kuo

    Full Text Available Current research in pulmonary pathology has focused on inflammatory reactions initiated by immunological responses to allergens and irritants. In addition to these biochemical stimuli, physical forces also play an important role in regulating the structure, function, and metabolism of the lung. Hyperstretch of lung tissues can contribute to the inflammatory responses in asthma, but the mechanisms of mechanically induced inflammation in the lung remain unclear. Our results demonstrate that excessive stretch increased the secretion of inflammatory cytokines by human bronchial epithelial cells (hBECs, including IL-8. This increase of IL-8 secretion was due to an elevated microRNA-155 (miR-155 expression, which caused the suppression of Src homology 2 domain-containing inositol 5-phosphatase 1 (SHIP1 production and the subsequent activation of JNK signaling. In vivo studies in our asthmatic mouse model also showed such changes in miR-155, IL-8, and SHIP1 expressions that reflect inflammatory responses. Co-culture with human mesenchymal stem cells (hMSCs reversed the stretch-induced hBEC inflammatory responses as a result of IL-10 secretion by hMSCs to down-regulate miR-155 expression in hBECs. In summary, we have demonstrated that mechanical stretch modulates the homeostasis of the hBEC secretome involving miR-155 and that hMSCs can be used as a potential therapeutic approach to reverse bronchial epithelial inflammation in asthma.

  6. Particle-induced indentation of the alveolar epithelium caused by surface tension forces.

    Science.gov (United States)

    Mijailovich, S M; Kojic, M; Tsuda, A

    2010-10-01

    Physical contact between an inhaled particle and alveolar epithelium at the moment of particle deposition must have substantial effects on subsequent cellular functions of neighboring cells, such as alveolar type-I, type-II pneumocytes, alveolar macrophage, as well as afferent sensory nerve cells, extending their dendrites toward the alveolar septal surface. The forces driving this physical insult are born at the surface of the alveolar air-liquid layer. The role of alveolar surfactant submerging a hydrophilic particle has been suggested by Gehr and Schürch's group (e.g., Respir Physiol 80: 17-32, 1990). In this paper, we extended their studies by developing a further comprehensive and mechanistic analysis. The analysis reveals that the mechanics operating in the particle-tissue interaction phenomena can be explained on the basis of a balance between surface tension force and tissue resistance force; the former tend to move a particle toward alveolar epithelial cell surface, the latter to resist the cell deformation. As a result, the submerged particle deforms the tissue and makes a noticeable indentation, which creates unphysiological stress and strain fields in tissue around the particle. This particle-induced microdeformation could likely trigger adverse mechanotransduction and mechanosensing pathways, as well as potentially enhancing particle uptake by the cells. PMID:20634359

  7. TGFβ signaling in lung epithelium regulates bleomycin-induced alveolar injury and fibroblast recruitment

    OpenAIRE

    Degryse, Amber L.; Tanjore, Harikrishna; Xu, Xiaochuan C.; Polosukhin, Vasiliy V.; Jones, Brittany R.; Boomershine, Chad S; Ortiz, Camila; Sherrill, Taylor P.; McMahon, Frank B.; Gleaves, Linda A.; Blackwell, Timothy S.; Lawson, William E.

    2011-01-01

    The response of alveolar epithelial cells (AECs) to lung injury plays a central role in the pathogenesis of pulmonary fibrosis, but the mechanisms by which AECs regulate fibrotic processes are not well defined. We aimed to elucidate how transforming growth factor-β (TGFβ) signaling in lung epithelium impacts lung fibrosis in the intratracheal bleomycin model. Mice with selective deficiency of TGFβ receptor 2 (TGFβR2) in lung epithelium were generated and crossed to cell fate reporter mice tha...

  8. Radiation-induced chromosome aberrations in cell populations from rat tracheal epithelium

    International Nuclear Information System (INIS)

    To determine cells at risk in the respiratory tract for the induction of cancer, it is essential to know not only the dose of toxic agent to the cells but also the sensitivity of each cell type to the agent. The purpose of this study is to define the radiation sensitivity of cells in the airway epithelium of the rat as the first step in determining the cells at risk for cancer induction by radiation. Tracheal epithelial cells were isolated, sorted by flow cytometry, grown in defined medium and exposed to graded doses of X rays. Survival and the frequency of chromosome aberrations were determined in the total cell population, in the sorted secretary and in the sorted basal cells. There was no difference in radiation-induced cytotoxicity of each cell type. The frequency of chromosome aberrations was determined by linear regression analysis and found to be 0.37 ± 0.01 aberrations/cell/Gy for the unsorted cells and 0.26 ± 0.02 for the sorted secretary cells. Because of the low number and cloning efficiency of basal cells, no data on X-ray-induced chromosome aberrations in these cells is available at the present time. There was a linear decrease in the chromatid-type aberration frequency as a function of time after the radiation exposure. The data suggest that, in terms of radiation sensitivity, all three cell populations are very similar. Thus, if there are differences in the response to a toxic agent such as radon, the differences should reflect differences in radiation dose to the cells. (author)

  9. Photoprotection of human retinal pigment epithelium cells against blue light-induced apoptosis by melanin free radicals from Sepia officinalis

    OpenAIRE

    Seagle, Brandon-Luke L.; Gasyna, Elzbieta M.; Mieler, William F.; Norris, James R.

    2006-01-01

    Cultured retinal pigment epithelium (RPE) cells can phagocytize large foreign particles. Heterogeneous melanin aggregates from Sepia officinalis, a species of cuttlefish, were fed to cultured human RPE cells to produce cells laden with Sepia melanin. Blue light-induced apoptosis (BLIA) assays were performed by flow cytometry on parallel cultures consisting of RPE cells isolated from independent eyes and evenly divided into two cultures, one fed Sepia melanin and one containing only native mel...

  10. Melanin photoprotection in the human retinal pigment epithelium and its correlation with light-induced cell apoptosis

    OpenAIRE

    Seagle, Brandon-Luke L.; Rezai, Kourous A.; Kobori, Yasuhiro; Gasyna, Elzbieta M.; Rezaei, Kasra A.; Norris, James R.

    2005-01-01

    Time-resolved electron paramagnetic resonance (TREPR) spectroscopy was used to study melanin free radicals in human retinal pigment epithelium (RPE) cells and tyrosine-derived synthetic melanin. TREPR signal traces from RPE cells reveal in vivo light-induced melanin free radical photochemistry in more detail than previously known. Electron spin polarization reflecting a non-Boltzmann population within the energy levels of the spin system is observed in RPE cells as the result of the triplet s...

  11. Abnormal Expression of Eukaryotic Translation Factors in Malignant Transformed Human Bronchial Epithelial Cells Induced by Crystalline Nickel Sulfide

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective To study the oncogenic potential of mouse translation initiation factor 3 (TIF3) and elongation factor-1δ (TEF-1δ) in malignant transformed human bronchial epithelial cells induced by crystalline nickel sulfide (NiS). Methods Abnormal expressions of human TIF3 and TEF-1δ genes in two kinds of NiS-transformed cells and NiS-tumorigenic cell lines were investigated and analyzed by the reverse transcript polymerase chain reaction (RT-PCR) and fluorescent quantitative polymerase chain reaction (FQ-PCR), respectively. Results RT-PCR analysis primarily showed that both human TIF3 and TEF-1δ mRNA expressions in two kinds of NiS-transformed cells and NiS-tumorigenic cell lines were increased as compared with controls. FQ-PCR assay showed that the levels of TIF3 expressions in the transformed cells and tumorigenic cells were 3 and 4 times higher respectively, and the elevated expressions of TEF-1δ cDNA copies were 2.7- to 3.5-fold in transformed cells and 4.1- to 5.2-fold in tumorigenic cells when compared with non-transformed cells, indicating that the over-expressions of human TIF3 and TEF-1δ genes were related to malignant degree of the cells induced by nickel. Conclusions These findings demonstrate that there are markedly abnormal expressions of TIF3 and TEF-1δ genes during malignant transformation of human bronchial epithelial cell lines induced by crystalline NiS. They seem to be the molecular mechanisms potentially responsible for human carcinogensis due to nickel.

  12. Quantitative assessment of microbicide-induced injury in the ovine vaginal epithelium using confocal microendoscopy

    Directory of Open Access Journals (Sweden)

    Vargas Gracie

    2012-02-01

    Full Text Available Abstract Background The development of safe topical microbicides that can preserve the integrity of cervicovaginal tract epithelial barrier is of great interest as this may minimize the potential for increased susceptibility to STI infections. High resolution imaging to assess epithelial integrity in a noninvasive manner could be a valuable tool for preclinical testing of candidate topical agents. Methods A quantitative approach using confocal fluorescence microendoscopy (CFM for assessment of microbicide-induced injury to the vaginal epithelium was developed. Sheep were treated intravaginally with one of five agents in solution (PBS; 0.02% benzalkonium chloride (BZK; 0.2% BZK or gel formulation (hydroxyethyl cellulose (HEC; Gynol II nonoxynol-9 gel (N-9. After 24 hours the vaginal tract was removed, labeled with propidium iodide (PI, imaged, then fixed for histology. An automated image scoring algorithm was developed for quantitative assessment of injury and applied to the data set. Image-based findings were validated with histological visual gradings that describe degree of injury and measurement of epithelial thickness. Results Distinct differences in PI staining were detected following BZK and N-9 treatment. Images from controls had uniformly distributed nuclei with defined borders, while those after BZK or N-9 showed heavily stained and disrupted nuclei, which increased in proportion to injury detected on histology. The confocal scoring system revealed statistically significant scores for each agent versus PBS controls with the exception of HEC and were consistent with histology scores of injury. Conclusions Confocal microendoscopy provides a sensitive, objective, and quantitative approach for non-invasive assessment of vaginal epithelial integrity and could serve as a tool for real-time safety evaluation of emerging intravaginal topical agents.

  13. IL-17A Induces Pendrin Expression and Chloride-Bicarbonate Exchange in Human Bronchial Epithelial Cells

    OpenAIRE

    Adams, Kelly M.; Abraham, Valsamma; Spielman, Daniel; Kolls, Jay K.; Rubenstein, Ronald C.; Conner, Gregory E.; Cohen, Noam A.; Kreindler, James L.

    2014-01-01

    The epithelium plays an active role in the response to inhaled pathogens in part by responding to signals from the immune system. Epithelial responses may include changes in chemokine expression, increased mucin production and antimicrobial peptide secretion, and changes in ion transport. We previously demonstrated that interleukin-17A (IL-17A), which is critical for lung host defense against extracellular bacteria, significantly raised airway surface pH in vitro, a finding that is common to ...

  14. Hypotonicity induced K+ and anion conductive pathways activation in eel intestinal epithelium

    DEFF Research Database (Denmark)

    Lionetto, M G; Giordano, M E; De Nuccio, F; Nicolardi, G; Hoffmann, E K; Schettino, T

    2005-01-01

    electrogenic V(te) and I(sc) responses to hypotonicity resulted from the activation of different K+ and anion conductive pathways on the apical and basolateral membranes of the epithelium: (a) iberiotoxin-sensitive K+ channels on the apical and basolateral membrane, (b) apamin-sensitive K+ channels mainly on...... the basolateral membrane, (c) DIDS-sensitive anion channels on the apical membrane. The functional integrity of the basal Cl- conductive pathway on the basolateral membrane is also required. The electrophysiological response to hypotonic stress was completely abolished by Ca2+ removal from the Ringer...... activation of 'emergency' systems of rapid cell volume regulation is fundamental in their physiology. The aim of the present work was to study the physiological response to hypotonic stress in a salt-transporting epithelium, the intestine of the euryhaline teleost Anguilla anguilla. Eel intestinal epithelium...

  15. Macrophages promote benzopyrene-induced tumor transformation of human bronchial epithelial cells by activation of NF-κB and STAT3 signaling in a bionic airway chip culture and in animal models

    OpenAIRE

    Li, Encheng; Xu, Zhiyun; Zhao, Hui; Sun, Zhao; Wang, Lei; Guo, Zhe; Zhao, Yang; GAO, ZHANCHENG; Wang, Qi

    2015-01-01

    We investigated the role of macrophages in promoting benzopyrene (BaP)-induced malignant transformation of human bronchial epithelial cells using a BaP-induced tumor transformation model with a bionic airway chip in vitro and in animal models. The bionic airway chip culture data showed that macrophages promoted BaP-induced malignant transformation of human bronchial epithelial cells, which was mediated by nuclear factor (NF)-κB and STAT3 pathways to induce cell proliferation, colony formation...

  16. Wood dusts induce the production of reactive oxygen species and caspase-3 activity in human bronchial epithelial cells

    International Nuclear Information System (INIS)

    Wood dusts are associated with several respiratory symptoms, e.g. impaired lung function and asthma, in exposed workers. However, despite the evidence from epidemiological studies, the underlying mechanisms are not well understood. In the present study, we investigated different wood dusts for their capacity to induce cytotoxicity and production of radical oxygen species (ROS) as well as activation of the apoptotic caspase-3 enzyme in human bronchial epithelial cells (BEAS-2B). Dusts from three different tree species widely used in wood industry were studied; birch and oak represented hardwood species, and pine a common softwood species. All the experiments were carried out in three different concentrations (10, 50, and 500 μg/ml) and the analysis was performed after 0.5, 2, 6, and 24 h exposure. All wood dusts studied were cytotoxic to human bronchial epithelial cells in a dose-dependent manner after 2 and 6 h treatment. Exposure to pine, birch, or oak dust had a significant stimulating effect on the production of ROS. Also an induction in caspase-3 protease activity, one of the central components of the apoptotic cascade, was seen in BEAS-2B cells after 2 and 6 h exposure to each of the wood dusts studied. In summary, we demonstrate that dusts from pine, birch and oak are cytotoxic, able to increase the production of ROS and the apoptotic response in human broncho-epithelial cells in vitro. Thus, our current data suggest oxidative stress by ROS as an important mechanism likely to function in wood dust related pulmonary toxicity although details of the cellular targets and cell-particle interactions remain to be solved. It is though tempting to speculate that redox-regulated transcription factors such as NFκB or AP-1 may play a role in this wood dust-evoked process leading to apparently induced apoptosis of target cells.

  17. Early LPS-induced ERK activation in retinal pigment epithelium cells is dependent on PIP 2 -PLC.

    Science.gov (United States)

    Mateos, Melina V; Kamerbeek, Constanza B; Giusto, Norma M; Salvador, Gabriela A

    2016-06-01

    This article presents additional data regarding the study "The phospholipase D pathway mediates the inflammatory response of the retinal pigment epithelium" [1]. The new data presented here show that short exposure of RPE cells to lipopolysaccharide (LPS) induces an early and transient activation of the extracellular signal-regulated kinase (ERK1/2). This early ERK1/2 activation is dependent on phosphatidylinositol bisphosphate-phospholipase C (PIP2-PLC). On the contrary, neither the phospholipase D 1 (PLD1) nor the PLD2 inhibition is able to modulate the early ERK1/2 activation induced by LPS in RPE cells. PMID:27006973

  18. [Cytomorphological analysis of remodeling of the bronchial wall in different types of bronchial asthma].

    Science.gov (United States)

    Gereng, E A; Sukhodolo, I V; Pleshko, R I; Ogorodova, L M; Selivanova, P A; Dziuman, A N

    2012-01-01

    The objective of the present work was to search for the tissue and cellular markers of remodeling of bronchial mucosa in the patients with different clinical forms of bronchial asthma (BA). The use of up-to-date morphometric techniques has demonstrated that mild and moderately severe forms of bronchial asthma are accompanied by the development of Th2-immune response associated with increased production of interleukin-4 and marked degranulation of eosinophilic granulocytes resulting in desquamation of epithelium and goblet cell hyperplasia. The severe BA phenotype of "chronic asthma with fixed obstruction" is associated with the development of non-atopic inflammation in the bronchial mucous membrane that manifests itself as the increased concentration of interleukin-8 in bronchial mucosa and its neutrophilic infiltration leading to the development of pronounced subepithelial fibrosis, thickening of the basal membrane, and atrophy of epithelium. Specific structural changes in bronchial mucosa of the patients presenting with BA underlie functional disturbances that cause severe bronchial obstructive syndrome. PMID:22645957

  19. Repair of tracheal epithelium by basal cells after chlorine-induced injury

    Directory of Open Access Journals (Sweden)

    Musah Sadiatu

    2012-11-01

    Full Text Available Abstract Background Chlorine is a widely used toxic compound that is considered a chemical threat agent. Chlorine inhalation injures airway epithelial cells, leading to pulmonary abnormalities. Efficient repair of injured epithelium is necessary to restore normal lung structure and function. The objective of the current study was to characterize repair of the tracheal epithelium after acute chlorine injury. Methods C57BL/6 mice were exposed to chlorine and injected with 5-ethynyl-2′-deoxyuridine (EdU to label proliferating cells prior to sacrifice and collection of tracheas on days 2, 4, 7, and 10 after exposure. Airway repair and restoration of a differentiated epithelium were examined by co-localization of EdU labeling with markers for the three major tracheal epithelial cell types [keratin 5 (K5 and keratin 14 (K14 for basal cells, Clara cell secretory protein (CCSP for Clara cells, and acetylated tubulin (AcTub for ciliated cells]. Morphometric analysis was used to measure proliferation and restoration of a pseudostratified epithelium. Results Epithelial repair was fastest and most extensive in proximal trachea compared with middle and distal trachea. In unexposed mice, cell proliferation was minimal, all basal cells expressed K5, and K14-expressing basal cells were absent from most sections. Chlorine exposure resulted in the sloughing of Clara and ciliated cells from the tracheal epithelium. Two to four days after chlorine exposure, cell proliferation occurred in K5- and K14-expressing basal cells, and the number of K14 cells was dramatically increased. In the period of peak cell proliferation, few if any ciliated or Clara cells were detected in repairing trachea. Expression of ciliated and Clara cell markers was detected at later times (days 7–10, but cell proliferation was not detected in areas in which these differentiated markers were re-expressed. Fibrotic lesions were observed at days 7–10 primarily in distal trachea. Conclusion

  20. Reactive oxygen species contribute to arsenic-induced EZH2 phosphorylation in human bronchial epithelial cells and lung cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Lingzhi; Qiu, Ping; Chen, Bailing; Lu, Yongju; Wu, Kai; Thakur, Chitra; Chang, Qingshan; Sun, Jiaying; Chen, Fei, E-mail: fchen@wayne.edu

    2014-05-01

    Our previous studies suggested that arsenic is able to induce serine 21 phosphorylation of the EZH2 protein through activation of JNK, STAT3, and Akt signaling pathways in the bronchial epithelial cell line, BEAS-2B. In the present report, we further demonstrated that reactive oxygen species (ROS) were involved in the arsenic-induced protein kinase activation that leads to EZH2 phosphorylation. Several lines of evidence supported this notion. First, the pretreatment of the cells with N-acetyl-L-cysteine (NAC), a potent antioxidant, abolishes arsenic-induced EZH2 phosphorylation along with the inhibition of JNK, STAT3, and Akt. Second, H{sub 2}O{sub 2}, the most important form of ROS in the cells in response to extracellular stress signals, can induce phosphorylation of the EZH2 protein and the activation of JNK, STAT3, and Akt. By ectopic expression of the myc-tagged EZH2, we additionally identified direct interaction and phosphorylation of the EZH2 protein by Akt in response to arsenic and H{sub 2}O{sub 2}. Furthermore, both arsenic and H{sub 2}O{sub 2} were able to induce the translocation of ectopically expressed or endogenous EZH2 from nucleus to cytoplasm. In summary, the data presented in this report indicate that oxidative stress due to ROS generation plays an important role in the arsenic-induced EZH2 phosphorylation. - Highlights:: • Arsenic (As{sup 3+}) induces EZH phosphorylation. • JNK, STAT3, and Akt contribute to EZH2 phosphorylation. • Oxidative stress is involved in As{sup 3+}-induced EZH2 phosphorylation. • As{sup 3+} induces direct interaction of Akt and EZH2. • Phosphorylated EZH2 localized in cytoplasm.

  1. Reactive oxygen species contribute to arsenic-induced EZH2 phosphorylation in human bronchial epithelial cells and lung cancer cells

    International Nuclear Information System (INIS)

    Our previous studies suggested that arsenic is able to induce serine 21 phosphorylation of the EZH2 protein through activation of JNK, STAT3, and Akt signaling pathways in the bronchial epithelial cell line, BEAS-2B. In the present report, we further demonstrated that reactive oxygen species (ROS) were involved in the arsenic-induced protein kinase activation that leads to EZH2 phosphorylation. Several lines of evidence supported this notion. First, the pretreatment of the cells with N-acetyl-L-cysteine (NAC), a potent antioxidant, abolishes arsenic-induced EZH2 phosphorylation along with the inhibition of JNK, STAT3, and Akt. Second, H2O2, the most important form of ROS in the cells in response to extracellular stress signals, can induce phosphorylation of the EZH2 protein and the activation of JNK, STAT3, and Akt. By ectopic expression of the myc-tagged EZH2, we additionally identified direct interaction and phosphorylation of the EZH2 protein by Akt in response to arsenic and H2O2. Furthermore, both arsenic and H2O2 were able to induce the translocation of ectopically expressed or endogenous EZH2 from nucleus to cytoplasm. In summary, the data presented in this report indicate that oxidative stress due to ROS generation plays an important role in the arsenic-induced EZH2 phosphorylation. - Highlights:: • Arsenic (As3+) induces EZH phosphorylation. • JNK, STAT3, and Akt contribute to EZH2 phosphorylation. • Oxidative stress is involved in As3+-induced EZH2 phosphorylation. • As3+ induces direct interaction of Akt and EZH2. • Phosphorylated EZH2 localized in cytoplasm

  2. Bronchi, Bronchial Tree, & Lungs

    Science.gov (United States)

    ... specific Modules Resources Archived Modules Updates Bronchi, Bronchial Tree, & Lungs Bronchi and Bronchial Tree In the mediastinum , at the level of the ... trachea. As the branching continues through the bronchial tree, the amount of hyaline cartilage in the walls ...

  3. In vitro transformation of immortalized human bronchial epithelial cells BEAS-2B induced by radon and cigarette smoke

    International Nuclear Information System (INIS)

    Objective: To establish a model of malignant transformation of human cells in vitro to study the lung cancer induced by radon and cigarette smoke. Methods: The immortalized human bronchial epithelial cells BEAS-2B were divided into control group (C), radon group (Rn), cigarette smoke group (Sm) and combined group (Rn-Sm). Cells were planted onto transwell membrane one day before exposure and were directly exposed to radon and cigarette smoke pumped in a gas inhalation box. After the exposure cells were trypsinized into dishes for further growth and malignancy transformation phenotype was detected in order to compare the effects due to radon and cigarette smoke exposure. Results: BEAS-2B cells showed malignantly transformed phenotype by exposure to radon and cigarette smoke. A series of sequential steps emerged among transformed cells, including altered growth kinetics, resistance to serum has changed from 0. 31 ± 0. 18 to 1.92 ± 0. 27,2. 03 ± 0. 14,2.95 ± 0. 60, and anchorage-independence growth increased from (0.01 ±0.02)% to (4.89 ±0.30)%,(8.36 ±0.50)%,(11.74 ±0.69)%.After being subculture for 20 generations, cell apoptosis of the fifth generation cells exposed to radon,cigarette smoke and both was significant decreased from ( 11.76 ± 0. 17 ) % to (4. 62 ± 0. 42 ) %, ( 8.63 ±0. 15 )%, (3.68 ± 0. 33 )%. Conclusions: BEAS-2B cells could be malignancy transformed by radon and cigarette smoke in vitro, which could be used as a cell model in lung bronchial carcinogenesis. (authors)

  4. Autophagy plays an essential role in cigarette smoke-induced expression of MUC5AC in airway epithelium.

    Science.gov (United States)

    Zhou, Jie-Sen; Zhao, Yun; Zhou, Hong-Bin; Wang, Yong; Wu, Yin-Fang; Li, Zhou-Yang; Xuan, Nan-Xia; Zhang, Chao; Hua, Wen; Ying, Song-Min; Li, Wen; Shen, Hua-Hao; Chen, Zhi-Hua

    2016-06-01

    Mucus hypersecretion is a common pathological feature of chronic airway inflammatory diseases including chronic obstructive pulmonary disease (COPD). However, the molecular basis for this condition remains incompletely understood. We have previously demonstrated a critical role of autophagy in COPD pathogenesis through mediating apoptosis of lung epithelial cells. In this study, we aimed to investigate the function of autophagy as well as its upstream and downstream signals in cigarette smoke-induced mucus production in human bronchial epithelial (HBE) cells and in mouse airways. Cigarette smoke extract (CSE), as well as the classical autophagy inducers starvation or Torin-1, significantly triggered MUC5AC expression, and inhibition of autophagy markedly attenuated CSE-induced mucus production. The CSE-induced autophagy was mediated by mitochondrial reactive oxygen species (mitoROS), which regulated mucin expression through the JNK and activator protein-1 pathway. Epidermal growth factor receptor (EGFR) was also required for CSE-induced MUC5AC in HBE cells, but it exerted inconsiderable effects on the autophagy-JNK signaling cascade. Airways of mice with dysfunctional autophagy-related genes displayed a markedly reduced number of goblet cells and attenuated levels of Muc5ac in response to cigarette smoke exposure. These results altogether suggest that mitoROS-dependent autophagy is essential for cigarette smoke-induced mucus hyperproduction in airway epithelial cells, and reemphasize autophagy inhibition as a novel therapeutic strategy for chronic airway diseases. PMID:27036871

  5. Spontaneous and cytokine induced expression and activity of matrix metalloproteinases in human colonic epithelium

    DEFF Research Database (Denmark)

    Pedersen, G; Saermark, T; Kirkegaard, T; Brynskov, J

    2009-01-01

    bond for MMP cleavage. HT-29 and DLD-1 expressed several MMPs and levels of MMP-3, -10 and -13 mRNA expression were increased significantly by tumour necrosis factor (TNF)-alpha exposure. Transcripts of MMP-1, -3, -7, -9, -10 and -12 were detected in CECs and all, except MMP12, at significantly...... increased levels in cells from inflamed IBD mucosa. MMP-2 and -8 mRNA were expressed inconsistently and MMP-11, -13 and -14 mRNA undetectable. Proteolytic MMP activity was detected in CEC supernatants and the level was increased significantly in inflamed IBD epithelium. The enzyme activity was inhibited......Matrix metalloproteinases (MMPs) have been implicated in tissue damage associated with inflammatory bowel disease (IBD).As the role of the intestinal epithelium in this process is unknown, we determined MMP expression and enzyme activity in human colonic epithelial cells (CEC). MMP mRNA expression...

  6. Particle-induced indentation of the alveolar epithelium caused by surface tension forces

    OpenAIRE

    Mijailovich, S. M.; Kojic, M.; Tsuda, A.

    2010-01-01

    Physical contact between an inhaled particle and alveolar epithelium at the moment of particle deposition must have substantial effects on subsequent cellular functions of neighboring cells, such as alveolar type-I, type-II pneumocytes, alveolar macrophage, as well as afferent sensory nerve cells, extending their dendrites toward the alveolar septal surface. The forces driving this physical insult are born at the surface of the alveolar air-liquid layer. The role of alveolar surfactant submer...

  7. Influence of epithelium on the inhibition of melittin-induced contraction of guinea-pig isolated trachea by the potassium channel opener NIP-121.

    OpenAIRE

    Shikada, K.; Tanaka, S

    1993-01-01

    1. We have investigated the effect of the potassium channel opener, NIP-121, on contraction elicited by melittin (a phospholipase A2 activator) in epithelium-intact and epithelium-denuded trachea isolated from guinea-pigs. The effects of NIP-121 were compared with those of isoprenaline, aminophylline and hydrocortisone. 2. In the presence of the cyclo-oxygenase inhibitor, indomethacin (5 microM), melittin (3 micrograms ml-1) caused time-dependent contraction. The melittin-induced contractile ...

  8. Immunotoxic effects of low level ozone exposure suggestive of an inducers in bronchial hyperresponiveness

    Institute of Scientific and Technical Information of China (English)

    SongH; LiDM

    2002-01-01

    For the city pollution of motor vehicle emissions,public air oxidizer exposure level has increasing tendence.As a representative of osidizer,ozone exposure is universal expecially at low levels in big city.Summarizing previous experimental study,which focuses on the exposure concentration at 0.125 ppm,the changes in inflammatory cytokines in animal airway suggest that low levels ozone expose activate cytokines resembling the bronchial hyperresponsiveness of atopy.Similarly the epidemiological study on adverse effects of ambient ozone exposure showed that the lower maxinal mid-expiratory flow of achoold children in exposed area where the concentration of ozone exceeded background levels only in the periphery of petroleum chemical enterprise were observed compared with those in control ares(P<0.05).This phenomenon of airway resistance increases as well as laboratory observation suggests that low level oxidizer exposure is one of the main risk factors of result in the increasing incidence of asthma in cities.

  9. Bronchial stents

    Directory of Open Access Journals (Sweden)

    Ibrahim Emad

    2006-01-01

    Full Text Available Bronchial stents are mostly used as a Palliative relief of symptoms often caused by airway obstruction, It is also used for sealing of stump fistulas after pneumonectomy and dehiscence after bronchoplastic operations. Advances in airway prosthetics have provided a variety of silicone stents, expandable metal stents, and pneumatic dilators, enabling the correction of increasingly complex anatomical problems. Several series have been published describing the application and results of these techniques. This manuscript reviews the historical development of stents, types, indication, outcome, and complications. Alternative therapies for tracheobronchial stenting were also reviewed

  10. Glutathione-S-transferase M1 regulation of diesel exhaust particle-induced pro-inflammatory mediator expression in normal human bronchial epithelial cells

    Directory of Open Access Journals (Sweden)

    Wu Weidong

    2012-08-01

    Full Text Available Abstract Background Diesel exhaust particles (DEP contribute substantially to ambient particulate matter (PM air pollution in urban areas. Inhalation of PM has been associated with increased incidence of lung disease in susceptible populations. We have demonstrated that the glutathione S-transferase M1 (GSTM1 null genotype could aggravate DEP-induced airway inflammation in human subjects. Given the critical role airway epithelial cells play in the pathogenesis of airway inflammation, we established the GSTM1 deficiency condition in primary bronchial epithelial cells from human volunteers with GSTM1 sufficient genotype (GSTM1+ using GSTM1 shRNA to determine whether GSTM1 deficiency could exaggerate DEP-induced expression of interleukin-8 (IL-8 and IL-1β proteins. Furthermore, the mechanisms underlying GSTM1 regulation of DEP-induced IL-8 and IL-1β expression were also investigated. Methods IL-8 and IL-1β protein levels were measured using enzyme-linked immunosorbent assay. GSTM1 deficiency in primary human bronchial epithelial cells was achieved using lentiviral GSTM1 shRNA particles and verified using real-time polymerase chain reaction and immunoblotting. Intracellular reactive oxygen species (ROS production was evaluated using flow cytometry. Phosphorylation of protein kinases was detected using immunoblotting. Results Exposure of primary human bronchial epithelial cells (GSTM1+ to 25-100 μg/ml DEP for 24 h significantly increased IL-8 and IL-1β protein expression. Knockdown of GSTM1 in these cells further elevated DEP-induced IL-8 and IL-1β expression, implying that GSTM1 deficiency aggravated DEP-induced pro-inflammatory response. DEP stimulation induced the phosphorylation of extracellular signal-regulated kinase (ERK and Akt, the downstream kinase of phosphoinositide 3-kinase (PI3K, in GSTM1+ bronchial epithelial cells. Pharmacological inhibition of ERK kinase and PI3K activity blocked DEP-induced IL-8 and IL-1β expression. DEP-induced

  11. YThe BigH3 Tumor Suppressor Gene in Radiation-Induced Malignant Transformation of Human Bronchial Epithelial Cells

    Science.gov (United States)

    Zhao, Y.; Shao, G.; Piao, C.; Hei, T.

    Carcinogenesis is a multi-stage process with sequences of genetic events governing the phenotypic expression of a series of transformation steps leading to the development of metastatic cancer Previous studies from this laboratory have identified a 7 fold down- regulation of the novel tumor suppressor Big-h3 among radiation induced tumorigenic BEP2D cells Furthermore ectopic re-expression of this gene suppresses tumorigenic phenotype and promotes the sensitivity of these tumor cells to etoposide-induced apoptosis To extend these studies using a genomically more stable bronchial cell line we ectopically expresses the catalytic subunit of telomerase hTERT in primary human small airway epithelial SAE cells and generated several clonal cell lines that have been continuously in culture for more than 250 population doublings and are considered immortal Comparably-treated control SAE cells infected with only the viral vector senesced after less than 10 population doublings The immortalized clones demonstrated anchorage dependent growth and are non-tumorigenic in nude mice These cells show no alteration in the p53 gene but a decrease in p16 expression Exponentially growing SAEh cells were exposed to graded doses of 1 GeV nucleon of 56 Fe ions accelerated at the Brookhaven National Laboratory Irradiated cells underwent gradual phenotypic alterations after extensive in vitro cultivation Transformed cells developed through a series of successive steps before becoming anchorage independent in semisolid medium These findings indicate

  12. Cadmium Induced Cell Apoptosis, DNA Damage, Decreased DNA Repair Capacity, and Genomic Instability during Malignant Transformation of Human Bronchial Epithelial Cells

    OpenAIRE

    Zhou, Zhiheng; Wang, Caixia; Liu, Haibai; Huang, Qinhai; Wang, Min; Lei, Yixiong

    2013-01-01

    Cadmium and its compounds are well-known human carcinogens, but the mechanisms underlying the carcinogenesis are not entirely understood. Our study was designed to elucidate the mechanisms of DNA damage in cadmium-induced malignant transformation of human bronchial epithelial cells. We analyzed cell cycle, apoptosis, DNA damage, gene expression, genomic instability, and the sequence of exons in DNA repair genes in several kinds of cells. These cells consisted of untreated control cells, cells...

  13. TNF-like weak inducer of apoptosis (TWEAK promotes beta cell neogenesis from pancreatic ductal epithelium in adult mice.

    Directory of Open Access Journals (Sweden)

    Fei Wu

    Full Text Available AIM/HYPOTHESIS: The adult mammalian pancreas has limited ability to regenerate in order to restore adequate insulin production from multipotent progenitors, the identity and function of which remain poorly understood. Here we test whether the TNF family member TWEAK (TNF-like weak inducer of apoptosis promotes β-cell neogenesis from proliferating pancreatic ductal epithelium in adult mice. METHODS: C57Bl/6J mice were treated with Fc-TWEAK and pancreas harvested at different time points for analysis by histology and immunohistochemistry. For lineage tracing, 4 week old double transgenic mice CAII-CreER(TM: R26R-eYFP were implanted with tamoxifen pellet, injected with Fc-TWEAK or control Ig twice weekly and analyzed at day 18 for TWEAK-induced duct cell progeny by costaining for insulin and YFP. The effect of TWEAK on pancreatic regeneration was determined by pancytokeratin immunostaining of paraffin embedded sections from wildtype and TWEAK receptor (Fn14 deficient mice after Px. RESULTS: TWEAK stimulates proliferation of ductal epithelial cells through its receptor Fn14, while it has no mitogenic effect on pancreatic α- or β-cells or acinar cells. Importantly, TWEAK induces transient expression of endogenous Ngn3, a master regulator of endocrine cell development, and induces focal ductal structures with characteristics of regeneration foci. In addition, we identify by lineage tracing TWEAK-induced pancreatic β-cells derived from pancreatic duct epithelial cells. Conversely, we show that Fn14 deficiency delays formation of regenerating foci after Px and limits their expansion. CONCLUSIONS/INTERPRETATION: We conclude that TWEAK is a novel factor mediating pancreatic β-cell neogenesis from ductal epithelium in normal adult mice.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. MicroRNA-146a modulates human bronchial epithelial cell survival in response to the cytokine-induced apoptosis

    International Nuclear Information System (INIS)

    MicroRNA plays an important role in cell differentiation, proliferation and cell death. The current study found that miRNA-146a was up-regulated in human bronchial epithelial cells (HBECs) in response to stimulation by TGF-ss1 plus cytomix (a mixture of IL-1ss, IFN-γ and TNF-α). TGF-ss1 plus cytomix (TCM) induced apoptosis in HBECs (3.4 ± 0.6% of control vs 83.1 ± 4.0% of TCM treated cells, p < 0.01), and this was significantly blocked by the miRNA-146a mimic (8.8 ± 1.5%, p < 0.01). In contrast, a miRNA-146a inhibitor had only a modest effect on cell survival but appeared to augment the induction of epithelial-mesenchymal transition (EMT) in response to the cytokines. The MicroRNA-146a mimic appears to modulate HBEC survival through a mechanism of up-regulating Bcl-XL and STAT3 phosphorylation, and by this mechanism it could contribute to tissue repair and remodeling.

  16. Multiplexed quantitative high content screening reveals that cigarette smoke condensate induces changes in cell structure and function through alterations in cell signaling pathways in human bronchial cells

    International Nuclear Information System (INIS)

    Human bronchial cells are one of the first cell types exposed to environmental toxins. Toxins often activate nuclear factor-κB (NF-κB) and protein kinase C (PKC). We evaluated the hypothesis that cigarette smoke condensate (CSC), the particulate fraction of cigarette smoke, activates PKC-α and NF-κB, and concomitantly disrupts the F-actin cytoskeleton, induces apoptosis and alters cell function in BEAS-2B human bronchial epithelial cells. Compared to controls, exposure of BEAS-2B cells to doses of 30 μg/ml CSC significantly activated PKC-α, while CSC doses above 20 μg/ml CSC significantly activated NF-κB. As NF-κB was activated, cell number decreased. CSC treatment of BEAS-2B cells induced a decrease in cell size and an increase in cell surface extensions including filopodia and lamellipodia. CSC treatment of BEAS-2B cells induced F-actin rearrangement such that stress fibers were no longer prominent at the cell periphery and throughout the cells, but relocalized to perinuclear regions. Concurrently, CSC induced an increase in the focal adhesion protein vinculin at the cell periphery. CSC doses above 30 μg/ml induced a significant increase in apoptosis in BEAS-2B cells evidenced by an increase in activated caspase 3, an increase in mitochondrial mass and a decrease in mitochondrial membrane potential. As caspase 3 increased, cell number decreased. CSC doses above 30 μg/ml also induced significant concurrent changes in cell function including decreased cell spreading and motility. CSC initiates a signaling cascade in human bronchial epithelial cells involving PKC-α, NF-κB and caspase 3, and consequently decreases cell spreading and motility. These CSC-induced alterations in cell structure likely prevent cells from performing their normal function thereby contributing to smoke-induced diseases.

  17. Accumulation of 8-nitroguanine in human gastric epithelium induced by Helicobacter pylori infection

    International Nuclear Information System (INIS)

    Helicobacter pylori infection causes chronic inflammation, which can lead to gastric carcinoma. A double immunofluorescence labeling study demonstrated that the level of 8-nitroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) apparent in gastric gland epithelium was significantly higher in gastritis patients with H. pylori infection than in those without infection. A significant accumulation of proliferating cell nuclear antigen, a prognostic factor for gastric cancer, was observed in gastric gland epithelial cells in patients with H. pylori infection as compared to those without infection, and its accumulation was closely correlated with the formation of 8-nitroguanine and 8-oxodG. These results suggest that nitrosative and oxidative DNA damage in gastric epithelial cells and their proliferation by H. pylori infection may lead to gastric carcinoma. 8-Nitroguanine could be not only a promising biomarker for inflammation but also a useful indicator of the risk of gastric cancer development in response to chronic H. pylori infection

  18. Epinephrine Activation of the β2-Adrenoceptor Is Required for IL-13-Induced Mucin Production in Human Bronchial Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Nour Al-Sawalha

    Full Text Available Mucus hypersecretion by airway epithelium is a hallmark of inflammation in allergic asthma and results in airway narrowing and obstruction. Others have shown that administration a TH2 cytokine, IL-13 is sufficient to cause mucus hypersecretion in vivo and in vitro. Asthma therapy often utilizes β2-adrenoceptor (β2AR agonists, which are effective acutely as bronchodilators, however chronic use may lead to a worsening of asthma symptoms. In this study, we asked whether β2AR signaling in normal human airway epithelial (NHBE cells affected mucin production in response to IL-13. This cytokine markedly increased mucin production, but only in the presence of epinephrine. Mucin production was blocked by ICI-118,551, a preferential β2AR antagonist, but not by CGP-20712A, a preferential β1AR antagonist. Constitutive β2AR activity was not sufficient for IL-13 induced mucin production and β-agonist-induced signaling is required. A clinically important long-acting β-agonist, formoterol, was as effective as epinephrine in potentiating IL-13 induced MUC5AC transcription. IL-13 induced mucin production in the presence of epinephrine was significantly reduced by treatment with selective inhibitors of ERK1/2 (FR180204, p38 (SB203580 and JNK (SP600125. Replacement of epinephrine with forskolin + IBMX resulted in a marked increase in mucin production in NHBE cells in response to IL-13, and treatment with the inhibitory cAMP analogue Rp-cAMPS decreased mucin levels induced by epinephrine + IL-13. Our findings suggest that β2AR signaling is required for mucin production in response to IL-13, and that mitogen activated protein kinases and cAMP are necessary for this effect. These data lend support to the notion that β2AR-agonists may contribute to asthma exacerbations by increasing mucin production via activation of β2ARs on epithelial cells.

  19. Role of reactive oxygen species in arsenic-induced transformation of human lung bronchial epithelial (BEAS-2B) cells

    International Nuclear Information System (INIS)

    Highlights: • Short term exposure of cells to arsenic causes ROS generation. • Chronical exposure of cells to arsenic causes malignant cell transformation. • Inhibition of ROS generation reduces cell transformation by arsenic. • Arsenic-transformed cells exhibit reduced capacity of generating ROS. • Arsenic-transformed cells exhibit increased levels of antioxidants. - Abstract: Arsenic is an environmental carcinogen, its mechanisms of carcinogenesis remain to be investigated. Reactive oxygen species (ROS) are considered to be important. A previous study (Carpenter et al., 2011) has measured ROS level in human lung bronchial epithelial (BEAS-2B) cells and arsenic-transformed BEAS-2B cells and found that ROS levels were higher in transformed cells than that in parent normal cells. Based on these observations, the authors concluded that cell transformation induced by arsenic is mediated by increased cellular levels of ROS. This conclusion is problematic because this study only measured the basal ROS levels in transformed and parent cells and did not investigate the role of ROS in the process of arsenic-induced cell transformation. The levels of ROS in arsenic-transformed cells represent the result and not the cause of cell transformation. Thus question concerning whether ROS are important in arsenic-induced cell transformation remains to be answered. In the present study, we used expressions of catalase (antioxidant against H2O2) and superoxide dismutase 2 (SOD2, antioxidant against O2·−) to decrease ROS level and investigated their role in the process of arsenic-induced cell transformation. Our results show that inhibition of ROS by antioxidant enzymes decreased arsenic-induced cell transformation, demonstrating that ROS are important in this process. We have also shown that in arsenic-transformed cells, ROS generation was lower and levels of antioxidants are higher than those in parent cells, in a disagreement with the previous report. The present study

  20. Role of reactive oxygen species in arsenic-induced transformation of human lung bronchial epithelial (BEAS-2B) cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Zhuo, E-mail: zhuo.zhang@uky.edu [Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536 (United States); Pratheeshkumar, Poyil; Budhraja, Amit; Son, Young-Ok [Center for Research on Environmental Diseases, University of Kentucky, Lexington, KY 40536 (United States); Kim, Donghern [Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536 (United States); Shi, Xianglin [Center for Research on Environmental Diseases, University of Kentucky, Lexington, KY 40536 (United States)

    2015-01-09

    Highlights: • Short term exposure of cells to arsenic causes ROS generation. • Chronical exposure of cells to arsenic causes malignant cell transformation. • Inhibition of ROS generation reduces cell transformation by arsenic. • Arsenic-transformed cells exhibit reduced capacity of generating ROS. • Arsenic-transformed cells exhibit increased levels of antioxidants. - Abstract: Arsenic is an environmental carcinogen, its mechanisms of carcinogenesis remain to be investigated. Reactive oxygen species (ROS) are considered to be important. A previous study (Carpenter et al., 2011) has measured ROS level in human lung bronchial epithelial (BEAS-2B) cells and arsenic-transformed BEAS-2B cells and found that ROS levels were higher in transformed cells than that in parent normal cells. Based on these observations, the authors concluded that cell transformation induced by arsenic is mediated by increased cellular levels of ROS. This conclusion is problematic because this study only measured the basal ROS levels in transformed and parent cells and did not investigate the role of ROS in the process of arsenic-induced cell transformation. The levels of ROS in arsenic-transformed cells represent the result and not the cause of cell transformation. Thus question concerning whether ROS are important in arsenic-induced cell transformation remains to be answered. In the present study, we used expressions of catalase (antioxidant against H{sub 2}O{sub 2}) and superoxide dismutase 2 (SOD2, antioxidant against O{sub 2}{sup ·−}) to decrease ROS level and investigated their role in the process of arsenic-induced cell transformation. Our results show that inhibition of ROS by antioxidant enzymes decreased arsenic-induced cell transformation, demonstrating that ROS are important in this process. We have also shown that in arsenic-transformed cells, ROS generation was lower and levels of antioxidants are higher than those in parent cells, in a disagreement with the previous

  1. Human bronchial epithelial BEAS-2B cells, an appropriate in vitro model to study heavy metals induced carcinogenesis.

    Science.gov (United States)

    Park, Youn-Hee; Kim, Donghern; Dai, Jin; Zhang, Zhuo

    2015-09-15

    Occupational and environmental exposure to arsenic (III) and chromium VI (Cr(VI)) have been confirmed to cause lung cancer. Mechanisms of these metals carcinogenesis are still under investigation. Selection of cell lines to be used is essential for the studies. Human bronchial epithelial BEAS-2B cells are the cells to be utilized by most of scientists. However, due to p53 missense mutation (CCG→TCG) at codon 47 and the codon 72 polymorphism (CGC→CCC) in BEAS-2B cells, its usage has frequently been questioned. The present study has examined activity and expression of 53 and its downstream target protein p21 upon acute or chronic exposure of BEAS-2B cells to arsenic and Cr(VI). The results show that short-term exposure of BEAS-2B cells to arsenic or Cr(VI) was able to activate both p53 and p21. Chronic exposure of BEAS-2B cells to these two metals caused malignant cell transformation and tumorigenesis. In arsenic-transformed BEAS-2B cells reductions in p53 promoter activity, mRNA expression, and phosphorylation of p53 at Ser392 were observed, while the total p53 protein level remained the same compared to those in passage-matched parent ones. p21 promoter activity and expression were decreased in arsenic-transformed cells. Cr(VI)-transformed cells exhibit elevated p53 promoter activity, mRNA expression, and phosphorylation at Ser15, but reduced phosphorylation at Ser392 and total p53 protein level compared to passage-matched parent ones. p21 promoter activity and expression were elevated in Cr(VI)-transformed cells. These results demonstrate that p53 is able to respond to exposure of arsenic or Cr(VI), suggesting that BEAS-2B cells are an appropriate in vitro model to investigate arsenic or Cr(VI) induced lung cancer. PMID:26091798

  2. Regulatory T Cells Promote β-Catenin–Mediated Epithelium-to-Mesenchyme Transition During Radiation-Induced Pulmonary Fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Xiong, Shanshan; Pan, Xiujie; Xu, Long; Yang, Zhihua [Beijing Institute of Radiation Medicine, Beijing (China); Guo, Renfeng [Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan (United States); Gu, Yongqing; Li, Ruoxi; Wang, Qianjun; Xiao, Fengjun; Du, Li; Zhou, Pingkun [Beijing Institute of Radiation Medicine, Beijing (China); Zhu, Maoxiang, E-mail: zhumx@nic.bmi.ac.cn [Beijing Institute of Radiation Medicine, Beijing (China)

    2015-10-01

    Purpose: Radiation-induced pulmonary fibrosis results from thoracic radiation therapy and severely limits radiation therapy approaches. CD4{sup +}CD25{sup +}FoxP3{sup +} regulatory T cells (Tregs) as well as epithelium-to-mesenchyme transition (EMT) cells are involved in pulmonary fibrosis induced by multiple factors. However, the mechanisms of Tregs and EMT cells in irradiation-induced pulmonary fibrosis remain unclear. In the present study, we investigated the influence of Tregs on EMT in radiation-induced pulmonary fibrosis. Methods and Materials: Mice thoraxes were irradiated (20 Gy), and Tregs were depleted by intraperitoneal injection of a monoclonal anti-CD25 antibody 2 hours after irradiation and every 7 days thereafter. Mice were treated on days 3, 7, and 14 and 1, 3, and 6 months post irradiation. The effectiveness of Treg depletion was assayed via flow cytometry. EMT and β-catenin in lung tissues were detected by immunohistochemistry. Tregs isolated from murine spleens were cultured with mouse lung epithelial (MLE) 12 cells, and short interfering RNA (siRNA) knockdown of β-catenin in MLE 12 cells was used to explore the effects of Tregs on EMT and β-catenin via flow cytometry and Western blotting. Results: Anti-CD25 antibody treatment depleted Tregs efficiently, attenuated the process of radiation-induced pulmonary fibrosis, hindered EMT, and reduced β-catenin accumulation in lung epithelial cells in vivo. The coculture of Tregs with irradiated MLE 12 cells showed that Tregs could promote EMT in MLE 12 cells and that the effect of Tregs on EMT was partially abrogated by β-catenin knockdown in vitro. Conclusions: Tregs can promote EMT in accelerating radiation-induced pulmonary fibrosis. This process is partially mediated through β-catenin. Our study suggests a new mechanism for EMT, promoted by Tregs, that accelerates radiation-induced pulmonary fibrosis.

  3. Regulatory T Cells Promote β-Catenin–Mediated Epithelium-to-Mesenchyme Transition During Radiation-Induced Pulmonary Fibrosis

    International Nuclear Information System (INIS)

    Purpose: Radiation-induced pulmonary fibrosis results from thoracic radiation therapy and severely limits radiation therapy approaches. CD4+CD25+FoxP3+ regulatory T cells (Tregs) as well as epithelium-to-mesenchyme transition (EMT) cells are involved in pulmonary fibrosis induced by multiple factors. However, the mechanisms of Tregs and EMT cells in irradiation-induced pulmonary fibrosis remain unclear. In the present study, we investigated the influence of Tregs on EMT in radiation-induced pulmonary fibrosis. Methods and Materials: Mice thoraxes were irradiated (20 Gy), and Tregs were depleted by intraperitoneal injection of a monoclonal anti-CD25 antibody 2 hours after irradiation and every 7 days thereafter. Mice were treated on days 3, 7, and 14 and 1, 3, and 6 months post irradiation. The effectiveness of Treg depletion was assayed via flow cytometry. EMT and β-catenin in lung tissues were detected by immunohistochemistry. Tregs isolated from murine spleens were cultured with mouse lung epithelial (MLE) 12 cells, and short interfering RNA (siRNA) knockdown of β-catenin in MLE 12 cells was used to explore the effects of Tregs on EMT and β-catenin via flow cytometry and Western blotting. Results: Anti-CD25 antibody treatment depleted Tregs efficiently, attenuated the process of radiation-induced pulmonary fibrosis, hindered EMT, and reduced β-catenin accumulation in lung epithelial cells in vivo. The coculture of Tregs with irradiated MLE 12 cells showed that Tregs could promote EMT in MLE 12 cells and that the effect of Tregs on EMT was partially abrogated by β-catenin knockdown in vitro. Conclusions: Tregs can promote EMT in accelerating radiation-induced pulmonary fibrosis. This process is partially mediated through β-catenin. Our study suggests a new mechanism for EMT, promoted by Tregs, that accelerates radiation-induced pulmonary fibrosis

  4. Smad Molecules Expression Pattern in Human Bronchial Airway Induced by Sulfur Mustard

    Directory of Open Access Journals (Sweden)

    Maryam Adelipour

    2011-09-01

    Full Text Available Airway remodelling is characterized by the thickening and reorganization of the airways seen in mustard  lung patients. Mustard lung is the  general description  for  the  chronic obstructive  pulmonary  disease induced  by  sulfur  mustard(SM. Pulmonary  disease was diagnosed as the most important  disorder in individuals that had been exposed to sulfur mustard. Sulfur mustard is a chemical warfare agent developed during Wars. Iraqi forces frequently used it against Iranian during Iran –Iraq in the 1980–1988. Peribronchial fibrosis result  from  airway remodeling  that  include  excess  of  collagen of  extracellular matrix deposition  in  the  airway wall. Some of  Smads families in  association with TGF-β  are involved in airway remodeling due to lung fibrosis. In the present study we compared the mRNA expression of Smad2, Smad3, and Smad4 and Smad7 genes in airway wall biopsies of chemical-injured patients with non-injured patients as control.We used airway wall biopsies of ten unexposed patients and fifteen SM-induced patients. Smads expression was evaluated by RT-PCR followed by bands densitometry.Expression levels of Smad3 and Smad4 in SM exposed patients were upregulated but Smad2 and Smad7 was not significantly altered.Our results revealed that Smad3, and 4 may be involved in airway remodeling process in SM induced  patients  by  activation of  TGF-β.  Smad pathway is  the  most  represented signaling mechanism for  airway remodeling and  peribronchial fibrosis. The  complex of Smads in the nucleus affects a series of genes that results in peribronchial fibrosis in SM- induced patients.

  5. Changes in liquid clearance of alveolar epithelium after oleic acid-induced acute lung injury in rats

    Institute of Scientific and Technical Information of China (English)

    陶军; 杨天德; 陈祥瑞; 黄河

    2004-01-01

    Objective:Impaired active fluid transport of alveolar epithelium may involve in the pathogenesis and resolution of alveolar edema. Thc objective of this study was to explore the changes in alveolar epithelial liquid clearance during lung edema following acute lung injury induced by oleic acid. Methods:Forty-eight Wistar rats were randomly divided into six groups, I.e. , injured, amiloride, ouabain, amiloride plus ouabain and terbutaline groups. Twenty- four hours after the induction of acute lung injury by intravenous oleic acid (0.25 ml/kg), 5% albumin solution with 1.5 μCi 125Ⅰ-labeled albumin (5 ml/kg) was delivered into both lungs via trachea. Alveolar liquid clearance (ALC), extravascular lung water ( EVLW ) content and arterial blood gases were measured one hour thereafter.Results: At 24 h after the infusion of oleic acid, the rats developed pulmonary edema and severe hypoxemia, with EVLW increased by 47.9% and ALC decreased by 49.2%. Addition of either 2 × 10-3 M amiloride or 5 × 10-4 M ouabain to the instillation further reduced ALC and increased EVLW. ALC increased by approximately 63.7% and EVLW decreased by 46.9% with improved hypoxemia in the Terbutaline (10-4 M) group, compared those in injured rats. A significant negative correlation was found between the increment of EVLW and the reduction of ALC. Onclusions:Active fluid transport of alveolar epithelium might play a role in the pathogenesis of lung edema in acute lung injury.

  6. Zinc Induced G2/M Blockage is p53 and p21 Dependent in Normal Human Bronchial Epithelial Cells

    Science.gov (United States)

    The involvement of the p53 and p21 signal pathway in the G2/M cell cycle progression of zinc supplemented normal human bronchial epithelial (NHBE) cells was examined using the siRNA approach. Cells were cultured for one passage in different concentrations of zinc: <0.4 microM (ZD) as zinc-deficient;...

  7. IL-13R alpha 2 reverses the effects of IL-13 and IL-4 on bronchial reactivity and acetylcholine-induced Ca2+ signaling

    OpenAIRE

    Kellner, Julia; Gamarra, Fernando; Welsch, Ulrich; Joerres, Rudolf A.; Huber, Rudolf M; Bergner, Albrecht

    2007-01-01

    Background: The interleukins IL-4 and IL-13 play a key role in the pathophysiology of asthma. The interleukin receptor IL-13R alpha 2 is believed to act as a decoy receptor, but until now, the functional significance of IL-13R alpha 2 remains vague. Methods: Bronchial reactivity was quantified in murine lung slices by digital video microscopy and acetylcholine (ACH)-induced Ca2+ signaling was measured in human airway smooth muscle cells (ASMC) using fluorescence microscopy. Results: IL-4 or I...

  8. Interleukin-17A and Toll-Like Receptor 3 Ligand Poly(I:C Synergistically Induced Neutrophil Chemoattractant Production by Bronchial Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Hirotaka Matsuzaki

    Full Text Available Chronic inflammatory airway diseases, such as bronchial asthma and chronic obstructive pulmonary disease, are common respiratory disorders worldwide. Exacerbations of these diseases are frequent and worsen patients' respiratory condition and overall health. However, the mechanisms of exacerbation have not been fully elucidated. Recently, it was reported that interleukin (IL-17A might play an important role in neutrophilic inflammation, which is characteristic of such exacerbations, through increased production of neutrophil chemoattractants. Therefore, we hypothesized that IL-17A was involved in the pathogenesis of acute exacerbation, due to viral infection in chronic inflammatory airway diseases. In this study, we assessed chemokine production by bronchial epithelial cells and investigated the underlying mechanisms. Comprehensive chemokine analysis showed that, compared with poly(I:C alone, co-stimulation of BEAS-2B cells with IL-17A and poly(I:C strongly induced production of such neutrophil chemoattractants as CXC chemokine ligand (CXCL8, growth-related oncogene (GRO, and CXCL1. Co-stimulation synergistically induced CXCL8 and CXCL1 mRNA and protein production by BEAS-2B cells and normal human bronchial epithelial cells. Poly(I:C induced chemokine expression by BEAS-2B cells mainly via Toll-like receptor 3/TIR-domain-containing adapter-inducing interferon-β-mediated signals. The co-stimulation with IL-17A and poly(I:C markedly activated the p38 and extracellular-signal-regulated kinase 1/2 pathway, compared with poly(I:C, although there was little change in nuclear factor-κB translocation into the nucleus or the transcriptional activities of nuclear factor-κB and activator protein 1. IL-17A promoted stabilization of CXCL8 mRNA in BEAS-2B cells treated with poly(I:C. In conclusion, IL-17A appears to be involved in the pathogenesis of chronic inflammatory airway disease exacerbation, due to viral infection by promoting release of neutrophil

  9. Directional Secretory Response of Double Stranded RNA-Induced Thymic Stromal Lymphopoetin (TSLP) and CCL11/Eotaxin-1 in Human Asthmatic Airways

    OpenAIRE

    Nino, Gustavo; Huseni, Shehlanoor; Perez, Geovanny F; Pancham, Krishna; Mubeen, Humaira; Abbasi, Aleeza; Wang, Justin; Eng, Stephen; Colberg-Poley, Anamaris M.; Pillai, Dinesh K; Rose, Mary C.

    2014-01-01

    Background Thymic stromal lymphoproetin (TSLP) is a cytokine secreted by the airway epithelium in response to respiratory viruses and it is known to promote allergic Th2 responses in asthma. This study investigated whether virally-induced secretion of TSLP is directional in nature (apical vs. basolateral) and/or if there are TSLP-mediated effects occurring at both sides of the bronchial epithelial barrier in the asthmatic state. Methods Primary human bronchial epithelial cells (HBEC) from con...

  10. Reconstruction of the corneal epithelium with induced marrow mesenchymal stem cells in rats

    OpenAIRE

    Jiang, Ting-Shuai; Cai, Li; Ji, Wei-Ying; Hui, Yan-Nian; Wang, Yu-Sheng; Hu, Dan; Zhu, Jie

    2010-01-01

    Purpose To explore the feasibility of bone marrow mesenchymal stem cells (MSCs) transdifferentiating into corneal epithelial cells in a limbal stem cell deficiency (LSCD) model in rats. Methods Rat MSCs were isolated and purified using a gradient isolation procedure. The cells were induced by rat corneal stromal cells (CSCs) in a transwell co-culture system. The induced MSCs were identified by immunofluorescence staining, flow cytometry, and scanning electron microscopy (SEM). A corneal LSCD ...

  11. Estradiol increases mucus synthesis in bronchial epithelial cells.

    Directory of Open Access Journals (Sweden)

    Anthony Tam

    Full Text Available Airway epithelial mucus hypersecretion and mucus plugging are prominent pathologic features of chronic inflammatory conditions of the airway (e.g. asthma and cystic fibrosis and in most of these conditions, women have worse prognosis compared with male patients. We thus investigated the effects of estradiol on mucus expression in primary normal human bronchial epithelial cells from female donors grown at an air liquid interface (ALI. Treatment with estradiol in physiological ranges for 2 weeks caused a concentration-dependent increase in the number of PAS-positive cells (confirmed to be goblet cells by MUC5AC immunostaining in ALI cultures, and this action was attenuated by estrogen receptor beta (ER-β antagonist. Protein microarray data showed that nuclear factor of activated T-cell (NFAT in the nuclear fraction of NHBE cells was increased with estradiol treatment. Estradiol increased NFATc1 mRNA and protein in ALI cultures. In a human airway epithelial (1HAE0 cell line, NFATc1 was required for the regulation of MUC5AC mRNA and protein. Estradiol also induced post-translational modification of mucins by increasing total fucose residues and fucosyltransferase (FUT-4, -5, -6 mRNA expression. Together, these data indicate a novel mechanism by which estradiol increases mucus synthesis in the human bronchial epithelium.

  12. Enriched inorganic compounds in diesel exhaust particles induce mitogen-activated protein kinase activation, cytoskeleton instability, and cytotoxicity in human bronchial epithelial cells.

    Science.gov (United States)

    Seriani, Robson; Junqueira, Mara S; Carvalho-Sousa, Claudia E; Arruda, Alessandra C T; Martinez, Diana; Alencar, Adriano M; Garippo, Ana L; Brito, Jôse Mara; Martins, Milton A; Saldiva, Paulo H N; Negri, Elnara M; Mauad, Thais; Macchione, Mariangela

    2015-04-01

    This study assessed the effects of the diesel exhaust particles on ERK and JNK MAPKs activation, cell rheology (viscoelasticity), and cytotoxicity in bronchial epithelial airway cells (BEAS-2B). Crude DEP and DEP after extraction with hexane (DEP/HEX) were utilized. The partial reduction of some DEP/HEX organics increased the biodisponibility of many metallic elements. JNK and ERK were activated simultaneously by crude DEP with no alterations in viscoelasticity of the cells. Mitochondrial activity, however, revealed a decrease through the MTT assay. DEP/HEX treatment increased viscoelasticity and cytotoxicity (membrane damage), and also activated JNK. Our data suggest that the greater bioavailability of metals could be involved in JNK activation and, consequently, in the reduction of fiber coherence and increase in the viscoelasticity and cytotoxicity of BEAS cells. The adverse findings detected after exposure to crude DEP and to DEP/HEX reflect the toxic potential of diesel compounds. Considering the fact that the cells of the respiratory epithelium are the first line of defense between the body and the environment, our data contribute to a better understanding of the pathways leading to respiratory cell injury and provide evidence for the onset of or worsening of respiratory diseases caused by inorganic compounds present in DEP. PMID:25769681

  13. Human bronchial epithelial BEAS-2B cells, an appropriate in vitro model to study heavy metals induced carcinogenesis

    International Nuclear Information System (INIS)

    Occupational and environmental exposure to arsenic (III) and chromium VI (Cr(VI)) have been confirmed to cause lung cancer. Mechanisms of these metals carcinogenesis are still under investigation. Selection of cell lines to be used is essential for the studies. Human bronchial epithelial BEAS-2B cells are the cells to be utilized by most of scientists. However, due to p53 missense mutation (CCG → TCG) at codon 47 and the codon 72 polymorphism (CGC → CCC) in BEAS-2B cells, its usage has frequently been questioned. The present study has examined activity and expression of 53 and its downstream target protein p21 upon acute or chronic exposure of BEAS-2B cells to arsenic and Cr(VI). The results show that short-term exposure of BEAS-2B cells to arsenic or Cr(VI) was able to activate both p53 and p21. Chronic exposure of BEAS-2B cells to these two metals caused malignant cell transformation and tumorigenesis. In arsenic-transformed BEAS-2B cells reductions in p53 promoter activity, mRNA expression, and phosphorylation of p53 at Ser392 were observed, while the total p53 protein level remained the same compared to those in passage-matched parent ones. p21 promoter activity and expression were decreased in arsenic-transformed cells. Cr(VI)-transformed cells exhibit elevated p53 promoter activity, mRNA expression, and phosphorylation at Ser15, but reduced phosphorylation at Ser392 and total p53 protein level compared to passage-matched parent ones. p21 promoter activity and expression were elevated in Cr(VI)-transformed cells. These results demonstrate that p53 is able to respond to exposure of arsenic or Cr(VI), suggesting that BEAS-2B cells are an appropriate in vitro model to investigate arsenic or Cr(VI) induced lung cancer. - Highlights: • Short-term exposure of BEAS-2B cells to arsenic or Cr(VI) activates p53 and p21. • Chronic exposure of BEAS-2B cells to arsenic or Cr(VI) causes cell transformation and tumorigenesis. • Arsenic-transformed cells exhibit

  14. Human bronchial epithelial BEAS-2B cells, an appropriate in vitro model to study heavy metals induced carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Park, Youn-hee; Kim, Donghern; Dai, Jin; Zhang, Zhuo, E-mail: zhuo.zhang@uky.edu

    2015-09-15

    Occupational and environmental exposure to arsenic (III) and chromium VI (Cr(VI)) have been confirmed to cause lung cancer. Mechanisms of these metals carcinogenesis are still under investigation. Selection of cell lines to be used is essential for the studies. Human bronchial epithelial BEAS-2B cells are the cells to be utilized by most of scientists. However, due to p53 missense mutation (CCG → TCG) at codon 47 and the codon 72 polymorphism (CGC → CCC) in BEAS-2B cells, its usage has frequently been questioned. The present study has examined activity and expression of 53 and its downstream target protein p21 upon acute or chronic exposure of BEAS-2B cells to arsenic and Cr(VI). The results show that short-term exposure of BEAS-2B cells to arsenic or Cr(VI) was able to activate both p53 and p21. Chronic exposure of BEAS-2B cells to these two metals caused malignant cell transformation and tumorigenesis. In arsenic-transformed BEAS-2B cells reductions in p53 promoter activity, mRNA expression, and phosphorylation of p53 at Ser392 were observed, while the total p53 protein level remained the same compared to those in passage-matched parent ones. p21 promoter activity and expression were decreased in arsenic-transformed cells. Cr(VI)-transformed cells exhibit elevated p53 promoter activity, mRNA expression, and phosphorylation at Ser15, but reduced phosphorylation at Ser392 and total p53 protein level compared to passage-matched parent ones. p21 promoter activity and expression were elevated in Cr(VI)-transformed cells. These results demonstrate that p53 is able to respond to exposure of arsenic or Cr(VI), suggesting that BEAS-2B cells are an appropriate in vitro model to investigate arsenic or Cr(VI) induced lung cancer. - Highlights: • Short-term exposure of BEAS-2B cells to arsenic or Cr(VI) activates p53 and p21. • Chronic exposure of BEAS-2B cells to arsenic or Cr(VI) causes cell transformation and tumorigenesis. • Arsenic-transformed cells exhibit

  15. The Role of the Epithelium in Airway Remodeling in Asthma

    OpenAIRE

    Davies, Donna E.

    2009-01-01

    The bronchial epithelium is the barrier to the external environment and plays a vital role in protection of the internal milieu of the lung. It functions within the epithelial-mesenchymal trophic unit to control the local microenvironment and help maintain tissue homeostasis. However, in asthma, chronic perturbation of these homeostatic mechanisms leads to alterations in the structure of the airways, termed remodeling. Damage to the epithelium is now recognized to play a key role in driving a...

  16. Effects of Respiratory Mycoplasma pneumoniae Infection on Allergen-Induced Bronchial Hyperresponsiveness and Lung Inflammation in Mice

    OpenAIRE

    Chu, Hong Wei; Honour, Joyce M.; Rawlinson, Catherine A.; Harbeck, Ronald J.; Richard J Martin

    2003-01-01

    Airway mycoplasma infection may be associated with asthma pathophysiology. However, the direct effects of mycoplasma infection on asthma remain unknown. Using a murine allergic-asthma model, we evaluated the effects of different timing of airway Mycoplasma pneumoniae infection on bronchial hyperresponsiveness (BHR), lung inflammation, and the protein levels of Th1 (gamma interferon [IFN-γ]) and Th2 (interleukin 4 [IL-4]) cytokines in bronchoalveolar lavage fluid. When mycoplasma infection occ...

  17. Insulin Restores an Altered Corneal Epithelium Circadian Rhythm in Mice with Streptozotocin-induced Type 1 Diabetes

    Science.gov (United States)

    Song, Fang; Xue, Yunxia; Dong, Dong; Liu, Jun; Fu, Ting; Xiao, Chengju; Wang, Hanqing; Lin, Cuipei; Liu, Peng; Zhong, Jiajun; Yang, Yabing; Wang, Zhaorui; Pan, Hongwei; Chen, Jiansu; Li, Yangqiu; Cai, Dongqing; Li, Zhijie

    2016-01-01

    The mechanisms of corneal epithelial lesions and delayed wound repair, as well as their association with diabetes mellitus, are critical issues for clinical ophthalmologists. To test whether the diabetic condition alters the circadian rhythm in a mouse cornea and whether insulin can synchronise the corneal clock, we studied the effects of streptozotocin-induced diabetes on the mitosis of epithelial cells, the recruitment of leukocytes to the cornea, and the expression of main core clock genes (Clock, Bmal1, Per2, Cry1, and Rev-erbα) in the corneal epithelium. We also assessed the possible effect of insulin on these modifications. Diabetes downregulated Clock, Bmal1, and Per2 expression, upregulated Cry1 and Rev-erbα expression, reduced corneal epithelial mitosis, and increased leukocyte (neutrophils and γδ T-cells) recruitment to the cornea. Early treatments with insulin partially restored the altered rhythmicity in the diabetic cornea. In conclusion, insulin-dependent diabetes altered the normal rhythmicity of the cornea, and insulin administration had a beneficial effect on restoring normal rhythmicity in the diabetic cornea. PMID:27611469

  18. The role of alveolar epithelium in radiation-induced lung injury.

    Directory of Open Access Journals (Sweden)

    Celine Almeida

    Full Text Available Pneumonitis and fibrosis are major lung complications of irradiating thoracic malignancies. In the current study, we determined the effect of thoracic irradiation on the lungs of FVB/N mice. Survival data showed a dose-dependent increase in morbidity following thoracic irradiation with single (11-13 Gy and fractionated doses (24-36 Gy of (137Cs γ-rays. Histological examination showed a thickening of vessel walls, accumulation of inflammatory cells, collagen deposition, and regional fibrosis in the lungs 14 weeks after a single 12 Gy dose and a fractionated 30 Gy dose; this damage was also seen 5 months after a fractionated 24 Gy dose. After both single and fractionated doses, i] aquaporin-5 was markedly decreased, ii] E-cadherin was reduced and iii] prosurfactant Protein C (pro-SP-c, the number of pro-SP-c(+ cells and vimentin expression were increased in the lungs. Immunofluorescence analysis revealed co-localization of pro-SP-c and α-smooth muscle actin in the alveoli after a single dose of 12 Gy. These data suggest that, i] the FVB/N mouse strain is sensitive to thoracic radiation ii] aquaporin-5, E-cadherin, and pro-SP-c may serve as sensitive indicators of radiation-induced lung injury; and iii] the epithelial-to-mesenchymal transition may play an important role in the development of radiation-induced lung fibrosis.

  19. Oral Lesions Induced by Chronic Khat Use Consist Essentially of Thickened Hyperkeratinized Epithelium

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    Ochiba Mohammed Lukandu

    2015-01-01

    Full Text Available Objectives. The habit of khat chewing is prevalent in many Middle Eastern and African cultures and has been associated with various adverse conditions in humans. This study aimed to describe histological changes induced by chronic khat chewing on the buccal mucosa. Methods. Biopsies of the buccal mucosa from 14 chronic khat chewers, 20 chronic khat chewers who also smoked tobacco, and 8 nonchewers were compared for epithelial thickness, degree and type of keratinization, and connective tissue changes. Results. Tissues from khat chewers depicted abnormal keratinization of the superficial cell layer and showed increased epithelial thickness affecting all layers. Epithelial thickness in control samples was 205 ± 26 μm whereas thickness in khat chewers and khat chewers who smoked tobacco was significantly higher measuring 330 ± 35 μm and 335 ± 19 μm, respectively. Tissues from khat chewers also showed increased intracellular edema, increased melanin pigment deposits, and increased number of rete pegs most of which were thin and deep. Conclusions. These results show that oral lesions induced by chronic chewing of khat in the buccal mucosa present with white and brown discoloration due to increased epithelial thickness, increased keratinization, and melanin deposition.

  20. Lipoxin A4 prevents tight junction disruption and delays the colonization of cystic fibrosis bronchial epithelial cells by Pseudomonas aeruginosa.

    Science.gov (United States)

    Higgins, Gerard; Fustero Torre, Coral; Tyrrell, Jean; McNally, Paul; Harvey, Brian J; Urbach, Valerie

    2016-06-01

    The specialized proresolution lipid mediator lipoxin A4 (LXA4) is abnormally produced in cystic fibrosis (CF) airways. LXA4 increases the CF airway surface liquid height and stimulates airway epithelial repair and tight junction formation. We report here a protective effect of LXA4 (1 nM) against tight junction disruption caused by Pseudomonas aeruginosa bacterial challenge together with a delaying action against bacterial invasion in CF airway epithelial cells from patients with CF and immortalized cell lines. Bacterial invasion and tight junction integrity were measured by gentamicin exclusion assays and confocal fluorescence microscopy in non-CF (NuLi-1) and CF (CuFi-1) bronchial epithelial cell lines and in primary CF cultures, grown under an air/liquid interface, exposed to either a clinical or laboratory strains of P. aeruginosa LXA4 delayed P. aeruginosa invasion and transepithelial migration in CF and normal bronchial epithelial cell cultures. These protective effects of LXA4 were inhibited by the ALX/FPR2 lipoxin receptor antagonist BOC-2. LXA4 prevented the reduction in mRNA biosynthesis and protein abundance of the tight junction protein ZO-1 and reduced tight junction disruption induced by P. aeruginsosa inoculation. In conclusion, LXA4 plays a protective role in bronchial epithelium by stimulating tight junction repair and by delaying and reducing the invasion of CF bronchial epithelial cells by P. aeruginsosa. PMID:27084849

  1. Protection of retinal pigment epithelium by OT-551 and its metabolite TEMPOL-H against light-induced damage in rats

    OpenAIRE

    Tanito, Masaki; Li, Feng; Anderson, Robert E.

    2010-01-01

    OT-551 (1-hydroxy-4-cyclopropanecarbonyloxy-2,2,6,6-tetramethylpiperidine hydrochloride), is a novel small molecule with antioxidant and anti-inflammatory effects. Protective efficacy of OT-551 and its metabolite TEMPOL-H (TP-H) against light-induced degeneration of retinal pigment epithelium (RPE) was tested. Albino rats were intraperitoneally injected with OT-551, TP-H, or water approximately 30 min prior to a 6 h exposure to 2700 lux white fluorescent light. Retinal protection was evaluate...

  2. Discrepancy between mRNA and Protein Expression of Neutrophil Gelatinase-Associated Lipocalin in Bronchial Epithelium Induced by Sulfur Mustard

    OpenAIRE

    Majid Ebrahimi; Mehryar Habibi Roudkenar; Abbas Ali Imani Fooladi; Raheleh Halabian; Mostafa Ghanei; Hisatake Kondo; Mohammad Reza Nourani

    2010-01-01

    Sulfur mustard (SM) is a potent vesicant that has been employed as a chemical weapon in various conflicts during the 20th century. More recently, mustard was used in the Iraq conflict against Iranian troops and civilians. At the present time there are more than 40.000 people suffering from pulmonary lesions special bronchiolitis obliterans (BOs) due to mustard gas. SM increases the endogenous production of reactive oxygen species (ROS). Neutrophil Gelatinase-associated Lipocalin 2 (Lcn2, NGAL...

  3. Clinical effects of HC 20-511 (ketotifen in bronchial asthma and its inhibitory effect on antigen-induced morphological changes of basophils

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    Tanizaki,Yoshiro

    1980-12-01

    Full Text Available Sixty-four patients with confirmed bronchial asthma were treated with HC 20-511 (Ketotifen. HC20-511 was evaluated to be very effective in 6.3%, effective in 50.0% and slightly effective in 10.9% of these patients. The appearance of reactive basophils was inhibited by HC 20-511 in 5 out of 6 cases of reaction to house dust, in all three cases with buckwheat allergy to their allergen and in 7 out of 11 cases to anti-IgE. These results confirm that HC 20-511 inhibits type I allergic reactions induced by specific allergen and IgE.

  4. Mechanical compression attenuates normal human bronchial epithelial wound healing

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    Malavia Nikita

    2009-02-01

    Full Text Available Abstract Background Airway narrowing associated with chronic asthma results in the transmission of injurious compressive forces to the bronchial epithelium and promotes the release of pro-inflammatory mediators and the denudation of the bronchial epithelium. While the individual effects of compression or denudation are well characterized, there is no data to elucidate how these cells respond to the application of mechanical compression in the presence of a compromised epithelial layer. Methods Accordingly, differentiated normal human bronchial epithelial cells were exposed to one of four conditions: 1 unperturbed control cells, 2 single scrape wound only, 3 static compression (6 hours of 30 cmH2O, and 4 6 hours of static compression after a scrape wound. Following treatment, wound closure rate was recorded, media was assayed for mediator content and the cytoskeletal network was fluorescently labeled. Results We found that mechanical compression and scrape injury increase TGF-β2 and endothelin-1 secretion, while EGF content in the media is attenuated with both injury modes. The application of compression after a pre-existing scrape wound augmented these observations, and also decreased PGE2 media content. Compression stimulated depolymerization of the actin cytoskeleton and significantly attenuated wound healing. Closure rate was partially restored with the addition of exogenous PGE2, but not EGF. Conclusion Our results suggest that mechanical compression reduces the capacity of the bronchial epithelium to close wounds, and is, in part, mediated by PGE2 and a compromised cytoskeleton.

  5. In-vivo kinetics of inhaled 5-Aminolevulinic acid-Induced Protoporphyrin IX fluorescence in bronchial tissue

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    Gamarra Fernando

    2007-04-01

    Full Text Available Abstract Background In the diagnosis of early-stage lung cancer photosensitizer-enhanced fluorescence bronchoscopy with inhaled 5-aminolevolinic acid (5-ALA increases sensitivity when compared to white-light bronchoscopy. This investigation was to evaluate the in vivo tissue pharmacokinetics of inhaled 5-ALA within the bronchial mucosa in order to define the time optimum for its application prior to bronchoscopy. Methods Patients with known or suspected bronchial carcinoma were randomized to receive 200 mg 5-ALA via inhalation 1, 2, 3, 4 or 6 hours before flexible fluorescence bronchoscopy was performed. Macroscopically suspicious areas as well as areas with visually detected porphyrin fluorescence and normal control sites were measured spectroscopically. Biopsies for histopathology were obtained from suspicious areas as well as from adjacent normal areas. Results Fluorescence bronchoscopy performed in 19 patients reveals a sensitivity for malignant and premalignant changes (moderate dysplasia which is almost twice as high as that of white-light bronchoscopy, whereas specificity is reduced. This is due to false-positive inflammatory lesions which also frequently show increased porphyrin fluorescence. Malignant and premalignant alterations produced fluorescence values that are up to 5 times higher than those of normal tissue. According to the pharmacokinetics of porphyrin fluorescence measured by spectroscopy, the optimum time range for 5-ALA application is 80–270 min prior to fluorescence bronchoscopy, with an optimum at 160 min. Conclusion According to our results we propose inhalation of 5-ALA 160 min prior to fluorescence bronchoscopy, suggesting that this time difference provides the best tumor/normal tissue fluorescence ratio.

  6. Pro-inflammatory response and oxidative stress induced by specific components in ambient particulate matter in human bronchial epithelial cells.

    Science.gov (United States)

    Yang, Lawei; Liu, Gang; Lin, Ziying; Wang, Yahong; He, Huijuan; Liu, Tie; Kamp, David W

    2016-08-01

    Previous studies have shown that biological effect of particulate matter (PM2.5) is involved in including chemical composition and mass concentration, but the precise components and biological action on human bronchial epithelial cell line (BEAS-2B) are still unclear. The aim of this study was to evaluate the in vitro toxicity of PM2.5 collected at six urban sites in China, and to investigate how particle composition affects cytotoxicity. We used human bronchial epithelial (BEAS-2B) cell lines as model in vitro to expose to PM2.5 from different source, and then reactive oxygen species (ROS), superoxide dismutase activity and total antioxidant capacity were analyzed. Furthermore, we estimated the polycyclic aromatic hydrocarbon (PAH) and transition metal and the endotoxin contents. The mRNA expression of IL-1β and IL-10 following exposure to PM2.5 was measured by QRT-PCR. We also observed the mitochondrial membrane potential (MMP) using JC-1 staining, and apoptosis of BEAS-2B using flow cytometry. In addition, double-stranded DNA breaks (DSBs) were assessed using γ-H2AX immunofluorescence. Our results show that high concentrations of PAHs and elemental Ni were strongly associated with high apoptosis rates and high expression of IL-1β, in addition, Fe element was associated with the ROS level, furthermore, Fe and Cr element were associated with DNA damage in BEAS-2B cells. The cytotoxic effects of urban PM2.5 derived from six different cities in China appear dependent on the specific components in each. Our results indicate that air quality standards based on PM2.5 components may be more relevant than concentration-response functions (CRF). © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 923-936, 2016. PMID:25533354

  7. Eosinophils promote epithelial to mesenchymal transition of bronchial epithelial cells.

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    Atsushi Yasukawa

    Full Text Available Eosinophilic inflammation and remodeling of the airways including subepithelial fibrosis and myofibroblast hyperplasia are characteristic pathological findings of bronchial asthma. Epithelial to mesenchymal transition (EMT plays a critical role in airway remodelling. In this study, we hypothesized that infiltrating eosinophils promote airway remodelling in bronchial asthma. To demonstrate this hypothesis we evaluated the effect of eosinophils on EMT by in vitro and in vivo studies. EMT was assessed in mice that received intra-tracheal instillation of mouse bone marrow derived eosinophils and in human bronchial epithelial cells co-cultured with eosinophils freshly purified from healthy individuals or with eosinophilic leukemia cell lines. Intra-tracheal instillation of eosinophils was associated with enhanced bronchial inflammation and fibrosis and increased lung concentration of growth factors. Mice instilled with eosinophils pre-treated with transforming growth factor(TGF-β1 siRNA had decreased bronchial wall fibrosis compared to controls. EMT was induced in bronchial epithelial cells co-cultured with human eosinophils and it was associated with increased expression of TGF-β1 and Smad3 phosphorylation in the bronchial epithelial cells. Treatment with anti-TGF-β1 antibody blocked EMT in bronchial epithelial cells. Eosinophils induced EMT in bronchial epithelial cells, suggesting their contribution to the pathogenesis of airway remodelling.

  8. Bystander autophagy mediated by radiation-induced exosomal miR-7-5p in non-targeted human bronchial epithelial cells.

    Science.gov (United States)

    Song, Man; Wang, Yu; Shang, Zeng-Fu; Liu, Xiao-Dan; Xie, Da-Fei; Wang, Qi; Guan, Hua; Zhou, Ping-Kun

    2016-01-01

    Radiation-induced bystander effect (RIBE) describes a set of biological effects in non-targeted cells that receive bystander signals from the irradiated cells. RIBE brings potential hazards to adjacent normal tissues in radiotherapy, and imparts a higher risk than previously thought. Excessive release of some substances from irradiated cells into extracellular microenvironment has a deleterious effect. For example, cytokines and reactive oxygen species have been confirmed to be involved in RIBE process via extracellular medium or gap junctions. However, RIBE-mediating signals and intercellular communication pathways are incompletely characterized. Here, we first identified a set of differentially expressed miRNAs in the exosomes collected from 2 Gy irradiated human bronchial epithelial BEP2D cells, from which miR-7-5p was found to induce autophagy in recipient cells. This exosome-mediated autophagy was significantly attenuated by miR-7-5p inhibitor. Moreover, our data demonstrated that autophagy induced by exosomal miR-7-5p was associated with EGFR/Akt/mTOR signaling pathway. Together, our results support the involvement of secretive exosomes in propagation of RIBE signals to bystander cells. The exosomes-containing miR-7-5p is a crucial mediator of bystander autophagy. PMID:27417393

  9. Use of salbutamol in detection of mechanism destructive to bronchial patency in dust-induced lung disease

    Energy Technology Data Exchange (ETDEWEB)

    Zhumabekova, B.K.

    1982-04-01

    Different mechanisms destroy the open passibility of the bronchi: bronchospasm, destruction of drop eliminator function of the bronchi, valvular mechanics, change in elastic properties of lungs, dyskinesia of the tracheobronchial tree and inflammatory edema of the mucous envelope. Bronchospasm is the most studied form of bronchial pathology. To detect the bronchospastic component, various bronchodilating means are used: (1) stimulators of adrenergic receptors, (2) blockers of acetylcholine (atropine, bella donna); preparations acting directly on smooth musculature of the bronchi (theophylline, euphylline). The pharmaceutical industry is now making aerosol bronchodilators. Since salbutamol is widely used as an aerosol and opinions of its effectiveness are not uniform, a test was made of it on 35 patients; 22 with chronic bronchitis and 13 with silicosis. The rate of air flow during inspiration and expiration was examined 10, 20, 30 and 40 minutes after administration of salbutamol aerosol. Results of the test are presented in a table and show that the use of a pharmacological test with salbutamol aerosol to detect bronchospasm as a cause of lung obstruction is valid. If 10 minutes after inhalation of salbutamol, a therapeutic effect is observed and inhalation and exhalation increase, bronchospasm as the cause of the pathology is demonstrated. The absence of a measurable reaction to salbutamol after 10 minutes indicates that other mechanisms are the basis of the obstruction. (11 refs.) (In Russian)

  10. Macrophages facilitate coal tar pitch extract-induced tumorigenic transformation of human bronchial epithelial cells mediated by NF-κB.

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    Feifei Feng

    Full Text Available OBJECTIVE: Chronic respiratory inflammation has been associated with lung cancer. Tumor-associated macrophages (TAMs play a critical role in the formation of inflammation microenvironment. We sought to characterize the role of TAMs in coal tar pitch extract (CTPE-induced tumorigenic transformation of human bronchial epithelial cells and the underlying mechanisms. METHODS: The expression of TAMs-specific CD68 in lung cancer tissues and paired adjacent tissues from cancer patients was determined using immunostaining. Co-culture of human bronchial epithelial cells (BEAS-2B and macrophage-like THP-1 cells were conducted to evaluate the promotive effect of macrophages on CTPE-induced tumorigenic transformation of BEAS-2B cells. BEAS-2B cells were first treated with 2.4 µg/mL CTPE for 72 hours. After removal of CTPE, the cells were continuously cultured either with or without THP-1 cells and passaged using trypsin-EDTA. Alterations of cell cycle, karyotype, colony formation in soft agar and tumor xenograft growth in nude mice of BEAS-2B cells at passages 10, 20 and 30, indicative of tumorigenecity, were determined, respectively. In addition, mRNA and protein levels of NF-κB in BEAS-2B cells were measured with RT-PCR and western blot, respectively. B(aP was used as the positive control. RESULTS: The over-expression of TAMs-specific CD68 around lung tumor tissues was detected and associated with lung cancer progression. The tumorigenic alterations of BEAS-2B cells including increase in cell growth rate, number of cells with aneuploidy, clonogenicity in soft agar, and tumor size in nude mice in vivo occurred at passage 10, becoming significant at passages 20 and 30 of the co-culture following CTPE removal in compared to BEAS-2B cells alone. In addition, the expression levels of NF-κB in BEAS-2B cells were positively correlated to the malignancy of BEAS-2B cells under different conditions of treatment. CONCLUSION: The presence of macrophages

  11. Engineering Airway Epithelium

    OpenAIRE

    John P. Soleas; Paz, Ana; Marcus, Paula; McGuigan, Alison; Waddell, Thomas K.

    2012-01-01

    Airway epithelium is constantly presented with injurious signals, yet under healthy circumstances, the epithelium maintains its innate immune barrier and mucociliary elevator function. This suggests that airway epithelium has regenerative potential (I. R. Telford and C. F. Bridgman, 1990). In practice, however, airway regeneration is problematic because of slow turnover and dedifferentiation of epithelium thereby hindering regeneration and increasing time necessary for full maturation and fun...

  12. Effect of inhaled furosemide and torasemide on bronchial response to ultrasonically nebulized distilled water in asthmatic subjects.

    Science.gov (United States)

    Foresi, A; Pelucchi, A; Mastropasqua, B; Cavigioli, G; Carlesi, R M; Marazzini, L

    1992-08-01

    Inhaled furosemide has been shown to reduce the bronchoconstriction induced by several indirect stimuli, including ultrasonically nebulized distilled water (UNDW). Because the protective effect could be due to the inhibition of the Na(+)-2Cl(-)-K+ cotransport system of bronchial epithelium, we have compared the protective effect of inhaled furosemide with that of inhaled torasemide, a new and more potent loop diuretic, on UNDW-induced bronchoconstriction in a group of 12 asthmatic subjects. UNDW challenge was performed by constructing a stimulus-response curve with five increasing volume outputs of distilled water (from 0.5 to 5.2 ml/min) and the bronchial response expressed as the provocative output causing a 20% fall in FEV1 (PO20UNDW). On different days, each subject inhaled an equal dose (28 mg) of furosemide and torasemide in a randomized, double-blind, placebo-controlled study 5 min prior to an UNDW challenge. Furosemide and torasemide had no significant effect on resting lung function. The geometric mean value of PO20UNDW measured after placebo was 1.73 ml/min. This was significantly lower than that recorded after furosemide (4.25 ml/min; p < 0.025), but not after torasemide (3.05 ml/min; p = 0.07). Inhaled furosemide totally blocked bronchial response to UNDW in five subjects. In two of five subjects the response was also blocked by inhaled torasemide. A remarkable increase in diuresis was noted only after torasemide in most subjects. We conclude that inhaled furosemide has a better protective effect than does inhaled torasemide against UNDW-induced bronchoconstriction. However, the protective effect of furosemide is variable, with some asthmatic patients showing no change in bronchial response to UNDW.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1489126

  13. Experimental Study onMalignant Transformation of Human Bronchial Epithelial CellsInduced by Glycidyl Methacrylate and Analysis on its Methylation

    Institute of Scientific and Technical Information of China (English)

    WANG An Na; WANG Quan Kai; YANG Min; HU Jie; DONG Lin; andXU Jian Ning

    2014-01-01

    ObjectiveTo establish the model of human bronchial epithelial cells(16HBE) malignant transformation induced by glycidyl methacrylate(GMA)and define the different methylation genes at different stages. MethodsDNA was extracted at different 16HBE malignant phasesandchanges of genes DNA methylation atdifferent stages weredetectedusing Methylation chip of‘NimbleGen HG18 CpG Promoter Microarray Methylation’. Methylation-specific PCR (MSP) was usedto observe the methylation status ofsome genes, and then compared with the control groups. ResultsThe resultshowed that GMA induced 16HBE morphorlogical transformation at the dose of 8µg/mL, and cell exposed to GMA had 1374 genes in protophase, 825 genes inmetaphase, 1149 genes in anaphase, respectively; 30 genes are all methylation in the 3 stages; 318 genes in protophase but not inmetaphase and anaphase; 272 genes in metaphase but not inprotophase and anaphase; 683 genes in anaphase but not inmetaphase and protophase; 73 genes inprotophase andmetaphase but not in anaphase; 67 genes in protophase and anaphase but not inmetaphase; 59 genes inmetaphase and anaphase but not in protophase. ConclusionThe pattern of DNA methylation could change in the process of 16HBEinduced by GMA.

  14. Cadmium induces cytotoxicity in human bronchial epithelial cells through upregulation of eIF5A1 and NF-kappaB

    Energy Technology Data Exchange (ETDEWEB)

    Chen, De-Ju; Xu, Yan-Ming; Du, Ji-Ying [Laboratory of Cancer Biology and Epigenetics, Shantou University Medical College, Shantou, Guangdong 515041 (China); Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041 (China); Huang, Dong-Yang [Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041 (China); Lau, Andy T.Y., E-mail: andytylau@stu.edu.cn [Laboratory of Cancer Biology and Epigenetics, Shantou University Medical College, Shantou, Guangdong 515041 (China); Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041 (China)

    2014-02-28

    Highlights: • Normal human bronchial epithelial cells (BEAS-2B) were dosed with cadmium (Cd). • A low level (2 μM) of Cd treatment for 36 h elicited negligible cytotoxicity. • High levels (20 or 30 μM) of Cd treatment for 36 h induced cell death. • High levels of Cd can upregulate the protein levels of eIF5A1 and NF-κB p65. • We suggest that eIF5A1 level is possibly modulated by NF-κB. - Abstract: Cadmium (Cd) and Cd compounds are widely-distributed in the environment and well-known carcinogens. Here, we report that in CdCl{sub 2}-exposed human bronchial epithelial cells (BEAS-2B), the level of p53 is dramatically decreased in a time- and dose-dependent manner, suggesting that the observed Cd-induced cytotoxicity is not likely due to the pro-apoptotic function of p53. Therefore, this prompted us to further study the responsive pro-apoptotic factors by proteomic approaches. Interestingly, we identified that high levels (20 or 30 μM) of Cd can significantly upregulate the protein levels of eukaryotic translation initiation factor 5A1 (eIF5A1) and redox-sensitive transcription factor NF-κB p65. Moreover, there is an enhanced NF-κB nuclear translocation as well as chromatin-binding in Cd-treated BEAS-2B cells. We also show that small interfering RNA-specific knockdown of eIF5A1 in Cd-exposed cells attenuated the Cd cytotoxicity, indicating the potential role of eIF5A1 in Cd cytotoxicity. As eIF5A1 is reported to be related with cell apoptosis but little is known about its transcriptional control, we hypothesize that NF-κB might likely modulate eIF5A1 gene expression. Notably, by bioinformatic analysis, several potential NF-κB binding sites on the upstream promoter region of eIF5A1 gene can be found. Subsequent chromatin immunoprecipitation assay revealed that indeed there is enhanced NF-κB binding on eIF5A1 promoter region of Cd-treated BEAS-2B cells. Taken together, our findings suggest for the first time a regulatory mechanism for the pro

  15. Cadmium induces cytotoxicity in human bronchial epithelial cells through upregulation of eIF5A1 and NF-kappaB

    International Nuclear Information System (INIS)

    Highlights: • Normal human bronchial epithelial cells (BEAS-2B) were dosed with cadmium (Cd). • A low level (2 μM) of Cd treatment for 36 h elicited negligible cytotoxicity. • High levels (20 or 30 μM) of Cd treatment for 36 h induced cell death. • High levels of Cd can upregulate the protein levels of eIF5A1 and NF-κB p65. • We suggest that eIF5A1 level is possibly modulated by NF-κB. - Abstract: Cadmium (Cd) and Cd compounds are widely-distributed in the environment and well-known carcinogens. Here, we report that in CdCl2-exposed human bronchial epithelial cells (BEAS-2B), the level of p53 is dramatically decreased in a time- and dose-dependent manner, suggesting that the observed Cd-induced cytotoxicity is not likely due to the pro-apoptotic function of p53. Therefore, this prompted us to further study the responsive pro-apoptotic factors by proteomic approaches. Interestingly, we identified that high levels (20 or 30 μM) of Cd can significantly upregulate the protein levels of eukaryotic translation initiation factor 5A1 (eIF5A1) and redox-sensitive transcription factor NF-κB p65. Moreover, there is an enhanced NF-κB nuclear translocation as well as chromatin-binding in Cd-treated BEAS-2B cells. We also show that small interfering RNA-specific knockdown of eIF5A1 in Cd-exposed cells attenuated the Cd cytotoxicity, indicating the potential role of eIF5A1 in Cd cytotoxicity. As eIF5A1 is reported to be related with cell apoptosis but little is known about its transcriptional control, we hypothesize that NF-κB might likely modulate eIF5A1 gene expression. Notably, by bioinformatic analysis, several potential NF-κB binding sites on the upstream promoter region of eIF5A1 gene can be found. Subsequent chromatin immunoprecipitation assay revealed that indeed there is enhanced NF-κB binding on eIF5A1 promoter region of Cd-treated BEAS-2B cells. Taken together, our findings suggest for the first time a regulatory mechanism for the pro

  16. Engineering Airway Epithelium

    Directory of Open Access Journals (Sweden)

    John P. Soleas

    2012-01-01

    Full Text Available Airway epithelium is constantly presented with injurious signals, yet under healthy circumstances, the epithelium maintains its innate immune barrier and mucociliary elevator function. This suggests that airway epithelium has regenerative potential (I. R. Telford and C. F. Bridgman, 1990. In practice, however, airway regeneration is problematic because of slow turnover and dedifferentiation of epithelium thereby hindering regeneration and increasing time necessary for full maturation and function. Based on the anatomy and biology of the airway epithelium, a variety of tissue engineering tools available could be utilized to overcome the barriers currently seen in airway epithelial generation. This paper describes the structure, function, and repair mechanisms in native epithelium and highlights specific and manipulatable tissue engineering signals that could be of great use in the creation of artificial airway epithelium.

  17. CpG DNA modulates interleukin 1β-induced interleukin-8 expression in human bronchial epithelial (16HBE14o- cells

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    Wong Hector R

    2006-06-01

    Full Text Available Abstract Background Recognition of repeat unmethylated CpG motifs from bacterial DNA through Toll-like receptor (TLR-9 has been shown to induce interleukin (IL-8 expression in immune cells. We sought to investigate the role of CpG oligodeoxynucleotides (ODN on a human bronchial epithelial cells. Methods RT-PCR and Western blot analysis were used to determine expression of TLR-9 in human bronchial epithelial cells (16HBE14o-. Cells were treated with CpG ODN in the presence or absence of IL-1β and IL-8 protein was determined using ELISA. In some cases cells were pretreated with chloroquine, an inhibitor of TLR-9 signaling, or SB202190, an inhibitor of the mitogen activated protein kinase p38, prior to treatment with IL-1β and CpG. TLR9 siRNA was used to silence TLR9 prior to treatment with IL-1β and CpG. IκBα and p38 were assessed by Western blot, and EMSA's were performed to determine NF-κB activation. To investigate IL-8 mRNA stability, cells were treated with IL-1β in the absence or presence of CpG for 2 h and actinomycin D was added to induce transcriptional arrest. Cells were harvested at 15 min intervals and Northern blot analysis was performed. Results TLR-9 is expressed in 16HBE14o- cells. CpG synergistically increased IL-1β-induced IL-8 protein abundance, however treatment with CpG alone had no effect. CpC (a control ODN had no effect on IL-1β-induced IL-8 levels. In addition, CpG synergistically upregulated TNFα-induced IL-8 expression. Silencing TLR9 using siRNA or pretreatment of cells with chloroquine had little effect on IL-1β-induced IL-8 levels, but abolished CpG-induced synergy. CpG ODN had no effect on NF-κB translocation or DNA binding in 16HBE14o- cells. Treatment with CpG increased phosphorylation of p38 and pretreatment with the p38 inhibitor SB202190 attenuated the synergistic increase in IL-8 protein levels. Analysis of the half-life of IL-8 mRNA revealed that IL-8 mRNA had a longer half-life following the co

  18. Cytochrome P450 2A13 enhances the sensitivity of human bronchial epithelial cells to aflatoxin B1-induced DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Xuejiao [Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 818 East Tiangyuan Rd., Nanjing 211166 (China); Jiaojiang District Center for Disease Control and Prevention, 518 Jingdong Rd., Taizhou 318000 (China); Zhang, Zhan; Wang, Xichen; Wang, Yun; Zhang, Xiaoming; Lu, Huiyuan [Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 818 East Tiangyuan Rd., Nanjing 211166 (China); Wang, Shou-Lin, E-mail: wangshl@njmu.edu.cn [Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 818 East Tiangyuan Rd., Nanjing 211166 (China)

    2013-07-15

    Cytochrome P450 2A13 (CYP2A13) mainly expresses in human respiratory system and mediates the metabolic activation of aflatoxin B1 (AFB1). Our previous study suggested that CYP2A13 could increase the cytotoxic and apoptotic effects of AFB1 in immortalized human bronchial epithelial cells (BEAS-2B). However, the role of CYP2A13 in AFB1-induced DNA damage is unclear. Using BEAS-2B cells that stably express CYP2A13 (B-2A13), CYP1A2 (B-1A2), and CYP2A6 (B-2A6), we compared their effects in AFB1-induced DNA adducts, DNA damage, and cell cycle changes. BEAS-2B cells that were transfected with vector (B-vector) were used as a control. The results showed that AFB1 (5–80 nM) dose- and time-dependently induced DNA damage in B-2A13 cells. AFB1 at 10 and 80 nM significantly augmented this effect in B-2A13 and B-1A2 cells, respectively. B-2A6 cells showed no obvious DNA damage, similar to B-vector cells and the vehicle control. Similarly, compared with B-vector, B-1A2 or B-2A6 cells, B-2A13 cells showed more sensitivity in AFB1-induced γH2AX expression, DNA adduct 8-hydroxy-deoxyguanosine formation, and S-phase cell-cycle arrest. Furthermore, AFB1 activated the proteins related to DNA damage responses, such as ATM, ATR, Chk2, p53, BRCA1, and H2AX, rather than the proteins related to DNA repair. These effects could be almost completely inhibited by 100 μM nicotine (a substrate of CYP2A13) or 1 μM 8-methoxypsoralen (8-MOP; an inhibitor of CYP enzyme). Collectively, these findings suggest that CYP2A13 plays an important role in low-concentration AFB1-induced DNA damage, possibly linking environmental airborne AFB1 to genetic injury in human respiratory system. - Highlights: • CYP2A13 plays a critical role in low concentration of AFB1-induced DNA damage. • B-2A13 cells were more sensitive to AFB1 than B-1A2 cells and B-2A6 cells. • AFB1 dose- and time-dependently induced DNA damage in B-2A13 cells • AFB1-induced DNA adducts and damage can be inhibited by nicotine and 8

  19. [Dexamethasone increases the expression of reversion-inducing cysteine-rich protein with Kazal motifs (RECK) in lung tissues of bronchial asthmatic mice].

    Science.gov (United States)

    Li, Zhenxing; He, Sheng; Wei, Liping; Lin, Lin; Xiong, Hanzhen; Li, Junhong; Chen, Peifen; Lai, Wenyan

    2016-05-01

    Objective To investigate the expression of reversion-inducing cysteine-rich protein with Kazal motifs (RECK) in the lung tissues of bronchial asthmatic mice and the effect of dexamethasone treatment on its expression. Methods Thirty BALB/c mice were randomly divided into three equal groups: a control group, an asthmatic group and a dexamethasone-treated group. The asthmatic mouse models were established by intraperitoneal injection and inhalation with ovalbumin (OVA). The number of eosinophils (EOS) and lymphocytes (Lym) in bronchoalveolar lavage fluid (BALF) were counted. HE staining was used to observe airway inflammation and remodeling. The mRNA and protein expression of RECK were determined by real-time PCR and immunohistochemistry, respectively. Results Compared with the control group and the dexamethasone-treated group, the total cell number and EOS number in the BALF of the asthma group significantly increased. The expression of RECK mRNA in the asthmatic group was significantly lower than that in the control group and the dexamethasone-treated group. Immunohistochemistry showed that RECK was mainly expressed in the airway epithelial cells and inflammatory cells. RECK protein expression was highest in the control group and lowest in the asthmatic group. Conclusion Dexamethasone can increase the expression of RECK in the lung tissues of asthmatic mice. PMID:27126937

  20. Changes of gene methylation profile in malignant transformation of immortalized human bronchial epithelial cell line induced by alpha-particle irradiation

    International Nuclear Information System (INIS)

    Objective: To identify the changes of DNA methylation profile in the process of malignant transformation of BEP2D cell induced by α particles. Methods: The genomic DNAs were isolated from the malignant transformation BERP35T4 cells and immortalized human bronchial epithelial cell line BEP2D. Genomic DNAs were digested by MseI and ligated of PCR linkers. Methylated DNAs were digested by BstUI and amplified by PCR. The methylated DNA probes were prepared by labeling with Cy3 and Cy5 fluorescence dyes individually and hybridized to the methylation CpG-Island microarray. The hybridization results were scanned and analyzed. Intensity values were quality controlled and normalized. The normalized data were used to identify the differentially expressed genes based on a 1.5 fold difference of the expression level. Results: There were 16 genes which showed changes of methylation level in malignant transformation BERP35T4 cells, 9 of them were hyper methylation and 7 were hypo methylation. These genes were including the SKIP gene, PPP3CC gene, MAP2K6 gene, KIR2DL1 gene, KIR2DL4 gene, KIR3DP1 gene, ZNF493 gene, ZNF100 gene, NKX2-5 gene, TFAP2D gene, DR1 gene, KCNJ16 gene, CCDC18 gene, FNBP1L gene, IRX4 gene, EPB41L3 gene, TCP10 gene and so on. Conclusions: The DNA methylation might have effects on ionizing radiation derived tumorigenesis. (authors)

  1. Pandemic H1N1 influenza A directly induces a robust and acute inflammatory gene signature in primary human bronchial epithelial cells downstream of membrane fusion

    International Nuclear Information System (INIS)

    Pandemic H1N1 influenza A (H1N1pdm) elicits stronger pulmonary inflammation than previously circulating seasonal H1N1 influenza A (sH1N1), yet mechanisms of inflammatory activation in respiratory epithelial cells during H1N1pdm infection are unclear. We investigated host responses to H1N1pdm/sH1N1 infection and virus entry mechanisms in primary human bronchial epithelial cells in vitro. H1N1pdm infection rapidly initiated a robust inflammatory gene signature (3 h post-infection) not elicited by sH1N1 infection. Protein secretion inhibition had no effect on gene induction. Infection with membrane fusion deficient H1N1pdm failed to induce robust inflammatory gene expression which was rescued with restoration of fusion ability, suggesting H1N1pdm directly triggered the inflammatory signature downstream of membrane fusion. Investigation of intra-virion components revealed H1N1pdm viral RNA (vRNA) triggered a stronger inflammatory phenotype than sH1N1 vRNA. Thus, our study is first to report H1N1pdm induces greater inflammatory gene expression than sH1N1 in vitro due to direct virus–epithelial cell interaction. - Highlights: • We investigated H1N1pdm/sH1N1 infection in primary epithelial cells. • H1N1pdm directly initiated a robust inflammatory gene signature, sH1N1 did not. • H1N1pdm viral RNA triggered a stronger response than sH1N1. • H1N1pdm induces greater response due to direct virus–cell interaction. • These results have potential to impact vaccine and therapeutic development

  2. Pandemic H1N1 influenza A directly induces a robust and acute inflammatory gene signature in primary human bronchial epithelial cells downstream of membrane fusion

    Energy Technology Data Exchange (ETDEWEB)

    Paquette, Stéphane G. [Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario (Canada); Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario (Canada); Banner, David [Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario (Canada); Chi, Le Thi Bao [Department of Microbiology, Hue University of Medicine and Pharmacy, Thua Thien Hue (Viet Nam); Carlo Urbani Centre, Hue University of Medicine and Pharmacy, Thua Thien Hue (Viet Nam); Leon, Alberto J. [Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario (Canada); International Institute of Infection and Immunity, Shantou University Medical College, Shantou, Guangdong (China); Xu, Luoling; Ran, Longsi [Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario (Canada); Huang, Stephen S.H. [Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario (Canada); Department of Immunology, Faculty of Medicine, University of Toronto, Toronto, Ontario (Canada); Farooqui, Amber [Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario (Canada); International Institute of Infection and Immunity, Shantou University Medical College, Shantou, Guangdong (China); and others

    2014-01-05

    Pandemic H1N1 influenza A (H1N1pdm) elicits stronger pulmonary inflammation than previously circulating seasonal H1N1 influenza A (sH1N1), yet mechanisms of inflammatory activation in respiratory epithelial cells during H1N1pdm infection are unclear. We investigated host responses to H1N1pdm/sH1N1 infection and virus entry mechanisms in primary human bronchial epithelial cells in vitro. H1N1pdm infection rapidly initiated a robust inflammatory gene signature (3 h post-infection) not elicited by sH1N1 infection. Protein secretion inhibition had no effect on gene induction. Infection with membrane fusion deficient H1N1pdm failed to induce robust inflammatory gene expression which was rescued with restoration of fusion ability, suggesting H1N1pdm directly triggered the inflammatory signature downstream of membrane fusion. Investigation of intra-virion components revealed H1N1pdm viral RNA (vRNA) triggered a stronger inflammatory phenotype than sH1N1 vRNA. Thus, our study is first to report H1N1pdm induces greater inflammatory gene expression than sH1N1 in vitro due to direct virus–epithelial cell interaction. - Highlights: • We investigated H1N1pdm/sH1N1 infection in primary epithelial cells. • H1N1pdm directly initiated a robust inflammatory gene signature, sH1N1 did not. • H1N1pdm viral RNA triggered a stronger response than sH1N1. • H1N1pdm induces greater response due to direct virus–cell interaction. • These results have potential to impact vaccine and therapeutic development.

  3. Bronchial secretion concentrations of tobramycin.

    Science.gov (United States)

    Alexander, M R; Schoell, J; Hicklin, G; Kasik, J E; Coleman, D

    1982-02-01

    The mean concentrations of tobramycin in bronchial secretions from patients with pneumonia were almost two times greater than secretions from patients free of lung infection. Mean tobramycin bronchial secretion to serum concentration ratios also were higher when obtained from infected lungs (0.66 versus 0.17) These data suggest that lung infection enhances the concentrations of tobramycin in bronchial secretions. PMID:7065524

  4. DNA repair in human bronchial epithelial cells

    International Nuclear Information System (INIS)

    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

  5. HIV Impairs Lung Epithelial Integrity and Enters the Epithelium to Promote Chronic Lung Inflammation.

    Directory of Open Access Journals (Sweden)

    Kieran A Brune

    Full Text Available Several clinical studies show that individuals with HIV are at an increased risk for worsened lung function and for the development of COPD, although the mechanism underlying this increased susceptibility is poorly understood. The airway epithelium, situated at the interface between the external environment and the lung parenchyma, acts as a physical and immunological barrier that secretes mucins and cytokines in response to noxious stimuli which can contribute to the pathobiology of chronic obstructive pulmonary disease (COPD. We sought to determine the effects of HIV on the lung epithelium. We grew primary normal human bronchial epithelial (NHBE cells and primary lung epithelial cells isolated from bronchial brushings of patients to confluence and allowed them to differentiate at an air- liquid interface (ALI to assess the effects of HIV on the lung epithelium. We assessed changes in monolayer permeability as well as the expression of E-cadherin and inflammatory modulators to determine the effect of HIV on the lung epithelium. We measured E-cadherin protein abundance in patients with HIV compared to normal controls. Cell associated HIV RNA and DNA were quantified and the p24 viral antigen was measured in culture supernatant. Surprisingly, X4, not R5, tropic virus decreased expression of E-cadherin and increased monolayer permeability. While there was some transcriptional regulation of E-cadherin, there was significant increase in lysosome-mediated protein degradation in cells exposed to X4 tropic HIV. Interaction with CXCR4 and viral fusion with the epithelial cell were required to induce the epithelial changes. X4 tropic virus was able to enter the airway epithelial cells but not replicate in these cells, while R5 tropic viruses did not enter the epithelial cells. Significantly, X4 tropic HIV induced the expression of intercellular adhesion molecule-1 (ICAM-1 and activated extracellular signal-regulated kinase (ERK. We demonstrate that HIV

  6. Glutamine supplementation attenuates ethanol-induced disruption of apical junctional complexes in colonic epithelium and ameliorates gut barrier dysfunction and fatty liver in mice.

    Science.gov (United States)

    Chaudhry, Kamaljit K; Shukla, Pradeep K; Mir, Hina; Manda, Bhargavi; Gangwar, Ruchika; Yadav, Nikki; McMullen, Megan; Nagy, Laura E; Rao, RadhaKrishna

    2016-01-01

    Previous in vitro studies showed that glutamine (Gln) prevents acetaldehyde-induced disruption of tight junctions and adherens junctions in Caco-2 cell monolayers and human colonic mucosa. In the present study, we evaluated the effect of Gln supplementation on ethanol-induced gut barrier dysfunction and liver injury in mice in vivo. Ethanol feeding caused a significant increase in inulin permeability in distal colon. Elevated permeability was associated with a redistribution of tight junction and adherens junction proteins and depletion of detergent-insoluble fractions of these proteins, suggesting that ethanol disrupts apical junctional complexes in colonic epithelium and increases paracellular permeability. Ethanol-induced increase in colonic mucosal permeability and disruption of junctional complexes were most severe in mice fed Gln-free diet. Gln supplementation attenuated ethanol-induced mucosal permeability and disruption of tight junctions and adherens junctions in a dose-dependent manner, indicating the potential role of Gln in nutritional intervention to alcoholic tissue injury. Gln supplementation dose-dependently elevated reduced-protein thiols in colon without affecting the level of oxidized-protein thiols. Ethanol feeding depleted reduced protein thiols and elevated oxidized protein thiols. Ethanol-induced protein thiol oxidation was most severe in mice fed with Gln-free diet and absent in mice fed with Gln-supplemented diet, suggesting that antioxidant effect is one of the likely mechanisms involved in Gln-mediated amelioration of ethanol-induced gut barrier dysfunction. Ethanol feeding elevated plasma transaminase and liver triglyceride, which was accompanied by histopathologic lesions in the liver; ethanol-induced liver damage was attenuated by Gln supplementation. These results indicate that Gln supplementation ameliorates alcohol-induced gut and liver injury. PMID:26365579

  7. Activation of Notch1 inhibits medial edge epithelium apoptosis in all-trans retinoic acid-induced cleft palate in mice.

    Science.gov (United States)

    Zhang, Yadong; Dong, Shiyi; Wang, Weicai; Wang, Jianning; Wang, Miao; Chen, Mu; Hou, Jinsong; Huang, Hongzhang

    2016-08-26

    Administration of all-trans retinoic acid (atRA) on E12.0 (embryonic day 12.0) leads to failure of medial edge epithelium (MEE) disappearance and cleft palate. However, the molecular mechanism underlying the relationship between atRA and MEE remains to be identified. In this study, atRA (200 mg/kg) administered by gavage induced a 75% incidence of cleft palate in C57BL/6 mice. Notch1 was up-regulated in MEE cells in the atRA-treated group compared with the controls at E15.0, together with reduced apoptosis and elevated proliferation. Next, we investigated the mechanisms underlying atRA, Notch1 and MEE degradation in palate organ culture. Our results revealed that down-regulation of Notch1 partially rescued the inhibition of atRA-induced palate fusion. Molecular analysis indicated that atRA increased the expression of Notch1 and Rbpj and decreased the expression of P21. In addition, depletion of Notch1 expression decreased the expression of Rbpj and increased the expression of P21. Moreover, inhibition of Rbpj expression partially reversed atRA-induced MEE persistence and increased P21 expression. These findings demonstrate that atRA inhibits MEE degradation, which in turn induces a cleft palate, possibly through the Notch1/RBPjk/P21 signaling pathway. PMID:27343556

  8. Menopause-induced uterine epithelium atrophy results from arachidonic acid/prostaglandin E2 axis inhibition-mediated autophagic cell death.

    Science.gov (United States)

    Zhou, Shengtao; Zhao, Linjie; Yi, Tao; Wei, Yuquan; Zhao, Xia

    2016-01-01

    Women experience menopause later in life. Menopause is characterized by dramatically decreased circulating estrogen level secondary to loss of ovarian function and atrophic state of genital organs. However, the molecular mechanisms for this process are not fully understood. In this study, we aimed to investigate the potential molecular mechanisms that underlie menopause-induced uterine endometrial atrophy. Our data showed that autophagy was activated in the uterine epithelial cells of both ovariectomized rats and peri-menopausal females. Endoplasmic reticulum (ER) stress occurred even prior to autophagy induction. Integrated bioinformatics analysis revealed that ER stress induced downstream decreased release of arachidonic acid (AA) and downregulation of AA/prostaglandin E2 (PGE2) axis, which led to Akt/mTOR signaling pathway inactivation. Consequently, autophagosomes were recruited and LC3-dependent autophagy was induced in uterine epithelial cells. Treatment with exogenous E2, PGE2, salubrinal or RNAi-mediated silencing of key autophagy genes could effectively counteract estrogen depletion-induced autophagy. Collectively, autophagy is a critical regulator of the uterine epithelium that accounts for endometrial atrophy after menopause. PMID:27506466

  9. Menopause-induced uterine epithelium atrophy results from arachidonic acid/prostaglandin E2 axis inhibition-mediated autophagic cell death

    Science.gov (United States)

    Zhou, Shengtao; Zhao, Linjie; Yi, Tao; Wei, Yuquan; Zhao, Xia

    2016-01-01

    Women experience menopause later in life. Menopause is characterized by dramatically decreased circulating estrogen level secondary to loss of ovarian function and atrophic state of genital organs. However, the molecular mechanisms for this process are not fully understood. In this study, we aimed to investigate the potential molecular mechanisms that underlie menopause-induced uterine endometrial atrophy. Our data showed that autophagy was activated in the uterine epithelial cells of both ovariectomized rats and peri-menopausal females. Endoplasmic reticulum (ER) stress occurred even prior to autophagy induction. Integrated bioinformatics analysis revealed that ER stress induced downstream decreased release of arachidonic acid (AA) and downregulation of AA/prostaglandin E2 (PGE2) axis, which led to Akt/mTOR signaling pathway inactivation. Consequently, autophagosomes were recruited and LC3-dependent autophagy was induced in uterine epithelial cells. Treatment with exogenous E2, PGE2, salubrinal or RNAi-mediated silencing of key autophagy genes could effectively counteract estrogen depletion-induced autophagy. Collectively, autophagy is a critical regulator of the uterine epithelium that accounts for endometrial atrophy after menopause. PMID:27506466

  10. Adamtsl2 deletion results in bronchial fibrillin microfibril accumulation and bronchial epithelial dysplasia – a novel mouse model providing insights into geleophysic dysplasia

    Directory of Open Access Journals (Sweden)

    Dirk Hubmacher

    2015-05-01

    Full Text Available Mutations in the secreted glycoprotein ADAMTSL2 cause recessive geleophysic dysplasia (GD in humans and Musladin–Lueke syndrome (MLS in dogs. GD is a severe, often lethal, condition presenting with short stature, brachydactyly, stiff skin, joint contractures, tracheal-bronchial stenosis and cardiac valve anomalies, whereas MLS is non-lethal and characterized by short stature and severe skin fibrosis. Although most mutations in fibrillin-1 (FBN1 cause Marfan syndrome (MFS, a microfibril disorder leading to transforming growth factor-β (TGFβ dysregulation, domain-specific FBN1 mutations result in dominant GD. ADAMTSL2 has been previously shown to bind FBN1 and latent TGFβ-binding protein-1 (LTBP1. Here, we investigated mice with targeted Adamtsl2 inactivation as a new model for GD (Adamtsl2−/− mice. An intragenic lacZ reporter in these mice showed that ADAMTSL2 was produced exclusively by bronchial smooth muscle cells during embryonic lung development. Adamtsl2−/− mice, which died at birth, had severe bronchial epithelial dysplasia with abnormal glycogen-rich inclusions in bronchial epithelium resembling the cellular anomalies described previously in GD. An increase in microfibrils in the bronchial wall was associated with increased FBN2 and microfibril-associated glycoprotein-1 (MAGP1 staining, whereas LTBP1 staining was increased in bronchial epithelium. ADAMTSL2 was shown to bind directly to FBN2 with an affinity comparable to FBN1. The observed extracellular matrix (ECM alterations were associated with increased bronchial epithelial TGFβ signaling at 17.5 days of gestation; however, treatment with TGFβ-neutralizing antibody did not correct the epithelial dysplasia. These investigations reveal a new function of ADAMTSL2 in modulating microfibril formation, and a previously unsuspected association with FBN2. Our studies suggest that the bronchial epithelial dysplasia accompanying microfibril dysregulation in Adamtsl2−/− mice

  11. Macrophages promote benzopyrene-induced tumor transformation of human bronchial epithelial cells by activation of NF-κB and STAT3 signaling in a bionic airway chip culture and in animal models

    Science.gov (United States)

    Sun, Zhao; Wang, Lei; Guo, Zhe; Zhao, Yang; Gao, Zhancheng; Wang, Qi

    2015-01-01

    We investigated the role of macrophages in promoting benzopyrene (BaP)-induced malignant transformation of human bronchial epithelial cells using a BaP-induced tumor transformation model with a bionic airway chip in vitro and in animal models. The bionic airway chip culture data showed that macrophages promoted BaP-induced malignant transformation of human bronchial epithelial cells, which was mediated by nuclear factor (NF)-κB and STAT3 pathways to induce cell proliferation, colony formation in chip culture, and tumorigenicity in nude mice. Blockage of interleukin (IL)-6 or tumor necrosis factor (TNF)-α signaling or inhibition of NF-κB, STAT3, or cyclinD1 expression abrogated the effect of macrophages on malignant transformation in the bionic airway chip culture. In vivo, macrophages promoted lung tumorigenesis in a carcinogen-induced animal model. Similarly, blockage of NF-κB, STAT3, or cyclinD1 using siRNA transfection decreased the carcinogen-induced tumorigenesis in rats. We demonstrated that macrophages are critical in promoting lung tumorigenesis and that the macrophage-initiated TNF-α/NF-κB/cyclinD1 and IL-6/STAT3/cyclinD1 pathways are primarily responsible for promoting lung tumorigenesis. PMID:25823926

  12. Altered melanocyte differentiation and retinal pigmented epithelium transdifferentiation induced by Mash1 expression in pigment cell precursors.

    Science.gov (United States)

    Lanning, Jessica L; Wallace, Jaclyn S; Zhang, Deming; Diwakar, Ganesh; Jiao, Zhongxian; Hornyak, Thomas J

    2005-10-01

    Transcription factor genes governing pigment cell development that are associated with spotting mutations in mice include members of several structural transcription factor classes but not members of the basic helix-loop-helix (bHLH) class, important for neurogenesis and myogenesis. To determine the effects of bHLH factor expression on pigment cell development, the neurogenic bHLH factor Mash1 was expressed early in pigment cell development in transgenic mice from the dopachrome tautomerase (Dct) promoter. Dct:Mash1 transgenic founders exhibit variable microphthalmia and patchy coat color hypopigmentation. Transgenic F1 mice exhibit microphthalmia with complete coat color dilution. Marker analysis demonstrates that Mash1 expression in the retinal pigmented epithelium (RPE) initiates neurogenesis in this cell layer, whereas expression in remaining neural crest-derived melanocytes alters their differentiation, in part by profoundly downregulating expression of the p (pink-eyed dilution) gene, while maintaining their cell fate. The effects of transcriptional perturbation of pigment cell precursors by Mash1 further highlight differences between pigment cells of distinct developmental origins, and suggest a mechanism for the alteration of melanogenesis to result in marked coat color dilution. PMID:16185282

  13. Organic extracts of urban air pollution particulate matter (PM2.5)-induced genotoxicity and oxidative stress in human lung bronchial epithelial cells (BEAS-2B cells).

    Science.gov (United States)

    Oh, Seung Min; Kim, Ha Ryong; Park, Yong Joo; Lee, Soo Yeun; Chung, Kyu Hyuck

    2011-08-16

    Traffic is a major source of particulate matter (PM), and ultrafine particulates and traffic intensity probably contribute significantly to PM-related health effects. As a strong relationship between air pollution and motor vehicle-originated pollutants has been shown to exist, air pollution genotoxicity studies of urban cities are steadily increasing. In Korea, the death rate caused by lung cancer is the most rapidly increased cancer death rate in the past 10 years. In this study, genotoxicity of PM2.5 (traffic area in Suwon City, Korea, was studied using cultured human lung bronchial epithelial cells (BEAS-2B) as a model system for the potential inhalation health effects. Organic extract of PM2.5 (CE) generated significant DNA breakage and micronucleus formation in a dose-dependent manner (1μg/cm(3)-50μg/cm(3)). In the acid-base-neutral fractionation of PM2.5, neutral samples including the aliphatic (F3), aromatic (F4) and slightly polar (F5) fractions generated significant DNA breakage and micronucleus formation. These genotoxic effects were significantly blocked by scavenging agents [superoxide dismutase (SOD), sodium selenite (SS), mannitol (M), catalase (CAT)]. In addition, in the modified Comet assay using endonucleases (FPG and ENDOIII), CE and its fractions (F3, F4, and F5) increased DNA breakage compared with control groups, indicating that CE and fractions of PM2.5 induced oxidative DNA damage. These results clearly suggest that PM2.5 collected in the Suwon traffic area has genotoxic effects and that reactive oxygen species may play a distinct role in these effects. In addition, aliphatic/chlorinated hydrocarbons, PAH/alkylderivatives, and nitro-PAH/ketones/quinones may be important causative agents of the genotoxic effects. PMID:21524716

  14. Carcinoid crisis induced by receptor radionuclide therapy with 90Y-DOTATOC in a case of liver metastases from bronchial neuroendocrine tumor (atypical carcinoid).

    Science.gov (United States)

    Davì, M V; Bodei, L; Francia, G; Bartolomei, M; Oliani, C; Scilanga, L; Reghellin, D; Falconi, M; Paganelli, G; Lo Cascio, V; Ferdeghini, M

    2006-06-01

    SS receptors are overexpressed in many tumors, mainly of neuroendocrine origin, thus enabling the treatment with SS analogs. The clinical experience of receptor radionuclide therapy with the new analog [90Y-DOTA0-Tyr3 ]-octreotide [90Y-DOTATOC] has been developed over the last decade and is gaining a pivotal role in the therapeutic workout of these tumors. It is well known that some procedures performed in diagnostic and therapeutic management of endocrine tumors, such as agobiopsy and hepatic chemoembolization, can be associated with the occurrence of symptoms related to the release of vasoactive amines and/or hormonal peptides from tumor cell lysis. This is the first report of a severe carcinoid crisis developed after receptor radionuclide therapy with 90Y-DOTATOC administered in a patient affected by liver metastases from bronchial neuroendocrine tumor (atypical carcinoid). Despite protection with H1 receptor antagonists, octreotide and corticosteroids, few days after the therapy the patient complained of persistent flushing of the face and upper trunk, severe labial and periocular oedema, diarrhoea and loss of appetite. These symptoms increased and required new hospitalisation. The patient received iv infusion of octreotide associated with H1 and H2 receptor antagonists and corticosteroid therapy, which induced symptom remission within few days. The case here reported confirms that radionuclide therapy is highly effective in determining early rupture of metastatic tissue and also suggests that pre-medication should be implemented before the radiopeptide administration associated with a close monitoring of the patient in the following days. PMID:16840837

  15. Human Mesenchymal Stem Cells Suppress the Stretch–Induced Inflammatory miR-155 and Cytokines in Bronchial Epithelial Cells

    OpenAIRE

    Kuo, Yi-Chun; Li, Yi-shuan Julie; Zhou, Jing; Shih, Yu-Ru Vernon; Miller, Marina; Broide, David; Lee, Oscar Kuang-Sheng; Chien, Shu

    2013-01-01

    Current research in pulmonary pathology has focused on inflammatory reactions initiated by immunological responses to allergens and irritants. In addition to these biochemical stimuli, physical forces also play an important role in regulating the structure, function, and metabolism of the lung. Hyperstretch of lung tissues can contribute to the inflammatory responses in asthma, but the mechanisms of mechanically induced inflammation in the lung remain unclear. Our results demonstrate that exc...

  16. Induced Sputum Substance P in Children with Difficult-to-Treat Bronchial Asthma and Gastroesophageal Reflux: Effect of Esomeprazole Therapy

    Directory of Open Access Journals (Sweden)

    Adel Salah Bediwy

    2011-01-01

    Full Text Available Objectives. To assess the induced sputum substance P (ISSP levels in children having difficult-to-treat asthma (DA with and without gastroesophageal reflux (GER. We aimed also to evaluate the association of GER with childhood DA, relationship of GER severity with childhood asthma control test (C-ACT, FEV1, peak expiratory flow (PEF variability, and ISSP. Finally, we tried to evaluate esomeprazole treatment effect on C-ACT and FEV1 in children with DA. Methods. Spirometry, C-ACT, upper gastrointestinal endoscopy, and ISSP measurement were done for children with DA compared to healthy controls. Results. ISSP was high in DA with higher levels in the group having associated GER. In the latter group, ISSP and C-ACT improved significantly after esomeprazole treatment while FEV1 and PEF variability did not improve. Reflux severity was positively correlated with ISSP and negatively correlated with FEV1. Conclusions. GER was found in 49% of our patients with childhood DA. Very high ISSP levels in children with DA may be used as a marker for presence of GERD. Esomeprazole therapy improved asthma symptoms but did not improve lung function.

  17. Relationship Between Atopy and Bronchial Hyperresponsiveness

    OpenAIRE

    Suh, Dong In; Koh, Young Yull

    2013-01-01

    Both atopy and bronchial hyperresponsiveness (BHR) are characteristic features of asthma. They are also found among non-asthmatic subjects, including allergic rhinitis patients and the general population. Atopy and BHR in asthma are closely related. Atopy induces airway inflammation as an IgE response to a specific allergen, which causes or amplifies BHR. Moreover, significant evidence of the close relationship between atopy and BHR has been found in non-asthmatic subjects. In this article, w...

  18. Pigment Epithelium-Derived Factor (PEDF) Protects Osteoblastic Cell Line from Glucocorticoid-Induced Apoptosis via PEDF-R.

    Science.gov (United States)

    Yao, Shengcheng; Zhang, Yingnan; Wang, Xiaoyu; Zhao, Fengchao; Sun, Maji; Zheng, Xin; Dong, Hongyan; Guo, Kaijin

    2016-01-01

    Pigment epithelial-derived factor (PEDF) is known as a widely expressed multifunctional secreted glycoprotein whose biological actions are cell-type dependent. Recent studies demonstrated that PEDF displays cytoprotective activity in several cell types. However, it remains unknown whether PEDF is involved in glucocorticoid-induced osteoblast death. The aim of this study was to examine the role of PEDF in osteoblast survival in response to dexamethasone, an active glucocorticoid analogue, and explore the underlying mechanism. In the present study, dexamethasone (DEX) was used to induce MC3T3-E1 pre-osteoblast apoptosis. PEDF mRNA and protein levels and cell apoptosis were determined respectively. Then PEDF receptor (PEDF-R)- and lysophosphatidic acid (LPA)-related signal transductions were assessed. Here we show that DEX down-regulates PEDF expression, which contributes to osteoblast apoptosis. As a result, exogenous recombinant PEDF (rPEDF) inhibited DEX-induced cell apoptosis. We confirmed that PEDF-R was expressed on MC3T3-E1 pre-osteoblast membrane and could bind to PEDF which increased the level of LPA and activated the phosphorylation of Akt. Our results suggest that PEDF attenuated DEX-induced apoptosis in MC3T3-E1 pre-osteoblasts through LPA-dependent Akt activation via PEDF-R. PMID:27187377

  19. Upregulation of miR-27a contributes to the malignant transformation of human bronchial epithelial cells induced by SV40 small T antigen.

    Science.gov (United States)

    Wang, Q; Li, D-C; Li, Z-F; Liu, C-X; Xiao, Y-M; Zhang, B; Li, X-D; Zhao, J; Chen, L-P; Xing, X-M; Tang, S-F; Lin, Y-C; Lai, Y-D; Yang, P; Zeng, J-L; Xiao, Q; Zeng, X-W; Lin, Z-N; Zhuang, Z-X; Zhuang, S-M; Chen, W

    2011-09-01

    The introduction of the Simian virus 40 (SV40) early region, the telomerase catalytic subunit (hTERT) and an oncogenic allele of H-Ras directly transforms primary human cells. SV40 small T antigen (ST), which forms a complex with protein phosphatase 2A (PP2A) and inhibits PP2A activity, is believed to have a critical role in the malignant transformation of human cells. Recent evidence has shown that aberrant microRNA (miRNA) expression patterns are correlated with cancer development. Here, we identified miR-27a as a differentially expressed miRNA in SV40 ST-expressing cells. miR-27a is upregulated in SV40 ST-transformed human bronchial epithelial cells (HBERST). Suppression of miR-27a expression in HBERST cells or lung cancer cell lines (NCI-H226 and SK-MES-1) that exhibited high levels of miR-27a expression lead to cell growth arrested in the G(0)-G(1) phase. In addition, suppression of miR-27a in HBERST cells attenuated the capacity of such cells to grow in an anchorage-independent manner. We also found that suppression of the PP2A B56γ expression resulted in upregulation of miR-27a similar to that achieved by the introduction of ST, indicating that dysregulation of miR-27a expression in ST-expressing cells was mediated by the ST-PP2A interaction. Moreover, we discovered that Fbxw7 gene encoding F-box/WD repeat-containing protein 7 was a potential miR-27a target validated by dual-luciferase reporter system analysis. The inverse correlation between miR-27a expression levels and Fbxw7 protein expression was further confirmed in both cell models and human tumor samples. Fbxw7 regulates cell-cycle progression through the ubiquitin-dependent proteolysis of a set of substrates, including c-Myc, c-Jun, cyclin E1 and Notch 1. Thus, promotion of cell growth arising from the suppression of Fbxw7 by miR-27a overexpression might be responsible for the viral oncoprotein ST-induced malignant transformation. These observations demonstrate that miR-27a functions as an oncogene

  20. [Bronchial mucoepidermoid carcinoma].

    Science.gov (United States)

    Bregante, J I; Rituerto, B; Font de Mora, F; Alonso, F; Andreu, M J; Figuerola, J; Mulet, J F

    1998-07-01

    We submit the case of a child afflicted with a mucoepidermoid bronchial tumor. The patient is a boy, aged seven, who after undergoing antibiotic treatment for six weeks because of a fever and atelectasia-condensation in the right lower lobe showed no signs of clinical improvement and was sent to our department to undergo further study and treatment. A bronchoscopy performed shows a polypoid mass that partially blocks the main bronchial tube a few milimiters under the access to the right upper lobe. A biopsy is carried out and the anatomopathological test shows there is a low degree epidermoid carcinoma. We decide to perform a lobectomy which for the tumor location and the lung condition has to be medium and lower right. We proceed to remove the adenopaty of hilium not affected by the tumor. The postoperative period develops without incidents. A check-up bronchoscopy performed three months later shows two polypoid masses in the right bronchial tube which, once a biopsy is performed, proved to be granulation tissue. Twelve months after undergoing surgery, the patient's condition is good, there is no evidence of tumor relapse and the breathing capacity is adequate, though there is an obstructive restrictive pattern in the espirometry. Even taking into consideration that lung tumors are extremely unusual, the epidermoid carcinoma is the one which most frequently occurs. The tumor's low malignancy is a sign that points to a good prognosis. Performing conservative surgery by means of bronchoplasty should be taken into account so as to keep the sequelae on the lung condition to a minimum, even though in this case the tumor location made it impossible. PMID:12602035

  1. Heavy ion induced DNA strand breaks and their repair in diploid cells of the epithelium of the lens

    International Nuclear Information System (INIS)

    This diploma thesis investigates by means of alkaline unwinding and neutral elution the induction of DNA strand breaks and of rejoining processes as an effect of irradiation with very heavy, accelerated ions. It is found that: The effectiveness of very heavy ions (Z > 18) increases per particle with higher ordinal number, and with increasing velocities. The relative biological effectiveness increases with higher particle masses and lower velocities. The effects of very heavy ions are determined both by the LET and by the particle track extension (specific energy) of the various particles. Heavy ions are much more effective than X-rays with regard to inducing double strand breaks, as compared to DNA single strand breaks induced. Rejoining processes induced by heavy ions have been found to be delayed and incomplete, as compared to the X-ray effects. The number of rejoining processes decreases with rising ordinal number. The experiments indicate that the irradiation with lead or uranium ions most probably makes rejoining impossible. (orig./MG)

  2. Malondialdehyde induces autophagy dysfunction and VEGF secretion in the retinal pigment epithelium in age-related macular degeneration.

    Science.gov (United States)

    Ye, Fuxiang; Kaneko, Hiroki; Hayashi, Yumi; Takayama, Kei; Hwang, Shiang-Jyi; Nishizawa, Yuji; Kimoto, Reona; Nagasaka, Yosuke; Tsunekawa, Taichi; Matsuura, Toshiyuki; Yasukawa, Tsutomu; Kondo, Takaaki; Terasaki, Hiroko

    2016-05-01

    Age-related macular degeneration (AMD) is a major cause of blindness in developed countries and is closely related to oxidative stress, which leads to lipid peroxidation. Malondialdehyde (MDA) is a major byproduct of polyunsaturated fatty acid (PUFA) peroxidation. Increased levels of MDA have been reported in eyes of AMD patients. However, little is known about the direct relationship between MDA and AMD. Here we show the biological importance of MDA in AMD pathogenesis. We first confirmed that MDA levels were significantly increased in eyes of AMD patients. In ARPE-19 cells, a human retinal pigment epithelial cell line, MDA treatment induced vascular endothelial growth factor (VEGF) expression alternation, cell junction disruption, and autophagy dysfunction that was also observed in eyes of AMD patients. The MDA-induced VEGF increase was inhibited by autophagy-lysosomal inhibitors. Intravitreal MDA injection in mice increased laser-induced choroidal neovascularization (laser-CNV) volumes. In a mouse model fed a high-linoleic acid diet for 3 months, we found a significant increase in MDA levels, autophagic activity, and laser-CNV volumes. Our study revealed an important role of MDA, which acts not only as a marker but also as a causative factor of AMD pathogenesis-related autophagy dysfunction. Furthermore, higher dietary intake of linoleic acid promoted CNV progression in mice with increased MDA levels. PMID:26923802

  3. Allergen-induced bronchial hyperreactivity and eosinophilic inflammation occur in the absence of IgE in a mouse model of asthma

    OpenAIRE

    Mehlhop, Paul D.; van de Rijn, Matthijs; Goldberg, Alison B.; Brewer, Joanne P.; Kurup, Viswanath P.; Martin, Thomas R.; Oettgen, Hans C.

    1997-01-01

    In patients with asthma, elevations of IgE correlate both with allergic inflammation of the airways and with bronchial hyperreactivity (BHR). Several investigations, using mouse models of this disease, have indicated a central role for IgE in the pathogenesis of the eosinophilic inflammation as well as in the obstructive airway physiology of BHR. Some diagnostic studies and therapeutic strategies for asthma are based on the putative role of IgE in asthma pathogenesis. Here, we use mice with a...

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

    OpenAIRE

    Doerner, Astrid M; Zuraw, Bruce L

    2009-01-01

    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 o...

  5. Requirement of the Shigella flexneri Virulence Plasmid in the Ability To Induce Trafficking of Neutrophils across Polarized Monolayers of the Intestinal Epithelium

    OpenAIRE

    McCormick, Beth A.; Siber, Andrew M.; Maurelli, Anthony T.

    1998-01-01

    Attachment of an array of enteric pathogens to epithelial surfaces is accompanied by recruitment of polymorphonuclear leukocytes (PMN) across the intestinal epithelium. In this report, we examine how Shigella-intestinal epithelium interactions evoke the mucosal inflammatory response. We modeled these interactions in vitro by using polarized monolayers of the human intestinal epithelial cell line, T84, isolated human PMNs, and Shigella flexneri. We show that Shigella attachment to T84-cell bas...

  6. Antioxidant ability and radiosensitivity in malignant transformed human bronchial epithelial cell line BEP2D induced by α-particle irradiation

    International Nuclear Information System (INIS)

    Objective: To investigate the antioxidant ability and radiosensitivity in the malignant transformed human bronchial epithelial cell line BEP2D induced by α-particle exposure. Methods: Glutathione Peroxidase (GPX), Catalase (CAT) and Glutathione (GSH) assay kits were employed to detect GPX and CAT enzyme abilities and the levels of GSH in BEP2D, RH21 (passage 21 of α-particle-irradiated BEP2D cells), and BERP35T-1 cells (derived from nude mice bearing malignant transformed cells generated from cells of passage 35 of α-particle-irradiated BEP2D cells). MTT assay were used to test the growth rate of BEP2D, RH21 and BERP35T-1 cells treated with 0, 30, 60, 90, 120, and 150 μmoL/L H2O2. Colony-forming test and MTT assay were used to examine the cell survival fraction and the growth rate of BEP2D, RH21 and BERP35T-1 cells exposed to 0, 2, 4, and 8 Gy of γ-rays,respectively. Results: GPX and CAT enzyme activities in RH21 and BERP35T-1 cells were obviously lower than in BEP2D (t=5.75-67.92, P<0.05). CAT enzyme activity in BERP35T-1 was lower than that in RH21 cells (t=22.25, P<0.01). Compared to BEP2D cells, decreased level of GSH was detected in BERP35T-1 cells (t=7.76, P<0.05), but there was no change in RH21. After treatment with 30, 60, 90, 120, and 150 μmol/L H2O2, the growth rates of BEP2D were all higher than those of BERP35T-1 cells (t=10.37-58.36, P<0.01). Meanwhile,the growth rates of BEP2D were all higher than those of RH21 cells after treatment with 60, 90, 120, and 150 μ mol/L H2O2 (t =29.90-84.68, P<0.01). In addition,compared to BEP2D cells,decreased cell survival fraction and growth rate of BERP35T-1 cells were observed after irradiation with 2, 4, and 8 Gy of y-rays (t=5.87-34.17, P<0.05). The cell survival fraction and growth rate of RH21 were all lower than those of BEP2D cells at 4 and 8 Gy post-irradiation (t=6.33- 45.00, P<0.05). Conclusion: The function of antioxidant system decreased in the α-particle-induced transformed cells, which could

  7. Tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces cell proliferation in normal human bronchial epithelial cells through NFκB activation and cyclin D1 up-regulation

    International Nuclear Information System (INIS)

    Cigarette smoke contains several carcinogens known to initiate and promote tumorigenesis as well as metastasis. Nicotine is one of the major components of the cigarette smoke and the 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a tobacco-specific carcinogen. Here, we demonstrated that NNK stimulated cell proliferation in normal human bronchial epithelial cells (NHBE) and small airway epithelial cells (SAEC). Cells exposed to NNK resulted in an increase in the level of cyclin D1 protein (as early as 3-6 h). Increased phosphorylation of the Rb Ser795 was detected at 6-15 h after NNK treatment and thereby promoted cells entering into the S phase (at 15-21 h). The increased cyclin D1 protein level was induced through activation of the transcription factor, nuclear factor kB (NFκB), in the NHBE cells. Treatment of the NHBE cells with PD98059, an ERK1/2 (extracellular signal-regulated protein kinase)-specific inhibitor, specifically suppressed the NNK-induced IκBα phosphorylation at position 32 of the serine residue, suggesting that the ERK1/2 kinase was involved in the IκBα phosphorylation induced by NFκB activation. To determine whether the NNK-induced NFκB activation and cyclin D1 induction were also observed in vivo, A/J mice were treated with NNK (9.1 mg) for 20 weeks and the results showed a significant induction of cyclin D1 and NFκB translocation determined by immunoblotting analyses. We further demonstrated that the nicotine acetylcholine receptor (nAchR), which contains the α3-subunit, was the major target mediating NNK-induced cyclin D1 expression in the NHBE cells. In summary, our findings demonstrate for the first time that NNK could stimulate normal human bronchial cell proliferation through activation of the NFκB, which in turn up-regulated the cyclin D1 expression

  8. Radioimmunological allergy diagnostics in infants suffering from asthmatoid bronchitis, bronchial asthma, and hay fever

    International Nuclear Information System (INIS)

    The occurence of circulating specific antibodies against milk protein, hen protein, fish (cod), against cat, dog and horse epithelium as well as against 2 types of house dust was investigated with 11 children in the age of 1-6 years having asthmatoid bronchitis, 23 children aging from 2-15 years with bronchial asthma and 3 children aging from 6-13 years with hay fever, using the radioallergosorbens test (RAST). Children having asthmatoid bronchitis for the first time exhibited a smaller number and a lesser extent of positive radioallergosorben test results then children with bronchial asthma. The children with hay fever exhibited exclusively negative test results. (orig./LN)

  9. Radiation-induced functional damages in the regeneration system for the gastrointestinal epithelium cell and analysis of its nutritional modification

    International Nuclear Information System (INIS)

    It has been known that the stem cells of villus-crypt zone are highly sensitive to radiation exposure. In this study, radiation-induced damages in gastrointestinal cell regeneration system were investigated from an aspect of nutritional factors to clarify the damages in digestive functions caused by X-ray exposure and recovery from them. The activities of digestive enzymes in the small intestine after in vivo X-ray exposure at 100 Gy were determined. The sucrose activity in the upper intestine was gradually reduced to about a half 3 days after the exposure. This change pattern of activity was also observed in other regions in the intestine. This tendency was similar to that of trehalase activity, but the changes in alkaline phosphatase and leucine amino-peptidase activities were less than the above two enzymes. Therefore, time course changes of sucrose and trehalase pattern in the villus-crypt zone were monitored after radiation exposure. Either of the two enzyme activities was low in the crypt and gradually increased from the basement of villus to its top. These activities were dose-dependently reduced by X-ray exposure. Especially it was marked for trehalose activity. Moreover, the amounts of short-chain fatty acids such as acetic acid, propionic acid, butylic acid in the cecum were determined. Significant increases in acetic acid and propionic acid contents were fount at 1 or 2 days after the X-ray exposure. These increases in fatty acids contents were more distinctive in the animals that received forced and free administration of food than those that received free administration alone. The presence of food components in the intestine might be effective for protecting the mucous membrane regeneration from radiation exposure. (M.N.)

  10. Immunomodulation of airway epithelium cell activation by mesenchymal stromal cells ameliorates house dust mite-induced airway inflammation in mice.

    Science.gov (United States)

    Duong, Khang M; Arikkatt, Jaisy; Ullah, M Ashik; Lynch, Jason P; Zhang, Vivian; Atkinson, Kerry; Sly, Peter D; Phipps, Simon

    2015-11-01

    Allergic asthma is underpinned by T helper 2 (Th2) inflammation. Redundancy in Th2 cytokine function and production by innate and adaptive immune cells suggests that strategies aimed at immunomodulation may prove more beneficial. Hence, we sought to determine whether administration of mesenchymal stromal cells (MSCs) to house dust mite (HDM) (Dermatophagoides pteronyssinus)-sensitized mice would suppress the development of Th2 inflammation and airway hyperresponsiveness (AHR) after HDM challenge. We report that the intravenous administration of allogeneic donor MSCs 1 hour before allergen challenge significantly attenuated the features of allergic asthma, including tissue eosinophilia, Th2 cytokine (IL-5 and IL-13) levels in bronchoalveolar lavage fluid, and AHR. The number of infiltrating type 2 innate lymphoid cells was not affected by MSC transfer, suggesting that MSCs may modulate the adaptive arm of Th2 immunity. The effect of MSC administration was long lasting; all features of allergic airway disease were significantly suppressed in response to a second round of HDM challenge 4 weeks after MSC administration. Further, we observed that MSCs decreased the release of epithelial cell-derived alarmins IL-1α and high mobility group box-1 in an IL-1 receptor antagonist-dependent manner. This significantly decreased the expression of the pro-Th2 cytokine IL-25 and reduced the number of activated and antigen-acquiring CD11c(+)CD11b(+) dendritic cells in the lung and mediastinal lymph nodes. Our findings suggest that MSC administration can ameliorate allergic airway inflammation by blunting the amplification of epithelial-derived inflammatory cytokines induced by HDM exposure and may offer long-term protection against Th2-mediated allergic airway inflammation and AHR. PMID:25789608

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

    Science.gov (United States)

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

    2012-01-01

    Persistent respiratory syncytial virus (RSV) infections have been associated with the exacerbation of chronic inflammatory diseases, including chronic obstructive pulmonary disease (COPD). This virus infects the respiratory epithelium, leading to chronic inflammation, and induces the release of mucins and the loss of cilia activity, two factors that determine mucus clearance and the increase in sputum volume. These alterations involve reactive oxygen species-dependent mechanisms. The antioxidant N-acetylcysteine (NAC) has proven useful in the management of COPD, reducing symptoms, exacerbations, and accelerated lung function decline. NAC inhibits RSV infection and mucin release in human A549 cells. The main objective of this study was to analyze the effects of NAC in modulating ciliary activity, ciliagenesis, and metaplasia in primary normal human bronchial epithelial cell (NHBEC) cultures infected with RSV. Our results indicated that RSV induced ultrastructural abnormalities in axonemal basal bodies and decreased the expression of β-tubulin as well as two genes involved in ciliagenesis, FOXJ1 and DNAI2. These alterations led to a decrease in ciliary activity. Furthermore, RSV induced metaplastic changes to the epithelium and increased the number of goblet cells and the expression of MUC5AC and GOB5. NAC restored the normal functions of the epithelium, inhibiting ICAM1 expression, subsequent RSV infection through mechanisms involving nuclear receptor factor 2, and the expression of heme oxygenase 1, which correlated with the restoration of the antioxidant capacity, the intracellular H(2)O(2) levels and glutathione content of NHBECs. The results presented in this study support the therapeutic use of NAC for the management of chronic respiratory diseases, including COPD. PMID:23118923

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

    Directory of Open Access Journals (Sweden)

    Manuel Mata

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

  13. Reflexology and bronchial asthma

    DEFF Research Database (Denmark)

    Brygge, T; Heinig, J H; Collins, P;

    2001-01-01

    Many asthma patients seek alternative or adjunctive therapies. One such modality is reflexology, whereby finger pressure is applied to certain parts of the body. The aim of the study was to examine the popular claim that reflexology treatment benefits bronchial asthma. Ten weeks of active or...... simulated (placebo) reflexology given by an experienced reflexologist, were compared in an otherwise blind, controlled trial of 20+20 outpatients with asthma. Objective lung function tests (peak flow morning and evening, and weekly spirometry at the clinic) did not change. Subjective scores (describing...... diaries was carried out. It was accompanied by a significant pattern compatible with subconscious unblinding, in that patients tended to guess which treatment they had been receiving. No evidence was found that reflexology has a specific effect on asthma beyond placebo influence....

  14. Functional Effects of WNT1-Inducible Signaling Pathway Protein-1 on Bronchial Smooth Muscle Cell Migration and Proliferation in OVA-Induced Airway Remodeling.

    Science.gov (United States)

    Yang, Mingjin; Du, Yuejun; Xu, Zhibo; Jiang, Youfan

    2016-02-01

    Upregulation of WISP1 has been demonstrated in lung remodeling. Moreover, it has been recently found that some signaling components of WNT pathway can activate GSK3β signaling to mediate remodeling of airway smooth muscle (ASM) in asthma. Therefore, we hypothesized that WISP1, a signaling molecule downstream of the WNT signaling pathway, is involved in PI3K/GSK3β signaling to mediate ASM remodeling in asthma. Our results showed that WISP1 depletion partly suppressed OVA-induced ASM hypertrophy in vivo. In vitro, WISP1 could induce hBSMC hypertrophy and proliferation, accompanied by upregulation of levels of PI3K, p-Akt, p-GSK3β, and its own expression. TGF-β treatment could increase expression of PI3K, p-Akt, p-GSK3β, and WISP1. SH-5 treatment could partly suppress TGF-β-induced hypertrophy and proliferation of hBSMC, and depress expression of p-GSK3β and WISP1. In conclusion, WISP1 may be a potential inducer of ASM proliferation and hypertrophy in asthma. The pro-remodeling effect of WISP1 is likely due to be involved in PI3K-GSK3β-dependent noncanonical TGF-β signaling. PMID:26242865

  15. EXPRESSION OF рSTAT3 TRANSCRIPTION FACTOR IN PERIPHERAL BLOOD MONONUCLEAR CELLS AND ITS LEPTIN-INDUCED MODULATION IN BRONCHIAL ASTHMA

    Directory of Open Access Journals (Sweden)

    V. N. Mineev

    2015-01-01

    Full Text Available The aim of this study was to evaluate expression rates of phosphorylated STAT3 (рSTAT3 transcription factor in peripheral blood mononuclear cells (PBMC and some features of its modulation by leptin in various clinical forma of bronchial asthma (BA. Materials and methods. We evaluated 25 healthy persons and 62 BA patients. pSTAT3 expression in PBMC was measured by means of flow cytometry.Results. A phenomenon of increased pSTAT3 expression was registered in PBMC from BA patients. A most sufficient elevation of pSTAT3 levels was revealed in allergic clinical variant of the disorder. Leptin was shown to increase pSTAT3 expression in PBMCs from healthy persons only. In allergic BA, such effect of leptin was not observed, whereas a trend for pSTAT increase was shown in non-allergic BA. In allergic BA, we have revealed a direct correlation between the STAT3-mediated leptin signaling index and bronchial patency parameters. Appropriate inverse correlation was registered in non-allergic BA.Conclusion. We have revealed some characteristics of рSTAT3 expression in PBMCs and its modulation by leptin in various clinical forms of BA, thus providing a potential basis for development of targeted therapy aimed for transduction of different cytokine signals mediated by STAT3 transcription factor.

  16. Statistical analysis of anionic detergent-induced changes in the goblet mucous cells of opercular epidermis and gill epithelium of Rita rita (Ham.) (Bagridae: Pisces).

    Science.gov (United States)

    Roy, D

    1988-06-01

    Rita rita exposed to 96-hr LC50 (6.9 mg/liter) of an anionic detergent, dodecylbenzene sodium sulfonate, show significant changes in the number and size of goblet mucous cells in the opercular epidermis as well as in the lining epithelium of the gill arch and the gill filament at different time intervals of treatment. A shift in the staining nature of these cells from acidic glycoprotein to neutral glycoprotein, acidic glycosaminoglycans in the opercular epidermis and acidic glycoprotein to neutral glycoprotein and then again to acidic glycoprotein + acidic glycosaminoglycans in the gill filament epithelium reflects a change in the physiological status of fish. PMID:3168874

  17. House dust mite allergen Der f enhanced bronchial epithelial cell cytokine expression

    Institute of Scientific and Technical Information of China (English)

    BAO QING SUN; WEI TANG; ALBERT CHAN; ADRIAN WU; NAN SHAN ZHONG

    2006-01-01

    The house dust mites ( Dermatophagoides farinae, Der f) are the major source of aeroallergens implicated in the expression of atopic disorders, including asthma, allergic rhinitis and atopic dermatitis. In particular, strong circumstantial evidence suggests that house dust mite antigens are important precipitating factors of asthma. Many house dust mite allergens are proteases that can elicit airway inflammation by stimulating the release of cytokines from bronchial epithelial cells. To investigate whether Derf allergen proteases induced cytokine production from the epithelial cell line BEAS-2B,BEAS-2B cells were cultured with 4 different concentrations of Derf (0.02, 0.2, 2, 20 μg/ml) for 24-96 h, after which supernatants were assayed for interleukin (IL)-6 and IL-8 with ELISA. Reverse transcription-PCR was also performed. The cell sheets were intact throughout the observation in control group without any exposure to Derf antigen. In the experimental groups cells treated with Der f allergen showed changes in the anchorage status of the monolayer. There was a significant increase in the level of cytokine production compared with the untreated sample. The release of IL-6 and IL-8 increased in a concentration-dependent manner ( P < 0.05, respectively) with the addition of increasing dosage of Der f to the cell sheets. Levels of IL-6 and IL-8 began to rise at 24 h and 48 h after allergen exposure, and they increased significantly in the supernatants at 72 h and 96 h. At the same time the concentration dependence of induction of IL-6 and IL-8 expression as well as an increase in the expression of IL-6 and IL-8 mRNA manifested evidently. HDM-induced airway inflammation may include Der f-mediated release of inflammatory mediators, and the proteolytic activity of an allergen may stimulate the release of proinflammatory cytokines from human bronchial epithelium. It is suggested that IL-6 and IL-8 production by bronchial epithelial cells may play a role in the

  18. Effect of COPD treatments on MRP1-mediated transport in bronchial epithelial cells

    Directory of Open Access Journals (Sweden)

    Margaretha van der Deen

    2008-10-01

    Full Text Available Margaretha van der Deen1, Sandra Homan1, Hetty Timmer-Bosscha1, Rik J Scheper2, Wim Timens3, Dirkje S Postma4, Elisabeth G de Vries1Departments of 1Medical Oncology, 3Pathology, 4Pulmonary Diseases, University Medical Center Groningen and University of Groningen, The Netherlands; 2Department of Pathology, VU University Medical Center, Amsterdam, The NetherlandsBackground: Smoking is the principle risk factor for development of chronic obstructive pulmonary disease (COPD. Multidrug resistance-associated protein 1 (MRP1 is known to protect against toxic compounds and oxidative stress, and might play a role in protection against smoke-induced disease progression. We questioned whether MRP1-mediated transport is influenced by pulmonary drugs that are commonly prescribed in COPD.Methods: The immortalized human bronchial epithelial cell line 16HBE14o- was used to analyze direct in vitro effects of budesonide, formoterol, ipratropium bromide and N-acetylcysteine (NAC on MRP1-mediated transport. Carboxyfluorescein (CF was used as a model MRP1 substrate and was measured with functional flow cytometry.Results: Formoterol had a minor effect, whereas budesonide concentration-dependently decreased CF transport by MRP1. Remarkably, addition of formoterol to the highest concentration of budesonide increased CF transport. Ipratropium bromide inhibited CF transport at low concentrations and tended to increase CF transport at higher levels. NAC increased CF transport by MRP1 in a concentration-dependent manner.Conclusions: Our data suggest that, besides their positive effects on respiratory symptoms, budesonide, formoterol, ipratropium bromide, and NAC modulate MRP1 activity in bronchial epithelial cells. Further studies are required to assess whether stimulation of MRP1 activity is beneficial for long-term treatment of COPD.Keywords: bronchus epithelium, COPD, drugs, MRP1, multidrug resistance, oxidative stress

  19. The gut microbiota engages different signaling pathways to induce Duox2 expression in the ileum and colon epithelium

    DEFF Research Database (Denmark)

    Sommer, F; Bäckhed, Gert Fredrik

    2015-01-01

    The epithelium is a first line of defense against microorganisms in the gut. Reactive oxygen species (ROS) have an important role in controlling the normal gut microbiota and pathogenic bacteria. Dual oxidase 2 (DUOX2) is an important source of hydrogen peroxide in the small and large intestine, ...

  20. [A case of pulmonary sarcoidosis complicated with bronchial asthma that proved eosinophilic invasion].

    Science.gov (United States)

    Harada, Tomoya; Kawasaki, Yuji; Touge, Hirokazu; Tokuyasu, Hirokazu; Yamasaki, Akira; Shimizu, Eiji

    2012-12-01

    A 33-year-old man complaining of cough admitted our hospital for examination of bilateral hilar and mediastinal lymphadenopathy. He diagnosed pulmonary sarcoidosis, because of elevation of serum angiotensin converting enzyme (ACE), epitheloid granuloma with noncaseating necrosis from transbronchial lung biopsy (TBLB) specimen, increasing of lymphocyte and elevation of the CD4/CD8 ratio in bronchoalveolar lavage fluid (BALF). Furthermore, eosinophil ratio in BALF was 3%, hyperplasia of goblet cell, eosinophilic invasion to bronchial epithelium, and thickened basal membrane were found in same biopsy specimen. He had mild reversible airway obstruction. He was diagnosed pulmonary sarcoidosis complicated with bronchial asthma. Sarcoidosis is characteristic of the T helper type 1 (Th1) mediated immune response, and bronchial asthma is characteristic of the Th2. This case histopathologically revealed that both Th1 mediated immune response and Th2 could be coexisted. PMID:23466616

  1. The innate immune response of equine bronchial epithelial cells is altered by training

    OpenAIRE

    Frellstedt, Linda; Gosset, Philippe; Kervoaze, Gwenola; Hans, Aymeric; Desmet, Christophe; Pirottin, Dimitri; Bureau, Fabrice; Lekeux, Pierre; Art, Tatiana

    2015-01-01

    AbstractRespiratory diseases, including inflammatory airway disease (IAD), viral and bacterial infections, are common problems in exercising horses. The airway epithelium constitutes a major physical barrier against airborne infections and plays an essential role in the lung innate immune response mainly through toll-like receptor (TLR) activation. The aim of this study was to develop a model for the culture of equine bronchial epithelial cells (EBEC) in vitro and to explore EBEC innate immun...

  2. The Impact of Allergic Rhinitis and Asthma on Human Nasal and Bronchial Epithelial Gene Expression

    OpenAIRE

    Ariane H. Wagener; Aeilko H Zwinderman; Luiten, Silvia; Fokkens, Wytske J; Bel, Elisabeth H; Sterk, Peter J.; van Drunen, Cornelis M

    2013-01-01

    Background The link between upper and lower airways in patients with both asthma and allergic rhinitis is still poorly understood. As the biological complexity of these disorders can be captured by gene expression profiling we hypothesized that the clinical expression of rhinitis and/or asthma is related to differential gene expression between upper and lower airways epithelium. Objective Defining gene expression profiles of primary nasal and bronchial epithelial cells from the same individua...

  3. Respiratory syncytial virus infection in sheep bronchial explants is associated with enhanced ETB receptor-mediate contractile functional and autoradiographic studies

    International Nuclear Information System (INIS)

    Full text: Respiratory syncytial virus (RSV) is an important precipitant of asthma in children. The impact of RSV infection on endothelin (ET) receptor density and function in airways is unknown. In the present study, sheep bronchial rings were maintained as explants in culture for up to 48 h. During this time, both the structural integrity of the epithelium and carbachol responsiveness were preserved. Bronchial rings in culture were exposed to non-infected culture medium or to RSV (1/50 TCID50) for 0, 24 and 48 h which caused marked damage to and loss of the epithelium. RSV infection did not significantly alter responsiveness to ET-1 at either 24 (Control EC40 = 102 nM, 95% confidence limits, 76-138 nM vs RSV EC40 = 66 nM, 95% confidence limits, 48-91 nM, n=5-6, P>0.05) or 48 h (Control EC40 35 nM, 95% confidence limits, 19-66 nM vs RSV EC40 = 55 nM, 95% confidence limits, 32-93 nM, n=8, P>0.05). As seen previously (Goldie et al., 1994), sarafotoxin S6c (StxS6c, ETB-selective) did not cause contraction in non-infected sheep bronchial explants. In contrast, StxS6c (300 nM) increased tone by 8±3% carbachol Emax (n=6-8) in explants exposed to RSV for 24 or 48 h. Light microscopic autoradiography was used to determine the relative distribution of ETA and ETB receptors using [125I]-ET-1, BQ-123 (ETA-selective) and StxS6c. Sheep airway smooth muscle contains a homogeneous population of ETA receptors (Goldie et al., 1994). Since StxS6c caused significant contraction in RSV-infected bronchial explants, it was surprising that autoradiographic techniques failed to detect airway smooth muscle ETB receptors in these preparations. It is likely that ETB receptors fell below the level of detection of autoradiography. The significant StxS6c-induced contraction of sheep bronchi suggests the novel expression of ETB receptors triggered by RSV which might be relevant to RSV-associated asthma. Copyright (2001) Australasian Society of Clinical and Experimental Pharmacologists and

  4. Bronchial mucoepidermoid carcinoma: CT findings

    International Nuclear Information System (INIS)

    Mucoepidermoid carcinoma of the bronchus is an extremely rare tracheobronchial neoplasm arising in the bronchial submucosal glands that shows an intimate admixture of glandular elements and sheets of cells with little or no definite squamous differentiation. We report 2 cases of mucoepidermoid carcinoma of the bronchus found in a 15-year-old boy and a 59-year-old woman. CT scans revealed a well-marginated, exophytic, endobronchial, polypoid soft tissue mass. Bronchial mucoepidermoid carcinoma should be included in the differential diagnosis of endobronchial tumors in young patients and non-smokers

  5. Bronchial mucoepidermoid carcinoma: CT findings

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyun; Kang, Si Won; Ahn, Kuk Jin; Bahk, Yong Whee [Daejeon St. Mary' s Hospital, Catholic University Medical Colleg, Daejeon (Korea, Republic of)

    1991-03-15

    Mucoepidermoid carcinoma of the bronchus is an extremely rare tracheobronchial neoplasm arising in the bronchial submucosal glands that shows an intimate admixture of glandular elements and sheets of cells with little or no definite squamous differentiation. We report 2 cases of mucoepidermoid carcinoma of the bronchus found in a 15-year-old boy and a 59-year-old woman. CT scans revealed a well-marginated, exophytic, endobronchial, polypoid soft tissue mass. Bronchial mucoepidermoid carcinoma should be included in the differential diagnosis of endobronchial tumors in young patients and non-smokers.

  6. Arrest in ciliated cell expansion on the bronchial lining of adult rats caused by chronic exposure to industrial noise

    International Nuclear Information System (INIS)

    Workers chronically exposed to high-intensity/low-frequency noise at textile plants show increased frequency of respiratory infections. This phenomenon prompted the herein investigation on the cytology of the bronchial epithelium of Wistar rats submitted to textile noise. Workplace noise from a cotton-mill room of a textile factory was recorded and reproduced in a sound-insulated animal room. The Wistar rats were submitted to a weekly schedule of noise treatment that was similar to that of the textile workers (8h/day, 5 days/week). Scanning electron microscopy (SEM) was used to compare the fine morphology of the inner surface of the bronchi in noise-exposed and control rats. SEM quantitative cytology revealed that exposure to noise for 5-7 months caused inhibition in the natural expansion of the area occupied by ciliated cells on the bronchial epithelium as adult rats grow older. This difference between noise-exposed and age-matched control rats was statistically significant (P0.05) and documents that the cytology of the rat bronchial epithelium is mildly altered by noise exposure. The decrease in the area of bronchial cilia may impair the mucociliar clearance of the respiratory airways and, thus, increase vulnerability to respiratory infection

  7. Nuclear respiratory factor 1 overexpression attenuates anti-benzopyrene‑7,8-diol-9,10-epoxide-induced S-phase arrest of bronchial epithelial cells.

    Science.gov (United States)

    Wu, Jing; Wang, Yaning; Wo, Da; Zhang, Lijuan; Li, Jue

    2016-05-01

    Nuclear respiratory factor 1 (NRF-1) has important roles in the regulation of several key metabolic genes required for cellular growth and respiration. A previous study by our group indicated that NRF‑1 is involved in mitochondrial dysfunction induced by the environmental pollutant benzo[a]pyrene in the 16HBE human bronchial epithelial cell line. In the present study, it was observed that its genotoxic metabolite, anti‑benzopyrene‑7,8‑diol‑9,10‑epoxide (BPDE), triggered cell cycle arrest in S‑phase in 16HBE cells by activating ataxia-telangiectasia (ATM)/checkpoint kinase (Chk)2 and ATM and Rad3 related (ATR)/Chk1 signaling pathways. NRF‑1 expression was suppressed by BPDE after treatment for 6 h. Flow cytometric analysis revealed that NRF‑1 overexpression attenuated cell cycle arrest in S‑phase induced by BPDE. In line with this result, DNA‑damage checkpoints were activated following NRF‑1 overexpression, as demonstrated by increased phosphorylation of ATM, Chk2 and γH2AX, but not ATR and Chk1, according to western blot analysis. It was therefore indicated that NRF‑1 overexpression attenuated BPDE‑induced S‑phase arrest via the ATM/Chk2 signaling pathway. PMID:27035420

  8. Bronchial neuroendocrine elements in late post-radiation stage in humans after total body irradiation

    International Nuclear Information System (INIS)

    It is not known how long-term total body irradiation affects the neuroendocrine cells (Nc) and peptidergic innervation in the bronchial wall. This study examined, by immunohistochemical and radioimmunoassay (RIA) techniques, the distribution of NC and neuropeptide-containing nerve fibres in the large bronchi of Chernobyl nuclear accident cleanup workers displaying pulmonary fibrosis and metaplastic epithelium. Bronchial mucous and submucous layers from 16 Chernobyl patients and 6 control subjects were examined by conventional light microscopy and immunohistochemical techniques for determination of protein gene product 9.5 (PGP), chromogranin A, chromogranin A and B (CAB), calcitonin gene-related peptide (CGRP), calcitonin, vasoactive intestinal peptide (VIP), gastrin-releasing peptide (GRP), helospectin I, neuropeptide Y (NPY), pituitary adenylate cyclase activating peptide (PACAP), serotonin (5-hydroxyltryptamine, 5-HT), and substance P (SP). Additionally, bronchial biopsies from 6 Chernobyl cleanup workers and 3 control patients were examined by RIA for VIP and NPY/peptideYY-Ievels. The Chernobyl patients were examined 10 years after exposure during the cleanup works in the Chernobyl Atomic Electric Power Station. PGP immunoreactive nerve fibres appeared to be more frequent in the bronchial wall after long term irradiation as compared with controls. However, no specific alterations in the amounts of NPY-, PACAP-, helospectin-, SP- and CGRP-immunoreactive nerve fibres were seen in bronchi of control and Chernobyl patients. 5-HT -immunoreactive NC appeared to be more numerous in normal bronchial epithelium adjacent to metaplastic epithelium, in which numerous CAB- immunoreactive NC were seen in Chernobyl patients. RIA for VIP and NPY/PYY showed individual variations in the levels of these peptides in the bronchial tissue. In two cases (one Chernobyl patient and one control patient) there was a high concentration of VIP in parallel with a high concentration of NPY

  9. Human bronchial epithelial cell injuries induced by fine particulate matter from sandstorm and non-sandstorm periods: Association with particle constituents.

    Science.gov (United States)

    Wang, Bin; Li, Ning; Deng, Furong; Buglak, Nicholas; Park, George; Su, Shu; Ren, Aiguo; Shen, Guofeng; Tao, Shu; Guo, Xinbiao

    2016-09-01

    Epidemiological studies have demonstrated the exacerbation of respiratory diseases following sandstorm-derived particulate matter (PM) exposure. The presence of anthropogenic and biological agents on the sandstorm PM and the escalation of PMsandstorms. We investigated how changes in PM2.5 composition, as the weather transitioned towards a sandstorm, affected human airway epithelial cells. Six PM2.5 samples covering two sandstorm events and their respective background and transition periods were collected in Baotou, an industrial city near the Gobi Desert in China. PM samples from all three periods had mild cytotoxicity in human bronchial epithelial cell line BEAS-2B, which was positively correlated with the contents of polycyclic aromatic hydrocarbons and several metals. All PM samples potently increased the release of interleukin-6 (IL-6) and interleukin-8 (IL-8). Endotoxin in all samples contributed significantly to the IL-6 response, with only a minor effect on IL-8. Cr was positively correlated with both IL-6 and IL-8 release, while Si was only associated with the increase of IL-6. Our study suggests that local agricultural and industrial surroundings in addition to the sandstorm play important roles in the respiratory effects of sandstorm-derived PM. PMID:27593287

  10. CHALLENGES IN BRONCHIAL CHALLENGE TESTING

    NARCIS (Netherlands)

    Lexmond, A. J.; Hagedoorn, P.; Frijlink, H. W.; de Boer, A. H.

    2013-01-01

    Background: In the adenosine 5'-monophosphate (AMP) bronchial challenge test, AMP is usually administered according to dosing protocols developed for histamine/methacholine. It has never been thoroughly investigated whether these protocols are suitable for AMP as well. Methods: The setup of the two-

  11. Impact Assessment of Cigarette Smoke Exposure on Organotypic Bronchial Epithelial Tissue Cultures: A Comparison of Mono-Culture and Coculture Model Containing Fibroblasts.

    Science.gov (United States)

    Iskandar, Anita R; Xiang, Yang; Frentzel, Stefan; Talikka, Marja; Leroy, Patrice; Kuehn, Diana; Guedj, Emmanuel; Martin, Florian; Mathis, Carole; Ivanov, Nikolai V; Peitsch, Manuel C; Hoeng, Julia

    2015-09-01

    Organotypic 3D cultures of epithelial cells are grown at the air-liquid interface (ALI) and resemble the in vivo counterparts. Although the complexity of in vivo cellular responses could be better manifested in coculture models in which additional cell types such as fibroblasts were incorporated, the presence of another cell type could mask the response of the other. This study reports the impact of whole cigarette smoke (CS) exposure on organotypic mono- and coculture models to evaluate the relevancy of organotypic models for toxicological assessment of aerosols. Two organotypic bronchial models were directly exposed to low and high concentrations of CS of the reference research cigarette 3R4F: monoculture of bronchial epithelial cells without fibroblasts (BR) and coculture with fibroblasts (BRF) models. Adenylate kinase (AK)-based cytotoxicity, cytochrome P450 (CYP) 1A1/1B1 activity, tissue histology, and concentrations of secreted mediators into the basolateral media, as well as transcriptomes were evaluated following the CS exposure. The results demonstrated similar impact of CS on the AK-based cytotoxicity, CYP1A1/1B1 activity, and tissue histology in both models. However, a greater number of secreted mediators was identified in the basolateral media of the monoculture than in the coculture models. Furthermore, annotation analysis and network-based systems biology analysis of the transcriptomic profiles indicated a more prominent cellular stress and tissue damage following CS in the monoculture epithelium model without fibroblasts. Finally, our results indicated that an in vivo smoking-induced xenobiotic metabolism response of bronchial epithelial cells was better reflected from the in vitro CS-exposed coculture model. PMID:26085348

  12. Biomechanics of liquid-epithelium interactions in pulmonary airways

    OpenAIRE

    Ghadiali, Samir N.; Gaver, Donald P.

    2008-01-01

    The delicate structure of the lung epithelium makes it susceptible to surface tension induced injury. For example, the cyclic reopening of collapsed and/or fluid-filled airways during the ventilation of injured lungs generates hydrodynamic forces that further damage the epithelium and exacerbate lung injury. The interactions responsible for epithelial injury during airway reopening are fundamentally multiscale, since air-liquid interfacial dynamics affect global lung mechanics, while surface ...

  13. ORMDL3 is an inducible lung epithelial gene regulating metalloproteases, chemokines, OAS, and ATF6

    OpenAIRE

    Miller, Marina; Tam, Arvin B.; Cho, Jae Youn; Doherty, Taylor A.; Pham, Alexa; Khorram, Naseem; Rosenthal, Peter; Mueller, James L.; Hoffman, Hal M.; Suzukawa, Maho; Niwa, Maho; Broide, David H.

    2012-01-01

    Orosomucoid like 3 (ORMDL3) has been strongly linked with asthma in genetic association studies, but its function in asthma is unknown. We demonstrate that in mice ORMDL3 is an allergen and cytokine (IL-4 or IL-13) inducible endoplasmic reticulum (ER) gene expressed predominantly in airway epithelial cells. Allergen challenge induces a 127-fold increase in ORMDL3 mRNA in bronchial epithelium in WT mice, with lesser 15-fold increases in ORMDL-2 and no changes in ORMDL-1. Studies of STAT-6–defi...

  14. Study of Therapeutic Mechanism of Acupuncture in Treating Bronchial Asthma

    Institute of Scientific and Technical Information of China (English)

    LI; Ji

    2001-01-01

    It has been considered by modern medicine that bronchial asthma is a chronic airway allergic inflammation (AAI) which is the major factor that induces reversible airway ventilating disturbance and bronchial hyper-responsiveness (BHR) in asthmatic patients, as well as a correlation between the delayed-phase onset of asthma and AAI is more significant than immediate-phase onset of asthma in its pathogenesis. Anti-inflammatory therapy as a fundamental principle of treatment for bronchial asthma has been brought forward during the interval phase so that a large number of anti-AAI drugs to significantly enhance the curative effect such as inhalant corticoid, disodium cromoglycate, and leukotriene receptors antagonist, etc., has been rapidly developed. Additionally, traditional Chinese medicine (TCM) and integration of TCM and western medicine (WM) therapies, including acupuncture, are gradually taken into account by the medical circle as a characteristic in our country for treatment of bronchial asthma. It is worthy of being pointed out that the curative effect of acupuncture and moxibustion in treating asthma is evident, and that its therapeutic mechanism has to a certain extent, been found along with the recent deep-going acupunctural research.……

  15. Study of Therapeutic Mechanism of Acupuncture in Treating Bronchial Asthma

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@  It has been considered by modern medicine that bronchial asthma is a chronic airway allergic inflammation (AAI) which is the major factor that induces reversible airway ventilating disturbance and bronchial hyper-responsiveness (BHR) in asthmatic patients, as well as a correlation between the delayed-phase onset of asthma and AAI is more significant than immediate-phase onset of asthma in its pathogenesis. Anti-inflammatory therapy as a fundamental principle of treatment for bronchial asthma has been brought forward during the interval phase so that a large number of anti-AAI drugs to significantly enhance the curative effect such as inhalant corticoid, disodium cromoglycate, and leukotriene receptors antagonist, etc., has been rapidly developed. Additionally, traditional Chinese medicine (TCM) and integration of TCM and western medicine (WM) therapies, including acupuncture, are gradually taken into account by the medical circle as a characteristic in our country for treatment of bronchial asthma. It is worthy of being pointed out that the curative effect of acupuncture and moxibustion in treating asthma is evident, and that its therapeutic mechanism has to a certain extent, been found along with the recent deep-going acupunctural research.

  16. Asbestos and benzo[a]pyrene act synergistically to induce squamous metaplasia and incorporation of [3H]thymidine in hamster tracheal epithelium

    International Nuclear Information System (INIS)

    When exposed to either crocidolite asbestos (single 1-h exposure to 0.4 mg/ml medium) or the polycyclic aromatic hydrocarbon, benzo[a]pyrene (BaP) (less than or equal to 2.5 micrograms/ml medium, 1x weekly for 4 weeks), the epithelium of hamster tracheal explants exhibits insignificant amounts of squamous metaplasia, an atypical lesion, in comparison to amounts observed in untreated tissues. Incorporation of [3H]thymidine, an indication of DNA synthesis by epithelial cells, likewise is unchanged. However, the extent of squamous metaplasia and numbers of labeled basal and suprabasal cells are increased substantially when BaP and asbestos are added in combination. These results suggest an important mechanism of co-carcinogenesis involving chemical and physical carcinogens and support epidemiologic observations documenting an increased risk of bronchogenic carcinoma in asbestos workers who smoke

  17. Oilseed rape and bronchial reactivity.

    OpenAIRE

    Soutar, A; Harker, C; Seaton, A.; Packe, G

    1995-01-01

    OBJECTIVES--To investigate atopy and changes in symptoms, peak flow rate, and bronchial reactivity in people complaining of symptoms during the oilseed rape flowering season. METHODS--37 people who had given positive answers to questions about the presence of symptoms in relation to the flowering season of oilseed rape and 24 controls with no such symptoms were studied, although not all took part in all parts of the study. All had been previously identified in a cross sectional survey of a ra...

  18. Role of acetylcholine and polyspecific cation transporters in serotonin-induced bronchoconstriction in the mouse

    Directory of Open Access Journals (Sweden)

    Koepsell Hermann

    2006-04-01

    Full Text Available Abstract Background It has been proposed that serotonin (5-HT-mediated constriction of the murine trachea is largely dependent on acetylcholine (ACh released from the epithelium. We recently demonstrated that ACh can be released from non-neuronal cells by corticosteroid-sensitive polyspecific organic cation transporters (OCTs, which are also expressed by airway epithelial cells. Hence, the hypothesis emerged that 5-HT evokes bronchoconstriction by inducing release of ACh from epithelial cells via OCTs. Methods We tested this hypothesis by analysing bronchoconstriction in precision-cut murine lung slices using OCT and muscarinic ACh receptor knockout mouse strains. Epithelial ACh content was measured by HPLC, and the tissue distribution of OCT isoforms was determined by immunohistochemistry. Results Epithelial ACh content was significantly higher in OCT1/2 double-knockout mice (42 ± 10 % of the content of the epithelium-denuded trachea, n = 9 than in wild-type mice (16.8 ± 3.6 %, n = 11. In wild-type mice, 5-HT (1 μM caused a bronchoconstriction that slightly exceeded that evoked by muscarine (1 μM in intact bronchi but amounted to only 66% of the response to muscarine after epithelium removal. 5-HT-induced bronchoconstriction was undiminished in M2/M3 muscarinic ACh receptor double-knockout mice which were entirely unresponsive to muscarine. Corticosterone (1 μM significantly reduced 5-HT-induced bronchoconstriction in wild-type and OCT1/2 double-knockout mice, but not in OCT3 knockout mice. This effect persisted after removal of the bronchial epithelium. Immunohistochemistry localized OCT3 to the bronchial smooth muscle. Conclusion The doubling of airway epithelial ACh content in OCT1/2-/- mice is consistent with the concept that OCT1 and/or 2 mediate ACh release from the respiratory epithelium. This effect, however, does not contribute to 5-HT-induced constriction of murine intrapulmonary bronchi. Instead, this activity involves 1 a non

  19. Imaging diagnosis of bronchial asthma and related diseases

    International Nuclear Information System (INIS)

    We describe imaging features of bronchial asthma and related diseases. The practical roles of imaging diagnosis are the evaluation of severity and complications of bronchial asthma and differential diagnosis of diseases showing asthmatic symptoms other than bronchial asthma. (author)

  20. Distal bronchial tubes damage in patients with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    M V Sheyanov

    2009-12-01

    Full Text Available Objective. To study prevalence and clinical picture of distal parts of bronchial tree(bronchiolitis in pts with rheumatoid arthritis (RA. Material and methods. 104 nonsmoking pts with RA and 100 pts without RA and chronic diseases of respiratory apparatus were included. General clinical examination, spirometry, bodyplethysmography, examination of lung diffusion capacity (LDC and multispiralcomputed tomography (MSCT of lungs were performed. Results. Direct and indirect bronchiolitis signs were revealed with MSCT in 36 (35% ptswith RA and 1 pt of control group (p<0,01. Pts with signs of bronchiolitis complained of shortness of breath (69% of pts, cough (56%, phlegm discharge (56%, heavy breathing (25%. Obstructive lung ventilation disturbances were revealed in 19 (53% RA pts with bronchiolitis. Restrictive disturbances and LDC decrease were present in 3 (8% pts. High frequency of oligosymptomatic bronchiolitis course was found in RA pts. Bronchiolitis symptoms in RA pts coincided with signs of proximal bronchial tubes damage forming picture of diffuse damage of bronchial tree. Conclusion. Bronchiolitis is a prevalent variant of respiratory apparatus damage in pts with RA. Pts with MSCT signs of bronchiolitis often have cough, phlegm discharge, shortness of breath, heavy breathing. Lung ventilation disturbances of obstructive type are common but part of pts has normal lung functional measures or restriction. Oligosymptomatic forms of distal bronchial tubes damage are prevalent in RA pts. Lung MSCT is the main method of bronchiolitis diagnostics because bronchiolitis induces nonspecific clinical signs and RA pts have multilevel respiratory apparatus damage. MSCT reveals signs of distal bronchial tubes damage in 35% of RA pts.

  1. A contribution to radiotherapy of the larger-celled bronchial carcinoma

    International Nuclear Information System (INIS)

    This work consists of a retrospective definition of disease courses of 859 patients with lung tumors and the definition of the survival curves in their dependence on histology, radiation dose and sex. With 721 larger-celled bronchial carcinomas the ratio of men to women was 12:1. The age peak lay between 60 and 70 years. The one/five year survival rate of all included larger-celled bronchial carcinomas (n=701) was, independent from the therapy form, 35.7, resp. 4.78%. The one year/five year survival rates were for the squamous epithelia 31.08/0.58%, for the undifferentiated carcinomas 25.34/3.41%, and for the lung tumors without histology 35.4/5.14%. Lobectomized patients with squamous epithelium carcinoma had in comparison to pneumonectomized patients a clearly higher survival chance. A clearly sex-dependent predisposition for a certain type of carcinoma was not present. (TRV)

  2. "Bronchial Artery Delivery of Viral Vectors for Gene delivery in Cystic Fibrosis; Superior to Airway Delivery?"

    Directory of Open Access Journals (Sweden)

    Coutelle Charles C

    2002-04-01

    Full Text Available Abstract Background Attempts at gene therapy for the pulmonary manifestations of Cystic Fibrosis have relied mainly on airway delivery. However the efficiency of gene transfer and expression in the airway epithelia has not reached therapeutic levels. Access to epithelial cells is not homogenous for a number of reasons and the submucosal glands cannot be reached via the airways. Presentation We propose to inject gene delivery vectors directly into bronchial arteries combined with pre-delivery of vascular endothelial growth factor to increase vascular endothelial permeability and post-delivery flow reduction by balloon occlusion. Thus it may be possible to reach mucous secreting cells of the bronchial luminal epithelium and the submucosal glands in an increased and homogenous fashion. Testing This combination of techniques to the best of our knowledge has not previously been investigated, and may enable us to overcome some of the current limitations to gene therapy for Cystic Fibrosis.

  3. THE ROLE OF EPITHELIUM IN EXPERIMENTAL IMMUNIZATION.

    Science.gov (United States)

    Sewall, H

    1925-10-01

    When a small amount of blood serum is dropped into the nose of a guinea pig the serum is absorbed by the mucous membrane and, after a definite period of incubation, the animal can be shown to have become profoundly changed. Depending upon the number of instillations, the interval between them and, especially, the quantity of serum instilled, the animal becomes either highly hypersensitive or strongly resistant to a toxic injection given by the vein. This resistance withstands a considerable series of increasing toxic injections and is strengthened with lapse of time,-contrary to the state of tolerance produced by traumatic methods. It is inferred that the absorption of foreign protein by the nose causes the formation of two different antibodies. One of these is allergic and excites to anaphylaxis; the other is protective and leads to true immuuity. The relative amount of either antibody can be regulated by modifying the amount of serum instilled. Added to a state of general allergy it is easy to produce, in the guinea pig, a special sensitization of the respiratory apparatus which leads, under appropriate stimulation, to attacks resembling those of bronchial asthma in man. No conclusion can be drawn at present concerning the nature or mode of action of the protective or immunizing antibody; but the indications are that its relations to the circulation and to tissue fixation resemble those which have been developed by other investigators in regard to the anaphylactic antibody. Evidence has been submitted that the living epithelium mediates between foreign protein and the organism in a way to favor specifically the elaboration of true immunity. PMID:17748743

  4. Ozone Induces a Proinflammatory Response in Primary Human Bronchial Epithelial Cells Through Mitogen-Activated Protein Kinase Activation Without Nuclear Factor-kB Activation

    Science.gov (United States)

    Ground-level ozone (O3) is a ubiquitous environmental air pollutant that is a potent inducer of airway inflammation and has been linked with both respiratory and cardiovascular morbidity and mortality. Some studies using transformed or immortalized cells have attributed O3-medi...

  5. [Control of the intracellular signaling induced by fibroblast growth factors (FGF) over the proliferation and survival of retinal pigment epithelium cells: example of the signaling regulation of growth factors endogenous to the retina ].

    Science.gov (United States)

    Mascarelli, F; Hecquet, C; Guillonneau, X; Courtois, Y

    2001-01-01

    Retinal pigmented epithelium (RPE) cells are of central importance in the maintenance of neural retinal function. RPE cell apoptosis is responsible for the development of a variety of retinal degeneration. The role of FGF2 was investigated on RPE cell proliferation and apoptosis in vitro. In the absence of serum, RPE cells died by apoptosis, while the addition of FGF2 greatly reduces apoptosis over a 7-day culture period. This is due to an autocrine loop involving secretion of endogenous FGF1 in the mechanism that govern FGF2-induced resistance to apoptosis. FGF2 induces long-term activation of FGFR1 and ERK1/2, and production of the anti-apoptotic protein BcL-x. Because FGF1 has no classical signal sequence to direct its secretion, we investigated the effects of FGF1 secretion on RPE proliferation and apoptosis in the absence of exogenous FGF2. Forced secretion of endogenous FGF1 by adding a signal peptide to the FGF1 molecule induces FGF1 secretion and cell proliferation in the presence of serum, while in FGF1 stops to be secreted and cell die in the absence of serum. Conversely, in cells cultured in the presence of serum, FGF1 without signal peptide is not secreted, but is secreted and rescue RPE cell from apoptosis when cells are cultured without serum. Thus, the proliferation and survival activities of endogenous FGF1 depend on the secretion of FGF1 which is determined by the cell environment. PMID:11723820

  6. Accelerated repair and reduced mutagenicity of DNA damage induced by cigarette smoke in human bronchial cells transfected with E.coli formamidopyrimidine DNA glycosylase.

    Directory of Open Access Journals (Sweden)

    Mara Foresta

    Full Text Available Cigarette smoke (CS is associated to a number of pathologies including lung cancer. Its mutagenic and carcinogenic effects are partially linked to the presence of reactive oxygen species and polycyclic aromatic hydrocarbons (PAH inducing DNA damage. The bacterial DNA repair enzyme formamidopyrimidine DNA glycosylase (FPG repairs both oxidized bases and different types of bulky DNA adducts. We investigated in vitro whether FPG expression may enhance DNA repair of CS-damaged DNA and counteract the mutagenic effects of CS in human lung cells. NCI-H727 non small cell lung carcinoma cells were transfected with a plasmid vector expressing FPG fused to the Enhanced Green Fluorescent Protein (EGFP. Cells expressing the fusion protein EGFP-FPG displayed accelerated repair of adducts and DNA breaks induced by CS condensate. The mutant frequencies induced by low concentrations of CS condensate to the Na(+K(+-ATPase locus (oua(r were significantly reduced in cells expressing EGFP-FPG. Hence, expression of the bacterial DNA repair protein FPG stably protects human lung cells from the mutagenic effects of CS by improving cells' capacity to repair damaged DNA.

  7. Physical conditioning programme for children with bronchial asthma.

    Science.gov (United States)

    Olivia, C K

    1990-04-01

    Exercise-induced bronchospasm limits physical activity in most asthmatic children. Twelve children with stable chronic asthma were enrolled in a physical conditioning program to improve ventilation mechanics and to promote physical activity. The program consisted of eight weekly sessions of one-and-a-half hours each, followed by three months of weekly swimming lessons. The activities were preceded by a warm-up period and interspersed with rest. Premedication with an aerosol bronchodilator or sodium cromoglycate was allowed before training. Cardiorespiratory status was studied before and after the program. The program was well received by the children with no bronchospasm. Five showed improvement in lung volumes and/or flow rates. Bronchial liability remained the same. The basal heart rate slowed in four children. No significant arrhythmia was detected. With continued practice, cardiorespiratory function might improve further. The program should be incorporated as part of the overall management of bronchial asthma. PMID:2116067

  8. Cigarette Smoke and the Induction of Urokinase Plasminogen Activator Receptor In Vivo: Selective Contribution of Isoforms to Bronchial Epithelial Phenotype.

    Science.gov (United States)

    Portelli, Michael A; Stewart, Ceri E; Hall, Ian P; Brightling, Christopher E; Sayers, Ian

    2015-08-01

    The urokinase plasminogen activator receptor (uPAR) gene (PLAUR) has been identified as an asthma susceptibility gene, with polymorphisms within that gene being associated with baseline lung function, lung function decline, and lung function in a smoking population. Soluble cleaved uPAR (scuPAR), a molecule identified as a marker of increased morbidity and mortality in a number of diseases, has been shown to be elevated in the airways of patients with asthma and in patients with chronic obstructive pulmonary disease. However, the functionality of soluble receptor isoforms and their relationship with an important initiator for obstructive lung disease, cigarette smoke, remains undefined. In this study, we set out to determine the effect of cigarette smoke on soluble uPAR isoforms, its regulatory pathway and the resultant effect on bronchial epithelial cell function. We identified a positive association between cigarette pack-years and uPAR expression in the airway bronchial epithelium of biopsies from patients with asthma (n = 27; P = 0.0485). In vitro, cigarette smoke promoted cleavage of uPAR from the surface of bronchial epithelial cells (1.5× induction; P bronchial epithelial cells. This suggests that cigarette smoke elevates soluble receptor isoforms in bronchial epithelial cells through direct (cleavage) and indirect (messenger RNA expression) means. These findings provide further insight into how cigarette smoke may influence changes in the airways of importance to airway remodeling and obstructive lung disease progression. PMID:25490122

  9. Lung cancer induced in hamsters by low doses of alpha radiation from 210Po

    International Nuclear Information System (INIS)

    Lung cancers have been induced in 9 to 53 percent of hamsters given multiple intratracheal instillations of polonium-210 in amounts yielding lifetime exposures of 15 to 300 rads to the lungs. Cigarette smokers have previously been estimated to receive 20 rads to areas of the bronchial epithelium from deposited polonium-210. This finding thus supports the hypothesis that alpha radiation resulting from the polonium-210 or lead-210 present in cigarette smoke may be a significant causative factor in human lung cancer. (U.S.)

  10. Effects of Radix Adenophorae and Cyclosporine A on an OVA-Induced Murine Model of Asthma by Suppressing to T Cells Activity, Eosinophilia, and Bronchial Hyperresponsiveness

    Directory of Open Access Journals (Sweden)

    Seong-Soo Roh

    2008-01-01

    Full Text Available The present study is performed to investigate the inhibitory effects of Radix Adenophorae extract (RAE on ovalbumin-induced asthma murine model. To study the anti-inflammatory and antiasthmatic effects of RAE, we examined the development of pulmonary eosinophilic inflammation and inhibitory effects of T cells in murine by RAE and cyclosporine A (CsA. We examined determination of airway hyperresponsiveness, flow cytometric analysis (FACS, enzyme-linked immunosorbent assay (ELISA, quantitative real time (PCR, hematoxylin-eosin staining, and Masson trichrome staining in lung tissue, lung weight, total cells, and eosinophil numbers in lung tissue. We demonstrated how RAE suppressed development on inflammation and decreased airway damage.

  11. Acute and chronic respiratory lesions induced by sulfur mustard in guinea pigs: Role of tachykinins

    Energy Technology Data Exchange (ETDEWEB)

    Calvet, J.H.; Trouiller, G.; Harf, A.

    1993-05-13

    We investigated in anesthetized guinea pigs the involvement of tachykinins in respiratory alterations after an airway intoxication by sulfur mustard (SM). Early lesions were evaluated after 5h. Respiratory system resistance (R) and compliance were measured by the occlusion method and airway microvascular permeability by measuring the Evans Blue dye concentration in the trachea and main bronchi. Two groups of animals were studied treated with capsaicin (which induces a tachykinin depletion) or by its vehicle. Capsaicin pretreatment had no effect on the measured parameters. We also measured 14 J after the intoxication tracheal epithelium neutral endopeptidase (NEP) (the main enzyme which degrades tachykinins). In addition bronchial responsiveness to exogenous substance P was studied in two groups of animals intoxicated with SM or not. Tracheal epithelium NEP activity was decreased from 0.448 + or 0.027 nmol.min- 1.mg protein- 1 in controls to 0. 182 + or 0.038 in intoxicated animals. Response to substance P was greater in intoxicated animals with R=2.98 + or - 1.57 cmH20.MI-1.s versus 0.35 + or 0.02 in controls, after 5.10-5 M aerosolized substance P These results suggest tachykinins are not preponderant in the early stage lesions but that bronchial hyperactivity is present at recovery, related to epithelium NEP depletion.

  12. CD4 T Cell Tolerance to Human C-reactive Protein, an Inducible Serum Protein, Is Mediated by Medullary Thymic Epithelium

    OpenAIRE

    Klein, Ludger; Klein, Thomas; Rüther, Ulrich; Kyewski, Bruno

    1998-01-01

    Inducible serum proteins whose concentrations oscillate between nontolerogenic and tolerogenic levels pose a particular challenge to the maintenance of self-tolerance. Temporal restrictions of intrathymic antigen supply should prevent continuous central tolerization of T cells, in analogy to the spatial limitation imposed by tissue-restricted antigen expression. Major acute-phase proteins such as human C-reactive protein (hCRP) are typical examples for such inducible self-antigens. The circul...

  13. Classification, staging and radiotherapy of bronchial carcinoma

    International Nuclear Information System (INIS)

    This thesis reports a study performed to evaluate the stage classification of bronchial carcinoma published by Thomas in 1963. The study was done in the radiotherapy department of a teaching hospital, and had three parts: a comparative analysis of the classifications and stage divisions described in the literature on bronchial carcinoma; an evaluation of the theoretical basis of the classification system introduced by Thomas as well as of the practical applicability of the division into stages, with respect to the assessment of the prognosis and the choice of therapy; and an analysis of various aspects of irradiation as well as of a number of prognostic factors in bronchial carcinoma. (Auth.)

  14. Interleukin-1α drives the dysfunctional cross-talk of the airway epithelium and lung fibroblasts in COPD.

    Science.gov (United States)

    Osei, Emmanuel T; Noordhoek, Jacobien A; Hackett, Tillie L; Spanjer, Anita I R; Postma, Dirkje S; Timens, Wim; Brandsma, Corry-Anke; Heijink, Irene H

    2016-08-01

    Chronic obstructive pulmonary disease (COPD) has been associated with aberrant epithelial-mesenchymal interactions resulting in inflammatory and remodelling processes. We developed a co-culture model using COPD and control-derived airway epithelial cells (AECs) and lung fibroblasts to understand the mediators that are involved in remodelling and inflammation in COPD.AECs and fibroblasts obtained from COPD and control lung tissue were grown in co-culture with fetal lung fibroblast or human bronchial epithelial cell lines. mRNA and protein expression of inflammatory mediators, pro-fibrotic molecules and extracellular matrix (ECM) proteins were assessed.Co-culture resulted in the release of pro-inflammatory mediators interleukin (IL)-8/CXCL8 and heat shock protein (Hsp70) from lung fibroblasts, and decreased expression of ECM molecules (e.g. collagen, decorin) that was not different between control and COPD-derived primary cells. This pro-inflammatory effect was mediated by epithelial-derived IL-1α and increased upon epithelial exposure to cigarette smoke extract (CSE). When exposed to CSE, COPD-derived AECs elicited a stronger IL-1α response compared with control-derived airway epithelium and this corresponded with a significantly enhanced IL-8 release from lung fibroblasts.We demonstrate that, through IL-1α production, AECs induce a pro-inflammatory lung fibroblast phenotype that is further enhanced with CSE exposure in COPD, suggesting an aberrant epithelial-fibroblast interaction in COPD. PMID:27418555

  15. Symptoms, physical findings and bronchial hypersensitivity in patients with bronchial asthma and normal spirometry

    OpenAIRE

    Aćimović Slobodan; Plavec Goran; Tomić Ilija; Karličić Vukoica; Aćimović Svetlana; Vuković Jelena; Lončarević Olivera

    2009-01-01

    Background/Aim. The diagnosis of bronchial asthma, a chronic inflammatory disease of the respiratory tract, is made on the basis of anamnesis, pathologic auscultatory findings of the lungs, lung function disturbances, skin tests, as well as the basic indices of immunologic condition in bronchial trunk. The aim of the study was to find out correlation of objective indices of the disease and than relation with the symptoms in the patients with bronchial asthma. Methods. The study included 60 yo...

  16. Distribution of immunocompetent cells in the bronchial wall of clinically healthy subjects showing bronchial hyperresponsiveness.

    OpenAIRE

    Power, C; Sreenan, S; Hurson, B.; Burke, C; Poulter, L W

    1993-01-01

    BACKGROUND--Nearly all asthmatic subjects show bronchial hyperresponsiveness, in that the provocative concentration of histamine reducing forced expiratory volume in one second (FEV1) by 20% (PC20FEV1) is < or = 8 mg/ml histamine, and have underlying chronic inflammation of the bronchial wall mediated by T cells. The possible cause and effect relationship between these phenomena remains an enigma. As a proportion of clinically healthy subjects show bronchial hyperresponsiveness, this study wa...

  17. Bronchial inflammation in chronic bronchitis assessed by measurement of cell products in bronchial lavage fluid.

    OpenAIRE

    Riise, G. C.; Ahlstedt, S.; Larsson, S.; Enander, I.; Jones, I; Larsson, P.; Andersson, B

    1995-01-01

    BACKGROUND--Bronchial inflammation in chronic bronchitis has not been characterised as well as in asthma. The present study was undertaken to assess whether a characteristic pattern of bronchial inflammatory markers could be found in patients with chronic bronchitis. METHODS--Bronchoscopy with bronchial lavage was performed in 42 patients with chronic bronchitis and in 13 healthy controls. Twenty three of the patients had non-obstructive chronic bronchitis and 19 had chronic bronchitis and ch...

  18. AKT1E17K Is Oncogenic in Mouse Lung and Cooperates with Chemical Carcinogens in Inducing Lung Cancer

    Science.gov (United States)

    Malanga, Donatella; Belmonte, Stefania; Colelli, Fabiana; Scarfò, Marzia; De Marco, Carmela; Oliveira, Duarte Mendes; Mirante, Teresa; Camastra, Caterina; Gagliardi, Monica; Rizzuto, Antonia; Mignogna, Chiara; Paciello, Orlando; Papparella, Serenella; Fagman, Henrik; Viglietto, Giuseppe

    2016-01-01

    The hotspot AKT1E17K mutation in the pleckstrin homology domain of AKT1 occurs in approximately 0.6–2% of human lung cancers. Recently, we have demonstrated that AKT1E17K transforms immortalized human bronchial cells. Here by use of a transgenic Cre-inducible murine strain in the wild type Rosa26 (R26) locus (R26-AKT1E17K mice) we demonstrate that AKT1E17K is a bona-fide oncogene and plays a role in the development of lung cancer in vivo. In fact, we report that mutant AKT1E17K induces bronchial and/or bronchiolar hyperplastic lesions in murine lung epithelium, which progress to frank carcinoma at very low frequency, and accelerates tumor formation induced by chemical carcinogens. In conclusion, AKT1E17K induces hyperplasia of mouse lung epithelium in vivo and cooperates with urethane to induce the fully malignant phenotype. PMID:26859676

  19. Role of mitochondrial hydrogen peroxide induced by intermittent hypoxia in airway epithelial wound repair in vitro.

    Science.gov (United States)

    Hamada, Satoshi; Sato, Atsuyasu; Hara-Chikuma, Mariko; Satooka, Hiroki; Hasegawa, Koichi; Tanimura, Kazuya; Tanizawa, Kiminobu; Inouchi, Morito; Handa, Tomohiro; Oga, Toru; Muro, Shigeo; Mishima, Michiaki; Chin, Kazuo

    2016-05-15

    The airway epithelium acts as a frontline barrier against various environmental insults and its repair process after airway injury is critical for the lung homeostasis restoration. Recently, the role of intracellular reactive oxygen species (ROS) as transcription-independent damage signaling has been highlighted in the wound repair process. Both conditions of continuous hypoxia and intermittent hypoxia (IH) induce ROS. Although IH is important in clinical settings, the roles of IH-induced ROS in the airway repair process have not been investigated. In this study, we firstly showed that IH induced mitochondrial hydrogen peroxide (H2O2) production and significantly decreased bronchial epithelial cell migration, prevented by catalase treatment in a wound scratch assay. RhoA activity was higher during repair process in the IH condition compared to in the normoxic condition, resulting in the cellular morphological changes shown by immunofluorescence staining: round cells, reduced central stress fiber numbers, pronounced cortical actin filament distributions, and punctate focal adhesions. These phenotypes were replicated by exogenous H2O2 treatment under the normoxic condition. Our findings confirmed the transcription-independent role of IH-induced intracellular ROS in the bronchial epithelial cell repair process and might have significant implications for impaired bronchial epithelial cell regeneration. PMID:27093911

  20. Permanent Cortical Blindness After Bronchial Artery Embolization

    Energy Technology Data Exchange (ETDEWEB)

    Doorn, Colette S. van, E-mail: cvandoorn@gmail.com; De Boo, Diederick W., E-mail: d.w.deboo@amc.uva.nl [Academic Medical Centre, Department of Radiology (Netherlands); Weersink, Els J. M., E-mail: e.j.m.weersink@amc.uva.nl [Academic Medical Centre, Department of Pulmonology (Netherlands); Delden, Otto M. van, E-mail: o.m.vandelden@amc.uva.nl; Reekers, Jim A., E-mail: j.a.reekers@amc.uva.nl; Lienden, Krijn P. van, E-mail: k.p.vanlienden@amc.uva.nl [Academic Medical Centre, Department of Radiology (Netherlands)

    2013-12-15

    A 35-year-old female with a known medical history of cystic fibrosis was admitted to our institution for massive hemoptysis. CTA depicted a hypertrophied bronchial artery to the right upper lobe and showed signs of recent bleeding at that location. Bronchial artery embolization (BAE) was performed with gelfoam slurry, because pronounced shunting to the pulmonary artery was present. Immediately after BAE, the patient developed bilateral cortical blindness. Control angiography showed an initially not opacified anastomosis between the embolized bronchial artery and the right subclavian artery, near to the origin of the right vertebral artery. Cessation of outflow in the bronchial circulation reversed the flow through the anastomosis and allowed for spill of embolization material into the posterior circulation. Unfortunately the cortical blindness presented was permanent.

  1. Selective bronchial intubation for pulmonary emphysema.

    OpenAIRE

    Campbell, A N; Zarfin, Y; Perlman, M

    1984-01-01

    Two neonates with respiratory distress syndrome developed unilateral pulmonary interstitial emphysema causing mediastinal shift and compressive atelectasis. Treatment with contralateral bronchial intubation for five days proved to be life saving.

  2. Permanent Cortical Blindness After Bronchial Artery Embolization

    International Nuclear Information System (INIS)

    A 35-year-old female with a known medical history of cystic fibrosis was admitted to our institution for massive hemoptysis. CTA depicted a hypertrophied bronchial artery to the right upper lobe and showed signs of recent bleeding at that location. Bronchial artery embolization (BAE) was performed with gelfoam slurry, because pronounced shunting to the pulmonary artery was present. Immediately after BAE, the patient developed bilateral cortical blindness. Control angiography showed an initially not opacified anastomosis between the embolized bronchial artery and the right subclavian artery, near to the origin of the right vertebral artery. Cessation of outflow in the bronchial circulation reversed the flow through the anastomosis and allowed for spill of embolization material into the posterior circulation. Unfortunately the cortical blindness presented was permanent

  3. Dynamic Properties of Human Bronchial Airway Tissues

    OpenAIRE

    Wang, Jau-Yi; Mesquida, Patrick; Pallai, Prathap; Corrigan, Chris J; Lee, Tak H

    2011-01-01

    Young's Modulus and dynamic force moduli were measured on human bronchial airway tissues by compression. A simple and low-cost system for measuring the tensile-strengh of soft bio-materials has been built for this study. The force-distance measurements were undertaken on the dissected bronchial airway walls, cartilages and mucosa from the surgery-removed lungs donated by lung cancer patients with COPD. Young's modulus is estimated from the initial slope of unloading force-displacement curve a...

  4. Recent developments regarding periostin in bronchial asthma

    OpenAIRE

    Kenji Izuhara; Hisako Matsumoto; Shoichiro Ohta; Junya Ono; Kazuhiko Arima; Masahiro Ogawa

    2015-01-01

    Although it is currently recognized that bronchial asthma is not a single disease but a syndrome, we have not yet made use of our new understanding of this heterogeneity as we treat asthma patients. To increase the efficacy of anti-asthma drugs and to decrease costs, it is important to stratify asthma patients into subgroups and to develop therapeutic strategies for each subgroup. Periostin has recently emerged as a biomarker for bronchial asthma, unique in that it is useful not in diagnosis ...

  5. Prevalence of Bronchial Asthma in Indian Children

    OpenAIRE

    Pal Ranabir; Dahal Sanjay; Pal Shrayan

    2009-01-01

    Background: The prevalence of childhood bronchial asthma and allergic disease has increased in developed countries. Studies have identified asthma among Indian children. Still, there is paucity of information on the overall prevalence of childhood asthma in India. Objective: To assess time trends and the overall prevalence rate of bronchial asthma among Indian children. Materials and Methods: Literature search for data sources was done through an extensive search in indexed literatures a...

  6. Epidemiological & Risk Factors In Childhood Bronchial Asthma

    OpenAIRE

    Singh Harmesh; Soni R.K; Gill P J S

    1998-01-01

    Research question: What are the epidemiological and risk factors associated with asthma in children. Objective: To determine epidemiological and risk factors in childhood bronchial asthma. Study design: Cross-sectional. Setting Hospital based. Participants: Children suffering from bronchial asthma and their parents/ attendants. Sample size: 235 children. Study variables: Age, sex place of residence, socio-economic status, age of onset of asthma, no of siblings, fuel used for cooking, smoking,...

  7. Influenza enhances caspase-1 in bronchial epithelial cells from asthmatic volunteers and is associated with pathogenesis

    Science.gov (United States)

    Background: The leading cause of asthma exacerbation is respiratory viral infection. Innate antiviral defense pathways are altered in the asthmatic epithelium, yet involvement of inflammasome signaling in virus-induced asthma exacerbation is not known. Objective: This study com...

  8. Recent developments regarding periostin in bronchial asthma.

    Science.gov (United States)

    Izuhara, Kenji; Matsumoto, Hisako; Ohta, Shoichiro; Ono, Junya; Arima, Kazuhiko; Ogawa, Masahiro

    2015-09-01

    Although it is currently recognized that bronchial asthma is not a single disease but a syndrome, we have not yet made use of our new understanding of this heterogeneity as we treat asthma patients. To increase the efficacy of anti-asthma drugs and to decrease costs, it is important to stratify asthma patients into subgroups and to develop therapeutic strategies for each subgroup. Periostin has recently emerged as a biomarker for bronchial asthma, unique in that it is useful not in diagnosis but in categorizing asthma patients. We first found that periostin is a novel component of subepithelial fibrosis in bronchial asthma downstream of IL-13 signals. Thereafter, it was shown that periostin can be a surrogate biomarker of type 2 immune responses, the basis of the notion that a detection system of serum periostin is potentially a companion diagnostic for type 2 antagonists. Furthermore, we have recently shown that serum periostin can predict resistance or hyporesponsiveness to inhaled corticosteroids, based on its contribution to tissue remodeling or fibrosis in bronchial asthma. Thus, serum periostin has two characteristics as a biomarker for bronchial asthma: it is both a surrogate biomarker of type 2 immune responses and a biomarker reflecting tissue remodeling or fibrosis. We can take advantage of these characteristics to develop stratified medicine in bronchial asthma. PMID:26344077

  9. Recent developments regarding periostin in bronchial asthma

    Directory of Open Access Journals (Sweden)

    Kenji Izuhara

    2015-09-01

    Full Text Available Although it is currently recognized that bronchial asthma is not a single disease but a syndrome, we have not yet made use of our new understanding of this heterogeneity as we treat asthma patients. To increase the efficacy of anti-asthma drugs and to decrease costs, it is important to stratify asthma patients into subgroups and to develop therapeutic strategies for each subgroup. Periostin has recently emerged as a biomarker for bronchial asthma, unique in that it is useful not in diagnosis but in categorizing asthma patients. We first found that periostin is a novel component of subepithelial fibrosis in bronchial asthma downstream of IL-13 signals. Thereafter, it was shown that periostin can be a surrogate biomarker of type 2 immune responses, the basis of the notion that a detection system of serum periostin is potentially a companion diagnostic for type 2 antagonists. Furthermore, we have recently shown that serum periostin can predict resistance or hyporesponsiveness to inhaled corticosteroids, based on its contribution to tissue remodeling or fibrosis in bronchial asthma. Thus, serum periostin has two characteristics as a biomarker for bronchial asthma: it is both a surrogate biomarker of type 2 immune responses and a biomarker reflecting tissue remodeling or fibrosis. We can take advantage of these characteristics to develop stratified medicine in bronchial asthma.

  10. Synthesis of tenascin and laminin beta2 chain in human bronchial epithelial cells is enhanced by cysteinyl leukotrienes via CysLT1 receptor

    Directory of Open Access Journals (Sweden)

    Rekker Erki

    2008-05-01

    Full Text Available Abstract Background Cysteinyl leukotrienes (CysLTs are key mediators of asthma, but their role in the genesis of airway remodeling is insufficiently understood. Recent evidence suggests that increased expression of tenascin (Tn and laminin (Ln β2 chain is indicative of the remodeling activity in asthma, but represents also an example of deposition of extracellular matrix, which affects the airway wall compliance. We tested the hypothesis that CysLTs affect production of Tn and Ln β2 chain by human bronchial epithelial cells and elucidated, which of the CysLT receptors, CysLT1 or CysLT2, mediate this effect. Methods Cultured BEAS-2B human bronchial epithelial cells were stimulated with leukotriene D4 (LTD4 and E4 (LTE4 and evaluated by immunocytochemistry, Western blotting, flow cytometry, and RT-PCR. CysLT receptors were differentially blocked with use of montelukast or BAY u9773. Results LTD4 and LTE4 significantly augmented the expression of Tn, whereas LTD4, distinctly from LTE4, was able to increase also the Ln β2 chain. Although the expression of CysLT2 prevailed over that of CysLT1, the up-regulation of Tn and Ln β2 chain by CysLTs was completely blocked by the CysLT1-selective antagonist montelukast with no difference between montelukast and the dual antagonist BAY u9773 for the inhibitory capacity. Conclusion These findings suggest that the CysLT-induced up-regulation of Tn and Ln β2 chain, an important epithelium-linked aspect of airway remodeling, is mediated predominantly by the CysLT1 receptor. The results provide a novel aspect to support the use of CysLT1 receptor antagonists in the anti-remodeling treatment of asthma.

  11. Effect of dietary fibers on cholic acid induced cell proliferation in the colonic epithelium of C57BL/6J mice

    International Nuclear Information System (INIS)

    It has been postulated that high fat diets promote tumorigenesis by increasing the level of secondary bile acids in the colonic lumen. Dietary fibers are thought to be protective perhaps through their interaction with bile acids. In the present study, animals were fed diets containing either 0%, 5%, or 10% cellulose (C), pectin (P), or wheat bran (WB). The diets were formulated to contain either 0% (control) or 0.2% cholic acid (test). After two weeks of dietary treatment the animals were injected with [3H]-thymidine and their colons were processed for autoradiography. The number of labeled cells (LC) in the colonic crypts was determined. Among the control diets, 10%P induced a two-fold increase in the LC. All the test groups had significantly higher LC than in their controls. However, the C group excited a higher LC than the P or WB groups (5.2 +/- 0.8 vs 3.9 +/- 0.8 or 3.9 +/- 0.6). These results were substantiated by metaphase arrest technique. The authors results show that nonfermentable fiber does not alleviate bile acid induced cell proliferative activity in the colon whereas fermentable fibers will counteract the promotional effect of a high fat diet

  12. Sports in extreme conditions: the impact of exercise in cold temperatures on asthma and bronchial hyper-responsiveness in athletes

    OpenAIRE

    Carlsen, Kai-Håkon

    2012-01-01

    Exercise-induced asthma (EIA) and bronchial hyper-responsiveness (BHR) are frequently reported among elite athletes of outdoor endurance winter sports, particularly in cross-country and biathlon skiers. The pathogenesis of EIA is related to water loss and heat-loss through the increased respiration during exercise, leading to mediator release, airways inflammation and increased parasympathetic nervous activity in the airways, causing bronchial constriction and BHR. In the competing elite athl...

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

    OpenAIRE

    Zuraw Bruce L; Doerner Astrid M

    2009-01-01

    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 tr...

  14. Dual pathway clearance of /sup 99m/Tc-DTPA from the bronchial mucosa

    International Nuclear Information System (INIS)

    Many studies have reported clearance rates of 99mTc-DTPA from the alveolar epithelial surface, but few have measured clearance of this solute from the bronchial mucosa. Those that have attempted such measurements have discounted the possibility that 99mTc-DTPA may be removed from the bronchial airways by mucocilliary transport as well as by absorption through the epithelium. This study was designed to better approximate the rate of 99mTc-DTPA absorption across the bronchial epithelium by correcting the measurements of total 99mTc-DTPA clearance for mucus transport. On two separate study days, each normal, nonsmoking subject (n = 8) breathed an aqueous aerosol (2.0 microns MMAD, sigma g = 2.0) containing 99mTc bound to DTPA or human serum ablumin (HSA) (a relatively nonpermeable solute that is cleared only by mucus transport over the period of measured clearance) while seated in front of a gamma camera. Breathing pattern was standardized to produce a similar central deposition of particles on both study days. From measurements of retention versus time over a 1-h period, exponential rate constants (Ktot and Km) were determined for the clearance of 99mTc-DTPA and 99mTc-HSA, respectively. By modeling the airways as a single compartment with two possible routes of clearance, we determined the permeability rate constant, Kp, as Ktot minus Km. Results showed that mucus clearance (Km) accounted for two thirds of the total rate of 99mTc-DTPA clearance (Ktot) (mean Ktot = 0.00985, Km = 0.00698, and Kp = 0.00287/min)

  15. The predictive value of bronchial histamine challenge in the diagnosis of bronchial asthma

    DEFF Research Database (Denmark)

    Madsen, F; Holstein-Rathlou, N H; Mosbech, H;

    1985-01-01

    A prospective survey aiming to study the predictive value of bronchial histamine challenge was performed on 151 patients with a forced expiratory volume1 (FEV1) above 60% of predicted. According to variations in peak expiratory flow rate (PEFR) and medical history the patients were classified as...... below 0.125 mg/ml the predictive value of a positive test was 1.00, but an increase in PC20 in the range from 4.00 to 16 mg/ml did not increase the predictive value of a negative test. In this study the prevalence of asthma was about 0.6. We therefore conclude that bronchial histamine challenge is a...... valuable test for detection and exclusion of bronchial asthma, when the prevalence of the disease is high. In populations with a lower frequency of bronchial asthma the diagnostic value of a positive bronchial challenge will be negligible....

  16. Bronchial hyperresponsiveness decreases through childhood.

    Science.gov (United States)

    Riiser, Amund; Hovland, Vegard; Mowinckel, Petter; Carlsen, Kai-Håkon; Carlsen, Karin Lødrup

    2012-02-01

    Limited knowledge exists about development of bronchial hyperresponsiveness (BHR) through adolescence. We aimed to assess changes in and risk factors for BHR in adolescence. From a Norwegian birth cohort 517 subjects underwent clinical examinations, structured interviews and methacholine challenges at age 10 and 16. BHR was divided into four categories: no BHR (cumulative methacholine dose required to reduce FEV(1) by 20% (PD(20)) >16 μmol), borderline BHR (PD(20) ≤16 and >8 μmol), mild to moderate BHR (PD(20) ≤8 and >1 μmol), and severe BHR (PD(20) ≤ 1 μmol). Logistic regression analysis was used to assess risk factors and possible confounders. The number of children with PD(20) ≤ 8 decreased from 172 (33%) to 79 (15%) from age 10-16 (p 25% change) of gender, active rhinitis, active asthma, height, FEV(1)/FVC, or allergic sensitization. BHR decreased overall in severity through adolescence, was stable for the majority of children and only a minority (8%) had increased BHR from age 10 to 16. Mild to moderate and severe BHR at age 10 were major risk factors for PD(20) ≤ 8 at 16 years and not modified by asthma or body size. PMID:22015380

  17. Risk factors inducing children bronchial asthma in Bao'an District of Shenzhen City%深圳市宝安区儿童支气管哮喘发病的危险因素

    Institute of Scientific and Technical Information of China (English)

    刘晓娟; 吴智娟; 钟文明

    2013-01-01

    [Objective] To learn the risk factors of bronchial asthma of children in Baoan District of Shenzhen City,and provide basis for early intervening and treating bronchial asthma.[Methods] With case-control study method,a total of 108 cases of children bronchial asthma as case group and 110 cases of non-bronchial asthma as control group.These cases were investigated with self-designed questionnaire,then used single factor analysis and multiple factors analysis method to screen the risk factors.[Results] The study results showed that the risk factors of children bronchial asthma included hypersensitiveness history (OR =2.646),family asthma history (OR =5.155),repeated respiratory infection history (OR =4.116),smoking history of parents (OR =3.028),bad habitation environment (OR =2.123),contacting allergens (OR =4.509),but usually airing quilt (OR =O.500) was the protective factor.[Conclusion] Children bronchial asthma is closely related with hereditary factors,host factors and environmental factors,so it is very important to prevent and intervene children bronchial asthma with high risk factors.%目的 了解深圳市宝安区儿童支气管哮喘(哮喘)发病的危险因素,为早期预防和治疗提供依据.方法 采用病例对照的研究方法,将确诊的108例儿童哮喘病例作为病例组,同时收集110例非支气管哮喘患儿作为对照组;对病例组和对照组进行问卷调查,采用单因素和多因素分析研究儿童哮喘发病的危险因素.结果 研究结果显示,患儿过敏史(OR=2.646)、父母哮喘史(OR=5.155)、呼吸道反复感染史(OR =4.116)、父母吸烟史(OR=3.028)、居住环境差(OR =2.123)、接触过敏原(OR =4.509)为危险因素,而经常晾晒被辱(OR=0.500)为保护因素.结论 儿童支气管哮喘发病与遗传因素、宿主因素、环境因素等密切相关,应针对高危因素和高危人群进行重点预防和干预.

  18. An antagonist of the platelet-activating factor receptor inhibits adherence of both nontypeable Haemophilus influenzae and Streptococcus pneumoniae to cultured human bronchial epithelial cells exposed to cigarette smoke

    Directory of Open Access Journals (Sweden)

    Shukla SD

    2016-07-01

    Full Text Available Shakti D Shukla,1,* Rory L Fairbairn,1,* David A Gell,1 Roger D Latham,1 Sukhwinder S Sohal,1,2 Eugene H Walters,1 Ronan F O’Toole11Breathe Well Centre, School of Medicine, Faculty of Health, University of Tasmania, Hobart, TAS, Australia; 2School of Health Sciences, Faculty of Health, University of Tasmania, Launceston, TAS, Australia*These authors contributed equally to this workBackground: COPD is emerging as the third largest cause of human mortality worldwide after heart disease and stroke. Tobacco smoking, the primary risk factor for the development of COPD, induces increased expression of platelet-activating factor receptor (PAFr in the lung epithelium. Nontypeable Haemophilus influenzae (NTHi and Streptococcus pneumoniae adhere to PAFr on the luminal surface of human respiratory tract epithelial cells.Objective: To investigate PAFr as a potential drug target for the prevention of infections caused by the main bacterial drivers of acute exacerbations in COPD patients, NTHi and S. pneumoniae.Methods: Human bronchial epithelial BEAS-2B cells were exposed to cigarette smoke extract (CSE. PAFr expression levels were determined using immunocytochemistry and quantitative polymerase chain reaction. The epithelial cells were challenged with either NTHi or S. pneumoniae labeled with fluorescein isothiocyanate, and bacterial adhesion was measured using immunofluorescence. The effect of a well-evaluated antagonist of PAFr, WEB-2086, on binding of the bacterial pathogens to BEAS-2B cells was then assessed. In silico studies of the tertiary structure of PAFr and the binding pocket for PAF and its antagonist WEB-2086 were undertaken.Results: PAFr expression by bronchial epithelial cells was upregulated by CSE, and significantly associated with increased bacterial adhesion. WEB-2086 reduced the epithelial adhesion by both NTHi and S. pneumoniae to levels observed for non-CSE-exposed cells. Furthermore, it was nontoxic toward the bronchial epithelial

  19. Detection of trisomy 7 in bronchial cells from uranium miners

    Energy Technology Data Exchange (ETDEWEB)

    Lechner, J.F.; Neft, R.E.; Belinsky, S.A. [and others

    1995-12-01

    New Mexico was the largest producer of uranium in the western world during 1960s and 1970s. Investigators at the University of New Mexico School of Medicine`s Epidemiology and Cancer Control Program have been conducting epidemiological studies on uranium miners over the past 2 decades. Currently, this cohort includes more than 3600 men who had completed at least 1 y of underground work experience in New Mexico by December 31, 1976. These miners, who are now in their 5th through 7th decades, the age when lung cancer incidence is highest, are at high risk for developing this disease because they were exposed to high levels of radon progeny in the mines, and they also smoked tobacco. However, not all people comparably exposed develop lung cancer; in fact, the lifetime risk of lung cancer for the smoking uranium miners has been projected by epidemiological analyses to be no higher than 50%. Therefore, the identification of gene alterations in bronchial epithelium would be a valuable tool to ascertain which miners are at greatest risk for lung cancer. The underlying significance of the current effort confirms the hypothesis that chronic exposure to high concentrations of {alpha}-particles and tobacco smoke produces genetically altered lung epithelial cells throughout the respiratory tract of some susceptible individuals before they develop clinical disease.

  20. Secondhand smoke exposure causes bronchial hyperreactivity via transcriptionally upregulated endothelin and 5-hydroxytryptamine 2A receptors

    DEFF Research Database (Denmark)

    Cao, Lei; Zhang, Yaping; Cao, Yong-Xiao; Edvinsson, Lars; Xu, Cang-Bao

    2012-01-01

    secondhand cigarette smoke (SHS) exposure upregulates the bronchial contractile receptors via activation of the Raf/ERK/MAPK pathway. METHODOLOGY/PRINCIPAL FINDINGS: Rats were exposed to SHS for 3 h daily for up to 8 weeks. The receptor agonists-induced bronchial contractile reactivity was analyzed with a......BACKGROUND: Cigarette smoke exposure is strongly associated with airway hyperreactivity (AHR) which is the main characteristic seen in asthma. The intracellular MAPK signaling pathways are suggested to be associated with the airway damage to the AHR. In the present study, we hypothesize that...

  1. The impact of allergic rhinitis and asthma on human nasal and bronchial epithelial gene expression.

    Directory of Open Access Journals (Sweden)

    Ariane H Wagener

    Full Text Available BACKGROUND: The link between upper and lower airways in patients with both asthma and allergic rhinitis is still poorly understood. As the biological complexity of these disorders can be captured by gene expression profiling we hypothesized that the clinical expression of rhinitis and/or asthma is related to differential gene expression between upper and lower airways epithelium. OBJECTIVE: Defining gene expression profiles of primary nasal and bronchial epithelial cells from the same individuals and examining the impact of allergic rhinitis with and without concomitant allergic asthma on expression profiles. METHODS: This cross-sectional study included 18 subjects (6 allergic asthma and allergic rhinitis; 6 allergic rhinitis; 6 healthy controls. The estimated false discovery rate comparing 6 subjects per group was approximately 5%. RNA was extracted from isolated and cultured epithelial cells from bronchial brushings and nasal biopsies, and analyzed by microarray (Affymetrix U133+ PM Genechip Array. Data were analysed using R and Bioconductor Limma package. For gene ontology GeneSpring GX12 was used. RESULTS: The study was successfully completed by 17 subjects (6 allergic asthma and allergic rhinitis; 5 allergic rhinitis; 6 healthy controls. Using correction for multiple testing, 1988 genes were differentially expressed between healthy lower and upper airway epithelium, whereas in allergic rhinitis with or without asthma this was only 40 and 301 genes, respectively. Genes influenced by allergic rhinitis with or without asthma were linked to lung development, remodeling, regulation of peptidases and normal epithelial barrier functions. CONCLUSIONS: Differences in epithelial gene expression between the upper and lower airway epithelium, as observed in healthy subjects, largely disappear in patients with allergic rhinitis with or without asthma, whilst new differences emerge. The present data identify several pathways and genes that might be

  2. Regulation of epithelium-specific Ets-like factors ESE-1 and ESE-3 in airway epithelial cells:potential roles in airway inflammation

    Institute of Scientific and Technical Information of China (English)

    Jing Wu; Martin Post; A Keith Tanswell; Jim Hu; Rongqi Duan; Huibi Cao; Deborah Field; Catherine M Newnham; David R Koehler; Noe Zamel; Melanie A Pritchard; Paul Hertzog

    2008-01-01

    Airway inflammation is the hallmark of many respiratory disorders,such as asthma and cystic fibrosis.Changes in airway gene expression triggered by inflammation play a key role in the pathogenesis of these diseases.Genetic linkage studies suggest that ESE-2 and ESE-3,which encode epithelium-specific Ets-domain-containing transcription factors,are candidate asthma susceptibility genes.We report here that the expression of another member of the Ets family transcription factors ESE-1,as well as ESE-3,is upregulated by the inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-a (TNF-a) in bronchial epithelial cell lines.Treatment of these cells with IL-1β and TNF-a resulted in a dramatic increase in mRNA expression for both ESE-1 and ESE-3.We demonstrate that the induced expression is mediated by activation of the transcription factor NF-kB.We have characterized the ESE-1 and ESE-3 promoters and have identified the NF-kB binding sequences that are required for the cytokine-induced expression.In addition,we also demonstrate that ESE-1 upregulates ESE-3 expression and downregulates its own induction by cytokines.Finally,we have shown that in Elf3 (homologous to human ESE-1) knockout mice,the expression of the inflammatory cytokine interleukin-6 (IL-6) is downregulated.Our findings suggest that ESE-1 and ESE-3 play an important role in airway inflammation.

  3. Clinical, radiographic, and bronchial cytologic features of cats with bronchial disease: 65 cases (1980-1986)

    International Nuclear Information System (INIS)

    Medical records, radiographs, and bronchial cytologic abnormalities of 65 cats with bronchial disease were reviewed. Bronchial disease was defined as abnormality of the lower airways to the exclusion of disease originating or mainly involving the alveoli, interstitium, vasculature, or pleura. Cats with bronchial disease were more likely to be female and older. Siamese cats were over represented and had more chronic disease. In order of frequency, the following clinical signs were reported: coughing, dyspnea, occasional sneezing, wheezing, and vomiting. Radiography revealed prominent bronchial markings, with some cats having collapse of the middle lobe of the right lung (n = 7), overinflation of the lungs (n = 9), or aerophagia (n = 13). Of 65 bronchial washes, 58 were considered exudative, with the predominant cell type being eosinophil in 24%, neutrophil in 33%, macrophage in 22%, and mixed population of cells in 21%. Cultures for bacteria were considered positive in 24% of the cats. Circulating eosinophilia was not helpful in predicting the predominant cell type in bronchial cytologic exudates. Hyperproteinemia without dehydration was present in a third of the cats, indicating an immunologic response. Half the cats had resolution of clinical signs, whereas half the cats required continuing medication with bronchodilators, antimicrobial agents, or corticosteroids

  4. Directional secretory response of double stranded RNA-induced thymic stromal lymphopoetin (TSLP and CCL11/eotaxin-1 in human asthmatic airways.

    Directory of Open Access Journals (Sweden)

    Gustavo Nino

    Full Text Available BACKGROUND: Thymic stromal lymphoproetin (TSLP is a cytokine secreted by the airway epithelium in response to respiratory viruses and it is known to promote allergic Th2 responses in asthma. This study investigated whether virally-induced secretion of TSLP is directional in nature (apical vs. basolateral and/or if there are TSLP-mediated effects occurring at both sides of the bronchial epithelial barrier in the asthmatic state. METHODS: Primary human bronchial epithelial cells (HBEC from control (n = 3 and asthmatic (n = 3 donors were differentiated into polarized respiratory tract epithelium under air-liquid interface (ALI conditions and treated apically with dsRNA (viral surrogate or TSLP. Sub-epithelial effects of TSLP were examined in human airway smooth muscle cells (HASMC from normal (n = 3 and asthmatic (n = 3 donors. Clinical experiments examined nasal airway secretions obtained from asthmatic children during naturally occurring rhinovirus-induced exacerbations (n = 20 vs. non-asthmatic uninfected controls (n = 20. Protein levels of TSLP, CCL11/eotaxin-1, CCL17/TARC, CCL22/MDC, TNF-α and CXCL8 were determined with a multiplex magnetic bead assay. RESULTS: Our data demonstrate that: 1 Asthmatic HBEC exhibit an exaggerated apical, but not basal, secretion of TSLP after dsRNA exposure; 2 TSLP exposure induces unidirectional (apical secretion of CCL11/eotaxin-1 in asthmatic HBEC and enhanced CCL11/eotaxin-1 secretion in asthmatic HASMC; 3 Rhinovirus-induced asthma exacerbations in children are associated with in vivo airway secretion of TSLP and CCL11/eotaxin-1. CONCLUSIONS: There are virally-induced TSLP-driven secretory immune responses at both sides of the bronchial epithelial barrier characterized by enhanced CCL11/eotaxin-1 secretion in asthmatic airways. These results suggest a new model of TSLP-mediated eosinophilic responses in the asthmatic airway during viral-induced exacerbations.

  5. Chronic Pulmonary Aspergillosis Complicating Bronchial Atresia

    Directory of Open Access Journals (Sweden)

    Mazen O. Al-Qadi

    2014-01-01

    Full Text Available Bronchial atresia is a rare pulmonary developmental anomaly characterized by the presence of a focal obliteration of a segmental or lobar bronchial lumen. The lung distal to the atretic bronchus is typically emphysematous along with the presence of mucus filled ectatic bronchi (mucoceles. BA is usually asymptomatic but pulmonary infections can rarely develop in the emphysematous lung distal to the atretic bronchus. We present a unique case of chronic pulmonary aspergillosis (CPA in a patient with BA with no evidence of immune dysfunction. The patient was treated initially with voriconazole and subsequently underwent surgical excision of the involved area. On follow-up, she has done extremely well with no evidence for recurrence. In summary, we describe the first case of chronic pulmonary aspergillosis in an immunocompetent patient with bronchial atresia.

  6. Upper respiratory tract disease and bronchial asthma

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930904 A clinical study on determination ofplasma vasoactive intestinal peptide and its rela-tionship with bronchial responsiveness in asth-matics.LIU Ao(刘翱),et al.Dept Respir Med,Kunming General Hosp,Kunming Command,Kunming,650032.Chin J Intern Med 1993;32(3):165-166.Vasoactive intestinal peptide(VIP),which islocalized in normal human lung,may play an im-portant role in regulating bronchial tone,pul-monary blood flow and mucus secretion.Thelevel of plasma VIP and bronchial responsivenesswere studied in patients with asthma,and chronicbronchitis and in the healthy subjects.The re-sults showed that the level of plasma VIP in

  7. Airway Responsiveness: Role of Inflammation, Epithelium Damage and Smooth Muscle Tension

    Directory of Open Access Journals (Sweden)

    K. I. Gourgoulianis

    1999-01-01

    Full Text Available The purpose of this study was the effect of epithelium damage on mechanical responses of airway smooth muscles under different resting tension. We performed acetylcholine (ACh (10-5M-induced contraction on tracheal strips from 30 rabbits in five groups (0.5, 1, 1.5, 2 and 2.5 g before and after epithelium removal. At low resting tension (0.5-1.5g, the epithelium removal decreased the ACh-induced contractions. At 2g resting tension, the epithelium removal increased the ACh-induced contractions of airways with intact epithelium about 20%. At 2.5 g resting tension, the elevation of contraction is about 25% (p<0.01. Consequently, after epithelium loss, the resting tension determines the airway smooth muscles responsiveness. In asthma, mediators such as ACh act on already contracted inflammatory airways, which results in additional increase of contraction. In contrast, low resting tension, a condition that simulates normal tidal breathing, protects from bronchoconstriction even when the epithelium is damaged.

  8. Differentiation of human bronchial epithelial cells: role of hydrocortisone in development of ion transport pathways involved in mucociliary clearance.

    Science.gov (United States)

    Zaidman, Nathan A; Panoskaltsis-Mortari, Angela; O'Grady, Scott M

    2016-08-01

    Glucocorticoids strongly influence the mucosal-defense functions performed by the bronchial epithelium, and inhaled corticosteroids are critical in the treatment of patients with inflammatory airway diseases such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis. A common pathology associated with these diseases is reduced mucociliary clearance, a defense mechanism involving the coordinated transport of salt, water, and mucus by the bronchial epithelium, ultimately leading to retention of pathogens and particles in the airways and to further disease progression. In the present study we investigated the role of hydrocortisone (HC) in differentiation and development of the ion transport phenotype of normal human bronchial epithelial cells under air-liquid interface conditions. Normal human bronchial epithelial cells differentiated in the absence of HC (HC0) showed significantly less benzamil-sensitive short-circuit current than controls, as well as a reduced response after stimulation with the selective β2-adrenergic receptor agonist salbutamol. Apical membrane localization of epithelial Na(+) channel α-subunits was similarly reduced in HC0 cells compared with controls, supporting a role of HC in the trafficking and density of Na(+) channels in the plasma membrane. Additionally, glucocorticoid exposure during differentiation regulated the transcription of cystic fibrosis transmembrane conductance regulator and β2-adrenergic receptor mRNAs and appeared to be necessary for the expression of cystic fibrosis transmembrane conductance regulator-dependent anion secretion in response to β2-agonists. HC had no significant effect on surface cell differentiation but did modulate the expression of mucin mRNAs. These findings indicate that glucocorticoids support mucosal defense by regulating critical transport pathways essential for effective mucociliary clearance. PMID:27306366

  9. Bronchial diverticula in smokers on thin-section CT

    International Nuclear Information System (INIS)

    The objective was to determine the prevalence of bronchial diverticula in smokers on thin-section CT and the relationship to clinical and other morphological features on CT. Thin-section CT images of 503 cigarette smokers were assessed for the profusion and location of diverticula in the major airways. The extent of the bronchial diverticula was recorded as follows: grade 0, none; grade 1, one to three diverticula; grade 2, more than three diverticula. The extent of emphysema, bronchial wall thickness, clinical features, and pulmonary function were compared in the sub-groups stratified according to the extent of bronchial diverticula. A total of 229/503 (45.5%) smokers had bronchial diverticula, with 168/503 (33.3%) and 61/503 (12.2%) having grade 1 and 2 bronchial diverticula respectively. Subjects with grade 2 bronchial diverticula were heavier smokers, reported a history of coughing more frequently, and showed more severe functional impairment, greater extent of emphysema and more severe bronchial wall thickening compared with subjects with grade 1 and those individuals without bronchial diverticula (P<0.05). Multivariate regression analysis revealed that only bronchial wall thickness predicted the extent of the bronchial diverticula (P<0.0001). Bronchial diverticula are a frequent finding in the major airways of smokers, and they are associated with other markers of smoking-related damage. (orig.)

  10. Bronchial diverticula in smokers on thin-section CT

    Energy Technology Data Exchange (ETDEWEB)

    Sverzellati, Nicola; Ingegnoli, Anna [University of Parma, Department of Clinical Sciences, Division of Radiology, Parma (Italy); Calabro, Elisa; Pastorino, Ugo [National Cancer Institute, Division of Thoracic Surgery, Milan (Italy); Randi, Giorgia; La Vecchia, Carlo [Mario Negri Institute, Department of Epidemiology, Milan (Italy); University of Milano, Institute of Medical Statistics and Biometry ' ' G. A. Maccacaro' ' , Milan (Italy); Marchiano, Alfonso [National Cancer Institute, Division of Radiology, Milan (Italy); Kuhnigk, Jan-Martin [Fraunhofer MEVIS - Institute for Medical Image Computing, Bremen (Germany); Hansell, David M. [Royal Brompton Hospital, Department of Radiology, London (United Kingdom); Zompatori, Maurizio [S. Orsola-Malpighi Hospital, Department of Radiology, Bologna (Italy)

    2010-01-15

    The objective was to determine the prevalence of bronchial diverticula in smokers on thin-section CT and the relationship to clinical and other morphological features on CT. Thin-section CT images of 503 cigarette smokers were assessed for the profusion and location of diverticula in the major airways. The extent of the bronchial diverticula was recorded as follows: grade 0, none; grade 1, one to three diverticula; grade 2, more than three diverticula. The extent of emphysema, bronchial wall thickness, clinical features, and pulmonary function were compared in the sub-groups stratified according to the extent of bronchial diverticula. A total of 229/503 (45.5%) smokers had bronchial diverticula, with 168/503 (33.3%) and 61/503 (12.2%) having grade 1 and 2 bronchial diverticula respectively. Subjects with grade 2 bronchial diverticula were heavier smokers, reported a history of coughing more frequently, and showed more severe functional impairment, greater extent of emphysema and more severe bronchial wall thickening compared with subjects with grade 1 and those individuals without bronchial diverticula (P<0.05). Multivariate regression analysis revealed that only bronchial wall thickness predicted the extent of the bronchial diverticula (P<0.0001). Bronchial diverticula are a frequent finding in the major airways of smokers, and they are associated with other markers of smoking-related damage. (orig.)

  11. Serial change of atelectasis in acute bronchial obstruction

    International Nuclear Information System (INIS)

    This study evaluated MR imaging (MRI) of atelectatic lungs caused by acute bronchial obstruction. In 12 Japanese white rabbits, sudden obstruction of one main bronchus was induced with compressed polyvinylalcohol sponge plugs, and three rabbits each were sacrificed at 3, 7, 14, and 21 days. Unilateral complete airway obstruction persisted in 8 of the 12 rabbits. After T1: [500/20/2 (TR/TE/excitations), 5 mm thickness, 12 cm FOV] and T2: [2500/80/4, 5 mm thickness, 12 cm FOV] weighted imaging, both lungs and heart were inflated, fixed (Heitzman's method) and embedded en bloc in collodion. MR images of the atelectatic portion were evaluated, and MRI findings of the atelectatic portion were correlated with pathologic findings. MRI, especially T2 weighted images showed some characteristic signal patterns in each period. Correlations of these MRI features were performed with the pathologic findings. The peripheral pulmonary parenchyma, on T2 weighted images showed signal increase with time which was attributed to edematous fluid retention in pulmonary alveoli. The difference between inhomogeneous and homogeneous signal intensities on T2 weighted images on the 7th day was attributed to the patchy and even distribution of inflammatory process in pulmonary parenchyma. On the 21th day, hypointensity bands were observed on T1 and T2 weighted images. These hypointensity bands were attributed to fibrotic changes in bronchial walls and nearby alveolar walls. MR images well demonstrated pathological changes in atelectatic lungs caused by acute bronchial obstruction with time, suggesting the clinical usefulness of this approach. (author)

  12. Surface reactivity and in vitro toxicity on human bronchial epithelial cells (BEAS-2B) of nanomaterials intermediates of the production of titania-based composites.

    Science.gov (United States)

    Vergaro, Viviana; Aldieri, Elisabetta; Fenoglio, Ivana; Marucco, Arianna; Carlucci, Claudia; Ciccarella, Giuseppe

    2016-08-01

    Titanium dioxide (TiO2) nanoparticles (NPs) are manufactured worldwide in large quantities for use in a wide range of applications. Evaluating the hazards associated with TiO2 NPs is crucial as it enables risk assessment related to human and environmental exposure. In this study the in vitro human toxicity of a set of TiO2 NPs modified with acetic, oleic and boric acids were studied in order to assess the hazard in view of a future scale-up of the synthesis. The surface reactivity of the powders under simulated solar illumination and in the dark has been evaluated by means of EPR spectroscopy. Human bronchial epithelial cells (BEAS-2B) have been chosen as a model for lung epithelium. Cytotoxicity has been assessed by measuring the cells membrane integrity by lactate dehydrogenase (LDH) assay, and the inflammatory response evaluated as nitric oxide (NO) and TNF-α production, and oxidative stress measured as intracellular reduced glutathione (GSH) levels, and induced lipoperoxidation. Aeroxide P25 was used for comparison. The results demonstrated a low photoreactivity and toxic effects lower than Aeroxide P25 of the nano-TiO2 powders, probably as a consequence of the presence of acidic moieties at the surface. PMID:27075777

  13. Gastrin-releasing peptide receptor expression in non-cancerous bronchial epithelia is associated with lung cancer: a case-control study

    Directory of Open Access Journals (Sweden)

    Egloff Ann Marie

    2012-02-01

    Full Text Available Abstract Background Normal bronchial tissue expression of GRPR, which encodes the gastrin-releasing peptide receptor, has been previously reported by us to be associated with lung cancer risk in 78 subjects, especially in females. We sought to define the contribution of GRPR expression in bronchial epithelia to lung cancer risk in a larger case-control study where adjustments could be made for tobacco exposure and sex. Methods We evaluated GRPR mRNA levels in histologically normal bronchial epithelial cells from 224 lung cancer patients and 107 surgical cancer-free controls. Associations with lung cancer were tested using logistic regression models. Results Bronchial GRPR expression was significantly associated with lung cancer (OR = 4.76; 95% CI = 2.32-9.77 in a multivariable logistic regression (MLR model adjusted for age, sex, smoking status and pulmonary function. MLR analysis stratified by smoking status indicated that ORs were higher in never and former smokers (OR = 7.74; 95% CI = 2.96-20.25 compared to active smokers (OR = 1.69; 95% CI = 0.46-6.33. GRPR expression did not differ by subject sex, and lung cancer risk associated with GRPR expression was not modified by sex. Conclusions GRPR expression in non-cancerous bronchial epithelium was significantly associated with the presence of lung cancer in never and former smokers. The association in never and former smokers was found in males and females. Association with lung cancer did not differ by sex in any smoking group.

  14. Relation between the bronchial obstructive response to inhaled lipopolysaccharide and bronchial responsiveness to histamine.

    OpenAIRE

    Michel, O; Ginanni, R; Sergysels, R

    1992-01-01

    BACKGROUND: Bronchoconstriction has developed after inhalation of lipopolysaccharide in a dose of 20 micrograms in asthmatic patients and of 200 micrograms in normal subjects. This study set out to determine whether the bronchial response to lipopolysaccharide was related to non-specific bronchial responsiveness and atopy. METHODS: Sixteen subjects with a fall in specific airway conductance of 40% (PD40sGaw) after inhaling up to 900 micrograms histamine inhaled 20 micrograms lipopolysaccharid...

  15. 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.

  16. Quantification of bronchial circulation perfusion in rats

    Science.gov (United States)

    Wietholt, Christian; Molthen, Robert C.; Haworth, Steven T.; Roerig, David L.; Dawson, Christopher A.; Clough, Anne V.

    2004-04-01

    The bronchial circulation is thought to be the primary blood supply for pulmonary carcinomas. Thus, we have developed a method for imaging and quantifying changes in perfusion in the rat lung due to development of the bronchial circulation. A dual-modality micro-CT/SPECT system was used to detect change in perfusion in two groups of rats: controls and those with a surgically occluded left pulmonary artery. Both groups were imaged following injections on separate days i) 2mCi of Tc99m labeled macroaggregated albumin (MAA) into the left carotid artery (IA) and ii) a similar injection into the femoral vein (IV). The IA injection resulted in Tc99m accumulation in capillaries of the systemic circulation including the bronchial circulation, whereas the IV resulted in Tc99m accumulation in the pulmonary capillaries. Ordered subset expectation maximization (OSEM) was used to reconstruct the SPECT image volumes and a Feldkamp algorithm was used to reconstruct the micro-CT image volumes. The micro-CT and SPECT volumes were registered, the SPECT image volume was segmented using the right and left lung boundaries defined from the micro-CT volume, and the ratio of IA radioactivity accumulation in the left lung to IV radioactivity accumulation in both lungs was used as a measure of left lung flow via the bronchial circulation. This ratio was ~0.02 for the untreated rats compared to the treated animals that had an increased flow ratio of ~0.21 40 days after left pulmonary artery occlusion. This increase in flow to the occluded left lung via the bronchial circulation suggests this will be a useful model for further investigating antiangiogenic treatments.

  17. Super scans associated with bronchial carcinoma

    International Nuclear Information System (INIS)

    Full text: Introduction: It is most unusual for bronchial carcinoma to present as a malignant super scan and is not mentioned in the literature as a specific cause for metabolic super scans. Yet the clinical impression developed that metabolic super scans are not uncommon with bronchial carcinoma possibly associated with paraneoplastic hyperparathyroidism. Purpose: (a) to determine the prevalence of super scans in bronchial carcinoma; (b) to determine a possible association with a specific histological type of carcinoma; (c) to determine the serum Ca++, PO4 and alkaline phosphatase levels pretreatment, thus a possible underlying paraneoplastic hyperparathyroidism. Methods: Hundred patients with bronchial carcinoma were drawn randomly from our files over the last 3 years and studied retrospectively for presence of a possible metabolic super scan. A metabolic super scan was defined as markedly increased diffuse bone uptake without irregularities or possible localized metastases. The kidneys must be absent or scarcely visible. These patients were further evaluated with regards to (a) histopathological type of carcinoma (b) pre therapeutic serum Ca++, PO4 and alkaline phosphatase levels. Results: (i) Metabolic super scans were observed in 11 % of our study group; (ii) The serum Ca++ was only slightly increased in one patient. Serum PO4 was normal in all the patients. Thus we could not prove a serum Ca++/PO4 profile suggestive of hyperparathyroidism in our patients. In two patients parathyroid hormone levels were available and were WNL; (iii) The alkaline phosphatase was moderately increased in 4 patients. (The reason uncertain but probably due to increased bone activity and bone turnover since liver metastases were confirmed in only one of these patients). (iv) Seven patients had non small cell carcinoma, three small cell and one unclassified, thus not limited to epidermoid cancer alone. Conclusion: In this study the underlying pathophysiology for the metabolic super

  18. Carbon black and titanium dioxide nanoparticles elicit distinct apoptotic pathways in bronchial epithelial cells

    OpenAIRE

    Baeza-Squiban Armelle; Fleury Jocelyne; Martens Johan A; Andreau Karine; Borot Marie-Caroline; Ferecatu Ioana; Thomassen Leen CJ; Hussain Salik; Marano Francelyne; Boland Sonja

    2010-01-01

    Abstract Background Increasing environmental and occupational exposures to nanoparticles (NPs) warrant deeper insight into the toxicological mechanisms induced by these materials. The present study was designed to characterize the cell death induced by carbon black (CB) and titanium dioxide (TiO2) NPs in bronchial epithelial cells (16HBE14o- cell line and primary cells) and to investigate the implicated molecular pathways. Results Detailed time course studies revealed that both CB (13 nm) and...

  19. Using radioaerosols to monitor physiotherapy-enhanced mucus clearance at different levels of the bronchial tree

    International Nuclear Information System (INIS)

    Patients with airways obstruction often find it difficult to clear excess lung secretions. Frequent coughing can clear the larger airways but may itself further damage the airways ciliated epithelium. Various physiotherapy regimes have been proposed yet objective evidence of their efficacy is sparse. Deposited aerosol particles - with an appropriate label for gamma imaging - can track clearance from different lung regions. Published reports have however tended to be equivocal in respect of clearance from the more distal conducting airways. Questions also arise as to coordination of transport rates at different levels of the bronchial tree. We therefore sought to re-assess requirements for effective analysis of physiotherapy-enhanced clearance to yield data on both peripheral and central airways clearance. (author)

  20. Using radioaerosols to monitor physiotherapy-enhanced mucus clearance at different levels of the bronchial tree

    Energy Technology Data Exchange (ETDEWEB)

    Hasani, A.; Pavia, D.; Clarke, S.W.; Agnew, J.E. (Royal Free Hospital, London (United Kingdom))

    1993-01-01

    Patients with airways obstruction often find it difficult to clear excess lung secretions. Frequent coughing can clear the larger airways but may itself further damage the airways ciliated epithelium. Various physiotherapy regimes have been proposed yet objective evidence of their efficacy is sparse. Deposited aerosol particles - with an appropriate label for gamma imaging - can track clearance from different lung regions. Published reports have however tended to be equivocal in respect of clearance from the more distal conducting airways. Questions also arise as to coordination of transport rates at different levels of the bronchial tree. We therefore sought to re-assess requirements for effective analysis of physiotherapy-enhanced clearance to yield data on both peripheral and central airways clearance. (author).

  1. Reinstatement of "germinal epithelium" of the ovary

    Directory of Open Access Journals (Sweden)

    Nishida Naoyo

    2006-08-01

    Full Text Available Abstract Background The existing dogma that the former term ovarian "germinal epithelium" resulted from a mistaken belief that it could give rise to new germ cells is now strongly challenged. Discussion Two years ago, a research group of the University of Tennessee led by Antonin Bukovsky successfully demonstrated the oogenic process from the human ovarian covering epithelium now commonly called the ovarian surface epithelium. They showed the new oocyte with zona pellucida and granulosa cells, both originated from the surface epithelium arising from mesenchymal cells in the tunica albuginea, and stressed that the human ovary could form primary follicles throughout the reproductive period. This gives a big impact not only to the field of reproductive medicine, but also to the oncologic area. The surface epithelium is regarded as the major source of ovarian cancers, and most of the neoplasms exhibit the histology resembling müllerian epithelia. Since the differentiating capability of the surface epithelium has now expanded, the histologic range of the neoplasms in this category may extend to include both germ cell tumors and sex cord-stromal cell tumors. Summary Since the oogenic capability of ovarian surface cells has been proven, it is now believed that the oocytes can originate from them. The term "germinal epithelium", hence, might reasonably be reinstated.

  2. 阿米卡星致聋大鼠鼓阶壁上皮超微结构的改变%Ultrastructural changes of epithelium on wall of scala tympani in rats with Amikacin induced hearing loss

    Institute of Scientific and Technical Information of China (English)

    李登科; 赵立东; 孙建和; 刘慧占; 杨仕明

    2012-01-01

    Objective To investigate ultrastructural changes of epithelium attached to the bony wall of scala tympani in rat cochleae after amikacin sulfate administration and the structural basis for migration of transplanted mouse embryonic stem cells. Methods Rats were randomly divided into an experiment group (n=20) and a control group(n=10).For rats in the experiment group, amikacin sulfate was injected hypodermically at a dose of 200 mg/kg/day for seven days, while rats in the control group received physiological saline of the same volume instead. The cochlea was removed on Od, 7d, 14, 21d and 28d after amikacin administration was finished. Cochlea on one randomly selected side was prepared for SEM observation and the other co-chlear for HE examination. Results Amikacin sulfate administred to rats induced hearing loss. Epithelia on the bony wall of scala tympani underwent serial ultrastructural changes, including inflammatory exudation and increase of the intercellular spaces, which recovered in a time dependent manner. Conclusion Besides injury and loss of the hair cells in the Organ of Corti, amikacin sulfate treatment can also induce ultrastructural changes on the bony wall of scala tympani which may be the structural base for transplanted stem cell migration from scala tympani in the cochlea. Our results show the time window for inner ear stem cell therapy after ototoxic drugs injury.%目的 观察大鼠经氨基糖苷类抗生素硫酸阿米卡星注射致聋后,耳蜗鼓阶壁上皮超微结构的改变;探索干细胞移植进入鼓阶后,干细胞在内耳发生迁移的结构基础.方法 出生7天的SD大鼠30只,随机分为实验组(20只)与对照组(10只).实验组连续7天经腹腔按照200mg/kg/day的剂量腹腔注射硫酸阿米卡星注射液;对照组注射相同体积的生理盐水.在停药后0天、7天、14天、21天、28天取耳蜗组织,随机选择其中一侧行扫描电镜观察耳蜗底回鼓阶的上皮的变化,另一侧耳蜗

  3. Dynamics of eosinophil infiltration in the bronchial mucosa before and after the late asthmatic reaction.

    Science.gov (United States)

    Aalbers, R; de Monchy, J G; Kauffman, H F; Smith, M; Hoekstra, Y; Vrugt, B; Timens, W

    1993-06-01

    We wanted to determine whether changes in bronchial hyperresponsiveness (BHR) following allergen challenge show a time relationship with inflammatory events in the airways of allergic asthmatic subjects. Lavage was performed and endobronchial biopsies were taken via the fiberoptic bronchoscope, before, and 3 and 24 h after, allergen challenge, on separate occasions, in nine dual asthmatic responders. The numbers of activated eosinophils, identified by immunohistochemistry, using the monoclonal anti-eosinophil cationic protein antibody, EG2, were significantly increased both at 3 h and at 24 h in the submucosa and bronchial lavage. A significant negative correlation was found between the number of EG2+ cells in the submucosa and in the bronchial lavage 24 h after the allergen challenge (r = -0.70). At 24 h, the amount of eosinophil cationic protein (ECP) was increased in the bronchial lavage. A significant correlation was observed between the amount of ECP at 3 h and the log provocative dose of house dust mite producing a 20% fall in forced expiratory volume in one second (PD20 HDM) (r = -0.63). The results suggest a recruitment of activated eosinophils to the submucosa and, further, to the epithelial lining, followed by degranulation. This process has already started 3 h after allergen challenge, and lasts for at least 24 h, which may result in mucosal damage and subsequent allergen-induced increase in BHR, before and after the late asthmatic reaction. PMID:8339804

  4. The innate immune response of equine bronchial epithelial cells is altered by training.

    Science.gov (United States)

    Frellstedt, Linda; Gosset, Philippe; Kervoaze, Gwenola; Hans, Aymeric; Desmet, Christophe; Pirottin, Dimitri; Bureau, Fabrice; Lekeux, Pierre; Art, Tatiana

    2015-01-01

    Respiratory diseases, including inflammatory airway disease (IAD), viral and bacterial infections, are common problems in exercising horses. The airway epithelium constitutes a major physical barrier against airborne infections and plays an essential role in the lung innate immune response mainly through toll-like receptor (TLR) activation. The aim of this study was to develop a model for the culture of equine bronchial epithelial cells (EBEC) in vitro and to explore EBEC innate immune responses in trained horses. Bronchial epithelial biopsies were taken from 6 adult horses during lower airway endoscopy. EBEC were grown in vitro by an explant method. The innate immune response of EBEC was evaluated in vitro by treatment with TLR ligands. TLR3 is the most strongly expressed TLR at the mRNA level in EBEC and stimulation of EBEC with Poly(I:C), an analog of viral dsRNA, triggers a strong secretion of IFN-β, TNF-α, IL-6 and CXCL8. We further evaluated the EBEC innate immune response in horses that underwent a 4-month-training program. While training had no effect on TLR mRNA expression in EBEC as well as in bronchial biopsies, it increased the production of IFN-β after stimulation with a TLR3 ligand and decreased the secretion of TNF-α and IL-6 after stimulation with a TLR2 and TLR3 ligand. These findings may be implicated in the increased risk for viral and bacterial infections observed in sport horses. Altogether, we report a successful model for the culture of EBEC that can be applied to the investigation of pathophysiologic conditions in longitudinal studies. PMID:25595212

  5. Arylamine N-acetyltransferase activity in bronchial epithelial cells and its inhibition by cellular oxidants

    International Nuclear Information System (INIS)

    Bronchial epithelial cells express xenobiotic-metabolizing enzymes (XMEs) that are involved in the biotransformation of inhaled toxic compounds. The activities of these XMEs in the lung may modulate respiratory toxicity and have been linked to several diseases of the airways. Arylamine N-acetyltransferases (NAT) are conjugating XMEs that play a key role in the biotransformation of aromatic amine pollutants such as the tobacco-smoke carcinogens 4-aminobiphenyl (4-ABP) and β-naphthylamine (β-NA). We show here that functional human NAT1 or its murine counterpart Nat2 are present in different lung epithelial cells i.e. Clara cells, type II alveolar cells and bronchial epithelial cells, thus indicating that inhaled aromatic amines may undergo NAT-dependent biotransformation in lung epithelium. Exposure of these cells to pathophysiologically relevant amounts of oxidants known to contribute to lung dysfunction, such as H2O2 or peroxynitrite, was found to impair the NAT1/Nat2-dependent cellular biotransformation of aromatic amines. Genetic and non genetic impairment of intracellular NAT enzyme activities has been suggested to compromise the important detoxification pathway of aromatic amine N-acetylation and subsequently to contribute to an exacerbation of untoward effects of these pollutants on health. Our study suggests that oxidative/nitroxidative stress in lung epithelial cells, due to air pollution and/or inflammation, could contribute to local and/or systemic dysfunctions through the alteration of the functions of pulmonary NAT enzymes.

  6. Morphology of the bronchial tree of coati lungs (Nasua nasua, Linnaeus, 1966

    Directory of Open Access Journals (Sweden)

    Amilton Cesar dos Santos

    2011-06-01

    Full Text Available The coati (Nasua nasua is a diurnal, terrestrial and arboricola procionidae. It feeds extensively on the ground and uses trees to procriate, to sleep overnight and to take refuge. Its diet is omnivorous and it feeds on fruits, small vertebrates and invertebrates, nectar, eggs and vegetables. The aim of this work was to characterize microscopically the bronchial tree of the coati. Four coatis (two males and two females, fixed in formaldehyde solution 10%, were used from previous research conducted at CECRIMPAS – UNIFEOB (IBAMA-02027.003731/04-76. For this work, the tissue samples were embedded in paraffin by routine technique and processed for light microscopy in HE staining for analysis under a light microscope. It was found that microscopically, the bronchial tree of the coati is similar to that of other mammals described in the literature, i.e. it has great variations in its architecture, such as a reduced height of the epithelium which changes from ciliated pseudostratified in the larger bronchi to being cubic in the smaller bronchioles, an absence of cilia and glands in the smaller bronchioles, and a decrease in diameter and thickness of its walls.

  7. Development of an in vitro model of human bronchial epithelial barrier to study nanoparticle translocation.

    Science.gov (United States)

    George, Isabelle; Vranic, Sandra; Boland, Sonja; Courtois, Arnaud; Baeza-Squiban, Armelle

    2015-02-01

    Inhalation is the most frequent route of unintentional exposure to nanoparticles (NPs). Our aim was to compare different in vitro models of human lung epithelial monolayers for their suitability to assess the translocation of 50 nm fluorescently labelled silica NPs (50 nm-SiO(2)-FITC-NPs). Human bronchial epithelial cell lines NCI-H292 and Calu-3 as well as human alveolar cell line A549 were seeded onto Transwell filters (TF) separating the well into an apical and a basal compartment. Measurements of the transepithelial electric resistance and monitoring the paracellular transport of a fluorescent marker (Lucifer Yellow) have shown that only Calu-3 cells formed a tight epithelium. In the absence of cells 4% of the initially applied NP concentration was found to cross the TF but the majority remained trapped inside the filter. After 24 h of treatment, 50 nm-SiO(2)-FITC-NPs were taken up by all cell types but their translocation was inversely correlated to the efficiency to prevent LY passage: translocation represented 3% of the initially apically applied NP concentration for Calu-3 cells, 9% for NCI-H292 cells and 35% for A549 cells. In conclusion, 50 nm-SiO(2)-FITC-NPs can cross different bronchial epithelial barriers, but the Calu-3 cell line appears to be the most relevant model for studying NP translocation. PMID:25197033

  8. Deposition of aerosols and bronchial clearance measurements

    International Nuclear Information System (INIS)

    A special inhalative device is described for reproducible deposition patterns of radioactive aerosols to measure mucociliary and tussive clearance and to evaluate the effect of drugs on the bronchial tree is described. Additive actions on mucus transport exist between β2-agonists and theophylline, but not incombination with inhalative quarternary ammonium compounds (ipatropium and oxitropium bromide). Mucolytics are generally less effective on mucociliary clearance than β2-agonists and theophylline, positive, negative and nonresponders are ofter seen due to the different viscoelastic properties of the mucus. Mucus transport is more than mucociliary clearance. Two-phase gas/liquid movement and coughing are also important transport mechanisms for bronchial mucus. Therefore, bronchodilators enhance mucus transport by increasing airway patency, which increases total and regional air flow and improves cough clearance. (orig.)

  9. Bronchial thermoplasty in asthma: current perspectives

    Directory of Open Access Journals (Sweden)

    Laxmanan B

    2015-05-01

    Full Text Available Balaji Laxmanan, D Kyle Hogarth Section of Pulmonary and Critical Care Medicine, University of Chicago Medicine, Chicago, IL, USA Abstract: Bronchial thermoplasty (BT is a novel therapy for patients with severe asthma. Using radio frequency thermal energy, it aims to reduce the airway smooth muscle mass. Several clinical trials have demonstrated improvements in asthma-related quality of life and a reduction in the number of exacerbations following treatment with BT. In addition, recent data has demonstrated the long-term safety of the procedure as well as sustained improvements in rates of asthma exacerbations, reduction in health care utilization, and improved quality of life. Further study is needed to elucidate the underlying mechanisms that result in these improvements. In addition, improved characterization of the asthma subphenotypes likely to exhibit the largest clinical benefit is a critical step in determining the precise role of BT in the management of severe asthma. Keywords: bronchial thermoplasty, severe asthma, airway smooth muscle

  10. The efficacy of a comprehensive lifestyle modification programme based on yoga in the management of bronchial asthma: a randomized controlled trial

    OpenAIRE

    Bijlani Ramesh; Vempati Ramaprabhu; Deepak Kishore

    2009-01-01

    Abstract Background There is a substantial body of evidence on the efficacy of yoga in the management of bronchial asthma. Many studies have reported, as the effects of yoga on bronchial asthma, significant improvements in pulmonary functions, quality of life and reduction in airway hyper-reactivity, frequency of attacks and medication use. In addition, a few studies have attempted to understand the effects of yoga on exercise-induced bronchoconstriction (EIB) or exercise tolerance capacity. ...

  11. Bronchial stenosis after tuberculosis - a case report

    International Nuclear Information System (INIS)

    The authors report a case of bronchial stenosis after pulmonary tuberculosis infection in a 46 year-old man presenting symptoms related to upper left lobe collapse, that was identified by chest roentgenograms. The evaluation by computed tomography showed narrowing of the left main bronchus and obliteration of the upper left bronchus. The patient had a postero-lateral thoracotomy, lower left bronchus and left main bronchus bronchoplasty, with upper left lobectomy. (author)

  12. Bronchial reactions to exposure to welding fumes.

    OpenAIRE

    Contreras, G R; Chan-Yeung, M.

    1997-01-01

    OBJECTIVES: To study the airway response and its mechanism to welding fumes in six welders with respiratory symptoms. METHODS: Methacholine and welding challenge tests were carried out. The concentration of welding fumes during the exposure test was measured. On two subjects who developed bronchoconstricition to welding challenge, additional tests were carried out including prick, patch, and inhalation challenges with metal salt solutions. RESULTS: Three subjects developed immediate bronchial...

  13. Dynamic Properties of Human Bronchial Airway Tissues

    CERN Document Server

    Wang, Jau-Yi; Pallai, Prathap; Corrigan, Chris J; Lee, Tak H

    2011-01-01

    Young's Modulus and dynamic force moduli were measured on human bronchial airway tissues by compression. A simple and low-cost system for measuring the tensile-strengh of soft bio-materials has been built for this study. The force-distance measurements were undertaken on the dissected bronchial airway walls, cartilages and mucosa from the surgery-removed lungs donated by lung cancer patients with COPD. Young's modulus is estimated from the initial slope of unloading force-displacement curve and the dynamic force moduli (storage and loss) are measured at low frequency (from 3 to 45 Hz). All the samples were preserved in the PBS solution at room temperature and the measurements were perfomed within 4 hours after surgery. Young's modulus of the human bronchial airway walls are fond ranged between 0.17 and 1.65 MPa, ranged between 0.25 to 1.96 MPa for cartilages, and between 0.02 to 0.28 MPa for mucosa. The storage modulus are found varying 0.10 MPa with frequency while the loss modulus are found increasing from ...

  14. Permeability and ultrastructure of human bladder epithelium

    DEFF Research Database (Denmark)

    Eldrup, J; Thorup, Jørgen Mogens; Nielsen, S L;

    1983-01-01

    Leakage of tight junctions as observed with electron microscopy and demonstration of solute transport across bladder epithelium was investigated in 13 patients with different bladder diseases: urinary retention and infection, bladder tumours and interstitial cystitis. The latter group showed cons...

  15. Epithelium-dependent effect of L-glutamate on airways: involvement of prostaglandins

    Directory of Open Access Journals (Sweden)

    Apostolia A. Hatziefthimiou

    2002-01-01

    Full Text Available We investigated the effect of the excitatory amino acid (EAA receptor agonists L-glutamate, N-methyl-D-aspartate (NMDA, (RS-a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA and kainic acid on KCl-induced contractions of rabbit tracheal smooth muscle, as well as the role of epithelium and endogenously produced nitric oxide and prostaglandins on these responses. L-Glutamate decreased KCl-induced contractions up to 30%. This effect was attenuated by epithelium removal, tetrodotoxin, methylene blue and indomethacin but not by NG-nitro-L-arginine methyl ester. While NMDA, AMPA and kainic acid had no effect, the combination of NMDA + kainic acid decreased KCl-induced contractions. These results suggest that, in rabbit trachea, L-glutamate has, at least in part, an epithelium-dependent effect mediated via prostaglandin formation and that the EAA receptors involved are nonclassical.

  16. Quantitative analyzation of bronchial wall regions using multi slice CT images

    International Nuclear Information System (INIS)

    As multi-slice CT develops, there are great expectations for an automatic and computer-support diagnoses. This research is on bronchial area which is composed of the bronchial wall regions and the air regions in the internal bronchial tube. Since to diagnose this is difficult, support diagnosis using CT images is desired. The thickness of bronchial wall changes as the airway of early lung cancer, bronchial asthma and the bronchial enhancing syndrome and others changes into a malignant state. These changes are detected and the thickness of bronchial wall becomes important information. In this research, the extraction accuracy of the algorithm for bronchial wall evaluation is good. (author)

  17. Symptoms, physical findings and bronchial hypersensitivity in patients with bronchial asthma and normal spirometry

    Directory of Open Access Journals (Sweden)

    Aćimović Slobodan

    2009-01-01

    Full Text Available Background/Aim. The diagnosis of bronchial asthma, a chronic inflammatory disease of the respiratory tract, is made on the basis of anamnesis, pathologic auscultatory findings of the lungs, lung function disturbances, skin tests, as well as the basic indices of immunologic condition in bronchial trunk. The aim of the study was to find out correlation of objective indices of the disease and than relation with the symptoms in the patients with bronchial asthma. Methods. The study included 60 young male non smokers with long lasting symptoms of bronchial asthma including shortness of breath, wheezing, hard breathing, nonproductive or productive cough, weakness and night hard breathing. There were no symptoms of respiratory infection over the past two months and lung radiography and spirometry were normal. Based on the results of nonspecific bronchoprovocative test two groups of the patients were formed, group I (n = 30 with positive histamine test (average value of the inhaled histamine concentration with FEV1 drop by 20% in regard with the initial value (PC20 = 2.99 ± 0.51 mg/ml of histamine and group II (n = 30 with negative histamine test (PC20(a = 14.58 ± 6.34 mg/ml of histamine. Results. The obtained spirometry results revealed a statistically significant difference in values of FEV1 between groups: I group - FEV1 = 93.2%; II group - FEV1 = 101.8%; (p < 0.05, Wilcoxon test, although all the FEV1 values were normal. Regarding the presence of the most common symptoms there was not statistically significant difference between the groups (p > 0. 05, chisquare test. Pathologic auscultatory lung findings were found in 73.4% of the patients in the group I and 27.5% of the patients in the group II. There was statistically significant difference (p < 0.05, chi-squared test. A positive correlation between the degree of hypersensitivity and lung physical findings was confirmed (p < 0.05 Spearman's rho, but there was no correlation with FEV1 values

  18. Radioaerosol inhalation lung scintigraphy in bronchial asthma

    International Nuclear Information System (INIS)

    A study on obstructive changes in airways and mucociliary clearance in children and youth with bronchial asthma was performed. Radioaerosol inhalation lung scintigraphies using 99Tc-human serum albumin (HSA) were applied to 50 children and youth with bronchial asthma. The deposition patterns of the radioaerosol and aerosol clearance curves were evaluated. Abnormal deposition patterns, which consisted of non-homogeneous distribution and/or hot spot formation, were likely to be seen in patients with asthmatic attacks at the time of measurements. However, a few asymptomatic patients also revealed abnormal deposition patterns. The deposition patterns were related to FEV1.0%, MMF, V50 and V25, but especially to FEV1.0%. As an index of mucociliary clearance, β, the rate constant of the 99mTc-HSA aerosol clearance curve, was introduced. β was significantly lower in patients with abnormal aerosol deposition patterns than in normal persons. β was also significantly lower in patients undergoing asthmatic attack at the time of the measurements than in asymptomatic patients. β correlated negatively with FEV1.0%, MMF, V50 and V25, but especially with FEV1.0%. Although patients with long term affection or moderate-to-severe asthma tended to reveal abnormal deposition patterns and had low β values, these differences were not statistically significant. Radioaerosol inhalation lung scintigraphy with 99mTc-HSA is useful for evaluating not only obstructive changes in the airways but also for evaluating mucociliary clearance in children with bronchial asthma. (author)

  19. BRONCHOSCOPIC THERAPY IN PATIENTS WITH INTRALUMINAL TYPICAL BRONCHIAL CARCINOID

    NARCIS (Netherlands)

    SUTEDJA, TG; SCHREURS, AJ; VANDERSCHUEREN, RG; KWA, B; VANDERWERF, TS; POSTMUS, PE

    1995-01-01

    Objective: To study the efficacy of bronchoscopic therapy in patients with intraluminal typical bronchial carcinoid. Design: Retrospective analysis of the data of patients with bronchial carcinoid, treated primarily with bronchoscopic techniques such as Nd-YAG laser in various hospitals in the Nethe

  20. Increased resting bronchial tone in normal subjects acclimatised to altitude

    OpenAIRE

    Wilson, C.; Bakewell, S; M. Miller; Hart, N; McMorrow, R; BARRY, P.; Collier, D; Watt, S; Pollard, A.

    2002-01-01

    Background: Normal subjects frequently experience troublesome respiratory symptoms when acclimatised to altitude. Bronchial hyperresponsiveness (BHR) and full and partial flow-volume loops were measured before and after ascent to 5000 m altitude to determine if there are changes in resting bronchial tone and BHR that might explain the symptoms.

  1. Asthma control during the year after bronchial thermoplasty

    DEFF Research Database (Denmark)

    Cox, Gerard; Thomson, Neil C.; Rubin, Adalberto S.; Niven, Robert M.; Corris, Paul A.; Siersted, Hans Christian; Olivenstein, Ronald; Pavord, Ian D.; McCormack, David; Chaudhuri, Rekha; Miller, John D.; Laviolette, Michel

    2007-01-01

    BACKGROUND: Bronchial thermoplasty is a bronchoscopic procedure to reduce the mass of airway smooth muscle and attenuate bronchoconstriction. We examined the effect of bronchial thermoplasty on the control of moderate or severe persistent asthma. METHODS: We randomly assigned 112 subjects who had...

  2. Radioaerosol Inhalation Imaging in Bronchial Asthma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Bum Soo; Park, Young Ha; Park, Jeong Mi; Chung, Myung Hee; Chung, Soo Kyo; Shinn, Kyung Sub; Bahk, Yong Whee [Catholic University College of Medicine, Seoul (Korea, Republic of)

    1991-03-15

    Radioaerosol inhalation imaging (RII) has been used in radionuclide pulmonary studies for the past 20 years. The method is well accepted for assessing regional ventilation because of its usefulness, easy fabrication and simple application system. To evaluate its clinical utility in the study of impaired regional ventilation in bronchial asthma, we obtained and analysed RIIs in 31 patients (16 women and 15 men; age ranging 21-76 years) with typical bronchial asthma at the Department of Radiology, Kangnam St. Mary's Hospital, Catholic University Medical college, from January, 1988 to August, 1989. Scintiscans were obtained with radioaerosol produced by a HARC(Bhabha Atomic Research Center, India) nebulizer with 15 mCi of {sup 99m}Tc-phytate. The scanning was performed in anterior, posterior and lateral projections following 5-minute inhalation of radioaerosol on sitting position. The scans were analysed and correlated with the results of pulmonary function study and the findings of chest radiography. Fifteen patients had concomitant lung perfusion image with {sup 99m}Tc-MAA. Follow-up scans were obtained in 5 patients after bronchodilator therapy. 1 he patients were divided into (1) attack type (4 patients), (2) resistant type (5 patients), (3) remittent type (10 patients) and (4) bronchitic type (12 patients). Chest radiography showed hyperinflation, altered pulmonary vascularity, thickening of the bronchial wall and accentuation of hasal interstitial markings in 26 of the 31 patients. Chest radiographs were normal in the remaining 5 patients. Regardless of type, the findings of RII were basically the same, and characterized by the deposition of radioaerosol in the central parts or in the main respiratory air ways along with mottled nonsegmental ventilation defects in the periphery. Peripheral parenchymal defects were more extensive than that of expected findings from clinical symptoms, pulmonary function test and chest radiograph. Broomstick sign was present

  3. Radioaerosol Inhalation Imaging in Bronchial Asthma

    International Nuclear Information System (INIS)

    Radioaerosol inhalation imaging (RII) has been used in radionuclide pulmonary studies for the past 20 years. The method is well accepted for assessing regional ventilation because of its usefulness, easy fabrication and simple application system. To evaluate its clinical utility in the study of impaired regional ventilation in bronchial asthma, we obtained and analysed RIIs in 31 patients (16 women and 15 men; age ranging 21-76 years) with typical bronchial asthma at the Department of Radiology, Kangnam St. Mary's Hospital, Catholic University Medical college, from January, 1988 to August, 1989. Scintiscans were obtained with radioaerosol produced by a HARC(Bhabha Atomic Research Center, India) nebulizer with 15 mCi of 99mTc-phytate. The scanning was performed in anterior, posterior and lateral projections following 5-minute inhalation of radioaerosol on sitting position. The scans were analysed and correlated with the results of pulmonary function study and the findings of chest radiography. Fifteen patients had concomitant lung perfusion image with 99mTc-MAA. Follow-up scans were obtained in 5 patients after bronchodilator therapy. 1 he patients were divided into (1) attack type (4 patients), (2) resistant type (5 patients), (3) remittent type (10 patients) and (4) bronchitic type (12 patients). Chest radiography showed hyperinflation, altered pulmonary vascularity, thickening of the bronchial wall and accentuation of hasal interstitial markings in 26 of the 31 patients. Chest radiographs were normal in the remaining 5 patients. Regardless of type, the findings of RII were basically the same, and characterized by the deposition of radioaerosol in the central parts or in the main respiratory air ways along with mottled nonsegmental ventilation defects in the periphery. Peripheral parenchymal defects were more extensive than that of expected findings from clinical symptoms, pulmonary function test and chest radiograph. Broomstick sign was present in 1.7 patients

  4. Sessile alveolar macrophages communicate with alveolar epithelium to modulate immunity

    Science.gov (United States)

    Westphalen, Kristin; Gusarova, Galina A.; Islam, Mohammad N.; Subramanian, Manikandan; Cohen, Taylor S.; Prince, Alice S.; Bhattacharya, Jahar

    2014-02-01

    The tissue-resident macrophages of barrier organs constitute the first line of defence against pathogens at the systemic interface with the ambient environment. In the lung, resident alveolar macrophages (AMs) provide a sentinel function against inhaled pathogens. Bacterial constituents ligate Toll-like receptors (TLRs) on AMs, causing AMs to secrete proinflammatory cytokines that activate alveolar epithelial receptors, leading to recruitment of neutrophils that engulf pathogens. Because the AM-induced response could itself cause tissue injury, it is unclear how AMs modulate the response to prevent injury. Here, using real-time alveolar imaging in situ, we show that a subset of AMs attached to the alveolar wall form connexin 43 (Cx43)-containing gap junction channels with the epithelium. During lipopolysaccharide-induced inflammation, the AMs remained sessile and attached to the alveoli, and they established intercommunication through synchronized Ca2+ waves, using the epithelium as the conducting pathway. The intercommunication was immunosuppressive, involving Ca2+-dependent activation of Akt, because AM-specific knockout of Cx43 enhanced alveolar neutrophil recruitment and secretion of proinflammatory cytokines in the bronchoalveolar lavage. A picture emerges of a novel immunomodulatory process in which a subset of alveolus-attached AMs intercommunicates immunosuppressive signals to reduce endotoxin-induced lung inflammation.

  5. Bronchial and pulmonary scintigraphy with radioactively marked aerosols

    International Nuclear Information System (INIS)

    In 97 patients with bronchitis, bronchial asthma, tuberculosis, sarcoidosis, pneumoconiosis, or tumors the mucociliary clearance and/or deposit pattern after inhalation of radioactively marked aerosols (1 mCi 99m Tc sulfur colloid) was studied. Normal values of the mucociliary 30 min. clearance for the central bronchial/lung periphery are 21%/15%. There was a decreased clearance with bronchitis (11/8%), bronchial asthma, emphysema, tuberculosis, sarcoidosis, trachiobronchial amyloidosis, pleural scarring or interstitial pneumona. Increased clearance (29/19%) was shown with pneumoconiosis. The correlation of deposit pattern and disease, for example, bronchitis, bronchial asthma, bullous emphysema, pleural scarring, partial lung resection, bronchopneumonia, or bronchial restriction, is described. In comparison of aerosol scintigraphy to perfusion scintigraphy and ventilation with gaseous xenon, the aerosol scintigraphy is superior to xenon for certain indications. The aerosol particles, which are larger in comparison to xenon, settle easier by obstructions or flow variations and thereby give better clinical indications of regional differences. (orig.)

  6. Usefulness of antioxidant drugs in bronchial asthma

    International Nuclear Information System (INIS)

    Bronchial asthma is a clinical syndrome with possible correlation to oxidative stress, therefore the effectiveness of some antioxidant drugs has been studied in management of chronic bronchial asthma. Methods: This study was carried out in the Al- Kadhimia Teaching Hospital between December 2008 to May 2009 on 56 patients of both sexes who were randomly allocated to 7 groups, plus 10 healthy volunteers as control group. Each group was given one of the following drugs: vitamin E, vitamin C, combination of vitamin E and C, selenium, zinc, allopurinol and garlic oil, in addition to their classical treatment of asthma and their pulmonary function tests were conducted as well as measuring the levels of serum zinc, calcium, and malondialdehyde (MDA) before and after treatment. Results: All asthmatic patients were suffering from oxidative stress and this was detected by measuring the level of serum MDA which was 2-3 folds more than the control group, and all antioxidants except allopurinol showed a beneficial effect of different degrees in the pulmonary function tests accompanied with clinical improvement of patients' condition and marked decrease in the number of daily attacks. Antioxidants can compensate the oxidative stress that correlates with asthma, can reduce the symptoms of asthma, and improve pulmonary functions. (author)

  7. Severe bronchial asthma induced by compound codeine phosphate and ibuprofen sustained release tablets%洛芬待因缓释片诱发重度支气管哮喘发作

    Institute of Scientific and Technical Information of China (English)

    张晓兰; 赵鹏; 马国贤; 高家义

    2015-01-01

    1例68岁女性右侧桡骨远端多发骨折患者于石膏外固定手术后给予洛芬待因缓释片(每片含布洛芬0.2 g,磷酸可待因13 mg)3片口服,2次/ d。患者首次服药后约10 min,出现喘憋、心悸、大汗、面色苍白、咳嗽、咳痰、恶心、呕吐,听诊双肺可闻及哮鸣音。立即给予吸氧,多索茶碱和甲泼尼龙琥珀酸钠静脉滴注,并给予硫酸特布他林雾化液和布地奈德混悬液雾化吸入。2 h 后患者喘憋缓解,肺部哮鸣音消失。经追问病史,得知患者半年前在服用“去痛片”后出现喘息,1个月前在外院被诊断为支气管哮喘。%A 68-year-old female patient with multiple fractures of the right distal radius received oral compound codeine phosphate and ibuprofen sustained release tablets(containing ibuprofen 0. 2 g,codeine phosphate 13 mg per tablet)3 tablets twice daily after plaster external fixation. Ten minutes after the first administration,the patient developed wheezing,palpitation,pale,cough,expectoration,nausea,and vomiting. Oxygen inhalation,IV infusion of doxofylline and methylprednisolone sodium succinate for injection,and terbutaline sulphate solution for nebulization and budesonide suspension for inhalation were given immediately. Two hours after treatments,wheezing was relieved and wheezing rales in the lung disappeared. By asking the medical history,it was found that the patient had developed wheezing after taking somedon and was diagnosed as bronchial asthma 1 month ago in another hospital.

  8. Bronchial reactivity in hyperresponsive patients and healthy individuals: demonstration with high resolution computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Schueller, G. E-mail: gerd.schueller@univie.ac.at; Neumann, K.; Helbich, T.; Riemer, H.; Backfrieder, W.; Sertl, K.; Herold, C.J

    2004-11-01

    Objective: High resolution computed tomography (HRCT) was used to assess the extent of bronchial reactivity after inhalative bronchoprovocation and dilation in hyperresponsive patients and healthy subjects. Patients and methods: Patients with mild intermittent asthma, 15 with a >20% decrease in FEV{sub 1} and a >10 mmHg (PC{sub 20}+) in PaO{sub 2}, 12 with a <20% decrease in FEV{sub 1} and a >10 mmHg (PC{sub 20}-) in PaO{sub 2} after provocation, and eight healthy humans were included in the study. Changes in cross-sectional area in a total of 1256 bronchi and in bronchial wall area (792 bronchi) were evaluated after histamine-triggered bronchoprovocation and salbutamol-induced bronchodilation at high lung volumes (FVC 80%). Data were compared with the results of pulmonary function tests (FEV{sub 1}, PaO{sub 2}, PaCO{sub 2}). Results: In all groups, a significant decrease in bronchial cross-sectional area (P<0.001) and a significant increase in bronchial wall area (P<0.001) were observed subsequent to bronchoprovocation. After bronchodilation, the increase in cross-sectional area (P<0.001) and the further increase in airway wall area (P<0.01) were significant in all groups. In PC{sub 20}+ and PC{sub 20}- asthmatics, significant differences (P<0.05) in PaO{sub 2}, >10 mmHg between baseline and provocation were observed. In healthy persons, the PaO{sub 2} decrease was <10 mmHg (P>0.05). After histamine provocation, the decrease in FEV{sub 1} was measured in the PC{sub 20}+ group, whereas a <20% FEV{sub 1} decrease was found in the PC{sub 20}- and the control groups, respectively. No significant correlations were observed between radiological data and the results of pulmonary function tests. Conclusions: HRCT demonstrated bronchial reactivity in hyperresponsive patients and, unexpectedly, in healthy subjects. The applied pulmonary function tests failed to characterize bronchial reactions in the healthy subjects. Based on these results, HRCT is a useful tool by which

  9. Mechanisms underlying epithelium-dependent relaxation in rat bronchioles

    DEFF Research Database (Denmark)

    Kroigaard, Christel; Dalsgaard, Thomas; Simonsen, Ulf

    2010-01-01

    (SK(Ca)) and intermediate (IK(Ca))-conductance calcium-activated potassium channels, NS309 (6,7-dichloro-1H-indole-2,3-dione 3-oxime) was used to induce EpDHF-type relaxation. IK(Ca) and SK(Ca)3 positive immunoreactions were observed mainly in the epithelium and endothelium of bronchioles and arteries......, respectively. In 5-hydroxytryptamine (1 microM)-contracted bronchioles (828 +/- 20 microm, n = 84) and U46619 (0.03 microM)-contracted arteries (720 +/- 24 microm, n = 68), NS309 (0.001-10 microM) induced concentration-dependent relaxations that were reduced by epithelium/endothelium removal and by blocking IK......(Ca) channels with charybdotoxin and in bronchioles also by blocking SK(Ca) channels with apamin. Inhibition of cyclooxygenase, nitric oxide synthase, and cytochrome 2C isoenzymes, or blockade of large (BK(Ca))-conductance calcium-activated potassium channels with iberiotoxin, failed to reduce NS309 relaxation...

  10. Heterogeneity of the intrahepatic biliary epithelium

    Institute of Scientific and Technical Information of China (English)

    Shannon Glaser; Heather Francis; Sharon DeMorrow; Gene LeSage; Giammarco Fava; Marco Marzioni; Julie Venter; Gianfranco Alpini

    2006-01-01

    The objectives of this review are to outline the recent findings related to the morphological heterogeneity of the biliary epithelium and the heterogeneous pathophysiological responses of different sized bile ducts to liver gastrointestinal hormones and peptides and liver injury/toxins with changes in apoptotic, proliferative and secretory activities. The knowledge of biliary function is rapidly increasing because of the recognition that biliary epithelial cells (cholangiocytes) are the targets of human cholangiopathies, which are characterized by proliferation/damage of bile ducts within a small range of sizes. The unique anatomy, morphology, innervation and vascularization of the biliary epithelium are consistent with function of cholangiocytes within different regions of the biliary tree. The in vivo models [e.g., bile duct ligation (BDL), partial hepatectomy, feeding of bile acids,carbon tetrachloride (CCl4) or α-naphthylisothiocyanate (ANIT)] and the in vivo experimental tools [e.g., freshly isolated small and large cholangiocytes or intrahepatic bile duct units (IBDU) and primary cultures of small and large murine cholangiocytes] have allowed us to demonstrate the morphological and functional heterogeneity of the intrahepatic biliary epithelium.These models demonstrated the differential secretory activities and the heterogeneous apoptotic and proliferative responses of different sized ducts. Similar to animal models of cholangiocyte proliferation/injury restricted to specific sized ducts, in human liver diseases bile duct damage predominates specific sized bile ducts.Future studies related to the functional heterogeneity of the intrahepatic biliary epithelium may disclose new pathophysiological treatments for patients with cholangiopathies.

  11. Status of glutathione in nasal epithelium

    International Nuclear Information System (INIS)

    During inhalation exposure to air-born toxicants, the nasal epithelium may be subjected to local toxicity. Since glutathione (GSH) is often involved in xenobiotic metabolism, GSH status in these tissues has been examined. GSH content and apparent first-order rate constants for GSH content and apparent first-order rate constants for GSH turnover and synthesis were determined for respiratory epithelium covering the anterior ventral septum, olfactory epithelium covering the dorsal posterior septum, olfactory epithelium covering the dorsal meatus from male Fischer rats. The three tissues had similar concentrations of GSH (approximately 3-3.4 umol/g tissue) as determined by the Ellman's assay or by HPLC equipped with an electrochemical detector. Animals were administered [35S]Cysteine (Cys) by tail vein injection and rate constants were estimated, after incorporation of Cys into tissue GSH pools, by the decrease in GSH specific activity 1-102 hr after administration. Total [35S]GSH was analyzed by HPLC with a flow-through radioactivity detector. The three nasal epithelial tissues had similar apparent biphasic rates of GSH turnover, with rapid-phase half-lives of less than 10 hr and slow-phase half-lives of approximately 30 hr. The high GSH concentrations and the apparent rapid GSH turnover may facilitate the GSH-mediated detoxification within nasal tissue

  12. "BRONCHIAL ARTERY EMBOLIZATION IN MASSIVE HEMOPTYSIS WITH A RARE CAUSE AND UNUSUAL BRONCHIAL ARTERY ANATOMY"

    Directory of Open Access Journals (Sweden)

    M.A. Shabani H. Saberi

    2004-09-01

    Full Text Available Massive hemoptysis is one of the most important respiratory emergencies and pulmonary infiltrating diseases are among the rare causes of hemoptysis. Bronchial artery embolization (BAE is a safe and effective treatment in these patients. Our case was a 45 years old woman with a 7 year history of Hodgkin's lymphoma who presented with massive hemoptysis of 20 days duration. CT scan revealed prebronchial infiltrating pattern. Diagnostic angiography showed hypervascularity in both hilar and perihilar areas and simultaneous opacification of both bronchial arteries from a right common trunk. BAE was successfully performed with 300 µ diameter polyvinyl alcohol. In follow up, hemoptysis did not recurred and patient was in good general health.

  13. 组织工程上皮移植对碱烧伤角膜新生血管的影响%Tissue-engineered epithelium transplantation on corneal neovascularization in alkali-induced limbal stem cell deficiency

    Institute of Scientific and Technical Information of China (English)

    郭青; 皮裕琍

    2012-01-01

    目的:评价组织工程上皮移植在碱烧伤角膜缘干细胞缺乏症中对角膜新生血管的抑制作用.方法:回顾性非随机的病例研究.2006/2011年我院收治的19例(23眼)完全性角膜缘干细胞缺乏症的碱烧伤患者,10例13眼行组织工程上皮移植,9例10眼行羊膜移植.所有患者在手术前后均用裂隙灯观察角膜新生血管情况,在术后第21,60d对角膜新生血管进行评分比较.结果:术后第21d和术后第60d组织工程上皮移植组和羊膜移植组角膜新生血管均较术前明显减少( P<0.05),在术后两个评价时间点,组织工程上皮移植组平均角膜新生血管分数明显低于羊膜移植组.结论:对碱烧伤所致角膜缘干细胞缺乏的患者,组织工程上皮移植抑制角膜新生血管的作用明显好于羊膜移植.%AIM: To evaluate the clinical outcomes of tissue-engineered epithelium transplantation on decreasing corneal neovascularization in patients with limbal stem cell deficiencies caused by alkali burns.eyes of 19 cases with severe corneal alkali burns from 2006 to 2011 in our hospital. All of these eyes had complete limbal stem cell deficiencies. Ten cases (13 eyes) were performed with tissue-engineered epithelium transplantation, and 9 cases (10 eyes) were performed with amnion membrane transplantation. Vascularization was observed in all cases by slit-lamp microscope before and after surgery. A neovascularization scoring system was used to evaluate each eye at the 21th and 60th after surgery.transplantation or amniotic membrane transplantation was performed, corneal neovascularization decreased significantly (P<0.05). And averaged scores of corneal neovascularization were significantly lower in tissue-engineered epithelium transplantation group at the 21th day and 60th day after surgery than those of amniotic membrane transplantation group(P<0.05). inhibitting the growth of corneal neovascularization in patients with limbal stem cell deficiencies

  14. CT diagnosis of traumatic bronchial rupture in children

    International Nuclear Information System (INIS)

    Bronchial rupture is a rare and serious complication of blunt chest trauma in children. The diagnosis of this injury is challenging and requires a high degree of clinical suspicion. It is frequently associated with other severe injuries that may draw the focus of attention away from this potentially catastrophic but treatable injury. The radiographic findings of bronchial rupture have been reported in very few series. We report the findings in two children with bronchial rupture diagnosed by CT, in whom CT resulted in a significant change in patient management. (orig.)

  15. 烹调油烟冷凝物诱导永生化人支气管上皮细胞恶性转化的研究%Study for Malignant Transformation of Immortalized Human Bronchial Epithelial (BEP-2D)Cells Induced by Cooking Oil Fumes Condensation

    Institute of Scientific and Technical Information of China (English)

    张诚; 李强; 吴庆琛; 朱茂祥; 杨陟华; 陈丹; 张敏

    2011-01-01

    Objective To find a good method for chronic malignant tranformation of immortalized human bronchial epithelial (BEP-2D) cells induced by cooking oil fumes condensation (COFC ), establish a model of malignant tranformation of BEP-2D cells and discuss the harm of COFC. Methods Cells was divided into control group and experimental group. MTT was used to decide the chronic exposure doses of the COFC. The malignant tendency of transformed BEP-2D cells was identified by anti-blood serum experiment and the malignant features of transformed BEP-2D cells were identified by the method of semisolid agar culture. The capability of COFC inducing differentiation in anti-blood serum experiment and the colony forming frequency of BEP-2D cells in semisolid agar medium in each group were compared. Results The best method for malignant tranformation of BEP-2D cells induced by the COFC was that the BEP-2D cells were treated with COFC at doses of 50 μg/mL respectively. Inoculated to the 20 generations, the cells inoculative efficiency were obviously disparity in the comparison of control group (P < 0.01). Inoculated to the 35th generation, the anchorage independent growth was appeared in the P35 (P < 0.05). The P35 BEP-2DCOFC cells formed tumors in nude mice, and tumors were poorly differentiated to squamous cell carcinoma confirmed by histopathological examination. Conclusion The malignant tranformation of immortalized human bronchial epithelial (BEP-2D) cells could be successfully induced by the COFC at the dose of 50 μg/mL, and the prompt cooking lampblack had the carcinogenicity to the human body.%目的 用烹调油烟冷凝物(COFC)诱导正常永生化人支气管上皮细胞(BEP-2D)慢性恶性转化,构建恶性转化的细胞模型,以探讨COFC的危害.方法 通过MTT法确定诱导物的染毒剂量,以COFC处理细胞,用血清抗性实验和锚着独立生长实验鉴定细胞恶性转化的倾向和恶性特征,比较对照组和实验组抗血清促分化的能力

  16. Neoplasia versus hyperplasia of the retinal pigment epithelium

    DEFF Research Database (Denmark)

    Heegaard, Steffen; Larsen, J.N.B.; Fledelius, Hans C.;

    2001-01-01

    ophthalmology, retinal pigment epithelium, adenoma, tumor-like hyperplasia, histology, immunohistochemistry, tumor, neoplasm, ultrasonography......ophthalmology, retinal pigment epithelium, adenoma, tumor-like hyperplasia, histology, immunohistochemistry, tumor, neoplasm, ultrasonography...

  17. Advances in mechanical ventilation onrespiratoryfailure as a result of chronic obstructive pulmonary disease and bronchial asthma

    Directory of Open Access Journals (Sweden)

    Zhuang MA

    2011-08-01

    Full Text Available Over years,great strides have been made in theories and practices of mechanical ventilation.The indications of non-invasive ventilation have been increasing,while invasive ventilation has been playing a vital role in patients who are critically ill with inadequate drainage of sputum and fail to benefit from non-invasive ventilation.Chronic diseases,including chronic obstructive pulmonary disease(COPD,one of the most common chronic diseases,and bronchial asthma,the incidence of which is ascending recent years,are main causes for respiratory failure.Accordingly,we focus in the present paper on discussion and elaboration of respiratory failure as a result of COPD and bronchial asthma.Type II respiratory failure is the major type of respiratory failure induced by COPD,both in acute exacerbation and stable stage,and mechanical ventilation is one of the most common treatments.Severe acute bronchial asthma complicated with respiratory failure is an emergency.In this situation,primary goal of mechanical ventilation is to make an efficient oxygenation and ventilation of patients,and to avoid hyperinflation to the utmost.For patients who are able to cooperate,non-invasive ventilation in early stage may be beneficial,avoiding tracheal intubation and application of invasive ventilation.But in those who can not achieve remission in a short term,an artificial airway should be established for invasive ventilation as soon as possible.

  18. A PATHOGENETIC ROLE OF TRANSCRIPTION COREPRESSOR Id2 IN BRONCHIAL ASTHMA

    Directory of Open Access Journals (Sweden)

    V. N. Mineev

    2016-01-01

    Full Text Available The aim of present study was to evaluate a possible role of Id2 (inhibitor of DNA-binding 2 in pathogenesis of bronchial asthma (BA. We have examined six healthy control persons, nine patients with allergic bronchial asthma (ABA and twenty-four patients with non-allergic bronchial asthma (NABA. The Id2 mRNA expression was evaluated by means of real-time PCR.No significant differences in Id2 mRNA expression levels were revealed between the control and asthma groups. Correlation analysis of Id2 mRNA expression has revealed significant positive correlation with AID (activation-induced cytidine deaminase mRNA levels and peripheric blood eosinophil contents in ABA. Healthy persons demonstrate strong positive correlation between Id2 mRNA expression and serum IgE levels, like as with ε-chain mRNA contents.It was suggested that the Id2 dysfunction may take place in the BA patients. These changes affect negative control over the AID expression, which is important for switching B-cells to IgE production.

  19. Ranking of CT in staging bronchial carcinoma

    International Nuclear Information System (INIS)

    The conventional radiological and CT findings in 347 patients with confirmed bronchial carcinomas have been compared. In 184 patients subjected to surgery, the post-operative TNM classification was compared with the pre-operative CT staging. It was found that CT staging of the T-classification was correct in 82% and of the lymph nodes in 62.5% of cases. CT had a sensitivity of 92% and 95% for the recognition of mediastinal and bronchopulmonary lymph nodes, respectively, and a specificity of 68% and 57%. In 163 patients not subjected to surgery the reasons for avoiding operation were also studied. In more than 80% of these patients it was the CT finding which had indicated that the patient was inoperable. (orig.)

  20. [Bronchial asthma - many types, different therapies].

    Science.gov (United States)

    Bergmann, Karl-Christian

    2016-05-01

    Around 9 % of the German population is affected by bronchial asthma. This serious problem diminishes the quality of life as well as performance of the patients. Triggers and individual courses of the illness are very diverse. Therapy for mild asthma (stage 1 and 2) can take place at the patient's general practitioner. Is the effect of the medication insufficient, the patient should be referred to a specialist. The aim of the therapy is controlled asthma without symptoms during day or night and patients who only rarely need medication on demand and who are not limited in their daily activities. With the help of three further escalation steps in medication including modern biologicals, specialists have extended possibilities to reach a controlled disease stage. PMID:27176061

  1. Clinical advances on Bronchial Asthma. Changing perceptions.

    Directory of Open Access Journals (Sweden)

    Iris González Morales

    2007-06-01

    Full Text Available Bronchial Asthma brepresents an important health problem worlwide due to the increment of its incidence in the last years. The general mortality is low in regard to morbidity but it could be potencially lethal. It is consider a frequent disease in our country when it is found in patients older than 15 years old and female sex is more prevalent than the male one. It has influence upon not only the ill person but also in the family ad society. The sanitary education is an important aspect for the correct control of sick patients. Within the following paper it is our intention to update the knowledge about this disease through a bibliographic revision. Epidemiology, physiopathology, classification, complementary explorations, as well as the factors that must be paid attention on its treatment are found among the processed aspects, all which will serve for consultation not only for students but also for professionals of the medical science branch.

  2. Expression of polycomb protein BMI-1 maintains the plasticity of basal bronchial epithelial cells.

    Science.gov (United States)

    Torr, Elizabeth; Heath, Meg; Mee, Maureen; Shaw, Dominick; Sharp, Tyson V; Sayers, Ian

    2016-08-01

    The airway epithelium is altered in respiratory disease and is thought to contribute to disease etiology. A caveat to disease research is that the technique of isolation of bronchial epithelial cells from patients is invasive and cells have a limited lifespan. The aim of this study was to extensively characterize the plasticity of primary human bronchial epithelial cells that have been engineered to delay cell senescence including the ability of these cells to differentiate. Cells were engineered to express BMI-1 or hTERT using viral vector systems. Cells were characterized at passage (p) early (p5), mid (p10), and late (p15) stage for: BMI-1, p16, and CK14 protein expression, viability and the ability to differentiate at air-liquid interface (ALI), using a range of techniques including immunohistochemistry (IHC), immunofluorescence (IF), transepithelial electrical resistance (TEER), scanning electron microscopy (SEM), MUC5AC and beta tubulin (BTUB) staining. BMI-1-expressing cells maintained elevated levels of the BMI-1 protein and the epithelial marker CK14 and showed a suppression of p16. BMI-1-expressing cells had a viability advantage, differentiated at ALI, and had a normal karyotype. In contrast, hTERT-expressing cells had a reduced viability, showed limited differentiation, and had an abnormal karyotype. We therefore provide extensive characterization of the plasticity of BMI-1 expressing cells in the context of the ALI model. These cells retain properties of wild-type cells and may be useful to characterize respiratory disease mechanisms in vitro over sustained periods. PMID:27558999

  3. 36. Study on p16INK4a and p15INK4b genes of human bronchial epithelial cells malignantly transformed by cyclophosphamide and thiotepa

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@Transformed human bronchial epithelial cells BEAS-2B induced by CP and TEPA were used to study abnormity of the tumor suppressor genes p15INK4b and p16INK4a, through which we can provide clues for explanations of the molecular mechanism in carcinogenesis of human bronchial epithelial cells induced by CP and TEPA. Analysis of the genomic DNA from the transformed BEAS-CP, and BEAS-T cells using PCR amplification, singe strand conformation polymorphism(SSCP) and DNA sequencing

  4. ATP-sensitive K(+) channels in rat colonic epithelium.

    Science.gov (United States)

    Pouokam, Ervice; Bader, Sandra; Brück, Brigitta; Schmidt, Bärbel; Diener, Martin

    2013-06-01

    ATP-sensitive K(+) (KATP) channels couple the metabolic state of a cell to its electrical activity. They consist of a hetero-octameric complex with pore-forming Kir6.x (Kir6.1, Kir6.2) and regulatory sulfonylurea receptor (SUR) subunits. Functional data indicate that KATP channels contribute to epithelial K(+) currents at colonic epithelia. However, their molecular identity and their properties are largely unknown. Therefore, changes in short-circuit current (I sc) induced by the KATP channel opener pinacidil (5 10(-4) mol l(-1)) were measured in Ussing chambers under control conditions and in the presence of different blockers of KATP channels. The channel subunits expressed by the colonic epithelium were identified by immunohistochemistry and by RT-PCR. The K(+) channel opener, when administered at the serosal side, induced an increase in I sc consistent with the induction of transepithelial Cl(-) secretion after activation of basolateral K(+) channels, whereas mucosal administration of pinacidil resulted in a negative I sc. The increase in I sc evoked by serosal pinacidil was inhibited by serosal administration of glibenclamide (5 10(-4) mol l(-1)) and gliclazide (10(-6) mol l(-1)), but was resistant even against a high concentration (10(-2) mol l(-1)) of tolbutamide. In contrast, none of these inhibitors (administered at the mucosal side) reduced significantly the negative I sc induced by mucosal pinacidil. Instead, pinacidil inhibited Cl(-) currents across apical Cl(-) channels in basolaterally depolarized epithelia indicating that the negative I sc induced by mucosal pinacidil is due to a transient inhibition of Cl(-) secretion. In mRNA prepared from isolated colonic crypts, messenger RNA for both pore-forming subunits, Kir6.1 and Kir6.2, and two regulatory subunits (SUR1 and SUR2B) was found. Expression within the colonic epithelium was confirmed for these subunits by immunohistochemistry. In consequence, KATP channels are present in the basolateral membrane

  5. Tracheal organ cultures as a useful tool to study Felid herpesvirus 1 infection in respiratory epithelium.

    Science.gov (United States)

    Leeming, Gail; Meli, Marina L; Cripps, Peter; Vaughan-Thomas, Anne; Lutz, Hans; Gaskell, Rosalind; Kipar, Anja

    2006-12-01

    Felid herpesvirus 1 (FeHV-1) is an important feline pathogen of the upper respiratory tract which can be identified in clinical cases by virus isolation and PCR. Studies on the effect and mode of spread of FeHV-1 in the respiratory epithelium, however, have previously only been performed in infected cats. Feline tracheal organ cultures which were inoculated with FeHV-1 at varying multiplicity of infection (MOI) were established. A dose-dependent response was observed. Low MOIs induced multifocal infection in the otherwise viable respiratory epithelium, which allowed monitoring of viral growth over several days. Therefore, tracheal organ cultures represent a suitable model for further study of the morphological and functional effects of FeHV-1 on respiratory epithelium, mimicking the in vivo situation. PMID:16926054

  6. Imaging findings of bronchial atresia in fetuses, neonates and infants

    Energy Technology Data Exchange (ETDEWEB)

    Alamo, Leonor; Meuli, Reto [University Hospital of Lausanne (CHUV) and University of Lausanne (UNIL), Department of Diagnostic and Interventional Radiology, Lausanne (Switzerland); Vial, Yvan [University Hospital of Lausanne (CHUV) and University of Lausanne (UNIL), Department of Obstetrics and Gynecology, Lausanne (Switzerland); Gengler, Carole [University Hospital of Lausanne (CHUV) and University of Lausanne (UNIL), Department of Pathology, Lausanne (Switzerland)

    2016-03-15

    Congenital lung malformations are increasingly detected before birth. However, bronchial atresia is rarely identified in utero and not always recognized in neonates. There are two types of atresia: (1) proximal, located at the level of the mainstem or the proximal lobar bronchi, which is extremely rare and usually lethal during pregnancy, causing a tremendous volume increase of the distal involved lung with secondary hypoplasia of the normal lung, and (2) peripheral, located at the segmental/subsegmental bronchial level, which may present as an isolated lesion or as part of a complex congenital malformation. Prenatal findings are mostly nonspecific. Postnatal exams show overinflated lung areas and focal bronchial dilations. The typical fluid-filled bronchoceles are not always observed in neonates but develop progressively in the first months of life. This pictorial essay describes the spectrum of imaging findings of bronchial atresia in fetuses, neonates and infants. (orig.)

  7. Imaging findings of bronchial atresia in fetuses, neonates and infants

    International Nuclear Information System (INIS)

    Congenital lung malformations are increasingly detected before birth. However, bronchial atresia is rarely identified in utero and not always recognized in neonates. There are two types of atresia: (1) proximal, located at the level of the mainstem or the proximal lobar bronchi, which is extremely rare and usually lethal during pregnancy, causing a tremendous volume increase of the distal involved lung with secondary hypoplasia of the normal lung, and (2) peripheral, located at the segmental/subsegmental bronchial level, which may present as an isolated lesion or as part of a complex congenital malformation. Prenatal findings are mostly nonspecific. Postnatal exams show overinflated lung areas and focal bronchial dilations. The typical fluid-filled bronchoceles are not always observed in neonates but develop progressively in the first months of life. This pictorial essay describes the spectrum of imaging findings of bronchial atresia in fetuses, neonates and infants. (orig.)

  8. Prostaglandin E2 release from dermis regulates sodium permeability of frog skin epithelium

    DEFF Research Database (Denmark)

    Rytved, Klaus A.; Brodin, Birger; Nielsen, Robert

    1995-01-01

    Arachidonic acid, cAMP, epithelium, frog skin, intracellular calcium, prostaglandin E*U2, sodium transport, tight epithelium.......Arachidonic acid, cAMP, epithelium, frog skin, intracellular calcium, prostaglandin E*U2, sodium transport, tight epithelium....

  9. Modern Technologies of Bronchial Asthma Control in Children (Review)

    OpenAIRE

    Т.I. Eliseeva; I.I. Balabolkin

    2015-01-01

    Bronchial asthma ranks among the most common allergic diseases in children. It is chronic inflammatory disease of the respiratory tract, in which many cells of innate and adaptive immune system participate together with epithelial cells causing the main clinical syndromes typical for the disease. Currently, bronchial asthma therapy aims at obtaining the control over the symptoms and course of asthma by providing an anti-inflammatory baseline therapy using different groups of pharmaceuticals: ...

  10. Therapeutic pulmonary artery stenting for metastatic bronchial carcinoid

    OpenAIRE

    Vawdrey, Daniel B F; Fitzsimmons, Samantha; Veldtman, Gruschen R; Carpenter, John-Paul

    2013-01-01

    We present a case of a middle-aged man with a 3-month history of progressive shortness of breath and peripheral oedema. Ten years prior to this, he had undergone a left pneumonectomy for metastatic bronchial carcinoid. Clinical examination revealed significant right heart failure, supported by transthoracic echocardiography. CT pulmonary angiogram revealed the cause to be marked progression of the bronchial carcinoid causing severe external compression of right pulmonary artery (RPA). In view...

  11. Rehabilitace u pacientů s astma bronchiale

    OpenAIRE

    Novák, Lukáš

    2011-01-01

    The topic of my thesis is the recovery of patients suffering from bronchial asthma. Asthma Bronchial (next asthma) is one of the most frequented civilisation diseases the prevalence of which has been increasing dramatically in the last 20 years. It is a chronic inflammatory disease of respiratory tract, which may appear at any age. The four major symptoms of asthma are whistling breath, shortness of breath, cough and tightness in the chest. Physiotherapy enables considerably a complex treatme...

  12. Eosinophils Promote Epithelial to Mesenchymal Transition of Bronchial Epithelial Cells

    OpenAIRE

    Yasukawa, Atsushi; Hosoki, Koa; Toda, Masaaki; Miyake, Yasushi; Matsushima, Yuki; Matsumoto, Takahiro; Boveda-Ruiz, Daniel; Gil-Bernabe, Paloma; Nagao, Mizuho; Sugimoto, Mayumi; Hiraguchi, Yukiko; Tokuda, Reiko; Naito, Masahiro; Takagi, Takehiro; D'Alessandro-Gabazza, Corina N.

    2013-01-01

    Eosinophilic inflammation and remodeling of the airways including subepithelial fibrosis and myofibroblast hyperplasia are characteristic pathological findings of bronchial asthma. Epithelial to mesenchymal transition (EMT) plays a critical role in airway remodelling. In this study, we hypothesized that infiltrating eosinophils promote airway remodelling in bronchial asthma. To demonstrate this hypothesis we evaluated the effect of eosinophils on EMT by in vitro and in vivo studies. EMT was a...

  13. Bronchial artery embolization in the treatment of massive hemoptysis

    International Nuclear Information System (INIS)

    Objective was to evaluate the efficacy of bronchial arteriography and bronchial artery embolization (BAE) in the management of massive hemoptysis in a developing Asian country. A retrospective review was carried out from March 2000 to March 2005 to evaluate the demographics, clinical presentation, radiographic studies, bronchoscopy results, and complications of bronchial arteriography and BAE at a tertiary care hospital in Pakistan. Fourteen patients (9males, 5 females) with a mean age of 49 years underwent bronchial arteriography and BAE for massive hemoptysis. Hemoptysis was caused by bronchiectasis (10 patients), active pulmonary tuberculosis (3 patients), and lung malignancy (one patient). A CT scan of the chest was carried out in 11 patients, which revealed bronchiectasis (8 patients), cavity with infiltrates (3 patients), and mass lesion (one patient). Bronchoscopy was performed in all patients. Bleeding lobe or segment was identified in 12 patients. Bronchial arteriography revealed hypervascularity (13 patients), bronchial artery hypertrophy (5 patients), hypervascularity with shunting (one patient), dense soft tissue staining (7 patients), extravasation of contrast (one patient) pseudoaneurysm (one patient). Bronchial artery embolization was carried out in all patients. Rebleeding occurred within 24 hours in 2 patients who underwent surgery and within one week another 2 patients who were managed with repeat BAE. The complication of embolization occurred in one patient (transverse myelitis). Thirteen patients improved and were discharged home. One patient with terminal lung carcinoma died due to cardiogenic shock secondary to acute myocardial infarction. Bronchial artery embolization is an effective method for management of massive hemoptysis in developing countries and has a low complication rate. (author)

  14. Undifferentiated bronchial fibroblasts derived from asthmatic patients display higher elastic modulus than their non-asthmatic counterparts.

    Directory of Open Access Journals (Sweden)

    Michal Sarna

    Full Text Available During asthma development, differentiation of epithelial cells and fibroblasts towards the contractile phenotype is associated with bronchial wall remodeling and airway constriction. Pathological fibroblast-to-myofibroblast transition (FMT can be triggered by local inflammation of bronchial walls. Recently, we have demonstrated that human bronchial fibroblasts (HBFs derived from asthmatic patients display some inherent features which facilitate their FMT in vitro. In spite of intensive research efforts, these properties remain unknown. Importantly, the role of undifferentiated HBFs in the asthmatic process was systematically omitted. Specifically, biomechanical properties of undifferentiated HBFs have not been considered in either FMT or airway remodeling in vivo. Here, we combine atomic force spectroscopy with fluorescence microscopy to compare mechanical properties and actin cytoskeleton architecture of HBFs derived from asthmatic patients and non-asthmatic donors. Our results demonstrate that asthmatic HBFs form thick and aligned 'ventral' stress fibers accompanied by enlarged focal adhesions. The differences in cytoskeleton architecture between asthmatic and non-asthmatic cells correlate with higher elastic modulus of asthmatic HBFs and their increased predilection to TGF-β-induced FMT. Due to the obvious links between cytoskeleton architecture and mechanical equilibrium, our observations indicate that HBFs derived from asthmatic bronchi can develop considerably higher static tension than non-asthmatic HBFs. This previously unexplored property of asthmatic HBFs may be potentially important for their myofibroblastic differentiation and bronchial wall remodeling during asthma development.

  15. Undifferentiated bronchial fibroblasts derived from asthmatic patients display higher elastic modulus than their non-asthmatic counterparts.

    Science.gov (United States)

    Sarna, Michal; Wojcik, Katarzyna A; Hermanowicz, Pawel; Wnuk, Dawid; Burda, Kvetoslava; Sanak, Marek; Czyż, Jarosław; Michalik, Marta

    2015-01-01

    During asthma development, differentiation of epithelial cells and fibroblasts towards the contractile phenotype is associated with bronchial wall remodeling and airway constriction. Pathological fibroblast-to-myofibroblast transition (FMT) can be triggered by local inflammation of bronchial walls. Recently, we have demonstrated that human bronchial fibroblasts (HBFs) derived from asthmatic patients display some inherent features which facilitate their FMT in vitro. In spite of intensive research efforts, these properties remain unknown. Importantly, the role of undifferentiated HBFs in the asthmatic process was systematically omitted. Specifically, biomechanical properties of undifferentiated HBFs have not been considered in either FMT or airway remodeling in vivo. Here, we combine atomic force spectroscopy with fluorescence microscopy to compare mechanical properties and actin cytoskeleton architecture of HBFs derived from asthmatic patients and non-asthmatic donors. Our results demonstrate that asthmatic HBFs form thick and aligned 'ventral' stress fibers accompanied by enlarged focal adhesions. The differences in cytoskeleton architecture between asthmatic and non-asthmatic cells correlate with higher elastic modulus of asthmatic HBFs and their increased predilection to TGF-β-induced FMT. Due to the obvious links between cytoskeleton architecture and mechanical equilibrium, our observations indicate that HBFs derived from asthmatic bronchi can develop considerably higher static tension than non-asthmatic HBFs. This previously unexplored property of asthmatic HBFs may be potentially important for their myofibroblastic differentiation and bronchial wall remodeling during asthma development. PMID:25679502

  16. Intestinal epithelium in inflammatory bowel disease

    DEFF Research Database (Denmark)

    Coskun, Mehmet

    2014-01-01

    The intestinal epithelium has a strategic position as a protective physical barrier to luminal microbiota and actively contributes to the mucosal immune system. This barrier is mainly formed by a monolayer of specialized intestinal epithelial cells (IECs) that are crucial in maintaining intestinal...... homeostasis. Therefore, dysregulation within the epithelial layer can increase intestinal permeability, lead to abnormalities in interactions between IECs and immune cells in underlying lamina propria, and disturb the intestinal immune homeostasis, all of which are linked to the clinical disease course of...... inflammatory bowel disease (IBD). Understanding the role of the intestinal epithelium in IBD pathogenesis might contribute to an improved knowledge of the inflammatory processes and the identification of potential therapeutic targets....

  17. Intestinal epithelium in inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    Mehmet eCoskun

    2014-08-01

    Full Text Available The intestinal epithelium has a strategic position as a protective physical barrier to luminal microbiota and actively contributes to the mucosal immune system. This barrier is mainly formed by a monolayer of specialized intestinal epithelial cells (IECs that are crucial in maintaining intestinal homeostasis. Therefore, dysregulation within the epithelial layer can increase intestinal permeability, lead to abnormalities in interactions between IECs and immune cells in underlying lamina propria, and disturb the intestinal immune homeostasis, all of which are linked to the clinical disease course of inflammatory bowel disease (IBD. Understanding the role of the intestinal epithelium in IBD pathogenesis might contribute to an improved knowledge of the inflammatory processes and the identification of potential therapeutic targets.

  18. Allergic bronchopulmonary aspergillosis among patients with bronchial asthma

    Directory of Open Access Journals (Sweden)

    Al-Najada M, Al-Nadi K, Sharara AM

    2010-06-01

    Full Text Available To determine the different presentations encountered upon diagnosis of ABPA among patients with bronchial asthma and the two-year-follow-up results. Patients and method All patients with bronchial asthma and ABPA were included in the study .Specially formulated sheet was done include age, gender, duration of bronchial asthma ,new clinical,radiological,and laboratory findings suggestive of ABPA and two year follow up of them. Diagnosis of ABPA was based on Rosenberg-Patterson criteria. Result Fifteen patients with ABPA 3.9% out of 385 patients with bronchial asthma were included in our study, (5malesand (10 females there mean age was 28.8 years , and mean duration of asthma was 8.9 years, and they represent all stages of asthma severity. Fleeting shadows mainly in the upper lobes were the most common radiological findings observed in nine patients (60%, five patients (33.3% had proximal bronchiectasis detected by high resolution chest ct-scan, one of our patients had collapsed consolidation. All patients had moderate to severe eosinophilia and positive immediate skin test for aspergillus. Conclusion As the prevalence of ABPA is not uncommon among patients with bronchial asthma regardless the severity and the level control of asthma, high index of suspicious for ABPA should be maintained when followed up any patient with bronchial asthma.

  19. Bronchial Artery Embolization for Massive Hemoptysis: a Retrospective Study

    Directory of Open Access Journals (Sweden)

    Ali Fani

    2013-05-01

    Full Text Available   Introduction: To assess the efficacy and safety of bronchial artery embolization in the treatment of massive hemoptysis.   Materials and Methods: A retrospective study on 46 patients (26 males and 20 females who were referred to the Razavi Hospital from April 2009 to May 2012 with massive hemoptysis and had bronchial artery embolization procedures. General characteristics of the patients including age, gender, etiology, and thorax computed tomograms, findings of bronchial angiographic, results of the embolization, complications related to bronchial artery embolization and clinical outcome during follow-up were reviewed. Results: The etiology included previous pulmonary tuberculosis in 20 cases, previous tuberculosis with bronchiectasis in 16 cases, bronchiectasis in 6 cases, and active pulmonary tuberculosis in one case. No identifiable causes could be detected in three patients. Moreover, massive hemoptysis was successfully and immediately controlled following the embolization procedure in all patients. One patient developed recurrent hemoptysis during one month following the procedure and was treated by re-embolization. No major procedure–related complication such as bronchial infarction was identified However none of the patientsexperienced neurological complications. Conclusion: Bronchial artery embolization is a safe and effective means of controlling massive hemoptysis and should be regarded as the first-line treatment for this condition.

  20. Oral epithelium in diabetics: A cytomorphometric correlation

    OpenAIRE

    Nandita, K. P; Karen Boaz; Srikant, N.; Lewis, Amitha J; Nidhi Manaktala

    2014-01-01

    Objectives: The study aims to establish an etiological association between diabetes and precancerous lesions of the oral cavity by cytomorphometric analysis of the oral epithelium. Study Design: Smears were obtained from three distinct oral sites - buccal mucosa, dorsum of the tongue and the floor of the mouth in ten controls and ten patients previously diagnosed with type II diabetes. The oral smears were stained with Papanicolaou SA-36 solution. An eye - piece graticule was used to obtain t...

  1. Shiga Toxin Interaction with Human Intestinal Epithelium

    OpenAIRE

    Stephanie Schüller

    2011-01-01

    After ingestion via contaminated food or water, enterohaemorrhagic E. coli colonises the intestinal mucosa and produces Shiga toxins (Stx). No Stx-specific secretion system has been described so far, and it is assumed that Stx are released into the gut lumen after bacterial lysis. Human intestinal epithelium does not express the Stx receptor Gb3 or other Stx binding sites, and it remains unknown how Stx cross the intestinal epithelial barrier and gain access to the systemic circulation. This ...

  2. Development of the ovarian follicular epithelium.

    Science.gov (United States)

    Rodgers, R J; Lavranos, T C; van Wezel, I L; Irving-Rodgers, H F

    1999-05-25

    A lot is known about the endocrine control of the development of ovarian follicles, but a key question now facing researchers is which molecular and cellular processes take part in control of follicular growth and development. The growth and development of ovarian follicles occurs postnatally and throughout adult life. In this review, we focus on the follicular epithelium (membrana granulosa) and its basal lamina. We discuss a model of how granulosa cells arise from a population of stem cells and then enter different lineages before differentiation. The structure of the epithelium at the antral stage of development is presented, and the effects that follicle growth has on the behavior of the granulosa cells are discussed. Finally, we discuss the evidence that during follicle development the follicular basal lamina changes in composition. This would be expected if the behavior of the granulosa cells changes, or if the permeability of the basal lamina changes. It will be evident that the follicular epithelium has similarities to other epithelia in the body, but that it is more dynamic, as gross changes occur during the course of follicle development. This basic information will be important for the development of future reproductive technologies in both humans and animals, and possibly for understanding polycystic ovarian syndrome in women. PMID:10411332

  3. [Bronchial rupture in blunt thoracic trauma].

    Science.gov (United States)

    López Espadas, F; Zabalo, M; Encinas, M; Díaz Regañón, G; Pagola, M A; González Fernández, C

    2000-12-01

    In closed chest trauma, bronchial rupture is an unusual but potentially serious complication, with an associated mortality rate of 30%. Recent decades have seen an increase in incidence parallel to greater use of transport. Eighty percent of injuries are located 2.5 cm from the carina. Diagnosis is based on clinical signs, imaging and bronchoscopy. Subcutaneous emphysema and respiratory insufficiency are the most common findings. Images show the presence of pneumothorax, pneumomediastinum or both. Bronchoscopy is the diagnostic method of choice and must be performed early. Treatment consists of reestablishing anatomical continuity of the tracheobronchial tree by surgical repair if the lesion affects more than a third of the circumference and/or pneumothorax is not resolved after two chest drainages. This type of injury should be recognized and treated early, both to restore lung function and to prevent associated complications caused by delay. However, initial findings are seldom specific, requiring the physician to display a high degree of suspicion and explaining why diagnosis often comes late. PMID:11171438

  4. Bronchial Artery Aneurysm Embolization with NBCA

    International Nuclear Information System (INIS)

    We present a case of asymptomatic bronchial artery aneurysm that formed a fistula with part of the pulmonary artery (there was no definite fistula with the pulmonary vein). We were able to catheterize the feeding vessel but could not reach the aneurysm. We therefore injected a mixture of N-butyl-2-cyanoacrylate (NBCA; Histoacryl, B. Braun, Melsungen, Germany) and iodized oil (Lipiodol; Guerbet, Aulnay-sous-Bois, France) from the feeding vessel. The fistula, aneurysm, and feeding vessel were almost totally occluded. After embolization, the patient coughed a little; there were no other definite side effects or complications. One and 3 months later, on chest CT, the aneurysm was almost completely occupied with hyperattenuating NBCA-Lipiodol embolization. NBCA is a liquid embolization material whose time to coagulation after injection can be controlled by diluting it with Lipiodol. It is therefore possible to embolize an aneurysm, feeding vessels, and efferent vessels (in our case, it was a fistula) by using an NBCA-Lipiodol mixture of an appropriate concentration, regardless of whether the catheter can reach the aneurysm or not

  5. Neurogene Entzündung in einem neuen chronischen Tiermodell für allergisches Asthma bronchiale

    OpenAIRE

    Hottenrott, Tilman

    2011-01-01

    In the pathophysiology of allergic bronchial asthma interactions between immunological and neuronal factors play an important role. So far, studies dealing with these mechanisms mostly have been conducted with acute allergen challenge. Nevertheless repetitive challenges are probably more relevant to the situation of human asthma, although they can induce allergen tolerance. Results from earlier studies suggest, that especially nerve growth factor (NGF) is involved in the origin of asthmatic s...

  6. Dipeptidyl peptidase-4 is highly expressed in bronchial epithelial cells of untreated asthma and it increases cell proliferation along with fibronectin production in airway constitutive cells

    OpenAIRE

    Shiobara, Taichi; Chibana, Kazuyuki; Watanabe, Taiji; Arai, Ryo; Horigane, Yukiko; Nakamura, Yusuke; Hayashi, Yumeko; Shimizu, Yasuo; Takemasa, Akihiro; Ishii, Yoshiki

    2016-01-01

    Background Type 2 helper T-cell cytokines including IL-13 play a central role in the pathogenesis of bronchial asthma (BA). During the course of our research, our attention was drawn to dipeptidyl peptidase-4 (DPP4) as one of the molecules that were induced from bronchial epithelial cells (BECs) by IL-13 stimulation. DPP4 could become a new biomarker or therapeutic target. The aim of this study was to investigate the expression of DPP4 in the asthmatic airway, and its role in the pathophysiol...

  7. Bronchial histamine challenge in the diagnosis of asthma. The predictive value of changes in airway resistance determined by the interrupter method

    DEFF Research Database (Denmark)

    Madsen, F; Holstein-Rathlou, N H; Frølund, L;

    1986-01-01

    The predictive value of a bronchial challenge with histamine was determined in a prospective survey on a population with a high prevalence of asthma (0.62). Without knowledge of the bronchial responsiveness 133 patients were classified as asthmatics (83) or non-asthmatics (50) according to...... variation in peak expiratory flow rate and medical history. Response to challenge was determined by the interrupter method, and the concentration of histamine inducing a 40% increase in resistance to breathing (PC40-Rt) was calculated from the log dose response curve. When defining a positive test as a test....../ml the predictive value of a negative test in the diagnosis of asthma was increased to 0.81. The interrupter technique is suitable for diagnostic purposes in the detection and exclusion of bronchial asthma....

  8. Diagnosis of bronchial carcinoma; Diagnostik des Bronchialkarzinoms

    Energy Technology Data Exchange (ETDEWEB)

    Praeuer, H.W. [Technische Univ. Muenchen (Germany). Sektion Thoraxchirurgie der Chirurgischen Klinik und Poliklinik; Helmberger, H. [Technische Univ. Muenchen (Germany). Inst. fuer Roentgendiagnostik; Weber, W. [Technische Univ. Muenchen (Germany). Nuklearmedizinische Klinik und Poliklinik

    1998-04-01

    In addition to conventional chest X-rays in AP and lateral projection, computed tomography of the chest, upper abdomen, and head, percutaneous ultrasonography of the abdomen, and bone scintigraphy represent the standard procedures for the primary diagnosis and staging of bronchial carcinoma. Magnetic resonance imaging should be reserved for special situations and patients with allergy to IV contrast medium. The clinical value of positron emission tomography (PET) primarily with respect to lymph-node staging is currently being evaluated in on-going studies. Due to the high sensitivity of the listed staging modalities in combination with rather low specifity, there is a general tendency towards `over staging`, which carries certain risk particularly for potentially operable patients. Consequently the criteria which indicate inoperability (T3, T4, N2, N3 and, in individual cases, M1) have to be confirmed histologically by biopsy employing interventional techniques or even by explorative thoracotomy before definite therapeutic decisions are made. (orig.) [Deutsch] Fuer Primaerdiagnostik und Staging des Bronchialkarzinoms stellt die Computertomographie (Thorax mit Oberbauch, Schaedel) neben den konventionellen Roentgenaufnahmen in 2 Ebenen die Standarduntersuchung dar und bildet mit Oberbauchsonographie und Skelettszintigraphie das diagnostische Basisprogramm. Die MRT sollte gezielt fuer spezielle Fragestellungen zum Einsatz kommen und bei Patienten mit Kontrastmittelallergie. Der klinische Stellenwert der Positronen-Emissions-Tomographie (PET) v.a. beim Lymphknotenstaging wird derzeit in Studien evaluiert. In Folge der hohen Sensitivitaet der genannten Untersuchungsmethoden bei relativ geringer Spezifitaet, besteht grundsaetzlich eine Tendenz zum `over-staging`, die v.a. fuer potentiell operable Patienten Risiken in sich birgt. Inoperabilitaet signalisierende Kriterien (T3, T4, N2, N3, in Einzelfaellen auch M1) muessen daher vor folgenschweren therapeutischen

  9. Histatin-1 Expression in Human Lacrimal Epithelium.

    Directory of Open Access Journals (Sweden)

    Dhara Shah

    Full Text Available Study of human lacrimal cell biology is limited by poor access to tissue samples, heterogeneous cell composition of tissue and a lack of established lacrimal epithelial markers. In order to further our understanding of lacrimal cell biology, we sought to find a better marker for human lacrimal epithelial cells, compared to what has been reported in the literature.We utilized human Muller's muscle conjunctival resection (MMCR specimens containing accessory lacrimal gland (ALG and cadaveric main lacrimal gland (MLG as sources of lacrimal tissue. Candidate markers were sought using human ALG tissue from MMCR specimens, isolated by laser capture microdissection (LCM. Affymetrix® analysis was performed on total RNA isolated from FFPE samples to profile transcription in ALG. MMCR tissue sections were assessed by immunofluorescence using antibodies for histatin-1, lactoferrin, E-cadherin (E-cad and alpha-smooth muscle actin (ASMA. Reverse transcriptase polymerase chain reaction (RT-PCR analysis was performed to analyze the expression of histatin-1, E-cad and lactoferrin from cadaveric MLG.Histatin-1 is expressed in ALG and MLG, localizes to lacrimal epithelium, and to a greater degree than do other putative lacrimal epithelial markers.Histatin-1 is a good marker for human lacrimal epithelium in ALG and MLG and can be used to identify lacrimal cells in future studies.

  10. Acid phosphatase and lipid peroxidation in human cataractous lens epithelium

    Directory of Open Access Journals (Sweden)

    Vasavada Abhay

    1993-01-01

    Full Text Available The anterior lens epithelial cells undergo a variety of degenerative and proliferative changes during cataract formation. Acid phosphatase is primarily responsible for tissue regeneration and tissue repair. The lipid hydroperoxides that are obtained by lipid peroxidation of polysaturated or unsaturated fatty acids bring about deterioration of biological membranes at cellular and tissue levels. Acid phosphatase and lipid peroxidation activities were studied on the lens epithelial cells of nuclear cataract, posterior subcapsular cataract, mature cataract, and mixed cataract. Of these, mature cataractous lens epithelium showed maximum activity for acid phosphatase (516.83 moles of p-nitrophenol released/g lens epithelium and maximum levels of lipid peroxidation (86.29 O.D./min/g lens epithelium. In contrast, mixed cataractous lens epithelium showed minimum activity of acid phosphatase (222.61 moles of p-nitrophenol released/g lens epithelium and minimum levels of lipid peroxidation (54.23 O.D./min/g lens epithelium. From our study, we correlated the maximum activity of acid phosphatase in mature cataractous lens epithelium with the increased areas of superimposed cells associated with the formation of mature cataract. Likewise, the maximum levels of lipid peroxidation in mature cataractous lens epithelium was correlated with increased permeability of the plasma membrane. Conversely, the minimum levels of lipid peroxidation in mixed cataractous lens epithelium makes us presume that factors other than lipid peroxidation may also account for the formation of mixed type of cataract.

  11. Differential deposition of fibronectin by asthmatic bronchial epithelial cells.

    Science.gov (United States)

    Ge, Qi; Zeng, Qingxiang; Tjin, Gavin; Lau, Edmund; Black, Judith L; Oliver, Brian G G; Burgess, Janette K

    2015-11-15

    Altered ECM protein deposition is a feature in asthmatic airways. Fibronectin (Fn), an ECM protein produced by human bronchial epithelial cells (HBECs), is increased in asthmatic airways. This study investigated the regulation of Fn production in asthmatic or nonasthmatic HBECs and whether Fn modulated HBEC proliferation and inflammatory mediator secretion. The signaling pathways underlying transforming growth factor (TGF)-β1-regulated Fn production were examined using specific inhibitors for ERK, JNK, p38 MAPK, phosphatidylinositol 3 kinase, and activin-like kinase 5 (ALK5). Asthmatic HBECs deposited higher levels of Fn in the ECM than nonasthmatic cells under basal conditions, whereas cells from the two groups had similar levels of Fn mRNA and soluble Fn. TGF-β1 increased mRNA levels and ECM and soluble forms of Fn but decreased cell proliferation in both cells. The rate of increase in Fn mRNA was higher in nonasthmatic cells. However, the excessive amounts of ECM Fn deposited by asthmatic cells after TGF-β1 stimulation persisted compared with nonasthmatic cells. Inhibition of ALK5 completely prevented TGF-β1-induced Fn deposition. Importantly, ECM Fn increased HBEC proliferation and IL-6 release, decreased PGE2 secretion, but had no effect on VEGF release. Soluble Fn had no effect on cell proliferation and inflammatory mediator release. Asthmatic HBECs are intrinsically primed to produce more ECM Fn, which when deposited into the ECM, is capable of driving remodeling and inflammation. The increased airway Fn may be one of the key driving factors in the persistence of asthma and represents a novel, therapeutic target. PMID:26342086

  12. Bronchial reactivity in patients with recent pulmonary sarcoidosis.

    OpenAIRE

    Olafsson, M; Simonsson, B. G.; Hansson, S B

    1985-01-01

    Non-specific bronchial reactivity was assessed in 17 consecutive non-smoking and non-steroid treated patients with recently diagnosed pulmonary sarcoidosis, 11 with stage I disease and six with stage II disease. Bronchial reactivity was measured by recording the FEV1 after increasing doses of methacholine. Three subjects with asthma were hyperreactive. The 14 subjects with no asthma had a mean FEV1 of 96% predicted. Only one was hyperreactive, with a fall in FEV1 of over 15% after 0.1% methac...

  13. A case of endobronchial lipoma mimicking bronchial asthma

    Directory of Open Access Journals (Sweden)

    Sevket Ozkaya

    2009-05-01

    Full Text Available Sevket Ozkaya1, Hasan Demir1, Serhat Findik21Samsun Chest Diseases and Thoracic Surgery Hospital, Samsun, Turkey; 2Department of Pulmonary Medicine, Faculty of Medicine, Ondokuz Mayis University, Kurupelit, Samsun, TurkeyAbstract: Endobronchial lipoma is a rare neoplasm of the tracheobronchial tree and it may cause irreversible pulmonary damage due to recurrent pneumonia. Rarely, it may mimic bronchial asthma. We present a 53-year-old woman with an endobronchial lipoma, which had been treated as a bronchial asthma for four years. She also had developed recurrent pneumonia three times.Keywords: endobronchial lipoma, asthma, radiology, bronchoscopy

  14. Exhaled Eicosanoids following Bronchial Aspirin Challenge in Asthma Patients with and without Aspirin Hypersensitivity: The Pilot Study

    Directory of Open Access Journals (Sweden)

    L. Mastalerz

    2012-01-01

    Full Text Available Background. Special regulatory role of eicosanoids has been postulated in aspirin-induced asthma. Objective. To investigate effects of aspirin on exhaled breath condensate (EBC levels of eicosanoids in patients with asthma. Methods. We determined EBC eicosanoid concentrations using gas chromatography/mass spectrometry (GC-MS and high-performance liquid chromatography/mass spectrometry (HPLC-MS2 or both. Determinations were performed at baseline and following bronchial aspirin challenge, in two well-defined phenotypes of asthma: aspirin-sensitive and aspirin-tolerant patients. Results. Aspirin precipitated bronchial reactions in all aspirin-sensitive, but in none of aspirin-tolerant patients (ATAs. At baseline, eicosanoids profile did not differ between both asthma groups except for lipoxygenation products: 5- and 15-hydroxyeicosatetraenoic acid (5-, 15-HETE which were higher in aspirin-induced asthma (AIA than inaspirin-tolerant subjects. Following aspirin challenge the total levels of cysteinyl-leukotrienes (cys-LTs remained unchanged in both groups. The dose of aspirin had an effect on magnitude of the response of the exhaled cys-LTs and prostanoids levels only in AIA subjects. Conclusion. The high baseline eicosanoid profiling of lipoxygenation products 5- and 15-HETE in EBC makes it possible to detect alterations in aspirin-sensitive asthma. Cysteinyl-leukotrienes, and eoxins levels in EBC after bronchial aspirin administration in stable asthma patients cannot be used as a reliable diagnostic index for aspirin hypersensitivity.

  15. Roles of the cytoskeleton and of Protein Phosphorylation Events in the Osmotic Stress Response in EEL Intestinal Epithelium

    DEFF Research Database (Denmark)

    Lionetto, Maria G; Pedersen, Stine F; Hoffmann, Else K;

    2002-01-01

    The eel intestinal epithelium responds to an acute hypertonic challenge by a biphasic increase of the rate of Cl(-) absorption (measured as short circuit current, Isc, and creating a negative transepithelial potential, V(te), at the basolateral side of the epithelium). While the first, transient....../threonine phosphorylation events in the osmotic stress-induced ion transport in the eel intestinal epithelium, focusing on the sustained RVI phase, as well as on the previously uncharacterized response to hypotonic stress. The study was carried out using confocal laser scanning microscopy, a quantitative F-actin assay......-actin and microtubules. In addition, the shrinkage-induced activation of NKCC appears to require the activity of both PKC and MLCK. It is suggested that NKCC regulation by hypertonic stress involves an interaction between the cytoskeleton and protein phosphorylation events....

  16. Cystic fibrosis bronchial epithelial cells are lipointoxicated by membrane palmitate accumulation.

    Directory of Open Access Journals (Sweden)

    Laurie-Anne Payet

    Full Text Available The F508del-CFTR mutation, responsible for Cystic Fibrosis (CF, leads to the retention of the protein in the endoplasmic reticulum (ER. The mistrafficking of this mutant form can be corrected by pharmacological chaperones, but these molecules showed limitations in clinical trials. We therefore hypothesized that important factors in CF patients may have not been considered in the in vitro assays. CF has also been associated with an altered lipid homeostasis, i. e. a decrease in polyunsaturated fatty acid levels in plasma and tissues. However, the precise fatty acyl content of membrane phospholipids from human CF bronchial epithelial cells had not been studied to date. Since the saturation level of phospholipids can modulate crucial membrane properties, with potential impacts on membrane protein folding/trafficking, we analyzed this parameter for freshly isolated bronchial epithelial cells from CF patients. Interestingly, we could show that Palmitate, a saturated fatty acid, accumulates within Phosphatidylcholine (PC in CF freshly isolated cells, in a process that could result from hypoxia. The observed PC pattern can be recapitulated in the CFBE41o(- cell line by incubation with 100 µM Palmitate. At this concentration, Palmitate induces an ER stress, impacts calcium homeostasis and leads to a decrease in the activity of the corrected F508del-CFTR. Overall, these data suggest that bronchial epithelial cells are lipointoxicated by hypoxia-related Palmitate accumulation in CF patients. We propose that this phenomenon could be an important bottleneck for F508del-CFTR trafficking correction by pharmacological agents in clinical trials.

  17. Crocidolite-induced pulmonary fibrosis in mice

    International Nuclear Information System (INIS)

    The responses of alveolar and bronchial cells to asbestos exposure were studied to relate the cytokinetic changes of injury and repair to the inflammatory process and subsequent fibroblast activity. Lesions were induced by intratracheal instillation of 1 mg crocidolite asbestos to mice which were killed up to 20 weeks; 3H thymidine was injected 1 hr before death. A rapid inflammatory response with elevated PMN and lysosomal enzyme release was largely over by 2 wks though an increase in alveolar macrophages (AM) was maintained. Within 48 hrs there was multifocal necrosis of bronchiolar epithelium, maximal at bifurcations where longer fibers tend to adhere. Subsequently, intralumenal exudates were overgrown by proliferating epithelial cells and were incorporated, with long fibers, into bronchiolar connective tissue where granulomas formed. Alveolar lesions were located in peribronchiolar air sacs where focal injury of Type 1 cells by short fibers was rapidly repaired by division of Type 2 cells. Most short fibers were cleared by AMs, only a few fibers reached the interstitium. After 2 wks the increase in labeling index was due to labeled peribronchial fibroblasts. Biochemically, collagen increased after 4 wks when fibrosis was seen in bronchiolar lumens and in peribronchiolar connective tissue with lesser amounts in the centrilobular alveolar interstitium. The results suggest that long fibers induce bronchiolar injury and a more severe fibrotic pattern similar to human asbestosis

  18. Pigment Epithelium-Derived Factor Is an Intrinsic Antifibrosis Factor Targeting Hepatic Stellate Cells

    OpenAIRE

    Ho, Tsung-Chuan; Chen, Show-Li; Shih, Shou-Chuan; Wu, Ju-Yun; Han, Wen-Hua; Cheng, Huey-Chuan; Yang, Su-Lin; Tsao, Yeou-Ping

    2010-01-01

    The liver is the major site of pigment epithelium-derived factor (PEDF) synthesis. Recent evidence suggests a protective role of PEDF in liver cirrhosis. In the present study, immunohistochemical analyses revealed lower PEDF levels in liver tissues of patients with cirrhosis and in animals with chemically induced liver fibrosis. Delivery of the PEDF gene into liver cells produced local PEDF synthesis and ameliorated liver fibrosis in animals treated with either carbon tetrachloride or thioace...

  19. Morphological evaluation of normal human corneal epithelium

    DEFF Research Database (Denmark)

    Ehlers, Niels; Heegaard, Steffen; Hjortdal, Jesper; Ivarsen, Anders; Nielsen, Kim; Prause, Jan Ulrik

    2010-01-01

    PURPOSE: The human corneal epithelium is usually described as a 50-µm-thick layer of regular stratified squamous non-keratinized cells with a thickness of 5-7 cells. The purpose of this study is systemically to revisit the histopathological appearance of 100 corneas. METHODS: 5-µm-thick sections of...... corneas from 100 consecutively selected paraffin-embedded eyes were stained with hematoxylin-eosin and Periodic Acid-Schiff (PAS). All specimens were evaluated by light microscopy. The eyes were enucleated from patients with choroidal melanoma. Corneas were considered to be normal. RESULTS: Ninety of 100...... eyes were evaluated. The central epithelial, stromal and total corneal thickness was measured as 36.0 µm, 618 µm and 651µm, respectively, with a variation coefficient from 0.21 to 0.22. Pathological appearances were found in 27% of corneas, including thickened basement membrane and alterations in...

  20. Shiga Toxin Interaction with Human Intestinal Epithelium

    Directory of Open Access Journals (Sweden)

    Stephanie Schüller

    2011-06-01

    Full Text Available After ingestion via contaminated food or water, enterohaemorrhagic E. coli colonises the intestinal mucosa and produces Shiga toxins (Stx. No Stx-specific secretion system has been described so far, and it is assumed that Stx are released into the gut lumen after bacterial lysis. Human intestinal epithelium does not express the Stx receptor Gb3 or other Stx binding sites, and it remains unknown how Stx cross the intestinal epithelial barrier and gain access to the systemic circulation. This review summarises current knowledge about the influence of the intestinal environment on Stx production and release, Stx interaction with intestinal epithelial cells and intracellular uptake, and toxin translocation into underlying tissues. Furthermore, it highlights gaps in understanding that need to be addressed by future research.

  1. Spatially limited growth of an epithelium

    Science.gov (United States)

    Deforet, Maxime; Cochet, Olivier; Buguin, Axel; Silberzan, Pascal

    2012-02-01

    We present a study dealing with the growth of an epithelium on a spatially limited adhesive substrate. Adhesive patterns (typical size: 50μm to 500μm) are created by micro-fabrication techniques: A protein repellent polymeric gel homogeneously grafted on a coverslip is selectively ablated by plasma treatment through a thin layer of photoresist. The technique achieves a high resolution of patterning (around 2μm). After seeding cells (MDCK) on circular adhesive patterns, we let the monolayer grow for 30 hours after reaching the confluence. We use physical descriptors to describe migration and compaction. Two days after the confluence, we observe and characterize by confocal microscopy, the appearance of a tridimensionnal assembly of cells in the peripherical zone of the adhesive pattern (a ``rim''). Moreover using other patterns, the existence of a tissue line tension and internal pressure is investigated.

  2. Radiation response of the mouse tongue epithelium

    International Nuclear Information System (INIS)

    Mouse tongue mucosa has been used as a model to study dose responses to local irradiation. Although the irradiation procedures is less feasible and more time-consuming than e.g. snout irradiation, the tongue is the only location where a reasonable area of intraoral, multilayered epithelium in the mouse can be locally treated and scored, and a relatively small burden is imposed on the animal. In pilot experiments with external 300 kV x-irradiation just tolerated by the lip, the authors did not see critical damage to the tongue. In the present model, the onset of denudation was not correctly predicted by the normal turnover time of the tissue. (UK)

  3. Airway Inflammation and Bronchial Hyperresponsiveness in Elite Cross-Country Skiers and in Patients with Newly Diagnosed Asthma: A Bronchial Biopsy Study

    OpenAIRE

    Karjalainen, Eeva-Maija

    2008-01-01

    The objective of these studies was to evaluate possible airway inflammation and remodeling at the bronchial level in cross-country skiers without a prior diagnosis of asthma, and relate the findings to patients with mild chronic asthma and patients with newly diagnosed asthma. We also studied the association of airway inflammatory changes and bronchial hyperresponsivess (BHR), and treatment effects in cross-country skiers and in patients with newly diagnosed asthma. Bronchial biopsies we...

  4. Accurate 3D quantification of the bronchial parameters in MDCT

    Science.gov (United States)

    Saragaglia, A.; Fetita, C.; Preteux, F.; Brillet, P. Y.; Grenier, P. A.

    2005-08-01

    The assessment of bronchial reactivity and wall remodeling in asthma plays a crucial role in better understanding such a disease and evaluating therapeutic responses. Today, multi-detector computed tomography (MDCT) makes it possible to perform an accurate estimation of bronchial parameters (lumen and wall areas) by allowing a quantitative analysis in a cross-section plane orthogonal to the bronchus axis. This paper provides the tools for such an analysis by developing a 3D investigation method which relies on 3D reconstruction of bronchial lumen and central axis computation. Cross-section images at bronchial locations interactively selected along the central axis are generated at appropriate spatial resolution. An automated approach is then developed for accurately segmenting the inner and outer bronchi contours on the cross-section images. It combines mathematical morphology operators, such as "connection cost", and energy-controlled propagation in order to overcome the difficulties raised by vessel adjacencies and wall irregularities. The segmentation accuracy was validated with respect to a 3D mathematically-modeled phantom of a pair bronchus-vessel which mimics the characteristics of real data in terms of gray-level distribution, caliber and orientation. When applying the developed quantification approach to such a model with calibers ranging from 3 to 10 mm diameter, the lumen area relative errors varied from 3.7% to 0.15%, while the bronchus area was estimated with a relative error less than 5.1%.

  5. Morgagni’s hernia in a woman with bronchial asthma

    Directory of Open Access Journals (Sweden)

    Gowrinath K

    2014-07-01

    Full Text Available A 59-year-old, other wise asymptomatic lady known to have bronchial asthma was found to have an anterior mediastinal mass on a chest radiograph incidentally obtained as a part of pre-operative work-up for cataract surgery. Computed tomography of the chest confirmed the diagnosis of Morgagni’s hernia.

  6. Critical role of constitutive type I interferon response in bronchial epithelial cell to influenza infection.

    Directory of Open Access Journals (Sweden)

    Alan C-Y Hsu

    Full Text Available Innate antiviral responses in bronchial epithelial cells (BECs provide the first line of defense against respiratory viral infection and the effectiveness of this response is critically dependent on the type I interferons (IFNs. However the importance of the antiviral responses in BECs during influenza infection is not well understood. We profiled the innate immune response to infection with H3N2 and H5N1 virus using Calu-3 cells and primary BECs to model proximal airway cells. The susceptibility of BECs to influenza infection was not solely dependent on the sialic acid-bearing glycoprotein, and antiviral responses that occurred after viral endocytosis was more important in limiting viral replication. The early antiviral response and apoptosis correlated with the ability to limit viral replication. Both viruses reduced RIG-I associated antiviral responses and subsequent induction of IFN-β. However it was found that there was constitutive release of IFN-β by BECs and this was critical in inducing late antiviral signaling via type I IFN receptors, and was crucial in limiting viral infection. This study characterizes anti-influenza virus responses in airway epithelial cells and shows that constitutive IFN-β release plays a more important role in initiating protective late IFN-stimulated responses during human influenza infection in bronchial epithelial cells.

  7. Bronchial airway gene expression in smokers with lung or head and neck cancer

    International Nuclear Information System (INIS)

    Cigarette smoking is the major cause of cancers of the respiratory tract, including non-small cell lung cancer (NSCLC) and head and neck cancer (HNC). In order to better understand carcinogenesis of the lung and upper airways, we have compared the gene expression profiles of tumor-distant, histologically normal bronchial biopsy specimens obtained from current smokers with NSCLC or HNC (SC, considered as a single group), as well as nonsmokers (NS) and smokers without cancer (SNC). RNA from a total of 97 biopsies was used for gene expression profiling (Affymetrix HG-U133 Plus 2.0 array). Differentially expressed genes were used to compare NS, SNC, and SC, and functional analysis was carried out using Ingenuity Pathway Analysis (IPA). Smoking-related cancer of the respiratory tract was found to affect the expression of genes encoding xenobiotic biotransformation proteins, as well as proteins associated with crucial inflammation/immunity pathways and other processes that protect the airway from the chemicals in cigarette smoke or contribute to carcinogenesis. Finally, we used the prediction analysis for microarray (PAM) method to identify gene signatures of cigarette smoking and cancer, and uncovered a 15-gene signature that distinguished between SNC and SC with an accuracy of 83%. Thus, gene profiling of histologically normal bronchial biopsy specimens provided insight into cigarette-induced carcinogenesis of the respiratory tract and gene signatures of cancer in smokers

  8. STAT6 expression in T cells, alveolar macrophages and bronchial biopsies of normal and asthmatic subjects

    Directory of Open Access Journals (Sweden)

    Tomita Katsuyuki

    2012-03-01

    Full Text Available Abstract Background Asthma is characterised by increased numbers of Th2-like cells in the airways and IgE secretion. Generation of Th2 cells requires interleukin (IL-4 and IL-13 acting through their specific receptors and activating the transcription factor, signal transducer and activator of transcription 6 (STAT6. STAT6 knockout mice fail to produce IgE, airway hyperresponsiveness and bronchoalveolar lavage eosinophilia after allergen sensitisation, suggesting a critical role for STAT6 in allergic responses. Methods We have investigated the expression of STAT6 in peripheral blood T-lymphocytes, alveolar macrophages and bronchial biopsies from 17 normal subjects and 18 mild-moderate steroid-naïve stable asthmatic patients. Results STAT6 expression was variable and was detected in T-lymphocytes, macrophages and bronchial epithelial cells from all subjects with no difference between normal and stable asthmatic subjects. Conclusions STAT6 expression in different cells suggests that it may be important in regulating the expression of not only Th2-like cytokines in T cells of man, but may also regulate STAT-inducible genes in alveolar macrophages and airway epithelial cells.

  9. Human normal bronchial epithelial cells: a novel in vitro cell model for toxicity evaluation.

    Directory of Open Access Journals (Sweden)

    Wenqiang Feng

    Full Text Available Human normal cell-based systems are needed for drug discovery and toxicity evaluation. hTERT or viral genes transduced human cells are currently widely used for these studies, while these cells exhibited abnormal differentiation potential or response to biological and chemical signals. In this study, we established human normal bronchial epithelial cells (HNBEC using a defined primary epithelial cell culture medium without transduction of exogenous genes. This system may involve decreased IL-1 signaling and enhanced Wnt signaling in cells. Our data demonstrated that HNBEC exhibited a normal diploid karyotype. They formed well-defined spheres in matrigel 3D culture while cancer cells (HeLa formed disorganized aggregates. HNBEC cells possessed a normal cellular response to DNA damage and did not induce tumor formation in vivo by xenograft assays. Importantly, we assessed the potential of these cells in toxicity evaluation of the common occupational toxicants that may affect human respiratory system. Our results demonstrated that HNBEC cells are more sensitive to exposure of 10~20 nm-sized SiO2, Cr(VI and B(aP compared to 16HBE cells (a SV40-immortalized human bronchial epithelial cells. This study provides a novel in vitro human cells-based model for toxicity evaluation, may also be facilitating studies in basic cell biology, cancer biology and drug discovery.

  10. Cigarette Smoke Delays Regeneration of the Olfactory Epithelium in Mice.

    Science.gov (United States)

    Ueha, Rumi; Ueha, Satoshi; Sakamoto, Takashi; Kanaya, Kaori; Suzukawa, Keigo; Nishijima, Hironobu; Kikuta, Shu; Kondo, Kenji; Matsushima, Kouji; Yamasoba, Tatsuya

    2016-08-01

    The olfactory system is a unique part of the mammalian nervous system due to its capacity for neurogenesis and the replacement of degenerating receptor neurons. Cigarette smoking is a major cause of olfactory dysfunction. However, the mechanisms by which cigarette smoke impairs the regenerative olfactory receptor neurons (ORNs) remain unclear. Here, we investigated the influence of cigarette smoke on ORN regeneration following methimazole-induced ORN injury. Administration of methimazole caused detachment of the olfactory epithelium from the basement membrane and induced olfactory dysfunction, thus enabling us to analyze the process of ORN regeneration. We found that intranasal administration of cigarette smoke solution (CSS) suppressed the recovery of ORNs and olfaction following ORN injury. Defective ORN recovery in CSS-treated mice was not associated with any change in the number of SOX2(+) ORN progenitor cells in the basal layer of the OE, but was associated with impaired recovery of GAP43(+) immature ORNs. In the nasal mucosa, mRNA expression levels of neurotrophic factors such as brain-derived neurotrophic factor, neurotrophin-3, neurotrophin-5, glial cell-derived neurotrophic factor, and insulin-like growth factor-1 (IGF-1) were increased following OE injury, whereas CSS administration decreased the ORN injury-induced IGF-1 expression. Administration of recombinant human IGF-1 prevented the CSS-induced suppression of ORN recovery following injury. These results suggest that CSS impairs regeneration of ORNs by suppressing the development of immature ORNs from ORN progenitors, at least partly by reducing IGF-1 in the nasal mucosa. PMID:27003941

  11. DIVALENT METAL TRANSPORTER-1 REGULATION BY IRON AND VANADIUM MODULATES HYDROGEN PEROXIDE-INDUCED DNA DAMAGE IN LUNG CELLS

    Science.gov (United States)

    The divalent metal transporter-1 (DMT1) participates in the detoxification of metals that can damage lung epithelium. Elevated iron levels increase the expression of DMT1 in bronchial epithelial cells stimulating its uptake and storage in ferritin, thus making iron unavailable t...

  12. File list: Unc.Oth.05.AllAg.Olfactory_epithelium [Chip-atlas[Archive

    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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  16. Cigarette Smoke Induces Human Epidermal Receptor 2-Dependent Changes in Epithelial Permeability.

    Science.gov (United States)

    Mishra, Rangnath; Foster, Daniel; Vasu, Vihas T; Thaikoottathil, Jyoti V; Kosmider, Beata; Chu, Hong Wei; Bowler, Russell P; Finigan, James H

    2016-06-01

    The airway epithelium constitutes a protective barrier against inhaled insults, such as viruses, bacteria, and toxic fumes, including cigarette smoke (CS). Maintenance of bronchial epithelial integrity is central for airway health, and defective epithelial barrier function contributes to the pathogenesis of CS-mediated diseases, such as chronic obstructive pulmonary disease. Although CS has been shown to increase epithelial permeability, current understanding of the mechanisms involved in CS-induced epithelial barrier disruption remains incomplete. We have previously identified that the receptor tyrosine kinase human epidermal receptor (HER) 2 growth factor is activated by the ligand neuregulin-1 and increases epithelial permeability in models of inflammatory acute lung injury. We hypothesized that CS activates HER2 and that CS-mediated changes in barrier function would be HER2 dependent in airway epithelial cells. We determined that HER2 was activated in whole lung, as well as isolated epithelial cells, from smokers, and that acute CS exposure resulted in HER2 activation in cultured bronchial epithelial cells. Mechanistic studies determined that CS-mediated HER2 activation is independent of neuregulin-1 but required upstream activation of the epidermal growth factor receptor. HER2 was required for CS-induced epithelial permeability as knockdown of HER2 blocked increases in permeability after CS. CS caused an increase in IL-6 production by epithelial cells that was dependent on HER2-mediated extracellular signal-regulated kinases (Erk) activation. Finally, blockade of IL-6 attenuated CS-induced epithelial permeability. Our data indicate that CS activates pulmonary epithelial HER2 and that HER2 is a central mediator of CS-induced epithelial barrier dysfunction. PMID:26600084

  17. Clinical efficiency of desloratadine therapy in children with persistent form of allergic rhinitis and its effect on bronchial asthma symptoms

    Directory of Open Access Journals (Sweden)

    V.I. Petrov

    2010-03-01

    Full Text Available The research goal was to study the clinical efficiency of desloratadine therapy in children with persistent form of allergic rhinitis and to evaluate its effect on bronchial asthma symptoms. A prospective, randomized, open, parallel-group study of the effectiveness of desloratadine in children with persistent allergic rhinitis aged 2 - 16 in a four-week term was carried out. the effectiveness of therapy was evaluated by dynamics of clinical symptoms and rhinomanometry. the study showed that desloratadine was an effective medication in treatment of persistent allergic rhinitis in children of different age groups. It controlled nasal and other symptoms of allergic rhinitis and provided the reduction of stuffiness in nose and improvement of breathing through the nose. the medication significantly effected histamine-induced symptoms (itching, sneezing, rhinorrhea. In children with allergic rhinitis and bronchial asthma the positive dynamics of symptoms of asthma was observed. the effectiveness of treatment with desloratadine in children with isolated allergic rhinitis was proved to be higher than in patients with concomitant bronchial asthma

  18. Combination of carbonic anhydrase inhibitor, acetazolamide, and sulforaphane, reduces the viability and growth of bronchial carcinoid cell lines

    International Nuclear Information System (INIS)

    Bronchial carcinoids are pulmonary neuroendocrine cell-derived tumors comprising typical (TC) and atypical (AC) malignant phenotypes. The 5-year survival rate in metastatic carcinoid, despite multiple current therapies, is 14-25%. Hence, we are testing novel therapies that can affect the proliferation and survival of bronchial carcinoids. In vitro studies were used for the dose–response (AlamarBlue) effects of acetazolamide (AZ) and sulforaphane (SFN) on clonogenicity, serotonin-induced growth effect and serotonin content (LC-MS) on H-727 (TC) and H-720 (AC) bronchial carcinoid cell lines and their derived NOD/SCID mice subcutaneous xenografts. Tumor ultra structure was studied by electron microscopy. Invasive fraction of the tumors was determined by matrigel invasion assay. Immunohistochemistry was conducted to study the effect of treatment(s) on proliferation (Ki67, phospho histone-H3) and neuroendocrine phenotype (chromogranin-A, tryptophan hydroxylase). Both compounds significantly reduced cell viability and colony formation in a dose-dependent manner (0–80 μM, 48 hours and 7 days) in H-727 and H-720 cell lines. Treatment of H-727 and H-720 subcutaneous xenografts in NOD/SCID mice with the combination of AZ + SFN for two weeks demonstrated highly significant growth inhibition and reduction of 5-HT content and reduced the invasive capacity of H-727 tumor cells. In terms of the tumor ultra structure, a marked reduction in secretory vesicles correlated with the decrease in 5-HT content. The combination of AZ and SFN was more effective than either single agent. Since the effective doses are well within clinical range and bioavailability, our results suggest a potential new therapeutic strategy for the treatment of bronchial carcinoids

  19. Hyperoxia-induced ciliary loss and oxidative damage in an in vitro bovine model: the protective role of antioxidant vitamins E and C.

    Science.gov (United States)

    Al-Shmgani, Hanady S; Moate, Roy M; Sneyd, J Robert; Macnaughton, Peter D; Moody, A John

    2012-12-14

    Although elevated oxygen fraction is used in intensive care units around the world, pathological changes in pulmonary tissue have been shown to occur with prolonged exposure to hyperoxia. In this work a bovine bronchus culture model has been successfully used to evaluate the effects of hyperoxia on ciliated epithelium in vitro. Samples were cultured using an air interface method and exposed to normoxia, 21% O(2) or hyperoxia, 95% O(2). Cilial coverage was assessed using scanning electron microscopy (SEM). Tissue damage (lactate dehydrogenase, LDH, in the medium), lipid peroxidation (thiobarbituric acid reactive substances, TBARS), DNA damage (comet assay), protein oxidation (OxyBlot kit) and antioxidant status (total glutathione) were used to assess whether the hyperoxia caused significant oxidative stress. Hyperoxia caused a time-dependent decline (t(½)=3.4d compared to 37.1d under normoxia) in cilial coverage (PDNA (18.7 ± 2.2 versus 11.1 ± 1.5); protein carbonyls (PVitamins E (10(-7)M) and C (10(-6) or 10(-7)M) alone or in combination (10(-7)M and 10(-6)M, respectively) had a significant protective effect on the hyperoxia-induced reduction in percentage cilial coverage (Pbovine bronchial epithelium and denudation of cilia. The antioxidant vitamins E and C significantly protected against hyperoxia-induced cilia loss. PMID:23142230

  20. Regulation of the vitamin D receptor and cornifin beta expression in vaginal epithelium of the rats through vitamin D3

    Directory of Open Access Journals (Sweden)

    G Abban

    2009-08-01

    Full Text Available The aim of the present study was to determine the respective role of 1,25-dihydroxyvitamin D3 on vaginal epithelium and 1,25-dihydroxyvitamin D3 receptor expression in ovariectomized rats and vitamin D3 treated rats. Bilateral ovariectomies were performed in 20 mature, non-pregnant Wistar female rats. All the animals were divided into 2 groups consisting of 10 rats each. Group I served as control. In group II, animals were injected intramuscularly with vitamin D3 (50, 00 IU/kg. Two weeks after the injections, vaginas of animals in group I and group II were removed removed and processed for immunohistochemistry. Epithelial differentiation, 1,25-dihydroxyvitamin D3 receptor and cornifin b expression were investigated in vaginal epithelium of control group (ovariectomized and vitamin D3 treated rats. Vaginal epithelial cells from vitamin D3 treated animals changed into highly- stratified keratinizing layers. 1,25-dihydroxyvitamin D3 receptor and cornifin b as a marker of squamous differentiation were present in ovariectomized rats treated with 1,25- dihydroxyvitamin D3. In contrast, cornifin b and 1,25-dihydroxyvitamin D3 receptor were absent in all layers of vaginal epithelium in control group. We demonstrated for the first time that 1,25-dihydroxyvitamin D3 induced proliferation of vaginal epithelium consistent with the cornifin b expression and 1,25-dihydroxyvitamin D3 up-regulated 1,25-dihydroxyvitamin D3 receptor expression in vaginal epithelium.

  1. Involvement of Xanthine Oxidoreductase-related Oxidative Stress in a Dermatophagoides farinae-induced Asthma Model of NC/Nga Mice.

    Science.gov (United States)

    Setiawan, Heri; Nagaoka, Kenjiro; Kubo, Masayuki; Fujikura, Yoshihisa; Ogino, Keiki

    2016-06-01

    Oxidative stress is widely known to play a role in asthma. However, the contribution of xanthine oxidoreductase (XOR) as a source of the superoxide anion radical (O2-) in oxidative stress associated with asthma has not yet been examined in detail. Here we investigated pathophysiological changes in XOR in an experimental model of asthma induced by the house dust mite Dermatophagoides farinae (Df). In the lungs of Df-treated mice, the production of O2 - from XOR increased and the nitrite concentrations decreased, whereas the protein expression of XOR remained unchanged. Moreover, the protein expression levels of XOR and the hydrogen peroxide (H2O2) concentrations in bronchoalveolar lavage fluid (BALF) were higher in the Df-treated mice than in saline-treated mice. Immunohistochemically, although XOR was highly localized in the bronchial epithelial cells of the saline-treated mice, immunostaining for XOR was absent in the bronchial epithelium of Df-treated mice. These results suggest that oxidative stress is up-regulated by increases in the conversion of the dehydrogenase form (xanthine dehydrogenase; XDH) of XOR to the oxidase form (xanthine oxidase; XOD). PMID:27339206

  2. Stroma-epithelium crosstalk in prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Yi-Nong Niu; Shu-Jie Xia

    2009-01-01

    The critical role played by stroma-epithelium crosstalk in carcinogenesis and progression of prostate cancer has been increasingly recognized.These interactions are mediated by a variety of paracrine factors secreted by cancer cells and/or stromal cells.In human prostate cancer,reactive stroma is characterized by an increase in myofibroblasts and a corresponding amplification of extracellular matrix production and angiogenesis.Permanent genetic mutations have been reported in stromal cells as well as in turnout cells.Transforming growth factor-β,vascular endothelial growth factor,platelet-derived growth factor and fibroblast growth factor signalling pathways are involved in the process of angiogenesis,whereas hepatocyte growth factor,insulin-like growth factor-1,epidermal growth factor,CXC12 and Interleukin-6 play active roles in the progression,androgen-independent conversion and distal metastasis of prostate cancer.Some soluble factors have reciprocal interactions with androgens and the androgen receptor (AR),and can even activate AR in the absence of the androgen ligand.In this article,we review the complex interactions between cancer cells and the surrounding microenvironment,and discuss the potential therapeutic targets in the stromal compartment of prostate cancer.

  3. Human vomeronasal epithelium development: An immunohistochemical overview.

    Science.gov (United States)

    Dénes, Lóránd; Pap, Zsuzsanna; Szántó, Annamária; Gergely, István; Pop, Tudor Sorin

    2015-06-01

    The vomeronasal organ (VNO) is the receptor structure of the vomeronasal system (VNS) in vertebrates. It is found bilaterally in the submucosa of the inferior part of the nasal septum. There are ongoing controversies regarding the functionality of this organ in humans. In this study we propose the immunohistochemical evaluation of changes in components of the human vomeronasal epithelium during foetal development. We used 45 foetuses of different age, which were included in three age groups. After VNO identification immunohistochemical reactions were performed using primary antibodies against the following: neuron specific enolase, calretinin, neurofilament, chromogranin, synaptophysin, cytokeratin 7, pan-cytokeratin and S100 protein. Digital slides were obtained and following colorimetric segmentation, surface area measurements were performed. The VNO was found in less than half of the studied specimens (42.2%). Neuron specific enolase and calretinin immunoexpression showed a decreasing trend with foetal age, while the other neural/neuroendocrine markers were negative in all specimens. Cytokeratin 7 expression increased with age, while Pan-Ctk had no significant variations. S100 protein immunoexpression also decreased around the VNO. The results of the present work uphold the theory of regression of the neuroepithelium that is present during initial stages of foetal development. PMID:26132837

  4. Oral epithelium in diabetics: A cytomorphometric correlation

    Directory of Open Access Journals (Sweden)

    K P Nandita

    2014-01-01

    Full Text Available Objectives: The study aims to establish an etiological association between diabetes and precancerous lesions of the oral cavity by cytomorphometric analysis of the oral epithelium. Study Design: Smears were obtained from three distinct oral sites - buccal mucosa, dorsum of the tongue and the floor of the mouth in ten controls and ten patients previously diagnosed with type II diabetes. The oral smears were stained with Papanicolaou SA-36 solution. An eye - piece graticule was used to obtain the cytoplasm and nuclear dimension; where larger dimension was denoted as "D" and the smaller dimension was denoted as "d". The nuclear area (NA, nuclear diameter (ND, cytoplasmic area (CA and the cytoplasmic / nuclear ratio (C/N were evaluated from 50 cells predominant in each oral site. Statistical Analysis: The cytomorphometric data obtained was compared between the group of diabetic patients and the control groups using the student′s t- test (SPSS version 11.0. Results: Results showed that the nuclear area and the nuclear diameter of oral epithelial cells were increased in diabetic patients, as compared to non- diabetics, while the non- diabetic patients demonstrated an increase in nuclear ratio. Conclusions: The results from this study suggest that diabetes mellitus can cause alterations in oral epithelial cells that are detectable with exfoliative cytology.

  5. Regulation of ion transport via apical purinergic receptors in intact rabbit airway epithelium

    DEFF Research Database (Denmark)

    Poulsen, Asser Nyander; Klausen, Thomas Levin; Pedersen, Peter Steen;

    2005-01-01

    (100 microM), while the stimulatory effect was potentiated, indicating that ATP and UTP inhibit Na+ and stimulate Cl- current. Ionomycin (1 microM) induced responses similar to UTP and ATP and desensitized the epithelium to the nucleotides, indicating involvement of intracellular Ca2+ (Ca2+ i....... Furthermore, ATP, UTP and ionomycin induced 21, 24, and 21% decreases, respectively, in transepithelial conductance. Measurements of unidirectional isotope fluxes showed a 39% decrease in the dominant net Na+ absorption in response to ATP, while the smaller net Cl- secretion increased only insignificantly and...

  6. Activation of muscarinic acetylcholine receptors elicits pigment granule dispersion in retinal pigment epithelium isolated from bluegill

    Directory of Open Access Journals (Sweden)

    Crittenden Elizabeth L

    2004-07-01

    Full Text Available Abstract Background In fish, melanin pigment granules in the retinal pigment epithelium disperse into apical projections as part of the suite of responses the eye makes to bright light conditions. This pigment granule dispersion serves to reduce photobleaching and occurs in response to neurochemicals secreted by the retina. Previous work has shown that acetylcholine may be involved in inducing light-adaptive pigment dispersion. Acetylcholine receptors are of two main types, nicotinic and muscarinic. Muscarinic receptors are in the G-protein coupled receptor superfamily, and five different muscarinic receptors have been molecularly cloned in human. These receptors are coupled to adenylyl cyclase, calcium mobilization and ion channel activation. To determine the receptor pathway involved in eliciting pigment granule migration, we isolated retinal pigment epithelium from bluegill and subjected it to a battery of cholinergic agents. Results The general cholinergic agonist carbachol induces pigment granule dispersion in isolated retinal pigment epithelium. Carbachol-induced pigment granule dispersion is blocked by the muscarinic antagonist atropine, by the M1 antagonist pirenzepine, and by the M3 antagonist 4-DAMP. Pigment granule dispersion was also induced by the M1 agonist 4-[N-(4-chlorophenyl carbamoyloxy]-4-pent-2-ammonium iodide. In contrast the M2 antagonist AF-DX 116 and the M4 antagonist tropicamide failed to block carbachol-induced dispersion, and the M2 agonist arecaidine but-2-ynyl ester tosylate failed to elicit dispersion. Conclusions Our results suggest that carbachol-mediated pigment granule dispersion occurs through the activation of Modd muscarinic receptors, which in other systems couple to phosphoinositide hydrolysis and elevation of intracellular calcium. This conclusion must be corroborated by molecular studies, but suggests Ca2+-dependent pathways may be involved in light-adaptive pigment dispersion.

  7. CARIOUS EXPERIENCE IN CHILDREN SUFFERING FROM BRONCHIAL ASTHMA

    Directory of Open Access Journals (Sweden)

    Mona Olar

    2012-03-01

    Full Text Available Bronchial asthma is one of the most common pathologies of the chronic diseases of childhood, recording an ever-increasing frequency. The paper develops a control-type case study on the carious experience of 25 children suffering from bronchial asthma, comparatively with 25 healthy children. In both groups, the dmf-t/DMFT indices were calculated and the presence of Streptococcus mutans (SM and Lactobacillus acidophillus (LA in stimulated saliva, in concentrations with high cariogeneity risk, was determined. Carious experience and the SM level in concentrations with cariogenic risk were statistically significant in children with bronchic asthma (p=0.02. The presence of LA in concentrations with cariogenic risk was also higher in these children, yet statistically insignificant, comparatively with the reference (p>0.05.

  8. Pulmonary ventilation and perfusion scintigraphy in patients with bronchial asthma

    International Nuclear Information System (INIS)

    Pulmonary ventilation and perfusion scan using Xe-133 gas and Tc-99m MAA were performed in 18 patients with bronchial asthma to evaluate the regional pulmonary function. The scintigraphic findings were compared with the results of the auscultation and the conventional pulmonary functioning examination (%FVC, %FEV1.0). Ventilation image showed abnormality in 12 (70.6%) out of the asymptomatic 17 patients and perfusion image showed abnormality in 7 (41.2%) out of 17 patients. These 7 patients with abnormality on perfusion image all showed abnormality on ventilation image. The grade of abnormality in scintigraphic findings was compatible with the values of %FVC and %FEV1.0. In conclusion Xe-133 ventilation and Tc-99m MAA perfusion scan were useful procedures to estimate the pulmonary function of patients with bronchial asthma. (author)

  9. STAT6 EXPRESSION BY PERIPHERAL BLOOD LYMPHOCYTES IN BRONCHIAL ASTHMA

    OpenAIRE

    Mineev, V.N.; L. N. Sorokina

    2014-01-01

    Abstract. The aim of present study was to determine the features of STAT6 and phospho-STAT6 (pSTAT6) expression in bronchial asthma (BA). Patients and methods. Eleven patients with allergic (atopic) steroidfree were examined, five healthy controls served as a control. Expression of proteins (STAT6 and pSTAT6) in peripheral blood lymphocytes was studied by Western blot analysis after cell lysis. Preparation of cell lysates and Western blotting were performed using a standard procedure (Amersha...

  10. Aeroallergen sensitivity among patients suffering from bronchial asthma in Bangalore

    Directory of Open Access Journals (Sweden)

    Giriyanna Gowda

    2013-01-01

    Full Text Available Background: Asthma is a serious public health problem throughout the world and its prevalence has increased in last 2-3 decades. Allergens are one of the many factors which trigger an attack of asthma. Skin prick test is useful in identifying the offending allergen in bronchial asthma. Aim: To identify the possible offending allergens in patients of bronchial asthma. Materials and Methods: The study was a descriptive study conducted at allergy center, Kempegowda Institute of Medical Sciences Hospital and Research Center, Bangalore from January to December 2011. Skin prick test was done in 139 patients suffering from bronchial asthma using 49 allergens extracts. Statistical Analysis: Frequency, proportions, Chi-square test, odds ratio, and 95% confidence interval was used. Results: Out of 139 patients who underwent the skin prick tests, 40% (56 were males and 60% (83 were females. Majority, that is, 60% were in the age group of 21-40 years. Forty-three percent (60 had family history of asthma/atopy, 80% (111 had allergic rhinitis, 24% (34 had chronic urticaria, and 24% (33 had allergic conjunctivitis. Out of 139 patients, 100 (71.94% were sensitive for one or more allergens. The common offending allergens found in the study were dust mites (Dermatophagoides farinae and D. pteronyssinus (DF and DP - 49.28%, dusts - 7.2%, pollens - 6.77%, insects - 6.62%, fungi - 4.53%, and epithelia - 1.92%. Conclusion: The most common allergens in bronchial asthma were dust mites followed by dusts and pollens. Identifying possible allergens in asthma patients help in allergen avoidance and immunotherapy in these patients.

  11. Respiratory symptoms and bronchial responsiveness in competitive swimmers

    OpenAIRE

    Stadelmann, Katrin; Stensrud, Trine; Carlsen, Kai-Håkon

    2011-01-01

    Purpose: A high prevalence of bronchial hyperresponsiveness (BHR) and respiratory symptoms has been reported among competitive swimmers. From the 2002 Winter Olympics, BHR measurements or bronchodilator reversibility have been required for approved use of [beta]2-agonists in sports. The first aim of this study was to evaluate the relationship among respiratory symptoms in young elite swimmers, eucapnic voluntary hyperpnea (EVH), and the inhaled dose of methacholine, causing a 20% decrease in ...

  12. Bronchial artery embolization: Clinical analysis of 129 cases

    International Nuclear Information System (INIS)

    Bronchial artery embolization is well-accepted and widely used for management of massive and recurrent hemoptysis. This may either provide a definite therapeutic measure or a stabilizing effect on the patient in preparation for surgery. Retrospectively we reviewed 129 cases(106 patients) of bronchial artery embolization with Gelfoam pudding and Ivalon for control of hemoptysis from July 1985 to January 1991. The causes of hemoptysis were pulmonary tuberculosis(80.2%), bronchiectasis(11.3%), aspergilloma(2.8%), and other (5.7%). The cases of pulmonary tuberculosis included tuberculous bronchiectasis(40.0%), active(34.1%), undetermined(14.1%) and inactive(11.8%). The results were as follows: Immediate control of hemoptysis was achieved in 104 of 122 cases(85.2%). Immediate control of massive hemoptysis was achieved in 94 of 107 cases(87.6%) and of chronic intermittent hemoptysis in 10 of 15 cases(76%). Hemoptysis recurred in 39 of 90 follow up cases(43.3%) on follow-up studies performed ranging in period from 2 to 49 month after the initial studies. Thirty three of 81 cases of massive hemoptysis recurred(40.7%) and six of 9 cases of chronic intermittent hemoptysis recurred(67.0%). One year rebleeding rate of massive hemoptysis was 34.6%. The rebleeding cases of massive hemoptysis were controlled by conservative treatment in 25 of 33 cases(75.8%). In conclusion, bronchial artery embolization for hemoptysis control is effective in massive hemoptysis, but nearly ineffective in chronic intermittent hemoptysis. The goal of bronchial artery embolization is life-saving procedure without permanent effect, especially hemoptysis related to pulmonary tuberculosis

  13. Use motion games in exercise with children with bronchial asthma

    Directory of Open Access Journals (Sweden)

    Viktoriya Polkovnyk-Markova

    2016-02-01

    Full Text Available Purpose: to analyze the possibility of using moving games in the rehabilitation of children with bronchial asthma. Material & Methods: the modern scientific literature on integrated prevention and treatment of children with asthma. Results: A high frequency of morphological and functional deviations at children with asthma. Classification and examples of mobile games, which can be used for this group of children. Conclusions: the results of modern research that show the effectiveness the use of physical rehabilitation, including moving games.

  14. Techniques of protection and revascularization of the bronchial anastomosis.

    Science.gov (United States)

    Venuta, Federico; Diso, Daniele; Anile, Marco; Rendina, Erino A

    2016-03-01

    Airway anastomosis has been traditionally considered at risk for the onset of complications, particularly dehiscence with consequent infection and erosion in the adjacent vessels. Although the modifications and improvements of the surgical technique has contributed to reduce the incidence of complications, the protection and revascularization of the anastomotic site is still considered mandatory at many centers Many techniques have been proposed for encircling the bronchial anastomosis. PMID:26981269

  15. Techniques of protection and revascularization of the bronchial anastomosis

    OpenAIRE

    Venuta, Federico; Diso, Daniele; Anile, Marco; Rendina, Erino A.

    2016-01-01

    Airway anastomosis has been traditionally considered at risk for the onset of complications, particularly dehiscence with consequent infection and erosion in the adjacent vessels. Although the modifications and improvements of the surgical technique has contributed to reduce the incidence of complications, the protection and revascularization of the anastomotic site is still considered mandatory at many centers Many techniques have been proposed for encircling the bronchial anastomosis.

  16. Histamine bronchial challenge: effect on regional ventilation and aerosol deposition.

    OpenAIRE

    Clague, H.; Ahmad, D.; Chamberlain, M. J.; Morgan, W K; Vinitski, S

    1983-01-01

    We studied regional changes in ventilation and aerosol deposition after histamine challenge in six patients with asthma and two with rhinitis and a history of wheezing. All were known to have bronchial hyperreactivity and all showed an increased response to histamine. Ventilation and aerosol deposition studies, using xenon-133 and an aerosol of sulphur colloid tagged with technetium 99m, were performed while they were sitting. Before administration of histamine radioaerosol scintiscans were a...

  17. Bronchial Hyperreactivity in Non-Cystic Fibrosis Bronchiectasis

    OpenAIRE

    Benan Müsellim

    2013-01-01

    Aim: Bronchiectasis is an abnormal dilatation of bronchi and bronchioles due to repeated cycles of airway infection and inflammation. There is a limited data that support the existence of bronchial hyperreactivity (BHR) in bronchiectasis. In the present study we investigated the existence of BHR and possible factors that could affect the BHR in bronchiectasis patients. Matherial and Method: Study performed in bronchiectasis outpatient clinic. We included 69 patients in which the diagnosis of ...

  18. The opaque chest: When to suspect a bronchial foreign body

    International Nuclear Information System (INIS)

    A bronchial foreign body should be strongly suspected in a child with an opaque chest without a previous history of airways disease when there is: (1) any sign of volume loss or atelectasis in the lung density and (2) bronchiectasis within the lung density. Ultrasound may be helpful to rule out the presence of pleural fluid and may even demonstrate the bronchiectasis when the bronchi are fluid-filled. (orig.)

  19. Adjuvant immunotherapy with BCG in squamous cell bronchial carcinoma.

    OpenAIRE

    Jansen, H.M.; The, T H; Orie, N G

    1980-01-01

    Fifty-four patients with evidence of locally advanced primary squamous cell bronchial carcinoma (SCC), and three patients with adenocarcinoma (AC) had lung resection to remove all the visible tumour. After operation an randomly chosen group of 20 SCC patients received adjuvant BCG immunostimulation by scarifications (BCG-A). An additional group of 14 SCC patients, and three AC patients received initially intrapleural BCG treatment and subsequently scarifications (BCG-B). A control group of 20...

  20. Sleeve resection for delayed presentation of traumatic bronchial transection.

    LENUS (Irish Health Repository)

    Mohamed, H Y

    2010-02-01

    Tracheobronchial disruption is uncommon in blunt chest trauma. Many of these patients die before reaching the hospital. In the majority of survivors diagnosis is occasionally delayed resulting in complications like airway stenosis and lung collapse. Thus it is important to have radiological follow up after severe thoracic trauma. Sleeve resection can be an excellent option to conserve lung tissue in delayed presentation of bronchial transection.

  1. Respiratory virus infections and aeroallergens in acute bronchial asthma.

    OpenAIRE

    Carlsen, K H; Orstavik, I; Leegaard, J; Høeg, H

    1984-01-01

    Two hundred and fifty six attacks of acute bronchial asthma occurring in 169 children aged over 2 years were studied during a two year period. More attacks occurred during spring and autumn than at other times of the year. In 73 patients (29%) a respiratory virus infection was diagnosed, with the same seasonal variation as the asthmatic attacks. Most of the virus infections were caused by rhinovirus (45%) and respiratory syncytial virus (19%). There was no significant correlation between asth...

  2. Histamine N-methyltransferase Modulates Human Bronchial Smooth Muscle Contraction

    OpenAIRE

    Tamaoki, J.; Chiyotani, A.; Tagaya, E; Isono, K; Konno, K

    1994-01-01

    To elucidate the modulatory role of histamine-degrading enzymes in airway constrictor responses, human bronchial strips were studied under isometric conditions in vitro. Pretreatment of tissues with the histamine N-methyltransferase (HMT) inhibitor SKF 91488 specifically potentiated the contractile responses to histamine, causing a leftward displacement of the concentration response curves, whereas the diamine oxidase inhibitor aminoguanidine had no effect. This potentiation was attenuated by...

  3. Multipotent Capacity of Immortalized Human Bronchial Epithelial Cells

    OpenAIRE

    Delgado, Oliver; Kaisani, Aadil A.; Spinola, Monica; Xie, Xian-Jin; Batten, Kimberly G.; Minna, John D.; Wright, Woodring E; Shay, Jerry W.

    2011-01-01

    While the adult murine lung utilizes multiple compartmentally restricted progenitor cells during homeostasis and repair, much less is known about the progenitor cells from the human lung. Translating the murine stem cell model to humans is hindered by anatomical differences between species. Here we show that human bronchial epithelial cells (HBECs) display characteristics of multipotent stem cells of the lung. These HBECs express markers indicative of several epithelial types of the adult lun...

  4. OUABAIN AND INSULIN INDUCE SODIUM PUMP ENDOCYTOSIS IN RENAL EPITHELIUM

    OpenAIRE

    Gupta, Shalini; Yan, Yanling; Malhotra, Deepak; Liu, Jiang; Xie, Zijian; Najjar, Sonia M.; Shapiro, Joseph I

    2012-01-01

    Cardiotonic steroids signaling through the basolateral sodium pump (Na/KATPase) have been shown to alter renal salt handling in intact animals. As the relationship between renal salt handling and blood pressure is a key determinant of hypertension, and patients with insulin resistance are frequently hypertensive, we chose to examine whether there might be competition for resources necessary for receptor mediated endocytosis.

  5. Buccal Epithelium in treating Ocular Surface Disorders

    Directory of Open Access Journals (Sweden)

    Srinivas KR

    2008-11-01

    Full Text Available Background - Ocular surface disorders due to limbal stem cell deficiency are an important cause of ocular morbidity and visual loss. Although autologous limbal stem cell transplants have helped in the management of unilateral disease, allografts in those with bilateral disease often fail due to immunological reasons. The use of autologous buccal epithelium cultivated on amniotic membrane has been described as a useful approach in the management of this condition. It is the purpose of this study to explore the feasibility of using a novel thermo-gelatin polymer (TGP as a substrate to culture these cells, and to characterize them using RNA extraction and RT-PCR. Methods - Oral cheek mucosal biopsies were obtained from 5 adult patients undergoing Modified Osteo-Odonto Keratoprosthesis surgery. The specimens were transported to the laboratory in transport medium. The cells were released using enzymatic digestion and seeded in both convention culture medium and TGP. The resulting cellular growth was characterized using RNA extraction and RT-PCR. Results - Cells could be cultured from 4 of the 5 specimens. In one specimen, contamination occurred and this was discarded. In the other specimens, the cheek epithelial cells could be cultured in both the conventional culture medium and TGP, with equal ease. RT-PCR revealed the presence of K3, a marker for epithelial cells, and GAPDH indicating the presence of some adipose tissue as well. Conclusions - It is possible to culture autologous cheek mucosal epithelial cells using TGP, a synthetic scaffold, without the need for other biological substrates. Since the specimens are obtained from the oral cavity, stringent asepsis is required. Further studies are required for histopathological characterization of the cultured cells and to create a model for delivery onto the ocular surface of eyes with bilateral surface disease due to limbal stem cell deficiency.

  6. Characterization of Side Population Cells from Human Airway Epithelium

    OpenAIRE

    Hackett, Tillie-Louise; Shaheen, Furquan; Johnson, Andrew; Wadsworth, Samuel; Pechkovsky, Dmitri V; Jacoby, David B.; Kicic, Anthony; Stick, Stephen M.; Knight, Darryl A.

    2008-01-01

    The airway epithelium is the first line of contact with the inhaled external environment and is continuously exposed to and injured by pollutants, allergens, and viruses. However, little is known about epithelial repair and in particular the identity and role of tissue resident stem/progenitor cells that may contribute to epithelial regeneration. The aims of the present study were to identify, isolate, and characterize side population (SP) cells in human tracheobronchial epithelium. Epithelia...

  7. Bronchial effects of leukotriene D4 inhalation in normal human lung

    DEFF Research Database (Denmark)

    Bisgaard, H; Groth, S

    1987-01-01

    The aim of the study was to investigate whether inhaled leukotriene (LT) D4 could mimic the characteristics of asthmatic patients after allergen-induced attack, i.e. a prolonged subclinical bronchial obstruction, an increased reactivity of the airways and a late reaction. The effects of LTD4 were...... compared with those of histamine and the mechanism of action sought. Thirty-three non-atopic individuals participated in the study. The two drugs were inhaled as an aerosol of small particles causing a relative peripheral deposition pattern in order to mimic the preferential involvement of peripheral...... obstruction had decreased by 50% of the maximum effect, and no delayed reaction was observed within 10 h. The reactivity of the airways did not change during 10 h after inhalation of LTD4 as tested by repeated exercise challenges. Pretreatment with ipratropium bromide prevented the effect of LTD4 on FEV1, yet...

  8. Modern Technologies of Bronchial Asthma Control in Children (Review

    Directory of Open Access Journals (Sweden)

    Т.I. Eliseeva

    2015-06-01

    Full Text Available Bronchial asthma ranks among the most common allergic diseases in children. It is chronic inflammatory disease of the respiratory tract, in which many cells of innate and adaptive immune system participate together with epithelial cells causing the main clinical syndromes typical for the disease. Currently, bronchial asthma therapy aims at obtaining the control over the symptoms and course of asthma by providing an anti-inflammatory baseline therapy using different groups of pharmaceuticals: inhaled glucocorticosteroids, leukotriene receptor antagonists, cromones, beta-2-agonists and long-acting theophyllines, systemic glucocorticosteroids and anti-IgE-therapy. However, despite a wide range of approaches to anti-inflammatory baseline therapy, it is still a problem to obtain the disease control in most patients indicating the necessity for searching new therapeutic approaches. In this regard, to optimize pathogenetic therapy of bronchial asthma, the work is being currently carried out to improve the existing anti-inflammatory drugs and their combinations. Moreover, there is a search for crucially new approaches to asthma treatment with due consideration of the disease phenotypes and endotypes including development and practical application of pharmaceutical drugs with anti-cytokine and anti-mediator effects. Probably, as far as the knowledge of molecular characteristics of asthma endotypes is being refined, and there being introduced the biomarkers enabling to diagnose asthma phenotypes and endotypes and monitor asthma control, there will be implemented an individual approach in individual therapy administration.

  9. Aerosol lung inhalation scintigraphy in children with bronchial asthma

    International Nuclear Information System (INIS)

    Aerosol lung inhalation scintigraphies performed on 37 children with bronchial asthma during asymptomatic periods were evaluated. The findings of their aerosol lung inhalation scintigrams were classified into 4 patterns, as type I: homogeneous distribution without hot spot formation, type II: peripheral homogeneity with central hot spot formation, type IIID (-): inhomogeneous distribution with hot spot formation, but without defect, and type IIID (+): with defect. These aerosol patterns were compared with those of previously reported adult cases and with the severity of bronchial asthma. Normal pattern of type I was found in 5 cases (12%) of our infantile asthmatics in contrast to previously reported adult cases, in which none of normal pattern was found. There were differences between type II and type III in both distribution and disappearance time of hot spot, which indicated that the two types differed from each other in radioaerosol deposition mechanism. There was no significant correlation between type I and type II in the severity of asthma and the frequency of asthmatic attack. Type II may be clinically considered to be the same type as type I. There is the statistically significant difference between type I, II and type III in the frequency of asthmatic attack, but not in the severity of asthma, although most of serious cases showed type III. Aerosol lung inhalation scintigraphy is a useful examination for children with bronchial asthma in which lung function tests may be difficult to perform. (author)

  10. HISTOGENESIS AND MORPHOGENESIS OF HUMAN LARYNGEAL EPITHELIUM: A PRENATAL STUDY

    Directory of Open Access Journals (Sweden)

    Rachna

    2015-04-01

    Full Text Available The anatomy of epithelium of human foetal larynx has not been fully described . In the present study we observed the development of epithelium of human larynx , in 40 fetuses with gestational ages ranging from 75mm C . R . L . ( crown rump length to 220mm C . R . L . ( C rown rump length . Tissues were prepared for microtomy by paraffin wax embedding method . Step sections ( every fifth were fixed and stained by Hematoxylin and Eosin ( H&E and Masson’s Trichrome method . In the present study , the entire laryngeal cavity is lined uniformily by respiratory epithelium initially , i . e ., ciliated pseudostratified columnar type . Later on the epithelium over the true vocal cords and dorsal surface of the epiglottis changes into stratified squamous type . Besides , there is flattenin g of epithelium , over the true vocal cords as a result of desquamation . Larynx , though is a common organ to reptiles , amphibians and mamm a ls with function of breathing , sound production and preventing food particles going into the trachea but the advancement of human has make it a very important organ for physicians , paediatricians , otorhinolaryngologists etc . So the knowle d ge of anatomy of fetal airway and its development is important for the diagnosis and treatment of various diseases . Our aim wa s to study the type of epithelium during different stages of development of human fetal larynx

  11. Protective responses to sublytic complement in the retinal pigment epithelium.

    Science.gov (United States)

    Tan, Li Xuan; Toops, Kimberly A; Lakkaraju, Aparna

    2016-08-01

    The retinal pigment epithelium (RPE) is a key site of injury in inherited and age-related macular degenerations. Abnormal activation of the complement system is a feature of these blinding diseases, yet how the RPE combats complement attack is poorly understood. The complement cascade terminates in the cell-surface assembly of membrane attack complexes (MACs), which promote inflammation by causing aberrant signal transduction. Here, we investigated mechanisms crucial for limiting MAC assembly and preserving cellular integrity in the RPE and asked how these are compromised in models of macular degeneration. Using polarized primary RPE and the pigmented Abca4(-/-) Stargardt disease mouse model, we provide evidence for two protective responses occurring within minutes of complement attack, which are essential for maintaining mitochondrial health in the RPE. First, accelerated recycling of the membrane-bound complement regulator CD59 to the RPE cell surface inhibits MAC formation. Second, fusion of lysosomes with the RPE plasma membrane immediately after complement attack limits sustained elevations in intracellular calcium and prevents mitochondrial injury. Cholesterol accumulation in the RPE, induced by vitamin A dimers or oxidized LDL, inhibits these defense mechanisms by activating acid sphingomyelinase (ASMase), which increases tubulin acetylation and derails organelle traffic. Defective CD59 recycling and lysosome exocytosis after complement attack lead to mitochondrial fragmentation and oxidative stress in the RPE. Drugs that stimulate cholesterol efflux or inhibit ASMase restore both these critical safeguards in the RPE and avert complement-induced mitochondrial injury in vitro and in Abca4(-/-) mice, indicating that they could be effective therapeutic approaches for macular degenerations. PMID:27432952

  12. 罗红霉素对哮喘大鼠NF-κB及气道炎症的影响%Effects of roxithromycin on NF-κB activity and bronchial hyperresponsiveness of asthma rats

    Institute of Scientific and Technical Information of China (English)

    颜孙舜; 戴元荣; 吴立琴; 夏晓东

    2009-01-01

    目的:观察罗红霉素对哮喘大鼠NF-κB、气道炎症、气道高反应性的影响.方法:30只雄性SD大鼠随机分成正常对照组(C组)、哮喘组(A组)、罗红霉素组(R组),每组10只.用卵白蛋白(OVA)制备哮喘大鼠模型.各组大鼠在末次激发后24 h,检测气道反应性后放血处死;ELISA测定支气管肺泡灌洗液(BALF)中的IL-4、IL-5、IFN-γ的浓度;免疫组化检测支气管上皮NF-κB p65活化.结果:哮喘组大鼠气道反应性高于对照组(P<0.01),罗红霉素组与哮喘组比较气道反应性下降(P<0.05);BALF中IL-4、IL-5,哮喘组含量均高于对照组(P<0.01),罗红霉素组均低于哮喘组(P<0.01),罗红霉素组BALF中IFN-γ低于对照组(P<0.01)但高于哮喘组;哮喘组大鼠支气管上皮NF-κB蛋白的活化明显高于对照组,罗红霉素组低于哮喘组(P<0.01).支气管上皮NF-κBp65活化与BALF中的IL-4、IL-5的含量呈显著正相关(r=0.856,P<0.01;r=0.912,P<0.01);大鼠BALF中的IL-4、IL-5的含量与Raw增加25%时(PC25Raw)呈显著负相关(r=-0.713,P<0.01;r=-0.772,P<0.01),与Cdyn下降15%时(PC15Cdyn)呈显著负相关(r=-0.738,P<0.01;r=-0.818,P<0.01).结论:罗红霉素可能部分通过抑制NF-κB活性而纠正哮喘Th1/Th2细胞因子失衡,罗红霉素降低哮喘大鼠的气道反应性可能和减少IL-4、IL-5的表达有关.%To investigate the effect of rox-ithromycin on the NF-κB activity, the airway inflamma-tion and bronchial hyperresponsiveness of asthma rats. METHODS: Thirty male adult Sprague-Dawley rats were randomly divided into the control group (Group C, n = 10) , asthma group (Group A, n = 10) and rox-ithromycin group (Group R, =10) . The asthma mod-el was induced by ovalbumin and Al(OH)_3 .The airway reactivity was detected and then rats in each group were sacrificed after 24 hours for the last provocation. The concentrations of IL-4, IL-5 and IFN-7 in bronchoalve-olar lavage fluid (BALF) were measured by ELISA, and the

  13. Bronchial asthma control after argon plasma coagulation turbinectomy in patients with chronic rhinitis

    OpenAIRE

    Jura-Szołtys, Edyta; Ficek, Rafał; Ficek, Joanna; Markowski, Jarosław; Chudek, Jerzy

    2013-01-01

    Bronchial asthma is frequently accompanied by chronic rhinitis. It has been observed that effective treatment of rhinitis may reduce asthma symptoms. The aim of the study was the evaluation of the control of bronchial asthma symptoms in patients with chronic rhinitis after argon plasma coagulation turbinectomy (APCt). The effect of APCt was assessed in 47 adults with drug-resistant chronic rhinitis and bronchial asthma 3-month post-procedure. Changes of asthma symptoms were scored using Asthm...

  14. The clinical significance of the substance P in bronchoalveolar lavage fluid in patients with bronchial asthma

    International Nuclear Information System (INIS)

    Using radioimmunoassay to measure the substance P (SP) in bronchoalveolar lavage fluid in thirty patients with bronchial asthma and thirty healthy persons. Compered with healthy group (33.4±24.5 pmol/L), the SP in bronchial asthma group (240.2±18.7 pmol/L) increased significantly (p < 0.01). SP may play a role in the development of bronchial asthma

  15. E-Cigarette Affects the Metabolome of Primary Normal Human Bronchial Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Argo Aug

    Full Text Available E-cigarettes are widely believed to be safer than conventional cigarettes and have been even suggested as aids for smoking cessation. However, while reasonable with some regards, this judgment is not yet supported by adequate biomedical research data. Since bronchial epithelial cells are the immediate target of inhaled toxicants, we hypothesized that exposure to e-cigarettes may affect the metabolome of human bronchial epithelial cells (HBEC and that the changes are, at least in part, induced by oxidant-driven mechanisms. Therefore, we evaluated the effect of e-cigarette liquid (ECL on the metabolome of HBEC and examined the potency of antioxidants to protect the cells. We assessed the changes of the intracellular metabolome upon treatment with ECL in comparison of the effect of cigarette smoke condensate (CSC with mass spectrometry and principal component analysis on air-liquid interface model of normal HBEC. Thereafter, we evaluated the capability of the novel antioxidant tetrapeptide O-methyl-l-tyrosinyl-γ-l-glutamyl-l-cysteinylglycine (UPF1 to attenuate the effect of ECL. ECL caused a significant shift in the metabolome that gradually gained its maximum by the 5th hour and receded by the 7th hour. A second alteration followed at the 13th hour. Treatment with CSC caused a significant initial shift already by the 1st hour. ECL, but not CSC, significantly increased the concentrations of arginine, histidine, and xanthine. ECL, in parallel with CSC, increased the content of adenosine diphosphate and decreased that of three lipid species from the phosphatidylcholine family. UPF1 partially counteracted the ECL-induced deviations, UPF1's maximum effect occurred at the 5th hour. The data support our hypothesis that ECL profoundly alters the metabolome of HBEC in a manner, which is comparable and partially overlapping with the effect of CSC. Hence, our results do not support the concept of harmlessness of e-cigarettes.

  16. Specific-sized hyaluronan fragments promote expression of human β-defensin 2 in intestinal epithelium.

    Science.gov (United States)

    Hill, David R; Kessler, Sean P; Rho, Hyunjin K; Cowman, Mary K; de la Motte, Carol A

    2012-08-31

    Hyaluronan (HA) is a glycosaminoglycan polymer found in the extracellular matrix of virtually all mammalian tissues. Recent work has suggested a role for small, fragmented HA polymers in initiating innate defense responses in immune cells, endothelium, and epidermis through interaction with innate molecular pattern recognition receptors, such as TLR4. Despite these advances, little is known regarding the effect of fragmented HA at the intestinal epithelium, where numerous pattern recognition receptors act as sentinels of an innate defense response that maintains epithelial barrier integrity in the presence of abundant and diverse microbial challenges. Here we report that HA fragments promote expression of the innate antimicrobial peptide human β-defensin 2 (HβD2) in intestinal epithelial cells. Treatment of HT-29 colonic epithelial cells with HA fragment preparations resulted in time- and dose-dependent up-regulated expression of HβD2 protein in a fragment size-specific manner, with 35-kDa HA fragment preparations emerging as the most potent inducers of intracellular HβD2. Furthermore, oral administration of specific-sized HA fragments promotes the expression of an HβD2 ortholog in the colonic epithelium of both wild-type and CD44-deficient mice but not in TLR4-deficient mice. Together, our observations suggest that a highly size-specific, TLR4-dependent, innate defense response to fragmented HA contributes to intestinal epithelium barrier defense through the induction of intracellular HβD2 protein. PMID:22761444

  17. Perception of bronchial obstruction in asthmatic patients. Relationship with bronchial eosinophilic inflammation and epithelial damage and effect of corticosteroid treatment.

    OpenAIRE

    Roisman, G L; Peiffer, C; Lacronique, J. G.; Le Cae, A; Dusser, D J

    1995-01-01

    We studied the perception of bronchoconstriction in asthmatic subjects who were randomly treated with inhaled beta 2 agonist given either alone (n = 9) or associated with inhaled corticosteroids (n = 9). Methacholine and bradykinin challenges, bronchoalveolar lavage, and bronchial biopsies were performed in all subjects. After each dose of agonist, breathlessness was assessed using a visual analog scale (VAS) and the forced expiratory volume in 1 s (FEV1) was measured. The relationship betwee...

  18. Gene expressions changes in bronchial epithelial cells

    DEFF Research Database (Denmark)

    Remy, S.; Verstraelen, S.; Van Den Heuvel, R.;

    2014-01-01

    cells were exposed during 6, 10, and 24 h to 4 respiratory sensitizers and 6 non-respiratory sensitizers (3 skin sensitizers and 3 respiratory irritants) at a concentration inducing 20% cell viability loss after 24 h. Changes in gene expression were evaluated using Agilent Whole Human Genome 4 x 44 K...... differentially expressed compared to vehicle control for each chemical. The results show that the NRF2-mediated oxidative stress response is activated in the cell line after stimulation with all of the chemicals that were selected in our study, and that - at the level of gene expression - this pathway shows no...

  19. Telomere shortening impairs regeneration of the olfactory epithelium in response to injury but not under homeostatic conditions.

    Directory of Open Access Journals (Sweden)

    Masami Watabe-Rudolph

    Full Text Available Atrophy of the olfactory epithelium (OE associated with impaired olfaction and dry nose represents one of the most common phenotypes of human aging. Impairment in regeneration of a functional olfactory epithelium can also occur in response to injury due to infection or nasal surgery. These complications occur more frequently in aged patients. Although age is the most unifying risk factor for atrophic changes and functional decline of the olfactory epithelium, little is known about molecular mechanisms that could influence maintenance and repair of the olfactory epithelium. Here, we analyzed the influence of telomere shortening (a basic mechanism of cellular aging on homeostasis and regenerative reserve in response to chemical induced injury of the OE in late generation telomere knockout mice (G3 mTerc(-/- with short telomeres compared to wild type mice (mTerc(+/+ with long telomeres. The study revealed no significant influence of telomere shortening on homeostatic maintenance of the OE during mouse aging. In contrast, the regenerative response to chemical induced injury of the OE was significantly impaired in G3 mTerc(-/- mice compared to mTerc(+/+ mice. Seven days after chemical induced damage, G3 mTerc(-/- mice exhibited significantly enlarged areas of persisting atrophy compared to mTerc(+/+ mice (p = 0.031. Telomere dysfunction was associated with impairments in cell proliferation in the regenerating epithelium. Deletion of the cell cycle inhibitor, Cdkn1a (p21 rescued defects in OE regeneration in telomere dysfunctional mice. Together, these data indicate that telomere shortening impairs the regenerative capacity of the OE by impairing cell cycle progression in a p21-dependent manner. These findings could be relevant for the impairment in OE function in elderly people.

  20. 樱桃汁和草莓汁激活Nrf2信号通路对砷诱导的人支气管上皮细胞损伤的保护作用%Juices of cherry and strawberry confer protection of human bronchial epithelial cells against arsenic-induced toxicity via activation of Nrf2 signaling pathway

    Institute of Scientific and Technical Information of China (English)

    孔得刚; 王莉莉; 周洪雷; 任冬梅; 娄红祥; 沈涛

    2014-01-01

    目的:研究草莓汁和樱桃汁对NF-E2相关因子2(Nrf2)信号通路的影响,以及两种果汁对砷诱导的人支气管上皮(HBE)细胞损伤的保护作用。方法选择人乳腺癌MDA-MB-231细胞系,分为空白对照组、萝卜硫素组,以及樱桃(草莓)汁1∶10、1∶20、1∶40和1∶80组(果汁稀释比例分别为1∶10、1∶20、1∶40和1∶80),采用抗氧化反应原件(ARE)荧光素酶报告基因和Westerm blotting筛选并确证两种果汁对Nrf2信号通路的影响;选择HBE细胞,分为空白对照组、萝卜硫素组,以及樱桃(草莓)汁1∶10、1∶20、1∶40组(果汁稀释比例分别为1∶10、1∶20和1∶40),采用QuantiChrom谷胱甘肽(GSH)试剂盒测定两种果汁对内源性抗氧化剂GSH水平的影响;采用MTT法和细胞转染技术评价两种果汁对砷诱导的HB E细胞的保护作用。结果草莓汁和樱桃汁能够剂量依赖地增强ARE荧光强度,上调MDA-MB-231细胞中Nrf2及其下游基因NADPH苯醌氧化还原醇(NQO1)和γ-谷氨酰半胱氨酸合成酶(γGCS)蛋白的表达;两种果汁能够提高HBE细胞内源性抗氧化剂GSH水平;两种果汁和砷处理HBE细胞后,果汁预处理的细胞生存率高于砷单独处理的细胞生存率,两种果汁表现出对砷诱导细胞毒性的保护作用,而这种保护作用在转染Nrf2-siRNA后消失。结论草莓汁和樱桃汁通过激活Nrf2信号通路抑制砷诱导的细胞毒性,对HBE细胞具有保护作用。%Objective To investigate the effects of cherry and strawberry juices on NF-E2-related factor 2(Nrf2)signa-ling pathway,and to evaluate their protection effects on arsenic-induced toxicity in human bronchial epithelial (HBE) cells.Methods Human breast cancer 23 1 cells were randomly divided into the control group,sulforaphen treated group,and juice treated groups (juice dilution ratios were 1∶10,1∶20,1∶40 and 1∶80,respectively

  1. Proteasome inhibitor MG-132 regulates the expression of VEGF in human bronchial epithelial cell line, BEAS-2B

    Institute of Scientific and Technical Information of China (English)

    Xuefan Cui; Kaisheng Yin; Mao Huang; Linfu Zhou

    2005-01-01

    Objective: To explore the effects of MG-132 on the expression of VEGF in bronchial epithelial cell line, BEAS2B. Methods: Semi-quantitive RT-PCR for VEGF mRNA and enzyme-linked immunosorbent assay (ELISA) for VEGF protein were performed. Results: MG-132 increased the expression of VEGF mRNA and protein BEAS-2B cells in time-and concentration-dependent manners. After 24-h stimulation, 25 μmol/L MG-132 increased the maximal levels of VEGF protein in cell-conditioned medium. When the cells were stimulated with cycloheximide(CHX) before treatment with MG-132, the MG-132-induced production of VEGF protein was inhibited compared to the unstimulated cells. Supernatant of condition-medium treatment with MG-132 enhanced the growth of HUVEC.Conclusion: MG-132 induces VEGF gene expression in human bronchial epithelial cells line, BEAS-2B, and the MG-132-induced expression of VEGF may modulate lung tissue injury due to airway inflammation.

  2. Characterization of side population cells from human airway epithelium.

    Science.gov (United States)

    Hackett, Tillie-Louise; Shaheen, Furquan; Johnson, Andrew; Wadsworth, Samuel; Pechkovsky, Dmitri V; Jacoby, David B; Kicic, Anthony; Stick, Stephen M; Knight, Darryl A

    2008-10-01

    The airway epithelium is the first line of contact with the inhaled external environment and is continuously exposed to and injured by pollutants, allergens, and viruses. However, little is known about epithelial repair and in particular the identity and role of tissue resident stem/progenitor cells that may contribute to epithelial regeneration. The aims of the present study were to identify, isolate, and characterize side population (SP) cells in human tracheobronchial epithelium. Epithelial cells were obtained from seven nontransplantable healthy lungs and four asthmatic lungs by pronase digestion. SP cells were identified by verapamil-sensitive efflux of the DNA-binding dye Hoechst 33342. Using flow cytometry, CD45(-) SP, CD45(+) SP, and non-SP cells were isolated and sorted. CD45(-) SP cells made up 0.12% +/- 0.01% of the total epithelial cell population in normal airway but 4.1% +/- 0.06% of the epithelium in asthmatic airways. All CD45(-) SP cells showed positive staining for epithelial-specific markers cytokeratin-5, E-cadherin, ZO-1, and p63. CD45(-) SP cells exhibited stable telomere length and increased colony-forming and proliferative potential, undergoing population expansion for at least 16 consecutive passages. In contrast with non-SP cells, fewer than 100 CD45(-) SP cells were able to generate a multilayered and differentiated epithelium in air-liquid interface culture. SP cells are present in human tracheobronchial epithelium, exhibit both short- and long-term proliferative potential, and are capable of generation of differentiated epithelium in vitro. The number of SP cells is significantly greater in asthmatic airways, providing evidence of dysregulated resident SP cells in the asthmatic epithelium. Disclosure of potential conflicts of interest is found at the end of this article. PMID:18653771

  3. Cell proliferation in rat nasal respiratory epithelium following three months exposure to formaldehyde gas

    International Nuclear Information System (INIS)

    Formaldehyde (HCHO), a ubiquitous chemical and rat nasal carcinogen, enhances cell proliferation in rat, monkey, and xenotransplanted human respiratory epithelium following short-term exposure. The present studies were designed to evaluate cell proliferation in relation to tumor induction in rat nasal respiratory epithelium following subchronic HCHO exposure. Male F-344 rats were whole-body exposed to either 0, 0.7, 2, 6, 10, or 15 ppm HCHO, for wither 4 d (6hr/d), 6 wks (5d/wk) or 3 months. Animals were labeled with tritiated thymidine prior to euthanasia. Nasal sections were processed for autoradiography and cell proliferation data was expressed as unit length labeling indices (ULLI). HCHO-induced lesions and increases in cell proliferation occurred in specific regions of the nose, primarily the wall of the lateral meatus and nasal septum of the anterior nasal cavity. Following 4 d exposure, significant elevations in cell proliferation were observed only in the 6, 10 and 15 ppm groups (16-, 18-, and 20-fold increase over control, respectively). Increases in ULLI were also present in the 6, 10 and 15 ppm groups after 6 wks of exposure (12-, 35-, and 40-fold increase over control). However, after 3 months exposure, elevations in ULLI were present only in the 10 and 15 ppm groups (9- and 14-fold increase over controls). These results demonstrate that (1) low levels of HCHO (0.7 and 2 ppm) do not increase cell proliferation in rat nasal respiratory epithelium; (2) 6 ppm HCHO induces transient increases in cell proliferation; and (3) clearly carcinogenic concentrations of HCHO (10 and 15 ppm) cause sustained elevations in cell proliferation which may play an important role in HCHO-induced carcinogenesis

  4. Efeito do índice de massa corpórea na gravidade da asma e na reatividade brônquica induzida pelo exercício em crianças asmáticas com sobrepeso e obesas Effect of body mass index on asthma severity and exercise-induced bronchial reactivity in overweight and obese asthmatic children

    Directory of Open Access Journals (Sweden)

    Joaquim Carlos Rodrigues

    2007-09-01

    bronchospasm (EIB. METHODS: 20 patients (age range: 6-18 years with persistent asthma, with overweight or obesity, were submitted to a standardized exercise test on an ergometric bicycle, followed by serial evaluations of spirometric parameters performed at 3, 6, 10, 15, 20 and 30 minutes after the exercise. EIB was defined as a decrease in FEV1>10% and/or FEF25-75% >26% when compared to pre-test values. The positivity of the test was evaluated as the highest decreases in FEV1 and FEF25-75% after the end of the exercise. RESULTS: Asthma severity was considered mild, moderate and severe in ten, five and five patients, respectively. EIB was observed in 50% of the studied children. There was no significant correlation among the following parameters: BMI and basal FEV1 and FEF25-75% in relation to the predicted value; BMI and the highest decrease in FEV1 and FEF25-75% in relation to the basal levels; BMI and asthma severity. The best correlation was obtained between BMI and the highest decreases in FEF25-75% in relation to basal levels. CONCLUSIONS: The BMI did not influence the degree of exercise-induced bronchial hyperresponsiveness in overweight and obese children and adolescents with asthma as well as the degree of basal obstruction measured by FEV1 and FEF25-75%.

  5. Human bocavirus 1 infects commercially-available primary human airway epithelium cultures productively

    OpenAIRE

    Deng, Xuefeng; Li, Yi; Qiu, Jianming

    2013-01-01

    Human bocavirus 1 (HBoV1), a human parvovirus, belongs to the genus Bocavirus of the Parvoviridae family. It causes wheezing in young children with acute respiratory tract infections. HBoV1 has been shown to infect polarized human airway epithelium (HAE) made in house, and induces airway epithelial damage. In this study, two commercially-available HAE cultures, EpiAirway and MucilAir HAE, were examined for HBoV1 infection. Both HAE cultures support fully productive HBoV1 infection. Infected E...

  6. Increase of corneal epithelium cell radioresistance during regeneration

    International Nuclear Information System (INIS)

    A comparative study of the radiosensitivity of the normal and regenerating cornea epithelium of C57Bl mice was performed on the cellular level, the duration of the cell cycle being taken into account. Criteria of radiation injuries were the number of chromosome aberrations, mitotic index and duration of mitotic block. The anterior part of the head was irradiated singly with 1.75, 3.5 or 7.0 Gy and also repeatedly 3.5 + 3.5 at a 24-hours interval. The corneas were fixed 2, 4, 6, 12, 24, 48, 72 and 96 hours after irradiation. In all cases of irradiated mice the regenerating epithelium showed a shorter mitotic block and significantly lower cytogenetic injury as compared with the controls. Effects of fractionated irradiation were only shown in the regenerating epithelium. The results obtained indicate that regenerating epithelium cells of the cornea are significantly more radioresistant than normal epithelium due to activation of post-radiation recovery, and also, possibly, due to an increase in the content of endogenous radioprotectors. (author)

  7. Prevention of bronchial hyperreactivity in a rat model of precapillary pulmonary hypertension

    Directory of Open Access Journals (Sweden)

    Beghetti Maurice

    2011-04-01

    Full Text Available Abstract Background The development of bronchial hyperreactivity (BHR subsequent to precapillary pulmonary hypertension (PHT was prevented by acting on the major signalling pathways (endothelin, nitric oxide, vasoactive intestine peptide (VIP and prostacyclin involved in the control of the pulmonary vascular and bronchial tones. Methods Five groups of rats underwent surgery to prepare an aorta-caval shunt (ACS to induce sustained precapillary PHT for 4 weeks. During this period, no treatment was applied in one group (ACS controls, while the other groups were pretreated with VIP, iloprost, tezosentan via an intraperitoneally implemented osmotic pump, or by orally administered sildenafil. An additional group underwent sham surgery. Four weeks later, the lung responsiveness to increasing doses of an intravenous infusion of methacholine (2, 4, 8 12 and 24 μg/kg/min was determined by using the forced oscillation technique to assess the airway resistance (Raw. Results BHR developed in the untreated rats, as reflected by a significant decrease in ED50, the equivalent dose of methacholine required to cause a 50% increase in Raw. All drugs tested prevented the development of BHR, iloprost being the most effective in reducing both the systolic pulmonary arterial pressure (Ppa; 28%, p = 0.035 and BHR (ED50 = 9.9 ± 1.7 vs. 43 ± 11 μg/kg in ACS control and iloprost-treated rats, respectively, p = 0.008. Significant correlations were found between the levels of Ppa and ED50 (R = -0.59, p = 0.016, indicating that mechanical interdependence is primarily responsible for the development of BHR. Conclusions The efficiency of such treatment demonstrates that re-establishment of the balance of constrictor/dilator mediators via various signalling pathways involved in PHT is of potential benefit for the avoidance of the development of BHR.

  8. Bronchial carcinoid tumors: clinical and radiological findings in 21 patients

    International Nuclear Information System (INIS)

    Bronchial carcinoid tumors are neoplasms that range from typical carcinoid s to the more aggressive atypical ones with similar imaging features. Considering the low prevalence of the tumor, we reviewed 21 patients. Patients and methods: in this retrospective observational study, we reviewed the clinical, pathological and imaging findings in 21 patients diagnosed with bronchial carcinoid tumors who were admitted to National Research Institute of Tuberculosis and Lung Disease in a 6 years period. Plain radiography and CT scan of patients were reviewed. Results: 52.4% of the patients were male and 47.6 % female. The mean age of patients was 39.1 years. The most frequent clinical symptoms were cough (n=15; 71.4%), hemoptysis (n.13; 61.9%). dyspnea (n=12; 57.1%). and pleuritic chest pain (n.7; 19%). Most of the lesions (68%) were in the right lung, 24% in the left lung. 8% in the trachea, and 19% were bilateral. Right upper lobe and right intermediate bronchus (24% and 32% respectively) were the most frequent sites of tumor. In radiologic examination, two cases (9.5%) had normal CXRs. Pulmonary collapse (52.4%) and mass (23.8%) were the most frequent findings. Reviewing CT scans showed endobronchial lesion in three (15%) and mass in 11 (55%) patients. The mass was well defined in 8 cases (72%) and ill-defined in 3 (28%). Other findings were: mediastinal invasion (45%), atelectasis (55%). post obstructive pneumonitis (2 0%) and eccentric calcification (15%). Pathological examination revealed typical (n=18: 86% ) and atypical (n.3: 14%) carcinoid tumors. Conclusion: although rare, bronchial carcinoid tumors should be considered a differential diagnosis in adult patients with cough, hemoptysis, dyspnea, and pleuritic chest pain. Chest xray and CT scan can help with diagnosis. Major imaging findings are central, round or ovoid well-defined mass, and obstruction signs like at electasis. Diagnosis and classification should be confirmed by pathological examination on sample

  9. The radioprotective effect and mechanism of captopril on radiation induced lung damage in rat

    International Nuclear Information System (INIS)

    It was reported that Captopril (angiotensin converting enzyme inhibitor) had an effect to reduce the pneumonitis and pulmonary fibrosis induced by radiation in rat. We performed this study to investigate the radioprotective effect and mechanism of Captopril. The comparison was made between the radiation only group and the combined Captopril and radiation group by examining histopathologic findings and immunohistochemical stains (TNF α and TGF β1) at 2 and 8 weeks after irradiation. Each group has 8 to 10 rats (Sprague-Dawley). 12.5 Gy of X-ray was irradiated to the left hemithorax in a single fraction. Captopril (50 mg/kg/d) mixed with water was given per oral and continuously from 1 week prior to irradiation up to 8th week of the experiment. In the combined Captopril and radiation group, the histopathologic changes which were hemorrhage into alveolar space, changes of alveolar epithelium, bronchial epithelium and blood vessels, and perivascular edema were less severe than in the radiation only group at 2 weeks. At 8 weeks, the alveolar epithelial changes and perivascular edema were less prominent in the combined Captopril and radiation group. At 2 weeks, the TNF α expression of the combined Captopril and radiation group was markedly decreased at the alveolar epithelium (p<0.01), lymphoid tissue (p=0.06) and the macrophage of alveolar space (p<0.01) compared with the radiation only group. Furthermore the TGF β1 expression was significantly prominent at the alveolar epithelium (p<0.02) and the macrophage in alveolar space (p< 0.02). At 8 weeks, the expression of TNF α and TGF β 1 of most sites, except TGF β1 of the macrophage of alveolar space (p=0.09), showed no significant difference between 2 groups. This study revealed that early lung damage induced by irradiation was reduced with the addition of Captopril in the latent and early pneumonitis phase. The expression of TNF α and TGF β 1 at 2 weeks and TGF β 1 at 8 weeks was further decreased in the

  10. The radioprotective effect and mechanism of captopril on radiation induced lung damage in rat

    Energy Technology Data Exchange (ETDEWEB)

    Song, Mi Hee; Lee, Kyung Ja; Koo, Hea Soo; Oh, Won Young [College of Medicine, Ewha Women Univ., Seoul (Korea, Republic of)

    2001-06-01

    It was reported that Captopril (angiotensin converting enzyme inhibitor) had an effect to reduce the pneumonitis and pulmonary fibrosis induced by radiation in rat. We performed this study to investigate the radioprotective effect and mechanism of Captopril. The comparison was made between the radiation only group and the combined Captopril and radiation group by examining histopathologic findings and immunohistochemical stains (TNF {alpha} and TGF {beta}1) at 2 and 8 weeks after irradiation. Each group has 8 to 10 rats (Sprague-Dawley). 12.5 Gy of X-ray was irradiated to the left hemithorax in a single fraction. Captopril (50 mg/kg/d) mixed with water was given per oral and continuously from 1 week prior to irradiation up to 8th week of the experiment. In the combined Captopril and radiation group, the histopathologic changes which were hemorrhage into alveolar space, changes of alveolar epithelium, bronchial epithelium and blood vessels, and perivascular edema were less severe than in the radiation only group at 2 weeks. At 8 weeks, the alveolar epithelial changes and perivascular edema were less prominent in the combined Captopril and radiation group. At 2 weeks, the TNF {alpha} expression of the combined Captopril and radiation group was markedly decreased at the alveolar epithelium (p<0.01), lymphoid tissue (p=0.06) and the macrophage of alveolar space (p<0.01) compared with the radiation only group. Furthermore the TGF {beta}1 expression was significantly prominent at the alveolar epithelium (p<0.02) and the macrophage in alveolar space (p< 0.02). At 8 weeks, the expression of TNF {alpha} and TGF {beta} 1 of most sites, except TGF {beta}1 of the macrophage of alveolar space (p=0.09), showed no significant difference between 2 groups. This study revealed that early lung damage induced by irradiation was reduced with the addition of Captopril in the latent and early pneumonitis phase. The expression of TNF {alpha} and TGF {beta} 1 at 2 weeks and TGF {beta} 1 at

  11. Polymorphisms and Haplotypes of Acid Mammalian Chitinase Are Associated with Bronchial Asthma

    OpenAIRE

    Bierbaum, Sibylle; Nickel, Renate; Koch, Anja; Lau, Susanne; Deichmann, Klaus A.; Wahn, Ulrich; Superti-Furga, Andrea; Heinzmann, Andrea

    2005-01-01

    Rationale: Chitinases are enzymes that cleave chitin, a polysaccharide contained in many parasites of humans. Recent studies in mouse models of bronchial asthma have shown that acid mammalian chitinase (AMCase) is involved in the pathophysiology of asthma. It acts downstream of interleukin-13; inhibition of AMCase leads to an abrogated T-helper cell 2 inflammation, less bronchial hyperreactivity, and fewer eosinophils.

  12. Moxifloxacin Penetration in Bronchial Secretions of Mechanically Ventilated Patients with Pneumonia

    OpenAIRE

    Leone, Marc; Albanèse, Jacques; Sampol-Manos, Emmanuelle; Simon, Nicolas; Lacarelle, Bruno; Bruguerolle, Bernard; Martin, Claude

    2004-01-01

    The pharmacokinetics of moxifloxacin was studied in 17 mechanically ventilated patients with pneumonia. Patients were given 400 mg of moxifloxacin intravenously. Blood samples and bronchial secretions were taken on days 1 and 4. A dose of 400 mg of moxifloxacin allows one to achieve efficient concentrations in bronchial secretions and plasma.

  13. Use of tracheal auscultation for the assessment of bronchial responsiveness in asthmatic children

    NARCIS (Netherlands)

    Sprikkelman, AB; Grol, MH; Lourens, MS; Gerritsen, J; Heymans, HSA; vanAalderen, WMC

    1996-01-01

    Background - It can be difficult to assess bronchial responsiveness in children because of their inability to perform spirometric tests reliably. In bronchial challenges lung sounds could be used to detect the required 20% fall in the forced expiratory volume in one second (FEV(1)). A study was unde

  14. Pulmonary artery--bronchial fistula: a new complication of Swan-Ganz catheterization.

    Science.gov (United States)

    Rubin, S A; Puckett, R P

    1979-04-01

    A patient with a Swan-Ganz catheter developed massive hemoptysis. Injection of radiographic contrast media through the catheter revealed rapid filling of the tracheo-bronchial tree, consistent with direct pulmonary artery-bronchial communication. Development of hemoptysis in a patient with a Swan-Ganz catheter should alert the clinician to this possibility. PMID:446146

  15. Transverse myelitis: a reversible complication of bronchial artery embolisation in cystic fibrosis

    OpenAIRE

    Fraser, K. L.; Grosman, H.; Hyland, R H; Tullis, D. E.

    1997-01-01

    The case history is presented of a young woman with cystic fibrosis and life threatening haemoptysis. Angiography revealed enlarged bronchial vessels, one of which supplied the contralateral lung. Transverse myelitis developed following bronchial artery embolisation but recovery was rapid and nearly complete. Haemoptysis did not recur during four years of follow up. 




  16. An increase in bronchial responsiveness is associated with continuing or restarting smoking

    NARCIS (Netherlands)

    Chinn, S; Jarvis, D; Luczynska, CM; Ackermann-Liebrich, U; Anto, JM; Cerveri, [No Value; de Marco, R; Gislason, T; Heinrich, J; Janson, C; Kunzli, N; Leynaert, N; Neukirch, FO; Schouten, JP; Sunyer, J; Svanes, C; Wjst, M; Burney, PG

    2005-01-01

    Rationale: Bronchial responsiveness (BHR) has been found to be associated with smoking, atopy, and lower lung function in cross-sectional studies, but there is little information on determinants of change in adults. Objectives: To analyze change in bronchial responsiveness in an international longit

  17. Scale dependence of branching in arterial and bronchial trees

    CERN Document Server

    Restrepo, J G; Hunt, B R; Restrepo, Juan G.; Ott, Edward; Hunt, Brian R.

    2005-01-01

    Although models of branching in arterial and bronchial trees often predict a dependence of bifurcation parameters on the scale of the bifurcating vessels, direct verifications of this dependence with data are uncommon. We compare measurements of bifurcation parameters in airways and arterial trees of different mammals as a function of scale to general features predicted by theoretical models. We find that the size dependence is more complex than existing theories based solely on energy minimization explain, and suggest additional factors that may govern the branching at different scales.

  18. Bronchial atresia in a neonate with congenital cytomegalovirus infection

    Directory of Open Access Journals (Sweden)

    Abdullah A Yousef

    2013-01-01

    Full Text Available Bronchial atresia (BA is characterized by a mucus-filled bronchocele in a blind-ending segmental or lobar bronchus with hyperinflation of the obstructed segment of the lung. We describe a neonate who presented on his 9 th day of life with respiratory distress. Chest computed tomography showed a soft tissue density involving the right middle lobe (RML. RML lobectomy confirmed the diagnosis of BA. Cytomegalovirus was detected by polymerase chain reaction in blood, urine, and tracheal aspirates which may provide further insight into the pathogenesis of BA.

  19. Alveolar epithelial permeability in bronchial asthma in children

    International Nuclear Information System (INIS)

    To evaluate alveolar epithelial permeability (kep) in children with bronchial asthma, 99mTc-DTPA (diethylene triamine penta acetate) aerosol lung inhalation scintigraphies were performed. There was no correlation between the kep value and the severity of asthma. On the other hand, out of 10 cases which had no aerosol deposition defect in the lung field, 4 showed high kep values on the whole lung field and 7 had high kep value areas, particularly apparent in the upper lung field. These results suggest that even when the central airway lesions are mild, severe damage exists in the alveolar region of the peripheral airway. (author)

  20. Bronchial carcinoid tumor: helical CT and virtual bronchoscopy

    International Nuclear Information System (INIS)

    The authors reported a case of a 61 years old man with recurrent neumonia of the inferior right lobe diagnosed by a chest radiography. A complementary helical CT showed an endobronquial mass on the right intermediate bronchus. Virtual bronchoscopy contributed to a better definition of this lesion, confirmed by a real bronchoscopy. The lesion was diagnosed as a carcinoid tumor by a bronchial biopsy. After surgery (sleeve resection of the tumor) the patient did not show any recurrence of his broncho-neumonic clinical features. (author)

  1. In vivo survival and stratification of cultured limbal epithelium.

    Science.gov (United States)

    Fatima, Anees; Vemuganti, Geeta K; Iftekhar, Ghazala; Rao, Gullapalli N; Sangwan, Virender S

    2007-01-01

    A 6-year-old Bangladeshi girl presented with total limbal stem cell deficiency in the left eye, secondary to a 6-month-old chemical injury. The patient had also previously undergone two limbal transplantation surgeries. At the authors' centre the child underwent autologous cultured limbal epithelium transplantation, on human amniotic membrane, without the use of air-lift technique. Symptomatic relief, re-epithelialization of the ocular surface, regression of corneal pannus and slight improvement in vision were all noted. The corneal button obtained at the time of keratoplasty (performed 4 months later) revealed stratified epithelium with basement membrane. Thirty-seven months post keratoplasty, the best-corrected visual acuity was 6/15 with clear graft and stable ocular surface. Herein, a case of limbal stem cell deficiency successfully managed by monolayer of cultured limbal epithelium is presented. PMID:17300583

  2. Remission of bronchial asthma after viral clearance in chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Norihiko Yamamoto; Kazumoto Murata; Takeshi Nakano

    2005-01-01

    A 53-year-old man with a history of blood transfusion at the age of 20 was admitted to our hospital because of liver dysfunction. He had bronchial asthma when he was 18 years old, which naturally resolved within 2 years. However, his bronchial asthma recurred at the age of 45 and was treated with oral theophylline. He was diagnosed as having chronic hepatitis C based on the histological and clinical findings, and then interferon (IFN) therapy was administered. The frequency of bronchial asthma attack was gradually decreasing after IFN therapy with marked improvement of hypereosinophilia. He achieved sustained viral response (SVR) and his bronchial asthma did not worsen even after the cessation of IFN. Hepatitis C virus (HCV) infection and IFN therapy were considered in the remission of asthma in this case. HCV infection could be the cause of bronchial asthma, especially in patients with late appearance of asthma.

  3. Karyotyping of Chromosomes in Human Bronchial Epithelial Cells Transformed by High Energy Fe Ions

    Science.gov (United States)

    Yeshitla, Samrawit; Zhang, Ye; Park, Seongmi; Story, Michael D.; Wilson, Bobby; Wu, Honglu

    2015-01-01

    Lung cancer induced from exposures to space radiation is one of the most significant health risks for long-term space travels. Evidences show that low- and high- Linear energy transfer (LET)-induced transformation of normal human bronchial epithelial cells (HBEC) that are immortalized through the expression of Cdk4 and hTERT. The cells were exposed to gamma rays and high-energy Fe ions for the selection of transformed clones. Transformed HBEC are identified and analyzed chromosome aberrations (i.e. genomic instability) using the multi-color fluorescent in situ hybridization (mFISH), as well as the multi-banding in situ hybridization (mBAND) techniques. Our results show chromosomal translocations between different chromosomes and several of the breaks occurred in the q-arm of chromosome 3. We also identified copy number variations between the transformed and the parental HBEC regardless of the exposure conditions. We observed chromosomal aberrations in the lowand high-LET radiation-induced transformed clones and they are imperfectly different from clones obtain in spontaneous soft agar growth.

  4. Heme oxygenase-1 protects corexit 9500A-induced respiratory epithelial injury across species.

    Directory of Open Access Journals (Sweden)

    Fu Jun Li

    Full Text Available The effects of Corexit 9500A (CE on respiratory epithelial surfaces of terrestrial mammals and marine animals are largely unknown. This study investigated the role of CE-induced heme oxygenase-1 (HO-1, a cytoprotective enzyme with anti-apoptotic and antioxidant activity, in human bronchial airway epithelium and the gills of exposed aquatic animals. We evaluated CE-mediated alterations in human airway epithelial cells, mice lungs and gills from zebrafish and blue crabs. Our results demonstrated that CE induced an increase in gill epithelial edema and human epithelial monolayer permeability, suggesting an acute injury caused by CE exposure. CE induced the expression of HO-1 as well as C-reactive protein (CRP and NADPH oxidase 4 (NOX4, which are associated with ROS production. Importantly, CE induced caspase-3 activation and subsequent apoptosis of epithelial cells. The expression of the intercellular junctional proteins, such as tight junction proteins occludin, zonula occludens (ZO-1, ZO-2 and adherens junctional proteins E-cadherin and Focal Adhesion Kinase (FAK, were remarkably inhibited by CE, suggesting that these proteins are involved in CE-induced increased permeability and subsequent apoptosis. The cytoskeletal protein F-actin was also disrupted by CE. Treatment with carbon monoxide releasing molecule-2 (CORM-2 significantly inhibited CE-induced ROS production, while the addition of HO-1 inhibitor, significantly increased CE-induced ROS production and apoptosis, suggesting a protective role of HO-1 or its reaction product, CO, in CE-induced apoptosis. Using HO-1 knockout mice, we further demonstrated that HO-1 protected against CE-induced inflammation and cellular apoptosis and corrected CE-mediated inhibition of E-cadherin and FAK. These observations suggest that CE activates CRP and NOX4-mediated ROS production, alters permeability by inhibition of junctional proteins, and leads to caspase-3 dependent apoptosis of epithelial cells, while

  5. The influence of inhaled propylene oxide on glutathione status and cell proliferation in the respiratory nasal epithelium of rats

    OpenAIRE

    Khan, Mohammad Delwar Hossain

    2010-01-01

    Inhaled propylene oxide (PO) induced tumors and cell proliferation at high concentrations (≥300 ppm) in rat respiratory nasal epithelium (RNE). The metabolic elimination of PO in the RNE occurs by the conjugation with Glutathione (GSH) which results the depletion of GSH. In order to substantiate the hypothesis that the increased cell proliferation is caused by GSH depletion, GSH status and cell proliferation were examined in the RNE of rats after inhalation exposure of PO, after co-treatment ...

  6. 水蛭渗滤液对凝血酶诱导的人视网膜色素上皮细胞周期的影响%The effects of leech percolate on cell dividing cycle of human retinal pigment epithelium cells induced by thrombin.

    Institute of Scientific and Technical Information of China (English)

    郑燕林; 左玉霞; 马素红

    2008-01-01

    Objective To investigate the effects of leech percolate on cell division cycle of culturedhuman retinal pigment epithelium (hRPE)cells induced by thrombin.Exploring mechanism of leech percolateon preventing and curing PVR.Methods (1)Human retinal pigment epithelium(hRPE)cells were cultured invitro with digest culture method. (2)The selected concentrations of leech percolate (128mg/ml,64mg/ml,32mg/ml,16mg/ml and 8mg/ml)were based on the previous experiments.With or without 0.5NIHU/mlthrombin, hRPE cells were treated with leech percolate by various concentrations for 24hrs, and the effects ofcell division cycle of leech percolate were studied with Flow Cytometer (FCM). (3)With or without0.5NIHU/ml thrombin, hRPE cells were treated with 64mg/ml leech percolate at different times(6hr, 12hr,24hrand 48hr), and the effects of cell division cycle of leech percolate were treated with FCM.Results (1)Therewas a general tendency that leech percolate of the selected concentrations arrested hRPE cells on G0/G1 phaseand 64mg/mi leech percolate inhibited 77.9% hRPE cells on G0/G1 phase and made hRPE cells on S phaseless especially. (2)During the period of 6hrs and 48hrs the longer the treat time of 64mg/ml leech percolate, themore the RPE cells arrested on G0/G1 phase.Conclusion The results approve leech percolate can inhibitproliferation of human RPE cells cultured in vitro.Its mechanism may be that leech percolate could act on celldivision cycle and arrest RPE cells on G0/G1 phase to make proliferation power of hRPE cells lower.%目的 研究水蛭渗滤液对凝血酶诱导的人视网膜色素上皮细胞周期的影响,从而探讨中药水蛭用于防治PVR的作用机制.方法 (1)采用消化培养法,对人视网膜色素上皮细胞进行体外传代培养. (2)在前期实验基础上选择128mg/ml、64mg/ml、32mg/ml、16mg/ml、8mg/ml浓度的水蛭渗滤液,用流式细胞仪测定细胞周期,观察水蛭渗滤液单独或与0.5NIHU/ml凝血酶共同作用

  7. Preoperative Assessment of Different Treatment Modalities in Bronchial Asthma Patients

    Directory of Open Access Journals (Sweden)

    Kawther A. Azzam M.D. and **Sahar S. Khattab MD

    2003-06-01

    Full Text Available This study was performed to assess the effectiveness of acupuncture and medical therapies of bronchial asthma preoperatively. Sixty patients suffered from mild to moderate bronchial asthma and coming for elective operations were chozen from the outpatient clinic of Al-Zahraa University Hospital. Patients were randomly divided into three equal groups (n=20 each. Group I patients (drug group received oral theophylline and Salbutamol (ventolin inhaler according to the needs. Group II patients (drug +ear acupuncture group received same medical treatment as in group I and added ear acupuncture. Group III patients (drug + ear and body acupuncture group received same medical treatment as in group I and II and added ear and body acupuncture. Ventilatory function tests through spirometer and interleukin-13 estimation were performed before treatment and after two weeks of treatment. Improvement of subjective and objective parameters had occurred with significant decrease in the mean serum level of interleukin-13 and decrease in the mean number of using b-agonist puffs after two weeks of treatment in the three groups, with the best results being in group III than in group II and then in group I. Conclusion: Interleukin-13 estimation togheter with ventilatory function tests is a useful parameter for pre-operative assessment and evaluation of asthmatic patients. Also medication was significantly reduced when combined with acupuncture.

  8. Radiologic management of haemoptysis. Diagnostic and interventional bronchial arterial embolisation

    Energy Technology Data Exchange (ETDEWEB)

    Ittrich, H.; Adam, G. [Univ. Medical Center Hamburg, Hamburg (Germany). Diagnostic and Interventional Radiology Dept. and Clinic; Klose, H. [Univ. Medical Center Hamburg, Hamburg (Germany). Section Pneumology

    2015-04-15

    Hemoptysis can be a life-threatening pulmonary emergency with high mortality, is symptomatic of an underlying severe pulmonary disease and requires immediate diagnosis and treatment. Diagnostically, bronchoscopy, conventional chest x-ray and contrast-enhanced multislice computed tomography (MSCT) with CT angiography (CTA) provide information regarding the underlying pulmonary disease, bleeding site, the vascular anatomy of the bronchial arteries (BA) and extrabronchial branches, as well a basis for planning of endovascular intervention. Therapeutically, bronchial artery embolization (BAE) is a safe and effective technique in the hands of an experienced interventionist with profound knowledge of the BA anatomy and possible pitfalls as well as experience with first-line therapy of recurrent and massive hemoptysis or as an intervention prior to elective surgery. Recurrent episodes of hemoptysis are not uncommon and require a prompt repeat BAE after exclusion of extrabronchial systemic and pulmonary artery bleeding sources. This review article should give an overview of the history, anatomical and pathophysiological basics and the clinical context of hemoptysis and diagnosis, as well as a survey of management, treatment and results of BAE.

  9. Hyperoxia-induced ciliary loss and oxidative damage in an in vitro bovine model: The protective role of antioxidant vitamins E and C

    International Nuclear Information System (INIS)

    Highlights: ► A new bovine bronchial model for studying hyperoxia-induced cilia loss is presented. ► Hyperoxia-induced cilia loss was associated with increased sloughing of cells. ► Hyperoxia led to higher epithelial glutathione levels, evidence of oxidative stress. ► Hyperoxia led to increased DNA damage (Comet), and lipid peroxidation (TBARS). ► Vitamins C and E partially protected against hyperoxia-induced cilia loss. -- Abstract: Although elevated oxygen fraction is used in intensive care units around the world, pathological changes in pulmonary tissue have been shown to occur with prolonged exposure to hyperoxia. In this work a bovine bronchus culture model has been successfully used to evaluate the effects of hyperoxia on ciliated epithelium in vitro. Samples were cultured using an air interface method and exposed to normoxia, 21% O2 or hyperoxia, 95% O2. Cilial coverage was assessed using scanning electron microscopy (SEM). Tissue damage (lactate dehydrogenase, LDH, in the medium), lipid peroxidation (thiobarbituric acid reactive substances, TBARS), DNA damage (comet assay), protein oxidation (OxyBlot kit) and antioxidant status (total glutathione) were used to assess whether the hyperoxia caused significant oxidative stress. Hyperoxia caused a time-dependent decline (t½ = 3.4 d compared to 37.1 d under normoxia) in cilial coverage (P 6 compared to 1.97 ± 0.23 × 106 ml−1 after 6 d), many apparently intact, in the medium (P −1 g−1 after 6 d; P −1 for hyperoxia and normoxia, respectively); % tail DNA (18.7 ± 2.2 versus 11.1 ± 1.5); protein carbonyls (P −1 versus 189 ± 15 μmol g−1). Vitamins E (10−7 M) and C (10−6 or 10−7 M) alone or in combination (10−7 M and 10−6 M, respectively) had a significant protective effect on the hyperoxia-induced reduction in percentage cilial coverage (P < 0.05). In conclusion, hyperoxia caused damage to cultured bovine bronchial epithelium and denudation of cilia. The antioxidant vitamins E

  10. Autophagy in the thymic epithelium is dispensable for the development of self-tolerance in a novel mouse model.

    Directory of Open Access Journals (Sweden)

    Supawadee Sukseree

    Full Text Available The thymic epithelium plays critical roles in the positive and negative selection of T cells. Recently, it was proposed that autophagy in thymic epithelial cells is essential for the induction of T cell tolerance to self antigens and thus for the prevention of autoimmune diseases. Here we have tested this hypothesis using mouse models in which autophagy was blocked specifically in epithelial cells expressing keratin 14 (K14, including the precursor of thymic epithelial cells. While the thymic epithelial cells of mice carrying the floxed Atg7 gene (ATG7 f/f showed a high level of autophagy, as determined by LC3 Western blot analysis and fluorescence detection of the recombinant green fluorescent protein (GFP-LC3 reporter protein on autophagosomes, autophagy in the thymic epithelium was efficiently suppressed by deletion of the Atg7 gene using the Cre-loxP system (ATG7 f/f K14-Cre. Suppression of autophagy led to the massive accumulation of p62/sequestosome 1 (SQSTM1 in thymic epithelial cells. However, the structure of the thymic epithelium as well as the organization and the size of the thymus were not altered in mutant mice. The ratio of CD4 to CD8-positive T cells, as well as the frequency of activated (CD69+ CD4 T cells in lymphoid organs, did not differ between mice with autophagy-competent and autophagy-deficient thymic epithelium. Inflammatory infiltrating cells, potentially indicative of autoimmune reactions, were present in the liver, lung, and colon of a similar fraction of ATG7 f/f and ATG7 f/f K14-Cre mice. In contrast to previously reported mice, that had received an autophagy-deficient thymus transplant, ATG7 f/f K14-Cre mice did not suffer from autoimmunity-induced weight loss. In summary, the results of this study suggest that autophagy in the thymic epithelium is dispensable for negative selection of autoreactive T cells.

  11. The ultrastructure of the midgut epithelium in millipedes (Myriapoda, Diplopoda)

    Czech Academy of Sciences Publication Activity Database

    Sosinka, A.; Rost-Roszkowska, M.M.; Vilímová, J.; Tajovský, Karel; Kszuk-Jendrysik, M.; Chajec, Ł.; Sonakowska, L.; Kamińska, K.; Hyra, M.; Poprawa, I.

    2014-01-01

    Roč. 43, č. 5 (2014), s. 477-492. ISSN 1467-8039 Institutional support: RVO:60077344 Keywords : digestive cells * midgut epithelium * millipedes * regenerative cells * secretory cells * ultrastructure Subject RIV: EG - Zoology Impact factor: 1.650, year: 2014

  12. Radioautographic DNA synthesis study on mice Mus musculus gingival epithelium

    International Nuclear Information System (INIS)

    The DNA-synthetizing cells frequency in the gingival epithelium basal layer of the first lower molar region in young and adult mice were studied. The 3H-thymidine and radioautography were used. The labeled cells frequency was determined by calculating their proportions. The data were statiscally analysed. (M.A.C.)

  13. Functional annotation of the human retinal pigment epithelium transcriptome

    NARCIS (Netherlands)

    J.C. Booij (Judith); S. van Soest (Simone); S.M.A. Swagemakers (Sigrid); A.H.W. Essing (Anke); J.H.M. Verkerk (Annemieke); P.J. van der Spek (Peter); T.G.M.F. Gorgels (Theo); A.A.B. Bergen (Arthur)

    2009-01-01

    textabstractBackground: To determine level, variability and functional annotation of gene expression of the human retinal pigment epithelium (RPE), the key tissue involved in retinal diseases like age-related macular degeneration and retinitis pigmentosa. Macular RPE cells from six selected healthy

  14. Quantum Dot Distribution in the Olfactory Epithelium After Nasal Delivery

    Science.gov (United States)

    Garzotto, D.; De Marchis, S.

    2010-10-01

    Nanoparticles are used in a wide range of human applications from industrial to bio-medical fields. However, the unique characteristics of nanoparticles, such as the small size, large surface area per mass and high reactivity raises great concern on the adverse effects of these particles on ecological systems and human health. There are several pioneer studies reporting translocation of inhaled particulates to the brain through a potential neuronal uptake mediated by the olfactory nerve (1, 2, 3). However, no direct evidences have been presented up to now on the pathway followed by the nanoparticles from the nose to the brain. In addition to a neuronal pathway, nanoparticles could gain access to the central nervous system through extracellular pathways (perineuronal, perivascular and cerebrospinal fluid paths). In the present study we investigate the localization of intranasally delivered fluorescent nanoparticles in the olfactory epithelium. To this purpose we used quantum dots (QDs), a model of innovative fluorescent semiconductor nanocrystals commonly used in cell and animal biology (4). Intranasal treatments with QDs were performed acutely on adult CD1 mice. The olfactory epithelium was collected and analysed by confocal microscopy at different survival time after treatment. Data obtained indicate that the neuronal components of the olfactory epithelium are not preferentially involved in QDs uptake, thus suggesting nanoparticles can cross the olfactory epithelium through extracellular pathways.

  15. Histomorphology of the corneal epithelium of anastrozole treated rabbits

    International Nuclear Information System (INIS)

    Objective: To evaluate the effects of prolonged use of anastrozole as an endocrine treatment of breast cancer on the corneal epithelium in an animal model. Study Design: Laboratory based randomized control trial. Place and Duration of Study: Department of Anatomy, Army Medical College, Rawalpindi in collaboration with National Institute of Health, Islamabad, six months from Jun 2012 to Nov 2012. Material and Methods: Twenty adult female NewZealand white rabbits were taken. Ten rabbits were placed in control group taking normal diet and 10 were given anastrozole orally in the normal dose of 1 mg/day (0.02 mg/kg/day). After the completion of the study, corneas were removed and grossly examined. The specimen were fixed and slides prepared for histomorphological examination. The epithelium in each slide was examined for any deposits, edema or increase in stratification and the height of the epithelium was measured for each eye. The results were compared between the groups for statistical significance. Results: The epithelium had normal shape with no areas of any deposits, edema or ulceration. The mean epithelial height in the control group was 21.25 +- 4.29 mu m and 21.00 +- 4.28 mu m in the right corneas and left corneas, respectively. The mean epithelial height taken from the experimental group was 20.50 +- 4.97 mu m and 21.00 +- 4.28 mu m in right sided and left sided corneas, respectively. The p value was calculated to be 0.722 and 1.00 for the right and left corneas, respectively and no statistical significance was found in between the two groups. Conclusion: Long term administration of anastrozole has no effect on the histological morphology of the corneal epithelium. (author)

  16. Anti-inflammatory effects of antibacterials on human bronchial epithelial cells

    Directory of Open Access Journals (Sweden)

    Hatz Rudolf

    2009-09-01

    Full Text Available Abstract Background Human Bronchial epithelial cells (hu-BEC have been claimed to play a significant role in the pathogenesis of chronic inflammatory airway diseases like COPD. In this context IL-8 and GM-CSF have been shown to be key cytokines. Some antibiotics which are routinely used to treat lower respiratory tract infections have been shown to exert additional immunomodulatory or anti-inflammatory effects. We investigated whether these effects can also be detected in hu-BEC. Methods Hu-BEC obtained from patients undergoing lung resections were transferred to air-liquid-interface (ALI culture. These cultures were incubated with cefuroxime (CXM, 10-62.5 mg/l, azithromycin (AZM, 0.1-1.5 mg/l, levofloxacin (LVX, 1-8 mg/l and moxifloxacin (MXF, 1-16 mg/l. The spontaneous and TNF-α (10 ng/ml induced expression and release of IL-8 and GM-CSF were measured using PCR and ELISA in the absence or presence of these antibiotics. Results The spontaneous IL-8 and GM-CSF release was significantly reduced with MXF (8 mg/l by 37 ± 20% and 45 ± 31%, respectively (both p Conclusion Using ALI cultures of hu-BEC we observed differential effects of antibiotics on spontaneous and TNF-α induced cytokine release. Our data suggest that MXF and AZM, beyond bactericidal effects, may attenuate the inflammatory process mediated by hu-BEC.

  17. Molecular Mechanisms of Malignant Transformation by Low Dose Cadmium in Normal Human Bronchial Epithelial Cells

    Science.gov (United States)

    Kluz, Thomas; Cohen, Lisa; Shen, Steven S.; Costa, Max

    2016-01-01

    Cadmium is a carcinogenic metal, the mechanisms of which are not fully understood. In this study, human bronchial epithelial cells were transformed with sub-toxic doses of cadmium (0.01, 0.05, and 0.1 μM) and transformed clones were characterized for gene expression changes using RNA-seq, as well as other molecular measurements. 440 genes were upregulated and 47 genes were downregulated in cadmium clones relative to control clones over 1.25-fold. Upregulated genes were associated mostly with gene ontology terms related to embryonic development, immune response, and cell movement, while downregulated genes were associated with RNA metabolism and regulation of transcription. Several embryonic genes were upregulated, including the transcription regulator SATB2. SATB2 is critical for normal skeletal development and has roles in gene expression regulation and chromatin remodeling. Small hairpin RNA knockdown of SATB2 significantly inhibited growth in soft agar, indicating its potential as a driver of metal-induced carcinogenesis. An increase in oxidative stress and autophagy was observed in cadmium clones. In addition, the DNA repair protein O6-methylguanine-DNA-methyltransferase was depleted by transformation with cadmium. MGMT loss caused significant decrease in cell viability after treatment with the alkylating agent temozolomide, demonstrating diminished capacity to repair such damage. Results reveal various mechanisms of cadmium-induced malignant transformation in BEAS-2B cells including upregulation of SATB2, downregulation of MGMT, and increased oxidative stress. PMID:27186882

  18. Col2-Cre recombinase is co-expressed with endogenous type II collagen in embryonic renal epithelium and drives development of polycystic kidney disease following inactivation of ciliary genes

    OpenAIRE

    Kolpakova-Hart, Elona; Nicolae, Claudia; Zhou, Jing; Olsen, Bjorn R

    2008-01-01

    Here we report on the severe defects in renal epithelium induced by the transgenic Col2-Cre line used previously for skeletal tissue-specific gene targeting. We demonstrate that conditional ablation of the Kif3a or Pkd1 genes encoding primary cilium/intraflagellar transport-associated proteins using type II collagen-specific Cre transgenic strain results in a severe form of polycystic kidney disease in mice. We detect Col2-Cre recombinase expression in kidney epithelium, which reflects expres...

  19. Cyclosporine Inhibits Apoptosis in Experimental Murine Xerophthalamia Conjunctival Epithelium

    Institute of Scientific and Technical Information of China (English)

    SUN Jinghua; WANG Jingxin

    2006-01-01

    This study examined the inhibitory effect of topical cyclosporine (CsA) treatment on conjunctiva epithelial apoptosis in a murine model of xerophthalamia. Dry eye was induced in 3 groups of C57BL6 mice by subcutaneous injection of scopolamine (t.i.d) and exposure to an air draft and low-humidity environment for 16 h each day for 12 days. The dry eye control group received no topical treatment; another group received 1 μL of 0.05 % CsA topically (t.i.d, dry eye+CsA); and the third group received 1 μL of the castor oil vehicle of CsA topically (t.i.d, dry eye + vehicle). Normal mice were used as untreated controls. Twelve days later, the mice were killed, and their conjunctivas were excised. The number of the conjunctival goblet cells was counted in tissue sections stained with periodic acid Schiff (PAS) reagent. Their conjunctiva epithelium had been investigated by immuno-histochemical staining to detect the goblet cells and the expression of Caspase-3, Bax and bcl-2.Our results showed that compared with dry eye control and dry eye mice + vehicle groups, the number of conjunctival epithelial goblet cells was significantly greater in the untreated controls and dry eye mice receiving CsA (P <0.01 for both groups). There was no significant difference in the number of conjunctival epithelial goblet cells between the dry eye control and dry eye+vehicle group. It was also true of the number of conjunctival epithelial goblet cells when comparison was made between the normal group and the dry eye+CsA group. Expressions of Caspas-3 and Bax were increased and ex-pression of bcl-2 was decreased in conjunctival epithelial cells in dry eye control and dry eye mice+vehicle groups. There was a significant positive correlation between goblet cell number and the number of cells that expressed bcl-2, and a negative correlation between goblet cells and Caspase-3 and Bax expression. It is concluded that the topical use of CsA could significantly reduce conjuncti-val epithelial

  20. Early survival factor deprivation in the olfactory epithelium enhances activity-dependent survival

    Directory of Open Access Journals (Sweden)

    Adrien eFrançois

    2013-12-01

    Full Text Available The neuronal olfactory epithelium undergoes permanent renewal because of environmental aggression. This renewal is partly regulated by factors modulating the level of neuronal apoptosis. Among them, we had previously characterized endothelin as neuroprotective. In this study, we explored the effect of cell survival factor deprivation in the olfactory epithelium by intranasal delivery of endothelin receptors antagonists to rat pups. This treatment induced an overall increase of apoptosis in the olfactory epithelium. The responses to odorants recorded by electroolfactogram were decreased in treated animal, a result consistent with a loss of olfactory sensory neurons (OSNs. However, the treated animal performed better in an olfactory orientation test based on maternal odor compared to non-treated littermates. This improved performance could be due to activity-dependent neuronal survival of OSNs in the context of increased apoptosis level. In order to demonstrate it, we odorized pups with octanal, a known ligand for the rI7 olfactory receptor (Olr226. We quantified the number of OSN expressing rI7 by RT-qPCR and whole mount in situ hybridization. While this number was reduced by the survival factor removal treatment, this reduction was abolished by the presence of its ligand. This improved survival was optimal for low concentration of odorant and was specific for rI7-expressing OSNs. Meanwhile, the number of rI7-expressing OSNs was not affected by the odorization in non-treated littermates; showing that the activity-dependant survival of OSNs did not affect the OSN population during the 10 days of odorization in control conditions. Overall, our study shows that when apoptosis is promoted in the olfactory mucosa, the activity-dependent neuronal plasticity allows faster tuning of the olfactory sensory neuron population towards detection of environmental odorants.

  1. Bronchial compression due to stent placement in pulmonary artery in a child with congenital heart disease.

    Science.gov (United States)

    Núñez, Mónica; Beleña, José; Cabeza, Raúl; Beltrán, María

    2005-12-01

    Congenital heart disease, such as transposition of the great vessels (TGV), requires surgical procedures which can lead to important complications. We report on a case of bronchial obstruction following placement of a pulmonary artery stent in a 4-year-old boy who had undergone a Rastelli procedure to correct TGV, ventricular septal defect and pulmonary stenosis. There are many complications that can arise as a consequence of intravascular stents in heart surgery, as well as many causes of bronchial compression. However we have not found any report which describes bronchial compression as a direct consequence of endovascular stent. PMID:16324040

  2. THE EPITHELIUM AS A TARGET IN SEPSIS.

    Science.gov (United States)

    Chawla, Lakhmir S; Fink, Mitchell; Goldstein, Stuart L; Opal, Steven; Gómez, Alonso; Murray, Patrick; Gómez, Hernando; Kellum, John A

    2016-03-01

    Organ dysfunction induced by sepsis has been consistently associated with worse outcome and death. Regardless of the organ compromised, epithelial dysfunction is present throughout the body, affecting those organs that contain epithelia like the skin, lungs, liver, gut, and kidneys. Despite their obvious differences, sepsis seems to alter common features of all epithelia, such as barrier function and vectorial ion transport. Such alterations in the lung, the gut, and the kidney have direct implications that may explain the profound organ functional impairments in the absence of overt cell death. Epithelial injury in this context is not only an explanatory real pathophysiologic event, but also represents a source of biomarkers that have been explored to identify organ compromise earlier, predict outcome, and even to test novel therapeutic interventions such as blood purification. However, this remains largely experimental, and despite promising results, work is still required to better understand the response of the epithelial cells to sepsis, to define their role in adaptation to insults, to comprehend the interorgan cross-talk that occurs in these circumstances, and to exploit these aspects in pursuit of targeted therapies like blood purification, which may improve outcome for these patients in the future. PMID:26863125

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  10. Low power laser therapy in treatment of bronchial asthma

    Directory of Open Access Journals (Sweden)

    Milojević Momir

    2003-01-01

    Full Text Available Introduction Modern concept of acupuncture is based on the fact there are designated locations on the surface of human body, which are related to integrative systems of an organism by means of sensory nerves, correlating and synchronizing organ functioning, depending on external and internal conditions, by means of nervous and neurohumoral regulation of metabolic and regenerative processes, including also mobilization of immunological, protective and antistress reactions. Apart from standard needle acupuncture, other methods of stimulating acupuncture points are also applied. Due to invention of low power lasers, irradiation laser acupuncture has been introduced into routine medical practice, characterized by painless and aseptic technique and outstanding clinical results. Material and methods The investigation was aimed at defining therapeutic effects of low power laser irradiation by stimulating acupuncture points or local treatment of asthma. A prospective analysis included 50 patients treated at the Institute of Pulmonary Diseases in Sremska Kamenica during 2000, 2001 and 2002. Together with conservative treatment of present disease, these patients were treated with laser stimulation of acupuncture points in duration of ten days. During treatment changes of functional respiratory parameters were recorded. Results were compared with those in the control group. The control group consisted of the same number of patients and differed from the examination group only by not using laser stimulation. Results Patients with bronchial asthma presented with significant improvement (p<0,0005 of all estimated lung function parameters just 30 minutes after laser stimulation. Improvements achieved on the third and the tenth day of treatment were significantly higher (p<0,001 to p<0,00005 in the examination group in comparison with the control group. Further investigation confirmed that improvement of measured lung function parameters was significantly

  11. Bronchial asthma: advice for patients traveling to high altitude.

    Science.gov (United States)

    Cogo, Annalisa; Fiorenzano, Giuseppe

    2009-01-01

    This article examines the possibility of traveling to altitude for patients suffering from bronchial asthma. The mountain environment, the adaptations of the respiratory system to high altitude, the underlying patho-physiologies of asthma, and the recommendations for patients, according to altitude, are discussed. In summary, staying at low altitude has a significant beneficial effect for asthmatic patients, due to the reduction of airway inflammation and the lower response to bronchoconstrictor stimuli; for staying at moderate altitude, there is conflicting information and no clinical data; at high altitude, the environment seems beneficial for well-controlled asthmatics, but intense exercise and upper airway infections (frequent during trekking) can be additional risks and should be avoided. Further, in remote areas health facilities are often difficult to reach. PMID:19519226

  12. The significance of enhanced radionuclide deposition at bronchial bifurcations

    International Nuclear Information System (INIS)

    Experiments were conducted to quantitate deposition patterns of monodisperse aerosols in surrogates of the human upper respiratory tract. Laryngeal casts and most upper airway bifurcations were sites of preferential particle deposition. Highly concentrated deposits were detected at carinal ridges within bifurcation zones. Together with impaired mucociliary clearance at branching sites, this initial deposition pattern results in localized accumulations of radionuclides within bifurcation zones. For inhaled radon progeny radiation doses are calculated for 3 regions of bronchial airways: tubular airway segments, bifurcation zones (including the carina), and carinal ridges. These calculations indicated that enhanced deposition at branching sites leads to significantly higher doses to epithelial cells located at bifurcations than along tubular airway segments. If cell killing is included in the analysis of lung cancer risk, it reduces carcinogenic potential at bifurcation sites, particularly at high doses. (author)

  13. Recurrent acute kidney injury associated with metastatic bronchial carcinoid.

    Science.gov (United States)

    Barton, James C; Barton, J Clayborn; Bertoli, Luigi F

    2012-01-01

    Acute kidney injury (AKI) is a rare complication of carcinoid syndrome. A 61-year-old man developed carcinoid syndrome 51 months after pneumonectomy for bronchial carcinoid, and 8 episodes of AKI 101 to 118 months after pneumonectomy. Serum chromogranin A and urine 5-hydroxyindoleacetic acid levels were elevated for more than 1 year before AKI occurred. Each episode was characterized by flushing, facial edema, mild diarrhea, necrosis of hepatic metastatic nodules, mild oliguria, hyponatremia, acidosis, hypokalemia, hypomagnesemia and hyperphosphatemia. He did not have elevated urine sodium levels or osmolality, hypotension or hypertension. Plasma levels of dopamine, epinephrine and norepinephrine, measured during a single episode, were markedly elevated. Serum creatinine levels returned to normal after most episodes. Hyponatremia persisted but was more severe during AKI. Elevated plasma levels of vasoactive substances other than 5-hydroxytryptamine, perhaps dopamine or other catecholamines, could explain recurrent AKI. The natriuretic effect of elevated plasma dopamine levels could explain chronic hyponatremia. PMID:22008780

  14. Ventilation and perfusion scintiscanning in unresectable bronchial carcinomas under radiotherapy

    International Nuclear Information System (INIS)

    Ventilation and perfusion scintiscanning using Kr-81m-gas and Tc-99m microspheres in addition to X-ray thorax control examination were performed in patients with inoperable bronchoscopically confirmed bronchial carcinoma prior to radiotherapy, during irradiation after 30 Gy and at the scheduled end of treatment. Compared with the static-morphological X-ray picture, lung scintigraphy provides additional information about regional lung functions. Perfusion scintiscanning shows to be more sensitive and more accurate a method than ventilation scintiscanning. In follow-up under radiotherapy, valuable suggestions concerning determination of target volume and final dose are supplied when aiming at a palliative objective. Early detection and confirmation of pulmonary metastases or of a lymphangiosis carcinomatosa allow to revise an originally curative objective. (orig.)

  15. Randomized controlled study of CBT in bronchial asthma

    Directory of Open Access Journals (Sweden)

    Grover Naveen

    2007-01-01

    Full Text Available The aim of the present study was to find out efficacy of cognitive behavior therapy, as an adjunct to standard pharmacotherapy, in bronchial asthma. In a random-ized two-group design with pre-and post assessments, forty asthma patients were randomly allotted to two groups: self management group and cognitive behavior therapy group. Both groups were exposed to 6-8 weeks of intervention, asthma self management program and cognitive behavior therapy. Assessment measures used were-Semi structured interview schedule, Asthma Symptom Checklist, Asthma di-ary, Asthma Bother Profile, Hospital Anxiety & Depression Scale, AQLQ and Peak Expiratory Flow Rate. Within group comparison showed significant improvement in both groups at the post assessment. Between group comparisons showed that CBT group reported significantly greater change than that of SM group. Cognitive behavior therapy helps in improving the managment of asthma.

  16. Variations of respiratory impedance with lung volume in bronchial hyperreactivity.

    Science.gov (United States)

    van den Elshout, F J; van de Woestijne, K P; Folgering, H T

    1990-08-01

    The total respiratory impedance was measured at various frequencies (4 to 52 Hz) with a pseudo-random-noise forced oscillation technique (FOT). The apparatus (Oscillaire) was connected with a spirometer forming a closed respiratory circuit in which gas concentrations were kept constant. Measurements were made in 15 healthy subjects (group 1) and in 30 asthmatic patients with bronchial hyperreactivity, subdivided into group 2 treated only with inhaled beta 2-mimetics (n = 15) and in group 3 using both beta 2-mimetics and steroids in inhalation (n = 15). No significant differences were found between the impedance data obtained with the Oscillaire alone and those obtained with the Oscillaire connected with the spirometer circuit. The impedance was measured at FRC level, and at FRC +1 L and -1 L. The relative changes of the resistance at 8 Hz were -23.2 percent (13.8) at FRC +1 L and +40.9 percent (29.3) at FRC -1 L relative to the values at resting FRC. This inverse relation between airway resistance and lung volume was similar in all groups. The average reactance decreased at FRC -1 L in all groups. However, at FRC +1 L the average reactance increased 50.6 percent in group 2 and 94.2 percent in group 3, but decreased in group 1. Concomitant changes were observed in the resonant frequency and in the frequency dependence of resistance. Because of these qualitatively different responses of the impedance data to changes in lung volume (both for the whole group and for each individual) between healthy subjects and asthmatic patients, this test might be useful for the diagnosis of bronchial hyperreactivity. PMID:2376168

  17. Bronchial stump closure with amniotic membrane in animal model

    Directory of Open Access Journals (Sweden)

    Gholamreza Mohajeri

    2014-01-01

    Full Text Available Background: Coverage of the bronchial stumps (BSs with adjacent tissues can improve healing and reduce bronchial complications in complex thoracic surgery. There is no evidence for the application of human amnion allograft for prevention of air leak from the BS. The comparison of the amniotic membrane (AM and pleural patch for BS healing after lobectomy in dogs was our aim in this study. Materials and Methods: A total of eight males and females 12-24-month-old dogs between 17 and 22 kg body-weight were used in this study in 2010, Isfahan University of Medical Sciences. Animals were separated into two groups: group A (n = 4; amniotic membrane and group P (n = 4; pleural patch according to the BS closure technique performed. After lobectomy of the right middle lobe, the BS was closed, while a small bronchopleural fistula (BPF was created by inserting a catheter via edges of closed stump. Then, it was covered with a piece of AM3 × 3 cm in group A and with a pedicle graft of pleura in group P. Rethoracotomy was performed after 15 days of observation, and the BS was removed for histological examination. Histological healing was classified as complete or incomplete healing. Neoangiogenesis was measured by Von Willebrand expression using immunohistochemistry (IHC. Data were analyzed by SPSS version 15 using Fisher′s exact test, Mann-Whitney test, and T tests. Results: BPF complications were not seen during observation period. There was no significant difference in histological healing between two groups. Similarly, no significant difference was observed between the groups in terms of neoangiogenesis based on IHC examination (P value = 0.69. Conclusion: Human amnion allograft could be as effective as pleural patch for BS wrapping following pulmonary resections.

  18. Expression of Toll-like receptors in nasal epithelium in allergic rhinitis.

    Science.gov (United States)

    Renkonen, Jutta; Toppila-Salmi, Sanna; Joenväärä, Sakari; Mattila, Pirkko; Parviainen, Ville; Hagström, Jaana; Haglund, Caj; Lehtonen, Mikko; Renkonen, Risto

    2015-08-01

    Toll-like receptors (TLRs) are important in barrier homeostasis, but their role in airborne allergies is not fully understood. The aim was to evaluate baseline and allergen-induced expression of TLR proteins in nasal epithelium during allergic rhinitis. Nineteen otherwise healthy non-smoking volunteers both allergic to birch pollen and non-allergic controls were enrolled. We took nasal biopsies before and after off-seasonal intranasal birch pollen or diluent challenge. The expression of epithelial TLR1-7, TLR9-10, and MyD88 proteins was immunohistochemically evaluated from the nasal biopsies. The TLR1-3 and TLR5-10 mRNAs were observed by RNA-microarray. Baseline epithelial expression of TLR proteins was wide and identical in controls and atopics. After off-seasonal intranasal birch pollen challenge, a negative change in the expression score of TLR1 and TLR6 proteins was detected in the atopic group. TLR mRNA expression was not affected by birch pollen challenge. Nasal epithelium seems to express all known TLRs. The mechanisms by which TLR1, and TLR6 proteins could affect pollen allergen transport need further studies. PMID:26061394

  19. Trop2 marks transient gastric fetal epithelium and adult regenerating cells after epithelial damage.

    Science.gov (United States)

    Fernandez Vallone, Valeria; Leprovots, Morgane; Strollo, Sandra; Vasile, Gabriela; Lefort, Anne; Libert, Frederick; Vassart, Gilbert; Garcia, Marie-Isabelle

    2016-05-01

    Mouse fetal intestinal progenitors lining the epithelium prior to villogenesis grow as spheroids when cultured ex vivo and express the transmembrane glycoprotein Trop2 as a marker. Here, we report the characterization of Trop2-expressing cells from fetal pre-glandular stomach, growing as immortal undifferentiated spheroids, and their relationship with gastric development and regeneration. Trop2(+) cells generating gastric spheroids differed from adult glandular Lgr5(+) stem cells, but appeared highly related to fetal intestinal spheroids. Although they shared a common spheroid signature, intestinal and gastric fetal spheroid-generating cells expressed organ-specific transcription factors and were committed to intestinal and glandular gastric differentiation, respectively. Trop2 expression was transient during glandular stomach development, being lost at the onset of gland formation, whereas it persisted in the squamous forestomach. Undetectable under homeostasis, Trop2 was strongly re-expressed in glands after acute Lgr5(+) stem cell ablation or following indomethacin-induced injury. These highly proliferative reactive adult Trop2(+) cells exhibited a transcriptome displaying similarity with that of gastric embryonic Trop2(+) cells, suggesting that epithelium regeneration in adult stomach glands involves the partial re-expression of a fetal genetic program. PMID:26989172

  20. Purinergic receptor antagonists inhibit odorant-mediated CREB phosphorylation in sustentacular cells of mouse olfactory epithelium.

    LENUS (Irish Health Repository)

    Dooley, Ruth

    2012-02-01

    BACKGROUND: Extracellular nucleotides have long been known to play neuromodulatory roles and to be involved in intercellular signalling. In the olfactory system, ATP is released by olfactory neurons, and exogenous ATP can evoke an increase in intracellular calcium concentration in sustentacular cells, the nonneuronal supporting cells of the olfactory epithelium. Here we investigate the hypothesis that olfactory neurons communicate with sustentacular cells via extracellular ATP and purinergic receptor activation. RESULTS: Here we show that exposure of mice to a mixture of odorants induced a significant increase in the levels of the transcription factor CREB phosphorylated at Ser-133 in the nuclei of both olfactory sensory neurons and sustentacular cells. This activation was dependent on adenylyl cyclase III-mediated olfactory signaling and on activation of P2Y purinergic receptors on sustentacular cells. Purinergic receptor antagonists inhibited odorant-dependent CREB phosphorylation specifically in the nuclei of the sustentacular cells. CONCLUSION: Our results point to a possible role for extracellular nucleotides in mediating intercellular communication between the neurons and sustentacular cells of the olfactory epithelium in response to odorant exposure. Maintenance of extracellular ionic gradients and metabolism of noxious chemicals by sustentacular cells may therefore be regulated in an odorant-dependent manner by olfactory sensory neurons.

  1. DNA Methylation Dynamics Regulate the Formation of a Regenerative Wound Epithelium during Axolotl Limb Regeneration.

    Directory of Open Access Journals (Sweden)

    Cristian Aguilar

    Full Text Available The formation of a blastema during regeneration of an axolotl limb involves important changes in the behavior and function of cells at the site of injury. One of the earliest events is the formation of the wound epithelium and subsequently the apical epidermal cap, which involves in vivo dedifferentiation that is controlled by signaling from the nerve. We have investigated the role of epigenetic modifications to the genome as a possible mechanism for regulating changes in gene expression patterns of keratinocytes of the wound and blastema epithelium that are involved in regeneration. We report a modulation of the expression DNMT3a, a de novo DNA methyltransferase, within the first 72 hours post injury that is dependent on nerve signaling. Treatment of skin wounds on the upper forelimb with decitabine, a DNA methyltransferase inhibitor, induced changes in gene expression and cellular behavior associated with a regenerative response. Furthermore, decitabine-treated wounds were able to participate in regeneration while untreated wounds inhibited a regenerative response. Elucidation of the specific epigenetic modifications that mediate cellular dedifferentiation likely will lead to insights for initiating a regenerative response in organisms that lack this ability.

  2. Purinergic receptor antagonists inhibit odorant-mediated CREB phosphorylation in sustentacular cells of mouse olfactory epithelium

    LENUS (Irish Health Repository)

    Dooley, Ruth

    2011-08-22

    Abstract Background Extracellular nucleotides have long been known to play neuromodulatory roles and to be involved in intercellular signalling. In the olfactory system, ATP is released by olfactory neurons, and exogenous ATP can evoke an increase in intracellular calcium concentration in sustentacular cells, the nonneuronal supporting cells of the olfactory epithelium. Here we investigate the hypothesis that olfactory neurons communicate with sustentacular cells via extracellular ATP and purinergic receptor activation. Results Here we show that exposure of mice to a mixture of odorants induced a significant increase in the levels of the transcription factor CREB phosphorylated at Ser-133 in the nuclei of both olfactory sensory neurons and sustentacular cells. This activation was dependent on adenylyl cyclase III-mediated olfactory signaling and on activation of P2Y purinergic receptors on sustentacular cells. Purinergic receptor antagonists inhibited odorant-dependent CREB phosphorylation specifically in the nuclei of the sustentacular cells. Conclusion Our results point to a possible role for extracellular nucleotides in mediating intercellular communication between the neurons and sustentacular cells of the olfactory epithelium in response to odorant exposure. Maintenance of extracellular ionic gradients and metabolism of noxious chemicals by sustentacular cells may therefore be regulated in an odorant-dependent manner by olfactory sensory neurons.

  3. Thymic epithelium determines a spontaneous chronic neuritis in Icam1(tm1Jcgr)NOD mice.

    Science.gov (United States)

    Meyer zu Horste, Gerd; Mausberg, Anne K; Cordes, Steffen; El-Haddad, Houda; Partke, Hans-Joachim; Leussink, Verena I; Roden, Michael; Martin, Stephan; Steinman, Lawrence; Hartung, Hans-Peter; Kieseier, Bernd C

    2014-09-15

    The NOD mouse strain spontaneously develops autoimmune diabetes. A deficiency in costimulatory molecules, such as B7-2, on the NOD genetic background prevents diabetes but instead triggers an inflammatory peripheral neuropathy. This constitutes a shift in the target of autoimmunity, but the underlying mechanism remains unknown. In this study, we demonstrate that NOD mice deficient for isoforms of ICAM-1, which comediate costimulatory functions, spontaneously develop a chronic autoimmune peripheral neuritis instead of diabetes. The disease is transferred by CD4(+) T cells, which infiltrate peripheral nerves together with macrophages and B cells and are autoreactive against peripheral myelin protein zero. These Icam1(tm1Jcgr)NOD mice exhibit unaltered numbers of regulatory T cells, but increased IL-17-producing T cells, which determine the severity, but not the target specificity, of autoimmunity. Ab-mediated ICAM-1 blockade triggers neuritis only in young NOD mice. Thymic epithelium from Icam1(tm1Jcgr)NOD mice features an altered expression of costimulatory molecules and induces neuritis and myelin autoreactivity after transplantation into nude mice in vivo. Icam1(tm1Jcgr)NOD mice exhibit a specifically altered TCR repertoire. Our findings introduce a novel animal model of chronic inflammatory neuropathies and indicate that altered expression of ICAM-1 on thymic epithelium shifts autoimmunity specifically toward peripheral nerves. This improves our understanding of autoimmunity in the peripheral nervous system with potential relevance for human diseases. PMID:25108020

  4. Erlotinib promotes endoplasmic reticulum stress-mediated injury in the intestinal epithelium

    International Nuclear Information System (INIS)

    Erlotinib, a popular drug for treating non-small cell lung cancer (NSCLC), causes diarrhea in approximately 55% of patients receiving this drug. In the present study, we found that erlotinib induced barrier dysfunction in rat small intestine epithelial cells (IEC-6) by increasing epithelial permeability and down-regulating E-cadherin. The mRNA levels of various pro-inflammatory cytokines (Il-6, Il-25 and Il-17f) were increased after erlotinib treatment in IEC-6 cells. Erlotinib concentration- and time-dependently induced apoptosis and endoplasmic reticulum (ER) stress in both IEC-6 and human colon epithelial cells (CCD 841 CoN). Intestinal epithelial injury was also observed in male C57BL/6J mice administrated with erlotinib. Knockdown of C/EBP homologous protein (CHOP) with small interference RNA partially reversed erlotinib-induced apoptosis, production of IL-6 and down-regulation of E-cadherin in cultured intestinal epithelial cells. In conclusion, erlotinib caused ER stress-mediated injury in the intestinal epithelium, contributing to its side effects of diarrhea in patients. - Highlights: • Erlotinib destroyed barrier integrity both in vitro and in vivo. • Erlotinib induced inflammation both in vitro and in vivo. • Erlotinib induced apoptosis both in vitro and in vivo. • ER stress contributed to erlotinib-induced barrier dysfunction

  5. Erlotinib promotes endoplasmic reticulum stress-mediated injury in the intestinal epithelium

    Energy Technology Data Exchange (ETDEWEB)

    Fan, Lu; Hu, Lingna; Yang, Baofang; Fang, Xianying; Gao, Zhe; Li, Wanshuai; Sun, Yang; Shen, Yan; Wu, Xuefeng [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093 (China); Shu, Yongqian [Department of Clinical Oncology, The First Affiliated Hospital of Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029 (China); Gu, Yanhong, E-mail: guluer@163.com [Department of Clinical Oncology, The First Affiliated Hospital of Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029 (China); Wu, Xudong, E-mail: xudongwu@nju.edu.cn [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093 (China); Xu, Qiang, E-mail: molpharm@163.com [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093 (China)

    2014-07-01

    Erlotinib, a popular drug for treating non-small cell lung cancer (NSCLC), causes diarrhea in approximately 55% of patients receiving this drug. In the present study, we found that erlotinib induced barrier dysfunction in rat small intestine epithelial cells (IEC-6) by increasing epithelial permeability and down-regulating E-cadherin. The mRNA levels of various pro-inflammatory cytokines (Il-6, Il-25 and Il-17f) were increased after erlotinib treatment in IEC-6 cells. Erlotinib concentration- and time-dependently induced apoptosis and endoplasmic reticulum (ER) stress in both IEC-6 and human colon epithelial cells (CCD 841 CoN). Intestinal epithelial injury was also observed in male C57BL/6J mice administrated with erlotinib. Knockdown of C/EBP homologous protein (CHOP) with small interference RNA partially reversed erlotinib-induced apoptosis, production of IL-6 and down-regulation of E-cadherin in cultured intestinal epithelial cells. In conclusion, erlotinib caused ER stress-mediated injury in the intestinal epithelium, contributing to its side effects of diarrhea in patients. - Highlights: • Erlotinib destroyed barrier integrity both in vitro and in vivo. • Erlotinib induced inflammation both in vitro and in vivo. • Erlotinib induced apoptosis both in vitro and in vivo. • ER stress contributed to erlotinib-induced barrier dysfunction.

  6. Features of application of medical physical culture for the children of patients by bronchial asthma.

    Directory of Open Access Journals (Sweden)

    Aleshina A.I.

    2012-07-01

    Full Text Available The purpose of work consists in generalization of scientific recommendations of scientists in relation to application of medical physical culture for children with bronchial asthma. The problem of bronchial asthma is analysed, as an enough widespread disease in the world, the basic tendencies of his prevalence, range of measures instrumental in diagnostics and treatment, are certain. It is presented statistical information about prevalence of bronchial asthma on Ukraine among children. Principal reasons of origin of disease and role of physical exercises in the process of rehabilitation of patients with bronchial asthma are certain. The features of the use and influencing of respiratory gymnastics on the method of Buteyko, Strel'nikovoy, drainage exercises, sound gymnastics, exercises of aerobic character are analysed. The necessity of application of medical physical culture at this disease is grounded.

  7. RATIONALE FOR A SPECIFIC THERAPY OF CYTOMEGALOVIRUS INFECTION IN CHILDREN WITH BRONCHIAL ASTHMA

    Directory of Open Access Journals (Sweden)

    E. N. Suprun

    2013-01-01

    Full Text Available Abstract. We propose a protocol of treatment in cases of bronchial asthma with cytomegalovirus (CMV persistence. This basic therapy is administered depending on the disease severity, according to the National Programme 2009. The treatment includes administration of human immunoglobulin, with dosage according on CMV antibodies titers. The study has revealed that such regimen of antibody administration based on the content of anti-CMV antibodies in bronchial asthma treatment stops active CMV replication in bronchial mucous membrane, alleviates clinical course of the disease, diminishes changes of immune system typical to children suffering from bronchial asthma and CMV reactivation, thus allowing to reduce the volume of basic therapy, along with maintaining control of asthma control.

  8. Origin of bronchial and pulmonary elastic fibers and their role in some pathological events.

    Science.gov (United States)

    Gabbrielli, S; Stanflin, N; Di Preta, F

    1994-06-01

    The purpose of this contribution is to place a higher value on the existence of a turn-over of bronchial and pulmonary elastic fibers: the former would derive from the smooth muscle cells of the bronchial wall, the latter from the interstitial myofibroblasts of the alveolar septa. The reduction of the number of the elastic fibers in the bronchial wall during chronic atrophic bronchitis depend on the atrophy of the bronchial smooth muscle cells; in the alveolar septa the hyperplasia of the elastic fibers during pulmonary fibroses depend on the myofibroblastic proliferation, while the reduction of the elastic fibers number during pulmonary enphysema depend on the reduction in the number of myofibroblasts. PMID:7808795

  9. A manual afterloading technique for the treatment of patients with bronchial carcinoma using iridium-192 wire

    International Nuclear Information System (INIS)

    A manual afterloading technique using iridium-192 wire is described for the palliative treatment of patients with bronchial or oesophageal lesions, where the purchase of expensive remote afterloading equipment is not immediately possible. (UK)

  10. Regional variations of cell surface carbohydrates in human oral stratified epithelium

    DEFF Research Database (Denmark)

    Vedtofte, P; Dabelsteen, Erik; Hakomori, S;

    1984-01-01

    such as non-keratinized, parakeratinized, and orthokeratinized stratified squamous epithelium. The material included buccal and palatal epithelium from 20 persons with blood group A or O, gingival, and alveolar epithelium from 10 persons with blood group A or B, and buccal metaplastically keratinized......-acetyllactosamine by murine monoclonal antibodies. Each antigen showed a similar staining pattern in buccal and alveolar epithelium (non-keratinized) which differed considerably from that seen in palatal and gingival epithelium (ortho- and parakeratinized). The expression of blood group antigens A or B and the...

  11. Nanoparticle incorporation of melittin reduces sperm and vaginal epithelium cytotoxicity.

    Directory of Open Access Journals (Sweden)

    Andrew P Jallouk

    Full Text Available Melittin is a cytolytic peptide component of bee venom which rapidly integrates into lipid bilayers and forms pores resulting in osmotic lysis. While the therapeutic utility of free melittin is limited by its cytotoxicity, incorporation of melittin into the lipid shell of a perfluorocarbon nanoparticle has been shown to reduce its toxicity in vivo. Our group has previously demonstrated that perfluorocarbon nanoparticles containing melittin at concentrations <10 µM inhibit HIV infectivity in vitro. In the current study, we assessed the impact of blank and melittin-containing perfluorocarbon nanoparticles on sperm motility and the viability of both sperm and vaginal epithelial cells. We found that free melittin was toxic to sperm and vaginal epithelium at concentrations greater than 2 µM (p<0.001. However, melittin nanoparticles were not cytotoxic to sperm (p = 0.42 or vaginal epithelium (p = 0.48 at an equivalent melittin concentration of 10 µM. Thus, nanoparticle formulation of melittin reduced melittin cytotoxicity fivefold and prevented melittin toxicity at concentrations previously shown to inhibit HIV infectivity. Melittin nanoparticles were toxic to vaginal epithelium at equivalent melittin concentrations ≥20 µM (p<0.001 and were toxic to sperm at equivalent melittin concentrations ≥40 µM (p<0.001. Sperm cytotoxicity was enhanced by targeting of the nanoparticles to the sperm surface antigen sperm adhesion molecule 1. While further testing is needed to determine the extent of cytotoxicity in a more physiologically relevant model system, these results suggest that melittin-containing nanoparticles could form the basis of a virucide that is not toxic to sperm and vaginal epithelium. This virucide would be beneficial for HIV serodiscordant couples seeking to achieve natural pregnancy.

  12. HVJ-E-mediated gene transfer into the intestinal epithelium

    OpenAIRE

    sprotocols

    2015-01-01

    This protocol describes a novel method that enables transfection of plasmids and siRNAs into the mouse intestinal epithelium. The mouse was anesthetized with isoflurane, and the small intestine was pulled out from the peritoneal cavity. The small intestinal lumen was then washed with buffer containing a reducing agent, dithiothreitol, to remove mucus, and injected with transfection solution. To achieve efficient gene delivery, we used a hemagglutinating virus of Japan envelope (HVJ-E)-based t...

  13. Molecular Mechanisms of Nasal Epithelium in Rhinitis and Rhinosinusitis

    OpenAIRE

    Toppila-Salmi, Sanna; van Drunen, Cornelis M; Fokkens, Wytske J; Golebski, Korneliuz; Mattila, Pirkko; Joenvaara, Sakari; Renkonen, Jutta; Renkonen, Risto

    2014-01-01

    Allergic rhinitis, nonallergic rhinitis, and chronic rhinosinusitis are multifactorial upper airway diseases with high prevalence. Several genetic and environmental factors are proposed to predispose to the pathogenesis of the inflammatory upper airway diseases. Still, the molecular mechanisms leading toward the onset and progression of upper airway diseases are largely unknown. The upper airway epithelium has an important role in sensing the environment and regulating the inhaled air. As suc...

  14. Immune defense mechanisms in the Caenorhabditis elegans intestinal epithelium

    OpenAIRE

    Pukkila-Worley, Read; Ausubel, Frederick M.

    2012-01-01

    Intestinal epithelial cells provide an essential line of defense for Caenorhabditis elegans against ingested pathogens. Because nematodes consume microorganisms as their food source, there has presumably been selection pressure to evolve and maintain immune defense mechanisms within the intestinal epithelium. Here we review recent advances that further define the immune signaling network within these cells and suggest mechanisms used by the nematode to monitor for infection. In reviewing stud...

  15. In vitro function of cyst epithelium from human polycystic kidney.

    OpenAIRE

    Perrone, R D

    1985-01-01

    It is thought that cysts in polycystic kidneys originate from nephron segments and function in a manner similar to the segment or origin. The indirect evidence for this derives from studies of microanatomy and cyst fluid composition. Cysts with low Na+ have been classified as distal, whereas cysts with high Na+ have been classified as proximal. In order to directly determine the transport characteristics of cyst epithelium, cysts from a human polycystic kidney were studied in vitro using Ussi...

  16. Early interactions of non-typhoidal Salmonella with human epithelium

    OpenAIRE

    Fang, S. -B

    2011-01-01

    Non-typhoidal Salmonella is an important bacterial pathogen causing worldwide morbidity and mortality. Early interactions between Salmonella Typhimurium and intestinal epithelium have been demonstrated in animal models, but little is known in humans. The aims of this thesis were to a) establish in vitro and ex vivo models to study such interactions, b) seek evidence of Salmonella invasion in human tissues in vivo, and c) identify virulence genes responsible for Salmonella adher...

  17. Zinc uptake in vitro by human retinal pigment epithelium

    International Nuclear Information System (INIS)

    Zinc, an essential trace element, is present in unusually high concentrations in the chorioretinal complex relative to most other tissues. Because little has been known about the interactions between the retinal pigment epithelium and free or protein-associated zinc, we studied 65Zn uptake by human retinal pigment epithelium in vitro. When monolayers were exposed to differing concentrations from 0 to 30 microM 65Zn in Dulbecco's modified Eagle's medium with 5.4 gm/l glucose at 37 degrees C and 4 degrees C, we observed a temperature-dependent saturable accumulation of the radiolabel. With 15 microM 65Zn, we saw a biphasic pattern of uptake with a rapid first phase and a slower second phase over 120 min. Uptake of 65Zn was inhibited by iodacetate and cold, and reduced approximately 50% by the addition of 2% albumin to the labelling medium. Neither ouabain nor 2-deoxyglucose inhibited uptake. Cells previously exposed to 65Zn retained approximately 70% of accumulated 65Zn 60 min after being changed to radiolabel-free medium. Following removal of cells from the extracellular matrix adherent to the dish bottom, a variable amount of nonspecific binding of 65Zn to the residual matrix was demonstrated. These observations are consistent with a facilitated type of transport and demonstrate the ability of human retinal pigment epithelium in vitro to accumulate and retain zinc

  18. Asthma-like symptoms, atopy, and bronchial responsiveness in furniture workers

    OpenAIRE

    Talini, D.; Monteverdi, A.; Benvenuti, A.(INFN Sezione di Bologna, Bologna, Italy); Petrozzino, M.; Di, P; M. Lemmi; Carletti, A.; P. Macchioni; Serretti, N.; Viegi, G; Paggiaro, P.

    1998-01-01

    OBJECTIVES: To study the role of individual and occupational risk factors for asthma in furniture workers. METHODS: 296 workers were examined (258 men, 38 women) with a questionnaire of respiratory symptoms and diseases, baseline spirometry, bronchial provocative test with methacholine, and skin prick tests. Non-specific bronchial hyperreactivity was defined as when a provocative dose with a fall of 20% in forced expiratory volume in 1 second (PD20FEV1) was < 0.8 mg and atopy in the pre...

  19. Bronchial Anthracotic Change in South Khorasan Province (Iran), Emphasizing its Association with Tuberculosis

    OpenAIRE

    Sayyed Gholamreza Mortazavi-Moghaddam; Sayyed Alireza Saadatjoo

    2014-01-01

    Background: There are many reports on the association between anthracosis and tuberculosis. This study focuses on bronchial anthracosis and associated diseases in the province of South Khorasan-Iran. Methods: This case-series study is performed on patients referred to the Vali-e-Asre Hospital (South Khorasan-Iran) for bronchoscopic evaluations during the period of 2009-2012. Written informed consents were obtained prior to bronchoscopic evaluations. The criterion for diagnosis of bronchial...

  20. DNA Extraction from Bronchial Aspirates for Molecular Cytology: Which Method to Take?

    OpenAIRE

    Grote, Hans Jürgen; Schmiemann, Viola; Sarbia, Mario; Böcking, Alfred

    2003-01-01

    Objective: To date, there are only few systematic reports on the quality of DNA extracted from routine diagnostic cytologic specimens. It was the aim of the present study to evaluate the ability of 50% ethanol/2% carbowax (Saccomanno fixative) to preserve bronchial secretions with high quality genomic DNA as well as to compare different DNA extraction methods. Methods: DNA was extracted from 45 bronchial aspirates by four different extraction protocols. Beside DNA yield, DNA quality with rega...