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Sample records for lung tissue density

  1. Lung density

    DEFF Research Database (Denmark)

    Garnett, E S; Webber, C E; Coates, G

    1977-01-01

    The density of a defined volume of the human lung can be measured in vivo by a new noninvasive technique. A beam of gamma-rays is directed at the lung and, by measuring the scattered gamma-rays, lung density is calculated. The density in the lower lobe of the right lung in normal man during quiet...... breathing in the sitting position ranged from 0.25 to 0.37 g.cm-3. Subnormal values were found in patients with emphsema. In patients with pulmonary congestion and edema, lung density values ranged from 0.33 to 0.93 g.cm-3. The lung density measurement correlated well with the findings in chest radiographs...... but the lung density values were more sensitive indices. This was particularly evident in serial observations of individual patients....

  2. Smooth muscle myosin regulation by serum and cell density in cultured rat lung connective tissue cells.

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    Babij, P; Zhao, J; White, S; Woodcock-Mitchell, J; Mitchell, J; Absher, M; Baldor, L; Periasamy, M; Low, R B

    1993-08-01

    RNA and protein analyses were used to detect expression of SM1 and SM2 smooth muscle myosin heavy chain (MHC) in cultured adult rat lung connective tissue cells (RL-90). Smooth muscle MHC mRNA expression in confluent cells grown in 10% serum was approximately 50% of the level in adult stomach. Similar results were obtained in cells cultured at low density (25% confluency) in 1% serum. However, in low-density cultures transferred to 10% serum for 24 h, the level of MHC mRNA decreased to approximately 20% of that in adult stomach. Smooth muscle alpha-actin showed a pattern of expression similar to that for smooth muscle MHC. Expression of nonmuscle MHC-A mRNA was higher in all culture conditions compared to stomach. MHC-A mRNA expression was less in low-density cultures in low serum and increased when low-density cultures were transferred to 10% serum for 24 h. MHC-B mRNA expression was less in low- vs. high-density cultures. In contrast to MHC-A, however, MHC-B mRNA expression in low-density cultures was higher in low serum. Immunofluorescence and immunoblotting with SM1-specific antibody demonstrated the presence of the SM1 protein isoform as well as reactivity to a protein band migrating slightly faster than SM2. These results demonstrate that cultured rat lung connective tissue cells express smooth muscle MHC and that expression is modulated by culture conditions.

  3. TBI lung dose comparisons using bilateral and anteroposterior delivery techniques and tissue density corrections.

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    Bailey, Daniel W; Wang, Iris Z; Lakeman, Tara; Hales, Lee D; Singh, Anurag K; Podgorsak, Matthew B

    2015-03-08

    This study compares lung dose distributions for two common techniques of total body photon irradiation (TBI) at extended source-to-surface distance calculated with, and without, tissue density correction (TDC). Lung dose correction factors as a function of lateral thorax separation are approximated for bilateral opposed TBI (supine), similar to those published for anteroposterior-posteroanterior (AP-PA) techniques in AAPM Report 17 (i.e., Task Group 29). 3D treatment plans were created retrospectively for 24 patients treated with bilateral TBI, and for whom CT data had been acquired from the head to the lower leg. These plans included bilateral opposed and AP-PA techniques- each with and without - TDC, using source-to-axis distance of 377 cm and largest possible field size. On average, bilateral TBI requires 40% more monitor units than AP-PA TBI due to increased separation (26% more for 23 MV). Calculation of midline thorax dose without TDC leads to dose underestimation of 17% on average (standard deviation, 4%) for bilateral 6 MV TBI, and 11% on average (standard deviation, 3%) for 23 MV. Lung dose correction factors (CF) are calculated as the ratio of midlung dose (with TDC) to midline thorax dose (without TDC). Bilateral CF generally increases with patient separation, though with high variability due to individual uniqueness of anatomy. Bilateral CF are 5% (standard deviation, 4%) higher than the same corrections calculated for AP-PA TBI in the 6 MV case, and 4% higher (standard deviation, 2%) for 23 MV. The maximum lung dose is much higher with bilateral TBI (up to 40% higher than prescribed, depending on patient anatomy) due to the absence of arm tissue blocking the anterior chest. Dose calculations for bilateral TBI without TDC are incorrect by up to 24% in the thorax for 6 MV and up to 16% for 23 MV. Bilateral lung CF may be calculated as 1.05 times the values published in Table 6 of AAPM Report 17, though a larger patient pool is necessary to better

  4. Comparison of Radiation-Induced Normal Lung Tissue Density Changes for Patients From Multiple Institutions Receiving Conventional or Hypofractionated Treatments

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    Diot, Quentin, E-mail: quentin.diot@ucdenver.edu [Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado (United States); Marks, Lawrence B. [Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina (United States); Bentzen, Soren M. [Division of Biostatistics and Bioinformatics, University of Maryland Greenbaum Cancer Center, and Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland (United States); Senan, Suresh [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Kavanagh, Brian D. [Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado (United States); Lawrence, Michael V. [Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina (United States); Miften, Moyed [Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado (United States); Palma, David A. [London Regional Cancer Program, London, Ontario (Canada)

    2014-07-01

    Purpose: To quantitatively assess changes in computed tomography (CT)–defined normal lung tissue density after conventional and hypofractionated radiation therapy (RT). Methods and Materials: The pre-RT and post-RT CT scans from 118 and 111 patients receiving conventional and hypofractionated RT, respectively, at 3 institutions were registered to each other and to the 3-dimensional dose distribution to quantify dose-dependent changes in normal lung tissue density. Dose-response curves (DRC) for groups of patients receiving conventional and hypofractionated RT were generated for each institution, and the frequency of density changes >80 Hounsfield Units (HU) was modeled depending on the fractionation type using a Probit model for different follow-up times. Results: For the pooled data from all institutions, there were significant differences in the DRC between the conventional and hypofractionated groups; the respective doses resulting in 50% complication risk (TD{sub 50}) were 62 Gy (95% confidence interval [CI] 57-67) versus 36 Gy (CI 33-39) at <6 months, 48 Gy (CI 46-51) versus 31 Gy (CI 28-33) at 6-12 months, and 47 Gy (CI 45-49) versus 35 Gy (32-37) at >12 months. The corresponding m values (slope of the DRC) were 0.52 (CI 0.46-0.59) versus 0.31 (CI 0.28-0.34) at <6 months, 0.46 (CI 0.42-0.51) versus 0.30 (CI 0.26-0.34) at 6-12 months, and 0.45 (CI 0.42-0.50) versus 0.31 (CI 0.27-0.35) at >12 months (P<.05 for all comparisons). Conclusion: Compared with conventional fractionation, hypofractionation has a lower TD{sub 50} and m value, both suggesting an increased degree of normal tissue density sensitivity with hypofractionation.

  5. Iron deposition and increased alveolar septal capillary density in nonfibrotic lung tissue are associated with pulmonary hypertension in idiopathic pulmonary fibrosis

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    Bartholmai Brian J

    2010-04-01

    Full Text Available Abstract Background Early diagnosis of pulmonary hypertension (PH in idiopathic pulmonary fibrosis (IPF has potential prognostic and therapeutic implications but can be difficult due to the lack of specific clinical manifestations or accurate non-invasive tests. Histopathologic parameters correlating with PH in IPF are also not known. Remodeling of postcapillary pulmonary vessels has been reported in the nonfibrotic areas of explanted lungs from IPF patients. We hypothesized that iron deposition and increased alveolar capillaries, the findings often seen in postcapillary PH, might predict the presence of clinical PH, independent of the severity of fibrosis or ventilatory dysfunction in IPF patients. To test this hypothesis, we examined the association between these histologic parameters and the degree of PH, with consideration of the severity of disease in IPF. Methods Iron deposition and alveolar septal capillary density (ASCD were evaluated on histologic sections with hematoxylin-eosin, iron, elastin and CD34 stainings. Percentage of predicted forced vital capacity (FVC% was used for grading pulmonary function status. Fibrosis score assessed on high resolution computed tomography (HRCT was used for evaluating overall degree of fibrosis in whole lungs. Right ventricular systolic pressure (RVSP by transthoracic echocardiography was used for the estimation of PH. Univariate and multivariate regression analyses were performed. Results A cohort of 154 patients was studied who had the clinicopathological diagnosis of IPF with surgical lung biopsies or explants during the period of 1997 to 2006 at Mayo Clinic Rochester. In univariate analysis, RVSP in our IPF cases was associated with both iron deposition and ASCD (p Conclusions Iron deposition and ASCD in non fibrotic lung tissue showed an association with RVSP, suggesting that these features are possible morphologic predictors of PH in IPF.

  6. Increased mean lung density: Another independent predictor of lung cancer?

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    Sverzellati, Nicola, E-mail: nicola.sverzellati@unipr.it [Department of Department of Surgical Sciences, Section of Diagnostic Imaging, University of Parma, Padiglione Barbieri, University Hospital of Parma, V. Gramsci 14, 43100 Parma (Italy); Randi, Giorgia, E-mail: giorgia.randi@marionegri.it [Department of Epidemiology, Mario Negri Institute, Via La Masa 19, 20156 Milan (Italy); Spagnolo, Paolo, E-mail: paolo.spagnolo@unimore.it [Respiratory Disease Unit, Center for Rare Lung Disease, Department of Oncology, Hematology and Respiratory Disease, University of Modena and Reggio Emilia, Via del Pozzo 71, 44124 Modena (Italy); Marchianò, Alfonso, E-mail: alfonso.marchiano@istitutotumori.mi.it [Department of Radiology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan (Italy); Silva, Mario, E-mail: mac.mario@hotmail.it [Department of Department of Surgical Sciences, Section of Diagnostic Imaging, University of Parma, Padiglione Barbieri, University Hospital of Parma, V. Gramsci 14, 43100 Parma (Italy); Kuhnigk, Jan-Martin, E-mail: Jan-Martin.Kuhnigk@mevis.fraunhofer.de [Fraunhofer MEVIS, Universitaetsallee 29, 28359 Bremen (Germany); La Vecchia, Carlo, E-mail: carlo.lavecchia@marionegri.it [Department of Occupational Health, University of Milan, Via Venezian 1, 20133 Milan (Italy); Zompatori, Maurizio, E-mail: maurizio.zompatori@unibo.it [Department of Radiology, Cardio-Thoracic Section, S. Orsola-Malpighi Hospital, Via Albertoni 15, 40138 Bologna (Italy); Pastorino, Ugo, E-mail: ugo.pastorino@istitutotumori.mi.it [Department of Surgery, Section of Thoracic Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan (Italy)

    2013-08-15

    Objectives: To investigate the relationship between emphysema phenotype, mean lung density (MLD), lung function and lung cancer by using an automated multiple feature analysis tool on thin-section computed tomography (CT) data. Methods: Both emphysema phenotype and MLD evaluated by automated quantitative CT analysis were compared between outpatients and screening participants with lung cancer (n = 119) and controls (n = 989). Emphysema phenotype was defined by assessing features such as extent, distribution on core/peel of the lung and hole size. Adjusted multiple logistic regression models were used to evaluate independent associations of CT densitometric measurements and pulmonary function test (PFT) with lung cancer risk. Results: No emphysema feature was associated with lung cancer. Lung cancer risk increased with decreasing values of forced expiratory volume in 1 s (FEV{sub 1}) independently of MLD (OR 5.37, 95% CI: 2.63–10.97 for FEV{sub 1} < 60% vs. FEV{sub 1} ≥ 90%), and with increasing MLD independently of FEV{sub 1} (OR 3.00, 95% CI: 1.60–5.63 for MLD > −823 vs. MLD < −857 Hounsfield units). Conclusion: Emphysema per se was not associated with lung cancer whereas decreased FEV{sub 1} was confirmed as being a strong and independent risk factor. The cross-sectional association between increased MLD and lung cancer requires future validations.

  7. [Human lung connective tissue in postnatal ontogeny].

    Science.gov (United States)

    Kasimtsev, A A; Nikolaev, V G

    1993-01-01

    Changes of the connective tissue structures, appearing during all postnatal ontogenesis stages were studied in 147 human lung specimens of different age groups (from newborns up to 82-year-olds). Qualitative and quantitative composition of connective tissue structures changes with the age which leads to the lateral aggregation of the fibers and growth of the general mass of the connective tissue. Heterochronia of the age variability manifestations in different regions of the lung framework was demonstrated. The original age transformations of connective tissue structures are characteristic for the basal lung regions. With the exception of perivasal connective tissue, similar changes in the region of the lung apexes appear 3-5 years later. This gives an opportunity to distinguish three anatomic zones in the lungs in an apico-basal direction, characterising the local nature of the age changes manifestations.

  8. Lung tissue classification using wavelet frames.

    Science.gov (United States)

    Depeursinge, Adrien; Sage, Daniel; Hidki, Asmâa; Platon, Alexandra; Poletti, Pierre-Alexandre; Unser, Michael; Müller, Henning

    2007-01-01

    We describe a texture classification system that identifies lung tissue patterns from high-resolution computed tomography (HRCT) images of patients affected with interstitial lung diseases (ILD). This pattern recognition task is part of an image-based diagnostic aid system for ILDs. Five lung tissue patterns (healthy, emphysema, ground glass, fibrosis and microdules) selected from a multimedia database are classified using the overcomplete discrete wavelet frame decompostion combined with grey-level histogram features. The overall multiclass accuracy reaches 92.5% of correct matches while combining the two types of features, which are found to be complementary.

  9. Method for calculating dose when lung tissue lies in the treatment field

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    McDonald, S.C.; Keller, B.E.; Rubin, P.

    1976-07-01

    The absorbed dose in lung and beyond lung as a result of increased lung transmission of x and ..gamma.. irradiation is described. The correction factor used to calculate the absorbed dose is a function of beam energy, field area, lung density, and lung and soft tissue depth. Agreement between measurements and calculations in the Alderson phantom is within 3%. An example of how this technique can be used is described. (AIP)

  10. Analysis of lung density by computed tomography before and during general anaesthesia.

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    Hachenberg, T; Lundquist, H; Tokics, L; Brismar, B; Hedenstierna, G

    1993-08-01

    Pulmonary structure was analysed by means of computed tomography (CT) in 20 lung-healthy patients, relating tissue density to the attenuation value (AV) of a picture element. Regional density of pulmonary tissue (rlung) was determined using mean lung density in five regions of interest (ROI1-5) (sector method). Vertical and horizontal distributions of x-ray attenuation were analysed by density profiles, relating AV values to evenly distributed and normalised length scales. In group I (n = 12), CT-densitometry was obtained in awake, supine patients and after induction of general anaesthesia. In group II (n = 8), the effect of mechanical ventilation with positive end-expiratory pressure (PEEP, 1.0 kPa [10 cmH2O]) was studied. In the awake state, a vertical tissue density difference between the top and bottom of the lung was found in all patients, accounting for a mean of 0.235 g.cm-3 (right lung) and 0.199 g.cm-3 (left lung). Only minor changes were seen in the horizontal lung density profiles. After induction of anaesthesia, x-ray attenuation of ROI1-4 showed no significant differences when compared with the awake state. The basal lung areas (ROI5) revealed a significantly increased tissue density (P < or = 0.01), reaching mean values of 0.94 g.cm-3 (right lung) and 0.814 g.cm-3 (left lung). Similarly, vertical density profiles showed a markedly enhanced rlung of the bottom of the lung in all patients, interpreted as atelectasis. The amount of atelectasis accounted for 4.8 +/- 2.6% (right lung) and 4.7 +/- 2.1% (left lung) of the intrapulmonary area.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Lung involvement in systemic connective tissue diseases

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    Plavec Goran

    2008-01-01

    Full Text Available Background/Aim. Systemic connective tissue diseases (SCTD are chronic inflammatory autoimmune disorders of unknown cause that can involve different organs and systems. Their course and prognosis are different. All of them can, more or less, involve the respiratory system. The aim of this study was to find out the frequency of respiratory symptoms, lung function disorders, radiography and high-resolution computerized tomography (HRCT abnormalities, and their correlation with the duration of the disease and the applied treatment. Methods. In 47 non-randomized consecutive patients standard chest radiography, HRCT, and lung function tests were done. Results. Hypoxemia was present in nine of the patients with respiratory symptoms (20%. In all of them chest radiography was normal. In five of these patients lung fibrosis was established using HRCT. Half of all the patients with SCTD had symptoms of lung involvement. Lung function tests disorders of various degrees were found in 40% of the patients. The outcome and the degree of lung function disorders were neither in correlation with the duration of SCTD nor with therapy used (p > 0.05 Spearmans Ro. Conclusion. Pulmonary fibrosis occurs in about 10% of the patients with SCTD, and possibly not due to the applied treatment regimens. Hypoxemia could be a sing of existing pulmonary fibrosis in the absence of disorders on standard chest radiography.

  12. Analysis of Lung Tissue Using Ion Beams

    Science.gov (United States)

    Alvarez, J. L.; Barrera, R.; Miranda, J.

    2002-08-01

    In this work a comparative study is presented of the contents of metals in lung tissue from healthy patients and with lung cancer, by means of two analytical techniques: Particle Induced X-ray Emission (PIXE) and Rutherford Backscattering Spectrometry (RBS). The samples of cancerous tissue were taken from 26 autopsies made to individuals died in the National Institute of Respiratory Disease (INER), 22 of cancer and 4 of other non-cancer biopsies. When analyzing the entirety of the samples, in the cancerous tissues, there were increments in the concentrations of S (4%), K (635%), Co (85%) and Cu (13%). Likewise, there were deficiencies in the concentrations of Cl (59%), Ca (6%), Fe (26%) and Zn (7%). Only in the cancerous tissues there were appearances of P, Ca, Ti, V, Cr, Mn, Ni, Br and Sr. The tissue samples were classified according to cancer types (adenocarcinomas, epidermoides and of small cell carcinoma), personal habits (smokers and alcoholic), genetic predisposition and residence place. There was a remarkable decrease in the concentration of Ca and a marked increment in the Cu in the epidermoide tissue samples with regard to those of adenocarcinoma or of small cells cancer. Also, decrements were detected in K and increments of Fe, Co and Cu in the sample belonging to people that resided in Mexico City with regard to those that resided in the State of Mexico.

  13. Rapid fall in lung density following smoking cessation in COPD

    DEFF Research Database (Denmark)

    Shaker, Saher B; Stavngaard, Trine; Laursen, Lars Christian

    2011-01-01

    Whether smoking-induced lung inflammation subsides after smoking cessation is currently a matter of debate. We used computed tomography (CT) to evaluate the effect of smoking cessation on lung density in patients with COPD.......Whether smoking-induced lung inflammation subsides after smoking cessation is currently a matter of debate. We used computed tomography (CT) to evaluate the effect of smoking cessation on lung density in patients with COPD....

  14. Rapid fall in lung density following smoking cessation in COPD

    DEFF Research Database (Denmark)

    Shaker, Saher B; Stavngaard, Trine; Laursen, Lars Christian;

    2011-01-01

    Whether smoking-induced lung inflammation subsides after smoking cessation is currently a matter of debate. We used computed tomography (CT) to evaluate the effect of smoking cessation on lung density in patients with COPD.......Whether smoking-induced lung inflammation subsides after smoking cessation is currently a matter of debate. We used computed tomography (CT) to evaluate the effect of smoking cessation on lung density in patients with COPD....

  15. A classification framework for lung tissue categorization

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    Depeursinge, Adrien; Iavindrasana, Jimison; Hidki, Asmâa; Cohen, Gilles; Geissbuhler, Antoine; Platon, Alexandra; Poletti, Pierre-Alexandre; Müller, Henning

    2008-03-01

    We compare five common classifier families in their ability to categorize six lung tissue patterns in high-resolution computed tomography (HRCT) images of patients affected with interstitial lung diseases (ILD) but also normal tissue. The evaluated classifiers are Naive Bayes, k-Nearest Neighbor (k-NN), J48 decision trees, Multi-Layer Perceptron (MLP) and Support Vector Machines (SVM). The dataset used contains 843 regions of interest (ROI) of healthy and five pathologic lung tissue patterns identified by two radiologists at the University Hospitals of Geneva. Correlation of the feature space composed of 39 texture attributes is studied. A grid search for optimal parameters is carried out for each classifier family. Two complementary metrics are used to characterize the performances of classification. Those are based on McNemar's statistical tests and global accuracy. SVM reached best values for each metric and allowed a mean correct prediction rate of 87.9% with high class-specific precision on testing sets of 423 ROIs.

  16. (18)FDG uptake associated with CT density on PET/CT in lungs with and without chronic interstitial lung diseases.

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    Inoue, Kentaro; Okada, Ken; Taki, Yasuyuki; Goto, Ryoi; Kinomura, Shigeo; Fukuda, Hiroshi

    2009-05-01

    The dependent-density of computed tomography (CT) images of positron emission tomography (PET)/CT is sometimes difficult to distinguish from chronic interstitial lung disease (ILD) when it accompanies increased (18)F-fluorodeoxy-D: -glucose ((18)FDG) uptake. Though the possible utility of (18)FDG-PET for the diagnosis of active ILD has been reported, the clinical relevance of mild lung (18)FDG uptake in ILD cases without signs and symptoms suggesting acute progression has not been described. This study aimed to test relationships between (18)FDG uptake and lung density on CT using PET/CT in patients with normal lung as well as clinically stable chronic ILD. Thirty-six patients with normal lungs (controls) and 28 patients with chronic ILD (ILD cases) without acute exacerbation were retrospectively selected from (18)FDG-PET/CT scans performed in examination of malignant neoplasms. Elliptical regions of interest (ROIs) were placed on the lung. The relationships between CT density and (18)FDG uptake between the control and ILD cases were tested. The CT density and (18)FDG uptake had a linear correlation in both the controls and the ILD cases without a difference in their regression slopes, and they were overlapped between the controls and the ILD cases with higher mean values in the ILD cases. Lung (18)FDG uptake was considered to reflect a gravity-dependent tissue density in the normal lung. Though the lung (18)FDG uptake as well as the CT density tended to be higher in chronic ILD patients, it may be difficult to distinguish them in normal dependent regions from those related to chronic ILD in some cases.

  17. Expression of PAH-DNA Adducts in Lung Tissues of Xuanwei Female Lung Cancer Patients

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    Kun WANG

    2010-05-01

    Full Text Available Background and objective The coal-fired pollution in Xuanwei area has been considered to be local main reason for high incidence of female lung cancer. The aim of this study is to explore the expression of PAH-DNA adducts in lung tissues of Xuanwei female lung cancer patients and to explore the relationship between the large number of coal-fired pollution PAHs materials and the high incidence of Xuanwei female lung cancer. Methods We totally collected each 20 cases of Xuanwei female lung cancer patients, Xuanwei male lung cancer patients, Non-Xuanwei female lung cancer patients and collect each 10 cases of Xuanwei, Non-Xuanwei female patients with benign lung lesions. The cancer tissues, adjacent cancer tissues and normal lung tissues were collected in lung cancer patients and only the normal tissues were collected in benign lung lesion patients. There were total 80 cases and 200 tissues. Immunofluorescence was used to detect the expression of PAHDNA adducts in each group. Image pro-plus 6.0 software was used to analyze the images and part quantified analysis. SPSS 13.0 statistical software was used to analyze the data. Results The positive expression of PAH-DNA adducts in lung cancer tissues, adjacent cancer tissues and normal lung tissues of Xuanwei female lung cancer patients were 90%, 80% and 65%. They were higher than the positive expression of PAH-DNA adducts in Xuanwei male lung cancer patients (35%, 30%, 30% and Non-Xuanwei female lung cancer patients (20%, 15%, 10%(P 0.05. Conclusion The expressions of PAHDNA adducts in lung tissues of Xuanwei female were higher than which in Xuanwei male and Non-Xuanwei female.

  18. Comparison of lung alveolar and tissue cells in silica-induced inflammation.

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    Sjöstrand, M; Absher, P M; Hemenway, D R; Trombley, L; Baldor, L C

    1991-01-01

    The silicon dioxide mineral, cristobalite (CRS) induces inflammation involving both alveolar cells and connective tissue compartments. In this study, we compared lung cells recovered by whole lung lavage and by digestion of lung tissue from rats at varying times after 8 days of exposure to aerosolized CRS. Control and exposed rats were examined between 2 and 36 wk after exposure. Lavaged cells were obtained by bronchoalveolar lavage with phosphate-buffered saline. Lung wall cells were prepared via collagenase digestion of lung tissue slices. Cells from lavage and lung wall were separated by Percoll density centrifugation. The three upper fractions, containing mostly macrophages, were cultured, and the conditioned medium was assayed for effect on lung fibroblast growth and for activity of the lysosomal enzyme, N-acetyl-beta-D-glucosaminidase. Results demonstrated that the cells separated from the lung walls exhibited different reaction patterns compared with those cells recovered by lavage. The lung wall cells exhibited a progressive increase in the number of macrophages and lymphocytes compared with a steady state in cells of the lung lavage. This increase in macrophages apparently was due to low density cells, which showed features of silica exposure. Secretion of a fibroblast-stimulating factor was consistently high by lung wall macrophages, whereas lung lavage macrophages showed inconsistent variations. The secretion of NAG was increased in lung lavage macrophages, but decreased at most observation times in lung wall macrophages. No differences were found among cells in the different density fractions regarding fibroblast stimulation and enzyme secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Computational fluid dynamics modeling of airflow inside lungs using heterogenous anisotropic lung tissue elastic properties.

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    Ilegbusi, Olusegun; Li, Ziang; Min, Yugang; Meeks, Sanford; Kupelian, Patrick; Santhanam, Anand P

    2012-01-01

    The aim of this paper is to model the airflow inside lungs during breathing and its fluid-structure interaction with the lung tissues and the lung tumor using subject-specific elastic properties. The fluid-structure interaction technique simultaneously simulates flow within the airway and anisotropic deformation of the lung lobes. The three-dimensional (3D) lung geometry is reconstructed from the end-expiration 3D CT scan datasets of humans with lung cancer. The lung is modeled as a poro-elastic medium with anisotropic elastic property (non-linear Young's modulus) obtained from inverse lung elastography of 4D CT scans for the same patients. The predicted results include the 3D anisotropic lung deformation along with the airflow pattern inside the lungs. The effect is also presented of anisotropic elasticity on both the spatio-temporal volumetric lung displacement and the regional lung hysteresis.

  20. Factors influencing the decline in lung density in a Danish lung cancer screening cohort

    DEFF Research Database (Denmark)

    Shaker, Saher B.; Dirksen, Asger; Lo, Pechin Chien Pau;

    2012-01-01

    Lung cancer screening trials provide an opportunity to study the natural history of emphysema by using CT lung density as a surrogate parameter.In the Danish Lung Cancer Screening Trial, 2,052 participants were included. At screening rounds, smoking habits were recorded and spirometry was performed...

  1. Lung density on high resolution computer tomography (HRCT) reflects degree of inflammation in smokers

    Science.gov (United States)

    2014-01-01

    Background Smokers have increased cell concentration in the lower respiratory tract indicating a chronic inflammatory state, which in some individuals may lead to development of chronic obstructive pulmonary disease (COPD). Computer tomography (CT) imaging provides means of quantifying pulmonary structure and early signs of disease. We investigated whether lung density on high resolution CT differs between smokers and never-smokers and if this were associated to intensity of inflammation. Methods Forty smoking volunteers with normal pulmonary function, 40 healthy never-smokers and 40 patients with COPD of GOLD stage I-II, were included. Mean lung attenuation and percentage of pixels in the lung with attenuation between −750 and −900 HU (percentage higher density spectrum (%HDS)) were calculated on inspiratory CT-scans. Markers of systemic inflammation in blood and cell counts in bronchoalveolar lavage (BAL) fluid were recorded. Results Lung density expressed as %HDS was increased in smokers (44.0 ± 5.8%) compared to both never-smokers (38.3 ± 5.8%) and patients with COPD (39.1 ± 5.8%), (p lungs than males, which was dependent on body height. Cell concentration in BAL were correlated to lung density in smokers (r = 0.50, p Lung density on CT is associated with cell concentration in BAL in smokers and may mirror an inflammatory response in the lung. Gender difference in lung density is dependent on height. In COPD with emphysema, loss of lung tissue may counterbalance the expected increase in density due to inflammation. The findings may help to interpret high resolution CT in the context of smoking and gender and highlight the heterogeneity of structural changes in COPD. PMID:24564813

  2. Expression of BCRP Gene in the Normal Lung Tissue and Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To investigate the expression of novel multidrugresistance transporter (BCRP gene) from human MCF-7/AdrVp breast cancer cells in normal lung tissue and non-small lung cancer tissue. Methods: RNA was extracted immediately from fresh normal lung tissue and viable tumor tissue harvested from surgically resected specimens of non-small cell lung cancer patients. cDNA of BCRP gene was prepared by RT-PCR and was then amplified by PCR. cDNA products from those specimens were transferred to blotting membrane through electrophoresis and transferring technique and southern blot hybridization was eventually performed to detect the expression of BCRP gene. Results: RNA were extracted from 8 tumor tissue alone and 12 pairs of tumor tissue and normal lung tissue harvested from the same lung. Four patients' RNA samples with poor quality due to degrading were discarded. cDNA products of BCRP gene were obtained by RT-PCR and were then amplified by PCR in the remain 16 patients' RNA samples. Through southern blot hybridization, BCRP gene was found to be slightly expressed in various amounts in all normal lung tissue (10/10) and only in a half of tumor tissue samples (8/16). Conclusion: BCRP gene is slightly expressed in different amount in all normal lung tissue and only in a half of tumor tissue of non-small cell lung cancer patients. It is possible to induce it's overexpression and to develop multidrug resistance during chemotherapy if using anthracycline anticancer drugs.

  3. Characterizing human lung tissue microbiota and its relationship to epidemiological and clinical features.

    Science.gov (United States)

    Yu, Guoqin; Gail, Mitchell H; Consonni, Dario; Carugno, Michele; Humphrys, Michael; Pesatori, Angela C; Caporaso, Neil E; Goedert, James J; Ravel, Jacques; Landi, Maria Teresa

    2016-07-28

    The human lung tissue microbiota remains largely uncharacterized, although a number of studies based on airway samples suggest the existence of a viable human lung microbiota. Here we characterized the taxonomic and derived functional profiles of lung microbiota in 165 non-malignant lung tissue samples from cancer patients. We show that the lung microbiota is distinct from the microbial communities in oral, nasal, stool, skin, and vagina, with Proteobacteria as the dominant phylum (60 %). Microbiota taxonomic alpha diversity increases with environmental exposures, such as air particulates, residence in low to high population density areas, and pack-years of tobacco smoking and decreases in subjects with history of chronic bronchitis. Genus Thermus is more abundant in tissue from advanced stage (IIIB, IV) patients, while Legionella is higher in patients who develop metastases. Moreover, the non-malignant lung tissues have higher microbiota alpha diversity than the paired tumors. Our results provide insights into the human lung microbiota composition and function and their link to human lifestyle and clinical outcomes. Studies among subjects without lung cancer are needed to confirm our findings.

  4. Molecular Signature of Smoking in Human Lung Tissues

    NARCIS (Netherlands)

    Bosse, Yohan; Postma, Dirkje S.; Sin, Don D.; Lamontagne, Maxime; Couture, Christian; Gaudreault, Nathalie; Joubert, Philippe; Wong, Vivien; Elliott, Mark; van den Berge, Maarten; Brandsma, Corry A.; Tribouley, Catherine; Malkov, Vladislav; Tsou, Jeffrey A.; Opiteck, Gregory J.; Hogg, James C.; Sandford, Andrew J.; Timens, Wim; Pare, Peter D.; Laviolette, Michel

    2012-01-01

    Cigarette smoking is the leading risk factor for lung cancer. To identify genes deregulated by smoking and to distinguish gene expression changes that are reversible and persistent following smoking cessation, we carried out genome-wide gene expression profiling on nontumor lung tissue from 853 pati

  5. Lung Cancer Presenting as a Soft-Tissue Metastasis

    Directory of Open Access Journals (Sweden)

    Candice Baldeo

    2015-04-01

    Full Text Available Soft-tissue metastasis refers to the growth of cancer cells, originating from internal cancer, in soft tissues. In most cases, soft-tissue metastases develop after initial diagnosis of the primary internal malignancy and late in the course of the disease. In very rare cases, they may occur at the same time or before the primary cancer has been detected. In our cases, the soft-tissue metastases and the primary lung cancer were diagnosed at the same time.

  6. Standardizing CT lung density measure across scanner manufacturers.

    Science.gov (United States)

    Chen-Mayer, Huaiyu Heather; Fuld, Matthew K; Hoppel, Bernice; Judy, Philip F; Sieren, Jered P; Guo, Junfeng; Lynch, David A; Possolo, Antonio; Fain, Sean B

    2017-03-01

    Computed Tomography (CT) imaging of the lung, reported in Hounsfield Units (HU), can be parameterized as a quantitative image biomarker for the diagnosis and monitoring of lung density changes due to emphysema, a type of chronic obstructive pulmonary disease (COPD). CT lung density metrics are global measurements based on lung CT number histograms, and are typically a quantity specifying either the percentage of voxels with CT numbers below a threshold, or a single CT number below which a fixed relative lung volume, nth percentile, falls. To reduce variability in the density metrics specified by CT attenuation, the Quantitative Imaging Biomarkers Alliance (QIBA) Lung Density Committee has organized efforts to conduct phantom studies in a variety of scanner models to establish a baseline for assessing the variations in patient studies that can be attributed to scanner calibration and measurement uncertainty. Data were obtained from a phantom study on CT scanners from four manufacturers with several protocols at various tube potential voltage (kVp) and exposure settings. Free from biological variation, these phantom studies provide an assessment of the accuracy and precision of the density metrics across platforms solely due to machine calibration and uncertainty of the reference materials. The phantom used in this study has three foam density references in the lung density region, which, after calibration against a suite of Standard Reference Materials (SRM) foams with certified physical density, establishes a HU-electron density relationship for each machine-protocol. We devised a 5-step calibration procedure combined with a simplified physical model that enabled the standardization of the CT numbers reported across a total of 22 scanner-protocol settings to a single energy (chosen at 80 keV). A standard deviation was calculated for overall CT numbers for each density, as well as by scanner and other variables, as a measure of the variability, before and after the

  7. The importance of correction for tissue fraction effects in lung PET: preliminary findings

    Energy Technology Data Exchange (ETDEWEB)

    Lambrou, Tryphon; Groves, Ashley M.; Erlandsson, Kjell; Endozo, Raymondo; Hutton, Brian F. [University College London, Institute of Nuclear Medicine, London (United Kingdom); Screaton, Nick [Papworth Hospital, Radiology, Cambridge (United Kingdom); Win, Thida [Lister Hospital, Respiratory Medicine, Stevenage (United Kingdom); Porter, Joanna C. [University College London Hospitals NHS Trust, Centre for Respiratory Diseases, London (United Kingdom)

    2011-12-15

    It has recently been recognized that PET/CT may play a role in diffuse parenchymal lung disease. However, interpretation can be confounded due to the variability in lung density both within and between individuals. To address this issue a novel correction method is proposed. A CT scan acquired during shallow breathing is registered to a PET study and smoothed so as to match the PET resolution. This is used to derive voxel-based tissue fraction correction factors for the individual. The method was evaluated in a lung phantom study in which the lung was simulated by a Styrofoam/water mixture. The method was further evaluated using {sup 18}F-FDG in 12 subjects free from pulmonary disease where ranges before and after correction were considered. Correction resulted in similar activity concentrations for the lung and background regions, consistent with the experimental phantom set-up. Correction resulted in reduced inter- and intrasubject variability in the estimated SUV. The possible application of the method was further demonstrated in five subjects with interstitial lung changes where increased SUV was demonstrated. Single study pre- and post-treatment studies were also analysed to further illustrate the utility of the method. The proposed tissue fraction correction method is a promising technique to account for variability of density in interpreting lung PET studies. (orig.)

  8. Decellularization of human and porcine lung tissues for pulmonary tissue engineering.

    Science.gov (United States)

    O'Neill, John D; Anfang, Rachel; Anandappa, Annabelle; Costa, Joseph; Javidfar, Jeffrey; Wobma, Holly M; Singh, Gopal; Freytes, Donald O; Bacchetta, Matthew D; Sonett, Joshua R; Vunjak-Novakovic, Gordana

    2013-09-01

    The only definitive treatment for end-stage organ failure is orthotopic transplantation. Lung extracellular matrix (LECM) holds great potential as a scaffold for lung tissue engineering because it retains the complex architecture, biomechanics, and topologic specificity of the lung. Decellularization of human lungs rejected from transplantation could provide "ideal" biologic scaffolds for lung tissue engineering, but the availability of such lungs remains limited. The present study was designed to determine whether porcine lung could serve as a suitable substitute for human lung to study tissue engineering therapies. Human and porcine lungs were procured, sliced into sheets, and decellularized by three different methods. Compositional, ultrastructural, and biomechanical changes to the LECM were characterized. The suitability of LECM for cellular repopulation was evaluated by assessing the viability, growth, and metabolic activity of human lung fibroblasts, human small airway epithelial cells, and human adipose-derived mesenchymal stem cells over a period of 7 days. Decellularization with 3-[(3-Cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) showed the best maintenance of both human and porcine LECM, with similar retention of LECM proteins except for elastin. Human and porcine LECM supported the cultivation of pulmonary cells in a similar way, except that the human LECM was stiffer and resulted in higher metabolic activity of the cells than porcine LECM. Porcine lungs can be decellularized with CHAPS to produce LECM scaffolds with properties resembling those of human lungs, for pulmonary tissue engineering. We propose that porcine LECM can be an excellent screening platform for the envisioned human tissue engineering applications of decellularized lungs. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  9. The Field of Tissue Injury in the Lung and Airway

    OpenAIRE

    Steiling, Katrina; Ryan, John; Brody, Jerome S.; Spira, Avrum

    2008-01-01

    The concept of field cancerization was first introduced over six decades ago in the setting of oral cancer. Later, field cancerization involving histologic and molecular changes of neoplasms and adjacent tissue began to be characterized in smokers with or without lung cancer. Investigators also described a diffuse, non-neoplastic field of molecular injury throughout the respiratory tract that is attributable to cigarette smoking and susceptibility to smoking-induced lung disease. The potentia...

  10. Comparative Proteome Analysis of Human Lung Squamous Carcinoma Tissue

    Institute of Scientific and Technical Information of China (English)

    LI Cui; TANG Can'e; DUAN Chaojun; YI Hong; XIAO Zhiqiang; CHEN Zhuchu

    2006-01-01

    Objective: To establish the two-dimensional electrophoresis profiles with high resolution and reproducibility from human lung squamous carcinoma tissue and paired normal tumor-adjacent bronchial epithelial tissue, and to identify differential expression tumor-associated proteins by using proteome analysis. Methods: Comparative proteome analysis with 20 human lung squamous carcinoma tissues and the paired normal bronchial epithelial tissues adjacent to tumors was carried out. The total proteins of human lung squamous carcinoma tissue and paired normal tumor-adjacent bronchial epithelial tissue were separated by means of immobilized pH gradient-based two-dimensional gel electrophoresis (2-DE) and silver staining. The differential expression proteins were analyzed and then identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). Results: (1) Well-resolved, reproducible 2-DE patterns of human lung squamous carcinoma and adjacent normal bronchial epithelial tissues were obtained. For tumor tissue, average spots of 3 gels were 1567±46, and 1436±54 spots were matched with an average matching rate of 91.6%. For control, average spots of 3 gels were 1349±58, and 1228±35 spots were matched with an average matching rate of 91.03%. The average position deviation of matched spots was 0.924±0.128 mm in IEF direction, and 1.022±0.205 mm in SDS-PAGE direction; (2)A total of 1178±56 spots were matched between the electrophoretic maps of 20 human lung squamous carcinoma tissues and paired normal tumor-adjacent bronchial epithelial tissues. Seventy-six differentially expressed proteins were screened; (3) Sixty-eight differential proteins were identified by PMF, some proteins were the products of oncogenes, and others involved in the regulation of cell cycle and signal transduction;(4) In order to validate the reliability of the identified results, the expression of 3 proteins mdm2, c-jun and EGFR, which was correlated with lung

  11. Nuclear magnetic resonance relaxation times for human lung cancer and lung tissues

    Energy Technology Data Exchange (ETDEWEB)

    Matsuura, Yoshifumi; Shioya, Sumie; Kurita, Daisaku; Ohta, Takashi; Haida, Munetaka; Ohta, Yasuyo [Tokai Univ., Isehara, Kanagawa (Japan). School of Medicine; Suda, Syuichi; Fukuzaki, Minoru

    1994-12-01

    We investigated the nuclear magnetic resonance (NMR) relaxation times, T{sub 1} and T{sub 2}, for lung cancer tissue, and other samples of lung tissue obtained from surgical specimens. The samples were nine squamous cell carcinomas, five necrotic squamous cell carcinomas, 15 adenocarcinomas, two benign mesotheliomas, and 13 fibrotic lungs. The relaxation times were measured with a 90 MHz NMR spectrometer and the results were correlated with histological changes. The values of T{sub 1} and T{sub 2} for squamous cell carcinoma and mesothelioma were significantly longer than those of adenocarcinoma and fibrotic lung tissue. There were no significant differences in values of T{sub 1} and T{sub 2} between adenocarcinoma and lung tissue. The values of T{sub 1} and T{sub 2} for benign mesothelioma were similar to those of squamous cell carcinoma, which suggested that increases in T{sub 1} and T{sub 2} are not specific to malignant tissues. (author).

  12. The Field of Tissue Injury in the Lung and Airway

    Science.gov (United States)

    Steiling, Katrina; Ryan, John; Brody, Jerome S.; Spira, Avrum

    2009-01-01

    The concept of field cancerization was first introduced over six decades ago in the setting of oral cancer. Later, field cancerization involving histologic and molecular changes of neoplasms and adjacent tissue began to be characterized in smokers with or without lung cancer. Investigators also described a diffuse, non-neoplastic field of molecular injury throughout the respiratory tract that is attributable to cigarette smoking and susceptibility to smoking-induced lung disease. The potential molecular origins of field cancerization and the field of injury following cigarette smoke exposure in lung and airway epithelia are critical to understanding the impact of the field of injury on clinical diagnostics and therapeutics for smoking-induced lung disease. PMID:19138985

  13. Relationship between the Expression of E-cadherin and Microvessel Density in Lung Cancer and Its Significance

    Institute of Scientific and Technical Information of China (English)

    WANGXinyun; YANGJuhong; MAYing; CHENGBo; ZHENGHongwei; ZHENGHaiyan; ZHUCongzhong; LIUTing; LIYan; WANGAixiang; SUNCuiyun

    2005-01-01

    Objective: To study the relationship between the expression of E-cadherin and microvessel density (MVD) in lung cancer. Methods: The expression of E-cadherin and factor Ⅷ was detected in 104 lung cancer tissues by an immunohistochemical method, and MVD was calculated by an imageanalysis system. Results: The expression of E-cadherin was significantly related to the differentiation of lung cancers (P<0.05). A negative correlation was found between E-cadherin expression and MVD in lung cancer tissues (P=0.047). Conclusion: Down-expression of E-cadherin and an increase of MVD may play an important role in the invasion and metastasis of lung cancer, and may also be used as a useful marker for tumor prognosis.

  14. Perivascular fluid cuffs decrease lung compliance by increasing tissue resistance

    Science.gov (United States)

    Lowe, Kevin; Alvarez, Diego F.; King, Judy A.; Stevens, Troy

    2010-01-01

    Objective Lung inflammation causes perivascular fluid cuffs to form around extra-alveolar blood vessels; however, the physiologic consequences of such cuffs remain poorly understood. Herein, we tested the hypothesis that perivascular fluid cuffs, without concomitant alveolar edema, are sufficient to decrease lung compliance. Design Prospective, randomized, controlled study. Setting Research laboratory. Subjects One hundred twenty male CD40 rats. Interventions To test this hypothesis, the plant alkaloid thapsigargin was used to activate store-operated calcium entry and increase cytosolic calcium in endothelium. Thapsigargin was infused into a central venous catheter of intact, sedated, and mechanically ventilated rats. Measurements Static and dynamic lung mechanics and hemodynamics were measured continuously. Main Results Thapsigargin produced perivascular fluid cuffs along extra-alveolar vessels but did not cause alveolar flooding or blood gas abnormalities. Lung compliance dose-dependently decreased after thapsigargin infusion, attributable to an increase in tissue resistance that was attributed to increased tissue damping and tissue elastance. Airway resistance was not changed. Neither central venous pressure nor left ventricular end diastolic pressure was altered by thapsigargin. Heart rate did not change, although thapsigargin decreased pressure over time sufficient to reduce cardiac output by 50%. Infusion of the type 4 phosphodiesterase inhibitor, rolipram, prevented thapsigargin from inducing perivascular cuffs and decreasing lung compliance. Rolipram also normalized pressure over time and corrected the deficit in cardiac output. Conclusions Our findings resolve for the first time that perivascular cuff formation negatively impacts mechanical coupling between the bronchovascular bundle and the lung parenchyma, decreasing lung compliance without impacting central venous pressure. PMID:20400904

  15. Impact of Statins on Gene Expression in Human Lung Tissues.

    Directory of Open Access Journals (Sweden)

    Jérôme Lane

    Full Text Available Statins are 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors that alter the synthesis of cholesterol. Some studies have shown a significant association of statins with improved respiratory health outcomes of patients with asthma, chronic obstructive pulmonary disease and lung cancer. Here we hypothesize that statins impact gene expression in human lungs and may reveal the pleiotropic effects of statins that are taking place directly in lung tissues. Human lung tissues were obtained from patients who underwent lung resection or transplantation. Gene expression was measured on a custom Affymetrix array in a discovery cohort (n = 408 and two replication sets (n = 341 and 282. Gene expression was evaluated by linear regression between statin users and non-users, adjusting for age, gender, smoking status, and other covariables. The results of each cohort were combined in a meta-analysis and biological pathways were studied using Gene Set Enrichment Analysis. The discovery set included 141 statin users. The lung mRNA expression levels of eighteen and three genes were up-regulated and down-regulated in statin users (FDR < 0.05, respectively. Twelve of the up-regulated genes were replicated in the first replication set, but none in the second (p-value < 0.05. Combining the discovery and replication sets into a meta-analysis improved the significance of the 12 up-regulated genes, which includes genes encoding enzymes and membrane proteins involved in cholesterol biosynthesis. Canonical biological pathways altered by statins in the lung include cholesterol, steroid, and terpenoid backbone biosynthesis. No genes encoding inflammatory, proteases, pro-fibrotic or growth factors were altered by statins, suggesting that the direct effect of statin in the lung do not go beyond its antilipidemic action. Although more studies are needed with specific lung cell types and different classes and doses of statins, the improved health outcomes and survival

  16. Interstitial lung disease in the connective tissue diseases.

    Science.gov (United States)

    Antin-Ozerkis, Danielle; Rubinowitz, Ami; Evans, Janine; Homer, Robert J; Matthay, Richard A

    2012-03-01

    The connective tissue diseases (CTDs) are inflammatory, immune-mediated disorders in which interstitial lung disease (ILD) is common and clinically important. Interstitial lung disease may be the first manifestation of a CTD in a previously healthy patient. CTD-associated ILD frequently presents with the gradual onset of cough and dyspnea, although rarely may present with fulminant respiratory failure. Infection and drug reaction should always be ruled out. A diagnosis of idiopathic ILD should never be made without a careful search for subtle evidence of underlying CTD. Treatment of CTD-ILD typically includes corticosteroids and immunosuppressive agents.

  17. Immune surveillance of the lung by migrating tissue monocytes

    Science.gov (United States)

    Rodero, Mathieu P; Poupel, Lucie; Loyher, Pierre-Louis; Hamon, Pauline; Licata, Fabrice; Pessel, Charlotte; Hume, David A; Combadière, Christophe; Boissonnas, Alexandre

    2015-01-01

    Monocytes are phagocytic effector cells in the blood and precursors of resident and inflammatory tissue macrophages. The aim of the current study was to analyse and compare their contribution to innate immune surveillance of the lung in the steady state with macrophage and dendritic cells (DC). ECFP and EGFP transgenic reporters based upon Csf1r and Cx3cr1 distinguish monocytes from resident mononuclear phagocytes. We used these transgenes to study the migratory properties of monocytes and macrophages by functional imaging on explanted lungs. Migratory monocytes were found to be either patrolling within large vessels of the lung or locating at the interface between lung capillaries and alveoli. This spatial organisation gives to monocytes the property to capture fluorescent particles derived from both vascular and airway routes. We conclude that monocytes participate in steady-state surveillance of the lung, in a way that is complementary to resident macrophages and DC, without differentiating into macrophages. DOI: http://dx.doi.org/10.7554/eLife.07847.001 PMID:26167653

  18. Automated characterization of normal and pathologic lung tissue by topological texture analysis of multidetector CT

    Science.gov (United States)

    Boehm, H. F.; Fink, C.; Becker, C.; Reiser, M.

    2007-03-01

    Reliable and accurate methods for objective quantitative assessment of parenchymal alterations in the lung are necessary for diagnosis, treatment and follow-up of pulmonary diseases. Two major types of alterations are pulmonary emphysema and fibrosis, emphysema being characterized by abnormal enlargement of the air spaces distal to the terminal, nonrespiratory bronchiole, accompanied by destructive changes of the alveolar walls. The main characteristic of fibrosis is coursening of the interstitial fibers and compaction of the pulmonary tissue. With the ability to display anatomy free from superimposing structures and greater visual clarity, Multi-Detector-CT has shown to be more sensitive than the chest radiograph in identifying alterations of lung parenchyma. In automated evaluation of pulmonary CT-scans, quantitative image processing techniques are applied for objective evaluation of the data. A number of methods have been proposed in the past, most of which utilize simple densitometric tissue features based on the mean X-ray attenuation coefficients expressed in terms of Hounsfield Units [HU]. Due to partial volume effects, most of the density-based methodologies tend to fail, namely in cases, where emphysema and fibrosis occur within narrow spatial limits. In this study, we propose a methodology based upon the topological assessment of graylevel distribution in the 3D image data of lung tissue which provides a way of improving quantitative CT evaluation. Results are compared to the more established density-based methods.

  19. Characterization of lung tissues using liquid-crystal tunable filter and hyperspectral imaging system.

    Science.gov (United States)

    Lee, Jong-Ha; Won, Chang-Hee

    2009-01-01

    Hyperspectral imaging system has been developed to characterize lung tissue for detecting emphysematous tissues in lung volume reduction surgery. The system consists of a charge-coupled device and liquid crystal tunable filter, which is continuously tunable in the near-infrared spectral range of 650 - 1100 nm with a mean bandwidth of 5 nm. Using hyperspectral data, the spectral signature of healthy lung tissue and simulated smokers lung tissue is obtained and compared. The data show the peak absorption intensity at four different wavelengths (760, 805, 915, and 970 nm). However, the reflectance intensity of simulated smoker's lung tissue over all spectral range is considerably higher than the normal lung tissue. The differences provide the basis for the detection and characterization of emphysema from healthy lung tissue.

  20. Critical transition in tissue homeostasis accompanies murine lung senescence.

    Directory of Open Access Journals (Sweden)

    Carla L Calvi

    Full Text Available BACKGROUND: Respiratory dysfunction is a major contributor to morbidity and mortality in aged populations. The susceptibility to pulmonary insults is attributed to "low pulmonary reserve", ostensibly reflecting a combination of age-related musculoskeletal, immunologic and intrinsic pulmonary dysfunction. METHODS/PRINCIPAL FINDINGS: Using a murine model of the aging lung, senescent DBA/2 mice, we correlated a longitudinal survey of airspace size and injury measures with a transcriptome from the aging lung at 2, 4, 8, 12, 16 and 20 months of age. Morphometric analysis demonstrated a nonlinear pattern of airspace caliber enlargement with a critical transition occurring between 8 and 12 months of age marked by an initial increase in oxidative stress, cell death and elastase activation which is soon followed by inflammatory cell infiltration, immune complex deposition and the onset of airspace enlargement. The temporally correlative transcriptome showed exuberant induction of immunoglobulin genes coincident with airspace enlargement. Immunohistochemistry, ELISA analysis and flow cytometry demonstrated increased immunoglobulin deposition in the lung associated with a contemporaneous increase in activated B-cells expressing high levels of TLR4 (toll receptor 4 and CD86 and macrophages during midlife. These midlife changes culminate in progressive airspace enlargement during late life stages. CONCLUSION/SIGNIFICANCE: Our findings establish that a tissue-specific aging program is evident during a presenescent interval which involves early oxidative stress, cell death and elastase activation, followed by B lymphocyte and macrophage expansion/activation. This sequence heralds the progression to overt airspace enlargement in the aged lung. These signature events, during middle age, indicate that early stages of the aging immune system may have important correlates in the maintenance of tissue morphology. We further show that time-course analyses of aging

  1. Lung Motion Model Validation Experiments, Free-Breathing Tissue Densitometry, and Ventilation Mapping using Fast Helical CT Imaging

    Science.gov (United States)

    Dou, Hsiang-Tai

    The uncertainties due to respiratory motion present significant challenges to accurate characterization of cancerous tissues both in terms of imaging and treatment. Currently available clinical lung imaging techniques are subject to inferior image quality and incorrect motion estimation, with consequences that can systematically impact the downstream treatment delivery and outcome. The main objective of this thesis is the development of the techniques of fast helical computed tomography (CT) imaging and deformable image registration for the radiotherapy applications in accurate breathing motion modeling, lung tissue density modeling and ventilation imaging. Fast helical CT scanning was performed on 64-slice CT scanner using the shortest available gantry rotation time and largest pitch value such that scanning of the thorax region amounts to just two seconds, which is less than typical breathing cycle in humans. The scanning was conducted under free breathing condition. Any portion of the lung anatomy undergoing such scanning protocol would be irradiated for only a quarter second, effectively removing any motion induced image artifacts. The resulting CT data were pristine volumetric images that record the lung tissue position and density in a fraction of the breathing cycle. Following our developed protocol, multiple fast helical CT scans were acquired to sample the tissue positions in different breathing states. To measure the tissue displacement, deformable image registration was performed that registers the non-reference images to the reference one. In modeling breathing motion, external breathing surrogate signal was recorded synchronously with the CT image slices. This allowed for the tissue-specific displacement to be modeled as parametrization of the recorded breathing signal using the 5D lung motion model. To assess the accuracy of the motion model in describing tissue position change, the model was used to simulate the original high-pitch helical CT scan

  2. A density-independent rigidity transition in biological tissues

    Science.gov (United States)

    Bi, Dapeng; Lopez, J. H.; Schwarz, J. M.; Manning, M. Lisa

    2015-12-01

    Cell migration is important in many biological processes, including embryonic development, cancer metastasis and wound healing. In these tissues, a cell’s motion is often strongly constrained by its neighbours, leading to glassy dynamics. Although self-propelled particle models exhibit a density-driven glass transition, this does not explain liquid-to-solid transitions in confluent tissues, where there are no gaps between cells and therefore the density is constant. Here we demonstrate the existence of a new type of rigidity transition that occurs in the well-studied vertex model for confluent tissue monolayers at constant density. We find that the onset of rigidity is governed by a model parameter that encodes single-cell properties such as cell-cell adhesion and cortical tension, providing an explanation for liquid-to-solid transitions in confluent tissues and making testable predictions about how these transitions differ from those in particulate matter.

  3. Decreased lung carcinoma cell density on select polymer nanometer surface features for lung replacement therapies

    Directory of Open Access Journals (Sweden)

    Lijuan Zhang

    2010-04-01

    Full Text Available Lijuan Zhang1, Young Wook Chun2, Thomas J Webster21Department of Chemistry and 2Division of Engineering, Brown University, Providence, RI USAAbstract: Poly(lactic-co-glycolic acid (PLGA has been widely used as a biomaterial in regenerative medicine because of its biocompatibility and biodegradability properties. Previous studies have shown that cells (such as bladder smooth muscle cells, chondrocytes, and osteoblasts respond differently to nanostructured PLGA surfaces compared with nanosmooth surfaces. The purpose of the present in vitro research was to prepare PLGA films with various nanometer surface features and determine whether lung cancer epithelial cells respond differently to such topographies. To create nanosurface features on PLGA, different sized (190 nm, 300 nm, 400 nm, and 530 nm diameter polystyrene beads were used to cast polydimethylsiloxane (PDMS molds which were used as templates to create nanofeatured PLGA films. Atomic force microscopy (AFM images and root mean square roughness (RMS values indicated that the intended spherical surface nanotopographies on PLGA with RMS values of 2.23, 5.03, 5.42, and 36.90 nm were formed by employing 190, 300, 400, and 530 nm beads. A solution evaporation method was also utilized to modify PLGA surface features by using 8 wt% (to obtain an AFM RMS value of 0.62 nm and 4 wt% (to obtain an AFM RMS value of 2.23 nm PLGA in chloroform solutions. Most importantly, lung cancer epithelial cells adhered less on the PLGA surfaces with RMS values of 0.62, 2.23, and 5.42 nm after four hours of culture compared with any other PLGA surface created here. After three days, PLGA surfaces with an RMS value of 0.62 nm had much lower cell density than any other sample. In this manner, PLGA with specific nanometer surface features may inhibit lung cancer cell density which may provide an important biomaterial for the treatment of lung cancer (from drug delivery to regenerative medicine.Keywords: nanotechnology

  4. [Determination of thirty three elements in lung cancer tissues of patients with lung cancer by microwave digestion-ICP-MS].

    Science.gov (United States)

    Zhang, Lin-Lin; Ma, Qian-Li; Huang, Yun-Chao; Wu, Guo-Ping; Wei, Fu-Sheng

    2009-12-01

    A method for determining 33 elements in lung tissues of patients with lung cancer was developed by using vacuum freeze-drying microwave digestion-ICP-MS. The lung tissue samples were treated by vacuum freeze-drying equipment. After microwave digestion in HNO3-H2O2 solution system, the samples were diluted with the method of constant volume. Under the optimized conditions the samples were analyzed by ICP-MS. The double internal standard elements Rh and Re were used to compensate for matrix suppression effect and sensitivity drift. The analytical results showed that the detection limits of the 33 elements were 0.01-0.45 ng x mL(-1). The national standard reference material GBW(E)080193 bovine liver was analyzed by the described method and the measured element values accorded with the standard values or the reference values. The relative standard deviation (RSD) of the method was 2.1%-14.3%. The recovery rates of the studied elements were 90.1%-117.5%. The contents of 33 elements in lung cancer tissues, paracancerous lung tissues and benign lung tissues of 6 patients with lung cancer were determined by the method. It was indicated that the method is rapid, simple and accurate for determining multi-elements in human lung tissue and other biological samples.

  5. Processing of CT images for analysis of diffuse lung disease in the lung tissue research consortium

    Science.gov (United States)

    Karwoski, Ronald A.; Bartholmai, Brian; Zavaletta, Vanessa A.; Holmes, David; Robb, Richard A.

    2008-03-01

    The goal of Lung Tissue Resource Consortium (LTRC) is to improve the management of diffuse lung diseases through a better understanding of the biology of Chronic Obstructive Pulmonary Disease (COPD) and fibrotic interstitial lung disease (ILD) including Idiopathic Pulmonary Fibrosis (IPF). Participants are subjected to a battery of tests including tissue biopsies, physiologic testing, clinical history reporting, and CT scanning of the chest. The LTRC is a repository from which investigators can request tissue specimens and test results as well as semi-quantitative radiology reports, pathology reports, and automated quantitative image analysis results from the CT scan data performed by the LTRC core laboratories. The LTRC Radiology Core Laboratory (RCL), in conjunction with the Biomedical Imaging Resource (BIR), has developed novel processing methods for comprehensive characterization of pulmonary processes on volumetric high-resolution CT scans to quantify how these diseases manifest in radiographic images. Specifically, the RCL has implemented a semi-automated method for segmenting the anatomical regions of the lungs and airways. In these anatomic regions, automated quantification of pathologic features of disease including emphysema volumes and tissue classification are performed using both threshold techniques and advanced texture measures to determine the extent and location of emphysema, ground glass opacities, "honeycombing" (HC) and "irregular linear" or "reticular" pulmonary infiltrates and normal lung. Wall thickness measurements of the trachea, and its branches to the 3 rd and limited 4 th order are also computed. The methods for processing, segmentation and quantification are described. The results are reviewed and verified by an expert radiologist following processing and stored in the public LTRC database for use by pulmonary researchers. To date, over 1200 CT scans have been processed by the RCL and the LTRC project is on target for recruitment of the

  6. Development of an inhalable, stimuli-responsive particulate system for delivery to deep lung tissue.

    Science.gov (United States)

    Abbas, Yasmine; Azzazy, Hassan M E; Tammam, Salma; Lamprecht, Alf; Ali, Mohamed Ehab; Schmidt, Annette; Sollazzo, Silvio; Mathur, Sanjay

    2016-10-01

    Lung cancer, the deadliest solid tumor among all types of cancer, remains difficult to treat. This is a result of unavoidable exposure to carcinogens, poor diagnosis, the lack of targeted drug delivery platforms and limitations associated with delivery of drug to deep lung tissues. Development of a non-invasive, patient-convenient formula for the targeted delivery of chemotherapeutics to cancer in deep lung tissue is the aim of this study. The formulation consisted of inhalable polyvinylpyrrolidone (PVP)/maltodextrin (MD)-based microparticles (MPs) encapsulating chitosan (CS) nanoparticles (NPs) loaded with either drug only or drug and magnetic nanoparticles (MNPs). Drug release from CS NPs was enhanced with the aid of MNPs by a factor of 1.7 in response to external magnetic field. Preferential toxicity by CS NPs was shown towards tumor cells (A549) in comparison to cultured fibroblasts (L929). The prepared spray freeze dried (SFD) powders for CS NPs and CS MNPs were of the same size at ∼6μm. They had a fine particle fraction (FPF≤5.2μm) of 40-42% w/w and mass median aerodynamic diameter (MMAD) of 5-6μm as determined by the Next Generation Impactor (NGI). SFD-MPs of CS MNPs possess higher MMAD due to the high density associated with encapsulated MNPs. The developed formulation demonstrates several capabilities including tissue targeting, controlled drug release, and the possible imaging and diagnostic values (due to its MNPs content) and therefore represents an improved therapeutic platform for drug delivery to cancer in deep lung tissue.

  7. [The biological significance of FHIT protein expression in lung cancer and precancerous tissues detected by tissue microarray].

    Science.gov (United States)

    Yuan, Ling; Wang, Xinyun; Zheng, Haiyan

    2007-06-20

    Fragile histidine triad (FHIT) is a candidate tumor suppressor gene. Aberrant expression of FHIT has been observed in multiple carcinomas induced by environmental carcinogens, especially in lung cancer. In this study, the expression of FHIT protein in lung cancer progression tissue microarray was detected and their roles in oncogenesis and progression of lung cancer were discussed. The expression of FHIT protein in tissue microarray with 270 cores was detected by SP immunohistochemistry method, in which there were 89 cases of primary lung cancer, 12 cases of lymph node metastasis of lung cancer, 12 cases of precancerous lesion and 10 cases of normal lung tissue, and the clinicopathological features of lung cancer were analyzed. The expression of FHIT was localized in the cytoplasm. Loss of FHIT expression in primary cancers, precancerous lesion and lymph node metastasis of lung cancer was 46.1%, 41.7% and 50.0% respectively, while 0 in 10 cases of normal tissues. A significant difference of FHIT expression was observed among four groups (P tissue (P 0.05). Loss of FHIT expression was related to tumor histologicol types, degree of cell differentiation and the smoking history of patients (P 0.05). The protein expression level of FHIT is reduced in primary cancers and precancerous tissues, especially in most squamous cell carcinomas, poorly differentiated group and the patients with a smoking history. These results indicate that loss of FHIT expression might correlate with carcinogenesis, development of lung cancer and the carcinogenesis induced by smoking.

  8. Expression and clinicopathological implication of DcR3 in lung cancer tissues: a tissue microarray study with 365 cases.

    Science.gov (United States)

    Zhang, Yu; Luo, Jie; He, Rongquan; Huang, Wenting; Li, Zuyun; Li, Ping; Dang, Yiwu; Chen, Gang; Li, Shikang

    2016-01-01

    Decoy receptor 3 (DcR3) has been reported to be involved in different cancers. However, few related researches have been accomplished on the role of DcR3 in lung cancer. To explore the expression level and clinicopathological implication of DcR3 protein in lung cancer tissues. Immunohistochemistry was used to examine DcR3 protein expression in lung cancer (n=365) and normal lung tissues (n=26). The relationships between DcR3 expression and clinical parameters were further investigated. Furthermore, the diagnostic and clinicopathological value of DcR3 mRNA was analyzed based on The Cancer Genome Atlas database in lung cancer patients. Compared to normal lung tissues, DcR3 expression was significantly higher in lung cancer (P=0.007) tissues, including small-cell lung cancer (P=0.001) and non-small-cell lung cancer (P=0.008). In addition, DcR3 expression was related to tumor-node-metastasis (TNM) stage (Ptissues than in noncancerous lung tissues (all P<0.0001) based on the data from The Cancer Genome Atlas. AUC of DcR3 was 0.726 (95% CI 0.644-0.788) for lung adenocarcinoma patients and 0.647 (95% CI 0.566-0.728) for squamous cell carcinoma patients. DcR3 expression was also related to the overall survival (P<0.001) and disease-free survival (P<0.001) of lung adenocarcinoma according to the data from The Cancer Genome Atlas. Our study confirms that DcR3 might be involved in the tumorigenesis and deterioration of lung cancer. Therefore, the detection of DcR3 gains the potential to be applied in the clinic for screening and progression prediction of lung cancer.

  9. The effect of different lung densities on the accuracy of various radiotherapy dose calculation methods: implications for tumour coverage

    DEFF Research Database (Denmark)

    Aarup, Lasse Rye; Nahum, Alan E; Zacharatou, Christina

    2009-01-01

    and tumour have unit density). The lung tissue was assigned five densities (rho(lung)): 0.01, 0.1, 0.2, 0.4 and 1g/cm(3). Four-field treatment plans were calculated with 6- and 18 MV narrow beams for each value of rho(lung). We considered the Pencil Beam Convolution (PBC(Ecl)) and the Analytical Anisotropic...... Algorithm (AAA(Ecl)) from Varian Eclipse and the Pencil Beam Convolution (PBC(OMP)) and the Collapsed Cone Convolution (CCC(OMP)) algorithms from Oncentra MasterPlan. RESULTS: When changing rho(lung) from 0.4 to 0.1g/cm(3), the MC median target dose decreased from 89.2% to 74.9% for 6 MV and from 83...... Treatment Planning System (TPS) algorithms and one Monte Carlo (MC) system (EGSnrc). We compared the performance of the algorithms in calculating the target dose for different degrees of lung inflation. The phantoms had a cubic 'body' and 'lung' and a central 2-cm diameter spherical 'tumour' (the body...

  10. RELATED GENES IN LUNG CANCER TISSUES ASSOCIATED WITH RESIDENTIAL HIGH RADON EXPOSURE

    Institute of Scientific and Technical Information of China (English)

    夏英; 杨梅英; 张守志; 叶常青

    2002-01-01

    Objective: To investigate the related genes in lung cancer tissues associated with residential high radon exposure. Methods: Differentially expressed gene fragments in lung cancer and normal lung tissues were discovered by differential display and reverse Northern blot hybridization method. The fragments positive in lung cancer and negative in normal lung tissue were determined. Results: Seven differential displayed fragments were sequenced. One of them named NA7 is 95% homologous with AI208667 in EAT of Genbank. Another fragment named NG2 is up to 98% homologous with five fragments. The remained one CA1 may be a new gene fragment. Conclusion: 3 gene fragments were discovered from lung cancer and normal lung tissues of high radon exposure resident.

  11. EXPRESSION OF INTERCELLULAR ADHESION MOLECULE IN LUNG TISSUES OF EXPERIMENTAL ACUTE LUNG INJURY AND THE AFFECT OF RHUBARB ON IT

    Institute of Scientific and Technical Information of China (English)

    李春盛; 桂培春; 何新华

    2000-01-01

    Objeaive. To approach the relation and the possible mechanism between the expression of intercellular adhesion molecule (ICAM-1) mRNA and acute lung injury (ALI) and the mechanisms of rhubarb in the prevention and treatment of the lung injury. Methods. Lipopolysaeeharide (LPS) was injected into the sublingual vein of male Wistar rats to perform ALI animal model. The rats were divided into 4 groups: LPS group, control group, rhubarb group and dexamethasoue group.Macroscopic and histopathological e~aminatiom were performed and biological markers were measured for the lung specimem. The markers included lung wet/dry weight, the rate of neutrophils and protein content in the pulmonary alveolar lavage fluid, pulmonary vascular permeability and pulmonary alveolar permeability index. Molecular hybridization method was used to determine the expression of ICAM-1 mRNA. Results. In the lung tissues, the ICAM-1 mRNA expression was increased in the endothelial cells of pulmonary veins and capillaries, rhubarb and dexamethasone had the action of decreasing the expression. The light reflex value in the gray scale scanning showed that in the comparison between the LPS and the control group, the gray scale value of the lung tissues in ALI was significantly increased, thus the light reflex value was markedly decreased (P < 0.01),demonstrating the expression of ICAM-1 mRNA was increased. In comparison with the LPS group, dexamethasoue and rhubarb emfld decrease the gray scale value of the lung tissue significantly, thus the light reflex value was elevated (P< 0.01, P < 0.05) ; the correslxmding pathologic changes of lung tissues and the biological markers of the lung injury were simifieantlv decreased or ameliorated. Conclusions. The increase of the expression d ICAM-1 mRNA in the lung tissues of ALI plays the roles in ALI.The application of rhubarb and dexamethasone can decrease the expression and ameliorate the lung damage; its mechanism is possibly via the inhibition of ICAM-1 m

  12. EXPRESSION OF INTERCELLULAR ADHESION MOLECULE IN LUNG TISSUES OF EXPERIMENTAL ACUTE LUNG INJURY AND THE AFFECT OF RHUBARB ON IT

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective. To approach the relation and the possible mechanism between the expression of intercellular adhesion molecule (ICAM-1) mRNA and acute lung injury (ALI) and the mechanisms of rhubarb in the prevention and treatment of the lung injury.Methods. Lipopolysaccharide (LPS) was injected into the sublingual vein of male Wistar rats to perform ALI animal model. The rats were divided into 4 groups: LPS group, control group, rhubarb group and dexamethasone group. Macroscopic and histopathological examinations were performed and biological markers were measured for the lung specimens. The markers included lung wet/dry weight, the rate of neutrophils and protein content in the pulmonary alveolar lavage fluid, pulmonary vascular permeability and pulmonary alveolar permeability index. Molecular hybridization method was used to determine the expression of ICAM-1 mRNA.Results. In the lung tissues, the ICAM-1 mRNA expression was increased in the endothelial cells of pulmonary veins and capillaries, rhubarb and dexamethasone had the action of decreasing the expression. The light reflex value in the gray scale scanning showed that in the comparison between the LPS and the control group, the gray scale value of the lung tissues in ALI was significantly increased, thus the light reflex value was markedly decreased (P<0.01), demonstrating the expression of ICAM-1 mRNA was increased. In comparison with the LPS group, dexamethasone and rhubarb could decrease the gray scale value of the lung tissue significantly, thus the light reflex value was elevated (P<0.01, P<0.05); the corresponding pathologic changes of lung tissues and the biological markers of the lung injury were significantly decreased or ameliorated.Conclusions. The increase of the expression of ICAM-1 mRNA in the lung tissues of ALI plays the roles in ALI. The application of rhubarb and dexamethasone can decrease the expression and ameliorate the lung damage; its mechanism is possibly via the inhibition of ICAM

  13. A novel SCID mouse model for studying spontaneous metastasis of human lung cancer to human tissue.

    Science.gov (United States)

    Teraoka, S; Kyoizumi, S; Seyama, T; Yamakido, M; Akiyama, M

    1995-05-01

    We established a novel severe combined immunodeficient (SCID) mouse model for the study of human lung cancer metastasis to human lung. Implantation of both human fetal and adult lung tissue into mammary fat pads of SCID mice showed a 100% rate of engraftment, but only fetal lung implants revealed normal morphology of human lung tissue. Using these chimeric mice, we analyzed human lung cancer metastasis to both mouse and human lungs by subcutaneous inoculation of human squamous cell carcinoma and adenocarcinoma cell lines into the mice. In 60 to 70% of SCID mice injected with human-lung squamous-cell carcinoma, RERF-LC-AI, cancer cells were found to have metastasized to both mouse lungs and human fetal lung implants but not to human adult lung implants 80 days after cancer inoculation. Furthermore, human-lung adenocarcinoma cells, RERF-LC-KJ, metastasized to the human lung implants within 90 days in about 40% of SCID mice, whereas there were no metastases to the lungs of the mice. These results demonstrate the potential of this model for the in vivo study of human lung cancer metastasis.

  14. Volume adjustment of lung density by computed tomography scans in patients with emphysema

    DEFF Research Database (Denmark)

    Shaker, S B; Dirksen, A; Laursen, Lars Christian

    2004-01-01

    package that detected the lung in contiguous images and subsequently generated a histogram of the pixel attenuation values. The total lung volume (TLV), lung weight, percentile density (PD), and relative area of emphysema (RA) were calculated from this histogram. RA and PD are commonly applied measures......PURPOSE: To determine how to adjust lung density measurements for the volume of the lung calculated from computed tomography (CT) scans in patients with emphysema. MATERIAL AND METHODS: Fifty patients with emphysema underwent 3 CT scans at 2-week intervals. The scans were analyzed with a software...... of pulmonary emphysema derived from CT scans. These parameters are markedly influenced by changes in the level of inspiration. The variability of lung density due to within-subject variation in TLV was explored by plotting TLV against PD and RA. RESULTS: The coefficients for volume adjustment for PD were...

  15. A density-independent glass transition in biological tissues

    CERN Document Server

    Bi, Dapeng; Schwarz, J M; Manning, M Lisa

    2014-01-01

    Cells must move through tissues in many important biological processes, including embryonic development, cancer metastasis, and wound healing. In these tissues, a cell's motion is often strongly constrained by its neighbors, leading to glassy dynamics. Recent work has demonstrated the existence of a non-equilibrium glass transition in self-propelled particle models for active matter, where the transition is driven by changes in density. However, this may not explain liquid-to-solid transitions in confluent tissues, where there are no gaps between cells and the packing fraction remains fixed and equal to unity. Here we demonstrate the existence of a different type of glass transition that occurs in the well-studied vertex model for confluent tissue monolayers. In this model, the onset of rigidity is governed by changes to single-cell properties such as cell-cell adhesion, cortical tension, and volume compressibility, providing an explanation for a liquid-to-solid transitions in confluent tissues.

  16. Oxidative Damage to Lung Tissue and Peripheral Blood in Endotracheal PM2.5-treated Rats

    Institute of Scientific and Technical Information of China (English)

    ZHI-QING LIN; ZHU-GE XI; DAN-FENG YANG; FU-HUAN CHAO; HUA-SHAN ZHANG; WEI ZHANG; HUANG-LIANG LIU; ZAI-MING YANG; RU-BAO SUN

    2009-01-01

    Objective To investigate the oxidative damage to lung tissue and peripherial blood in PM2.5-treated rats.Methods PM2.5 samples were collected using an auto-sampling instrument in summer and winter.Treated samples were endotracheally instilled into rats.Activity of reduced glutathione peroxidase (GSH-Px) and concentration of malondialdehyde (MDA) were used as oxidative damage biomarkers of lung tissue and peripheral blood detected with the biochemical method.DNA migration length (μm) and rate of tail were used as DNA damage biomarkers of lung tissue and peripheral blood detected with the biochemical method. Results The activity of GSH-Px and the concentration of MDA in lung tissue significantly decreased after exposure to PM2.5 for 7-14 days.In peripheral blood,the concentration of MDA decreased,but the activity of GSH-Px increased 7 and 14 days after experiments.The two indicators had a dose-effect relation and similar changing tendency in lung tissue and peripheral blood.The DNA migration length (μm) and rate of tail in lung tissue and peripheral blood significantly increased 7 and 14 days after exposure to PM2.5.The two indicators had a dose-effect relation and similar changing tendency in lung tissue and peripheral blood. Conclusion PM2.5 has a definite oxidative effect on lung tissue and peripheral blood.The activity of GSH-Px and the concentration of MDA are valuable biomarkers of oxidative lung tissue damage induced by PM2.5.The DNA migration length (μm) and rate of tail are simple and valuable biomarkers of PM2.5-induced DNA damage in lung tissues and peripheral blood.The degree of DNA damage in peripheral blood can predict the degree of DNA damage in lung tissue.

  17. Hyaluronic Acid is Overexpressed in Fibrotic Lung Tissue and Promotes Collagen Expression

    Science.gov (United States)

    2009-04-01

    injured adult tissue (1-4). Periostin has also been shown to regulate inflammatory cell infiltration in allergic disease in the esophagus and lung (5...model for scleroderma lung disease because both bleomycin treatment and scleroderma lung disease produce inflammatory alveolitis and overproduction...t, a fibroblastic lineage 4. essential for cardiac healing after 5. ., ltration in allergic lung and esophageal responses. 6. r, D.E

  18. Measurement of histamine release from human lung tissue ex vivo by microdialysis technique

    DEFF Research Database (Denmark)

    Nissen, Dan; Petersen, Lars Jelstrup; Nolte, H

    1998-01-01

    responses were observed but data could be reproduced within individual donors. Monocyte chemoattractant protein-1, a potent basophil secretagogue, did not induce histamine release in lung tissue which indicated mast cells to be the histamine source. Substance P did not release histamine in the lung tissue...

  19. Cystic changes in mucosa-associated lymphoid tissue lymphoma of lung: a case report

    Institute of Scientific and Technical Information of China (English)

    MIAO Li-yun; CAI Hou-rong

    2009-01-01

    @@ Mucosa-associated lymphoid tissue (MALT) is a term that describes lymphoid tissue in various sites of the body, such as the gastrointestinal tract, thyroid, breast, lung, salivary glands, eye, and skin. MALT lymphoma of the lung is a subset of primary pulmonary lymphomas which originates from the MALT. Previously reported computed tomographic (CT) features of MALT lymphoma are the presence of consolidation or nodules in the lungs. 1-4

  20. Lung tissue remodeling in the acute respiratory distress syndrome

    Directory of Open Access Journals (Sweden)

    Souza Alba Barros de

    2003-01-01

    Full Text Available Acute respiratory distress syndrome (ARDS is characterized by diffuse alveolar damage, and evolves progressively with three phases: exsudative, fibroproliferative, and fibrotic. In the exudative phase, there are interstitial and alveolar edemas with hyaline membrane. The fibropro­liferative phase is characterized by exudate organization and fibroelastogenesis. There is proliferation of type II pneumocytes to cover the damaged epithelial surface, followed by differentiation into type I pneumocytes. The fibroproliferative phase starts early, and its severity is related to the patient?s prognosis. The alterations observed in the phenotype of the pulmonary parenchyma cells steer the tissue remodeling towards either progressive fibrosis or the restoration of normal alveolar architecture. The fibrotic phase is characterized by abnormal and excessive deposition of extracellular matrix proteins, mainly collagen. The dynamic control of collagen deposition and degradation is regulated by metalloproteinases and their tissular regulators. The deposition of proteoglycans in the extracellular matrix of ARDS patients needs better study. The regulation of extracellular matrix remodeling, in normal conditions or in several pulmonary diseases, such as ARDS, results from a complex mechanism that integrate the transcription of elements that destroy the matrix protein and produce activation/inhibition of several cellular types of lung tissue. This review article will analyze the ECM organization in ARDS, the different pulmonary parenchyma remodeling mechanisms, and the role of cytokines in the regulation of the different matrix components during the remodeling process.

  1. Flow cytometric determination of stem/progenitor content in epithelial tissues: an example from nonsmall lung cancer and normal lung.

    Science.gov (United States)

    Donnenberg, Vera S; Landreneau, Rodney J; Pfeifer, Melanie E; Donnenberg, Albert D

    2013-01-01

    Single cell analysis and cell sorting has enabled the study of development, growth, differentiation, repair and maintenance of "liquid" tissues and their cancers. The application of these methods to solid tissues is equally promising, but several unique technical challenges must be addressed. This report illustrates the application of multidimensional flow cytometry to the identification of candidate stem/progenitor populations in non-small cell lung cancer and paired normal lung tissue. Seventeen paired tumor/normal lung samples were collected at the time of surgical excision and processed immediately. Tissues were mechanically and enzymatically dissociated into single cell suspension and stained with a panel of antibodies used for negative gating (CD45, CD14, CD33, glycophorin A), identification of epithelial cells (intracellular cytokeratin), and detection of stem/progenitor markers (CD44, CD90, CD117, CD133). DAPI was added to measure DNA content. Formalin fixed paraffin embedded tissue samples were stained with key markers (cytokeratin, CD117, DAPI) for immunofluorescent tissue localization of populations detected by flow cytometry. Disaggregated tumor and lung preparations contained a high proportion of events that would interfere with analysis, were they not eliminated by logical gating. We demonstrate how inclusion of doublets, events with hypodiploid DNA, and cytokeratin+ events also staining for hematopoietic markers reduces the ability to quantify epithelial cells and their precursors. Using the lung cancer/normal lung data set, we present an approach to multidimensional data analysis that consists of artifact removal, identification of classes of cells to be studied further (classifiers) and the measurement of outcome variables on these cell classes. The results of bivariate analysis show a striking similarity between the expression of stem/progenitor markers on lung tumor and adjacent tumor-free lung.

  2. Characterizing the lung tissue mechanical properties using a micromechanical model of alveolar sac

    Science.gov (United States)

    Karami, Elham; Seify, Behzad; Moghadas, Hadi; Sabsalinejad, Masoomeh; Lee, Ting-Yim; Samani, Abbas

    2017-03-01

    According to statistics, lung disease is among the leading causes of death worldwide. As such, many research groups are developing powerful tools for understanding, diagnosis and treatment of various lung diseases. Recently, biomechanical modeling has emerged as an effective tool for better understanding of human physiology, disease diagnosis and computer assisted medical intervention. Mechanical properties of lung tissue are important requirements for methods developed for lung disease diagnosis and medical intervention. As such, the main objective of this study is to develop an effective tool for estimating the mechanical properties of normal and pathological lung parenchyma tissue based on its microstructure. For this purpose, a micromechanical model of the lung tissue was developed using finite element (FE) method, and the model was demonstrated to have application in estimating the mechanical properties of lung alveolar wall. The proposed model was developed by assembling truncated octahedron tissue units resembling the alveoli. A compression test was simulated using finite element method on the created geometry and the hyper-elastic parameters of the alveoli wall were calculated using reported alveolar wall stress-strain data and an inverse optimization framework. Preliminary results indicate that the proposed model can be potentially used to reconstruct microstructural images of lung tissue using macro-scale tissue response for normal and different pathological conditions. Such images can be used for effective diagnosis of lung diseases such as Chronic Obstructive Pulmonary Disease (COPD).

  3. Mean Organ Doses Resulting From Non-Human Primate Whole Thorax Lung Irradiation Prescribed to Mid-Line Tissue.

    Science.gov (United States)

    Prado, Charlotte; Kazi, Abdul; Bennett, Alexander; MacVittie, Thomas; Prado, Karl

    2015-11-01

    Multi-organ dose evaluations and the effects of heterogeneous tissue dose calculations have been retrospectively evaluated following irradiation to the whole thorax and lung in non-human primates (NHP). A clinical-based approach was established to evaluate actual doses received in the heart and lungs during whole thorax lung irradiation. Anatomical structure and organ densities have been introduced in the calculations to show the effects of dose distribution through heterogeneous tissue. Mean organ doses received by non-human primates undergoing whole thorax lung irradiations were calculated using a treatment planning system that is routinely used in clinical radiation oncology. The doses received by non-human primates irradiated following conventional dose calculations have been retrospectively reconstructed using computerized tomography-based, heterogeneity-corrected dose calculations. The use of dose volume descriptors for irradiation to organs at risk and tissue exposed to radiation is introduced. Mean and partial-volume doses to lung and heart are presented and contrasted. The importance of exact dose definitions is highlighted, and the relevance of precise dosimetry to establish organ-specific dose response relationships in NHP models of acute and delayed effects of acute radiation exposure is emphasized.

  4. Monte Carlo study of voxel S factor dependence on tissue density and atomic composition

    Energy Technology Data Exchange (ETDEWEB)

    Amato, Ernesto, E-mail: eamato@unime.it [University of Messina, Department of Biomedical Sciences and of Morphologic and Functional Imaging, Section of Radiological Sciences, via Consolare Valeria, 1, I-98125 Messina (Italy); Italiano, Antonio [INFN – Istituto Nazionale di Fisica Nucleare, Gruppo Collegato di Messina (Italy); Baldari, Sergio [University of Messina, Department of Biomedical Sciences and of Morphologic and Functional Imaging, Section of Radiological Sciences, via Consolare Valeria, 1, I-98125 Messina (Italy)

    2013-11-21

    Voxel dosimetry is a common approach to the internal dosimetry of non-uniform activity distributions in nuclear medicine therapies with radiopharmaceuticals and in the estimation of the radiation hazard due to internal contamination of radionuclides. Aim of the present work is to extend our analytical approach for the calculation of voxel S factors to materials different from the soft tissue. We used a Monte Carlo simulation in GEANT4 of a voxelized region of each material in which the source of monoenergetic electrons or photons was uniformly distributed within the central voxel, and the energy deposition was scored over the surrounding 11×11×11 voxels. Voxel S factors were obtained for the following standard ICRP materials: Adipose tissue, Bone cortical, Brain, Lung, Muscle skeletal and Tissue soft with 1 g cm{sup −3} density. Moreover, we considered the standard ICRU materials: Bone compact and Muscle striated. Voxel S factors were represented as a function of the “normalized radius”, defined as the ratio between the source–target voxel distance and the voxel side. We found that voxel S factors and related analytical fit functions are mainly affected by the tissue density, while the material composition gives only a slight contribution to the difference between data series, which is negligible for practical purposes. Our results can help in broadening the dosimetric three-dimensional approach based on voxel S factors to other tissues where diagnostic and therapeutic radionuclides can be taken up and radiation can propagate.

  5. Preferential elevation of Prx I and Trx expression in lung cancer cells following hypoxia and in human lung cancer tissues.

    Science.gov (United States)

    Kim, H J; Chae, H Z; Kim, Y J; Kim, Y H; Hwangs, T S; Park, E M; Park, Y M

    2003-10-01

    Transient/chronic microenvironmental hypoxia that exists within a majority of solid tumors has been suggested to have a profound influence on tumor growth and therapeutic outcome. Since the functions of novel antioxidant proteins, peroxiredoxin I (Prx I) and II, have been implicated in regulating cell proliferation, differentiation, and apoptosis, it was of our special interest to probe a possible role of Prx I and II in the context of hypoxic tumor microenvironment. Since both Prx I and II use thioredoxin (Trx) as an electron donor and Trx is a substrate for thioredoxin reductase (TrxR), we investigated the regulation of Trx and TrxR as well as Prx expression following hypoxia. Here we show a dynamic change of glutathione homeostasis in lung cancer A549 cells and an up-regulation of Prx I and Trx following hypoxia. Western blot analysis of 10 human lung cancer and paired normal lung tissues also revealed an elevated expression of Prx I and Trx proteins in lung cancer tissues. Immunohistochemical analysis of the lung cancer tissues confirmed an augmented Prx I and Trx expression in cancer cells with respect to the parenchymal cells in adjacent normal lung tissue. Based on these results, we suggest that the redox changes in lung tumor microenvironment could have acted as a trigger for the up-regulation of Prx I and Trx in lung cancer cells. Although the clinical significance of our finding awaits more rigorous future study, preferential augmentation of the Prx I and Trx in lung cancer cells may well represent an attempt of cancer cells to manipulate a dynamic redox change in tumor microenvironment in a manner that is beneficial for their proliferation and malignant progression.

  6. Elastin Cables Define the Axial Connective Tissue System in the Murine Lung.

    Science.gov (United States)

    Wagner, Willi; Bennett, Robert D; Ackermann, Maximilian; Ysasi, Alexandra B; Belle, Janeil; Valenzuela, Cristian D; Pabst, Andreas; Tsuda, Akira; Konerding, Moritz A; Mentzer, Steven J

    2015-11-01

    The axial connective tissue system is a fiber continuum of the lung that maintains alveolar surface area during changes in lung volume. Although the molecular anatomy of the axial system remains undefined, the fiber continuum of the lung is central to contemporary models of lung micromechanics and alveolar regeneration. To provide a detailed molecular structure of the axial connective tissue system, we examined the extracellular matrix of murine lungs. The lungs were decellularized using a 24 hr detergent treatment protocol. Systematic evaluation of the decellularized lungs demonstrated no residual cellular debris; morphometry demonstrated a mean 39 ± 7% reduction in lung dimensions. Scanning electron microscopy (SEM) demonstrated an intact structural hierarchy within the decellularized lung. Light, fluorescence, and SEM of precision-cut lung slices demonstrated that alveolar duct structure was defined by a cable line element encased in basement membrane. The cable line element arose in the distal airways, passed through septal tips and inserted into neighboring blood vessels and visceral pleura. The ropelike appearance, collagenase resistance and anti-elastin immunostaining indicated that the cable was an elastin macromolecule. Our results indicate that the helical line element of the axial connective tissue system is composed of an elastin cable that not only defines the structure of the alveolar duct, but also integrates the axial connective tissue system into visceral pleura and peripheral blood vessels.

  7. Undifferentiated connective tissue disease-associated interstitial lung disease: changes in lung function.

    Science.gov (United States)

    Kinder, Brent W; Shariat, Cyrus; Collard, Harold R; Koth, Laura L; Wolters, Paul J; Golden, Jeffrey A; Panos, Ralph J; King, Talmadge E

    2010-04-01

    Undifferentiated connective tissue disease (UCTD) is a distinct clinical entity that may be accompanied by interstitial lung disease (ILD). The natural history of UCTD-ILD is unknown. We hypothesized that patients with UCTD-ILD would be more likely to have improvement in lung function than those with idiopathic pulmonary fibrosis (IPF) during longitudinal follow-up. We identified subjects enrolled in the UCSF ILD cohort study with a diagnosis of IPF or UCTD. The primary outcome compared the presence or absence of a > or = 5% increase in percent predicted forced vital capacity (FVC) in IPF and UCTD. Regression models were used to account for potential confounding variables. Ninety subjects were identified; 59 subjects (30 IPF, 29 UCTD) had longitudinal pulmonary function data for inclusion in the analysis. After accounting for baseline pulmonary function tests, treatment, and duration between studies, UCTD was associated with substantial improvement in FVC (odds ratio = 8.23, 95% confidence interval, 1.27-53.2; p = 0.03) during follow-up (median, 8 months) compared with IPF. Patients with UCTD-ILD are more likely to have improved pulmonary function during follow-up than those with IPF. These findings demonstrate the clinical importance of identifying UCTD in patients presenting with an "idiopathic" interstitial pneumonia.

  8. Tissue hyaluronan expression, as reflected in the sputum of lung cancer patients, is an indicator of malignancy

    Energy Technology Data Exchange (ETDEWEB)

    Rangel, M.P.; Sá, V.K. de; Martins, V. [Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Martins, J.R.M. [Disciplina de Biologia Molecular, Departamento de Bioquímica, Faculdade de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Disciplina de Endocrinologia e Metabolismo, Laboratório de Endocrinologia Molecular e Translacional-LEMT, Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Parra, E.R. [Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Mendes, A. [Disciplina de Biologia Molecular, Departamento de Bioquímica, Faculdade de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Andrade, P.C. [Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Reis, R.M. [Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga (Portugal); ICVS/3B' s - PT Government Associate Laboratory, Guimarães (Portugal); Centro de Pesquisa em Oncologia Molecular, Hospital de Câncer de Barretos, Fundação Pio XII, Barretos, SP (Brazil); Longatto-Filho, A. [Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga (Portugal); ICVS/3B' s - PT Government Associate Laboratory, Guimarães (Portugal); Laboratório de Investigação Médica (LIM 14), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Centro de Pesquisa em Oncologia Molecular, Hospital de Câncer de Barretos, Fundação Pio XII, Barretos, SP (Brazil); Oliveira, C.Z. [Centro de Pesquisa em Oncologia Molecular, Hospital de Câncer de Barretos, Fundação Pio XII, Barretos, SP (Brazil); Takagaki, T. [Divisão de Pneumologia, Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Carraro, D.M. [Centro Internacional de Pesquisa/CIPE, AC Camargo Cancer Center, São Paulo, SP (Brazil); Nader, H.B. [Disciplina de Biologia Molecular, Departamento de Bioquímica, Faculdade de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Capelozzi, V.L. [Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

    2015-05-08

    Hyaluronan (HA) shows promise for detecting cancerous change in pleural effusion and urine. However, there is uncertainty about the localization of HA in tumor tissue and its relationship with different histological types and other components of the extracellular matrix, such as angiogenesis. We evaluated the association between HA and degree of malignancy through expression in lung tumor tissue and sputum. Tumoral tissue had significantly increased HA compared to normal tissue. Strong HA staining intensity associated with cancer cells was significant in squamous cell carcinoma compared to adenocarcinoma and large cell carcinoma. A significant direct association was found between tumors with a high percentage of HA and MVD (microvessel density) in tumoral stroma. Similarly significant was the direct association between N1 tumors and high levels of HA in cancer cells. Cox multivariate analysis showed significant association between better survival and low HA. HA increased in sputum from lung cancer patients compared to cancer-free and healthy volunteers and a significant correlation was found between HA in sputum and HA in cancer tissue. Localization of HA in tumor tissue was related to malignancy and reflected in sputum, making this an emerging factor for an important diagnostic procedure in patients suspected to have lung cancer. Further study in additional patients in a randomized prospective trial is required to finalize these results and to validate our quantitative assessment of HA, as well as to couple it to gold standard sputum cytology.

  9. Implementation of several mathematical algorithms to breast tissue density classification

    Science.gov (United States)

    Quintana, C.; Redondo, M.; Tirao, G.

    2014-02-01

    The accuracy of mammographic abnormality detection methods is strongly dependent on breast tissue characteristics, where a dense breast tissue can hide lesions causing cancer to be detected at later stages. In addition, breast tissue density is widely accepted to be an important risk indicator for the development of breast cancer. This paper presents the implementation and the performance of different mathematical algorithms designed to standardize the categorization of mammographic images, according to the American College of Radiology classifications. These mathematical techniques are based on intrinsic properties calculations and on comparison with an ideal homogeneous image (joint entropy, mutual information, normalized cross correlation and index Q) as categorization parameters. The algorithms evaluation was performed on 100 cases of the mammographic data sets provided by the Ministerio de Salud de la Provincia de Córdoba, Argentina—Programa de Prevención del Cáncer de Mama (Department of Public Health, Córdoba, Argentina, Breast Cancer Prevention Program). The obtained breast classifications were compared with the expert medical diagnostics, showing a good performance. The implemented algorithms revealed a high potentiality to classify breasts into tissue density categories.

  10. Clinic application of tissue engineered bronchus for lung cancer treatment

    Science.gov (United States)

    Liu, Ruijun; Chen, Xiaoke; Wu, Jingxiang; Pan, Yinggen; Lu, Shun; Weder, Walter; Luo, Qingquan

    2017-01-01

    Background Delayed revascularization process and substitute infection remain to be key challenges in tissue engineered (TE) airway reconstruction. We propose an “in-vivo bioreactor” design, defined as an implanted TE substitutes perfused with an intra-scaffold medium flow created by an extracorporeal portable pump system for in situ organ regeneration. The perfusate keeps pre-seeded cells alive before revascularization. Meanwhile the antibiotic inside the perfusate controls topical infection. Methods A stage IIIA squamous lung cancer patient received a 5-cm TE airway substitute, bridging left basal segment bronchus to carina, with the in-vivo bioreactor design to avoid left pneumonectomy. Continuous intra-scaffold Ringer’s-gentamicin perfusion lasted for 1 month, together with orthotopic peripheral total nucleated cells (TNCs) injection twice a week. Results The patient recovered uneventfully. Bronchoscopy follow-up confirmed complete revascularization and reepithelialization four months postoperatively. Perfusate waste test demonstrated various revascularization growth factors secreted by TNCs. The patient received two cycles of chemotherapy and 30 Gy radiotherapy thereafter without complications related to the TE substitute. Conclusions In-vivo bioreactor design combines the traditionally separated in vitro 3D cell-scaffold culture system and the in vivo regenerative processes associated with TE substitutes, while treating the recipients as bioreactors for their own TE prostheses. This design can be applied clinically. We also proved for the first time that TE airway substitute is able to tolerate chemo-radiotherapy and suitable to be used in cancer treatment.

  11. The effect of activated alveolar macrophages on experimental lung emphysema development. III. Morphological analysis of the lung tissue and alveolar macrophages in situ.

    Science.gov (United States)

    Sulkowski, S; Nowak, H F; Sulkowska, M; Sobaniec-Lotowska, M; Andrzejewska, A; Sulik, M; Dziecioł, J; Famulski, W; Poczopko, B

    1995-01-01

    Morphological (in light and transmission electron microscope) as well as morphometrical analysis of the lungs was performed on experimental, papain-induced lung emphysema. Development of emphysematous changes was studied seven days after a single intratracheal instillation of papain solution. The effect of alveolar macrophages (AM) activation by BCG-vaccine on changes in pulmonary tissue was analyzed. In the rats given BCG the number of AM increased and demonstrated enhanced activity. Increase in reticulin fibre density in places of AM cumulation, particularly in BCG+papain-treated rats was observed. The lungs of animals treated with BCG+papain showed enhancing of emphysema comparing with the papain-treated rats. Development of emphysematous changes, especially in BCG+papain-treated rats coexisted with cumulation of activated alveolar macrophages and collagen fibres as well as type II alveolar epithelial cells proliferation. Our data support the inflammatory-repair hypothesis of emphysema pathogenesis and indicate that AM regulate collagen production in the lung. Type II alveolar epithelial cells seem be important in lung injury and repair.

  12. Texture feature extraction for the lung lesion density classification on computed tomography scan image

    Directory of Open Access Journals (Sweden)

    Hasnely

    2016-05-01

    Full Text Available The radiology examination by computed tomography (CT scan is an early detection of lung cancer to minimize the mortality rate. However, the assessment and diagnosis by an expert are subjective depending on the competence and experience of a radiologist. Hence, a digital image processing of CT scan is necessary as a tool to diagnose the lung cancer. This research proposes a morphological characteristics method for detecting lung cancer lesion density by using the histogram and GLCM (Gray Level Co-occurrence Matrices. The most well-known artificial neural network (ANN architecture that is the multilayers perceptron (MLP, is used in classifying lung cancer lesion density of heterogeneous and homogeneous. Fifty CT scan images of lungs obtained from the Department of Radiology of RSUP Dr. Sardjito Hospital, Yogyakarta are used as the database. The results show that the proposed method achieved the accuracy of 98%, sensitivity of 96%, and specificity of 96%.

  13. Rituximab efficiently depletes B cells in lung tumors and normal lung tissue [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Albane Joly-Battaglini

    2016-01-01

    Full Text Available Rituximab is a monoclonal antibody that targets the CD20 B-cell-specific antigen and is widely used as therapy for B-cell lymphoma. Since rituximab depletes both malignant and normal B cells, it is increasingly being used to treat various conditions in which normal B cells have a pathogenic role, such as rheumatoid arthritis and multiple sclerosis. It is well-established that rituximab efficiently eliminates B cells in blood, lymph nodes, and spleen. In contrast, the effect of rituximab in non-lymphoid tissues remains poorly documented and is debated. Here, we report a rheumatoid arthritis patient who was treated with rituximab before receiving thoracic surgery for non-small cell lung cancer. Using flow cytometry and immunohistochemistry, we show that rituximab efficiently depleted CD20-positive B cells in a primary lung tumor, in lung-associated lymph nodes, and in normal lung tissue. We conclude that rituximab may be very efficient at depleting normal B cells in the lungs. This property of rituximab may potentially be exploited for the treatment of conditions in which pathogenic B cells reside in the lungs. On the other hand, the clearance of lung B cells may provide an explanation for the rare cases of severe non-infectious pulmonary toxicity of rituximab.

  14. Mineral density volume gradients in normal and diseased human tissues.

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    Sabra I Djomehri

    Full Text Available Clinical computed tomography provides a single mineral density (MD value for heterogeneous calcified tissues containing early and late stage pathologic formations. The novel aspect of this study is that, it extends current quantitative methods of mapping mineral density gradients to three dimensions, discretizes early and late mineralized stages, identifies elemental distribution in discretized volumes, and correlates measured MD with respective calcium (Ca to phosphorus (P and Ca to zinc (Zn elemental ratios. To accomplish this, MD variations identified using polychromatic radiation from a high resolution micro-computed tomography (micro-CT benchtop unit were correlated with elemental mapping obtained from a microprobe X-ray fluorescence (XRF using synchrotron monochromatic radiation. Digital segmentation of tomograms from normal and diseased tissues (N=5 per group; 40-60 year old males contained significant mineral density variations (enamel: 2820-3095 mg/cc, bone: 570-1415 mg/cc, cementum: 1240-1340 mg/cc, dentin: 1480-1590 mg/cc, cementum affected by periodontitis: 1100-1220 mg/cc, hypomineralized carious dentin: 345-1450 mg/cc, hypermineralized carious dentin: 1815-2740 mg/cc, and dental calculus: 1290-1770 mg/cc. A plausible linear correlation between segmented MD volumes and elemental ratios within these volumes was established, and Ca/P ratios for dentin (1.49, hypomineralized dentin (0.32-0.46, cementum (1.51, and bone (1.68 were observed. Furthermore, varying Ca/Zn ratios were distinguished in adapted compared to normal tissues, such as in bone (855-2765 and in cementum (595-990, highlighting Zn as an influential element in prompting observed adaptive properties. Hence, results provide insights on mineral density gradients with elemental concentrations and elemental footprints that in turn could aid in elucidating mechanistic processes for pathologic formations.

  15. Development of LC-QTOF-MS method for human lung tissue fingerprinting. A preliminary application to nonsmall cell lung cancer.

    Science.gov (United States)

    Ciborowski, Michal; Kisluk, Joanna; Pietrowska, Karolina; Samczuk, Paulina; Parfieniuk, Ewa; Kowalczyk, Tomasz; Kozlowski, Miroslaw; Kretowski, Adam; Niklinski, Jacek

    2017-09-01

    The major histologic subtypes of non-small cell lung cancer (NSCLC) include adenocarcinoma (ADC), squamous cell lung carcinoma (SCC), and large-cell carcinoma (LCC). Clinical trials of targeted agents and newer chemotherapy agents yielded differences in outcomes according to histologic subgroups providing a rationale for histology-based treatment in NSCLC. Currently, NSCLC subtyping is performed based on histopathological examinations and immunohistochemistry. However available methods leave about 10% of NSCLC cases as not otherwise specified. The purpose of this study was development of an LC-QTOF-MS method for human lung tissue metabolic fingerprinting that could discriminate NSCLC histological subtypes and propose biomarkers candidates that could support proper NSCLC diagnosis. Metabolites were extracted with acetonitrile or methanol/ethanol and different chromatographic conditions were tested. In the final method 10 mg of lung tissue was homogenized with 50% methanol and metabolites were extracted with acetonitrile. Metabolites were separated on C8-RP and HILIC columns. About 3500 and 2000 of metabolic features (in both ion modes) were detected with good repeatability (CV Lung tumor and control tissue samples obtained from NSCLC patients were analyzed with developed methodology. Acylcarnitines, fatty acids, phospholipids, and amino acids were found more abundant in tumor as compared to control tissue. Acylcarnitines, lysophospholipids, creatinine, creatine, and alanine were identified as potential targets enabling classification of NSCLC subtypes. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Lung density measurements in spontaneous pneumathorax demonstrate air trapping.

    NARCIS (Netherlands)

    Smit, H.J.M.; Golding, R.P.; Schramel, F.M.N.H.; Devillé, W.L.; Manoliu, R.A.; Postmus, P.E.

    2004-01-01

    PURPOSE: Idiopathic spontaneous pneumothorax (SP) is the result of leakage of air from the lung parenchyma through a ruptured visceral pleura into the pleural cavity. This rupture is thought to be caused by an increased pressure difference between parenchymal airspace and pleural cavity. We hypothes

  17. The association of systemic microvascular changes with lung function and lung density: a cross-sectional study.

    Directory of Open Access Journals (Sweden)

    Bianca Harris

    Full Text Available Smoking causes endothelial dysfunction and systemic microvascular disease with resultant end-organ damage in the kidneys, eyes and heart. Little is known about microvascular changes in smoking-related lung disease. We tested if microvascular changes in the retina, kidneys and heart were associated with obstructive spirometry and low lung density on computed tomography. The Multi-Ethnic Study of Atherosclerosis recruited participants age 45-84 years without clinical cardiovascular disease. Measures of microvascular function included retinal arteriolar and venular caliber, urine albumin-to-creatinine ratio and, in a subset, myocardial blood flow on magnetic resonance imaging. Spirometry was measured following ATS/ERS guidelines. Low attenuation areas (LAA were measured on lung fields of cardiac computed tomograms. Regression models adjusted for pulmonary and cardiac risk factors, medications and body size. Among 3,397 participants, retinal venular caliber was inversely associated with forced expiratory volume in one second (FEV(1 (P<0.001 and FEV(1/forced vital capacity (FVC ratio (P = 0.04. Albumin-to-creatinine ratio was inversely associated with FEV(1 (P = 0.002 but not FEV(1/FVC. Myocardial blood flow (n = 126 was associated with lower FEV(1 (P = 0.02, lower FEV(1/FVC (P = 0.001 and greater percentage LAA (P = 0.04. Associations were of greater magnitude among smokers. Low lung function was associated with microvascular changes in the retina, kidneys and heart, and low lung density was associated with impaired myocardial microvascular perfusion. These cross-sectional results suggest that microvascular damage with end-organ dysfunction in all circulations may pertain to the lung, that lung dysfunction may contribute to systemic microvascular disease, or that there may be a shared predisposition.

  18. Adsorption Properties of Typical Lung Cancer Breath Gases on Ni-SWCNTs through Density Functional Theory

    Directory of Open Access Journals (Sweden)

    Qianqian Wan

    2017-01-01

    Full Text Available A lot of useful information is contained in the human breath gases, which makes it an effective way to diagnose diseases by detecting the typical breath gases. This work investigated the adsorption of typical lung cancer breath gases: benzene, styrene, isoprene, and 1-hexene onto the surface of intrinsic and Ni-doped single wall carbon nanotubes through density functional theory. Calculation results show that the typical lung cancer breath gases adsorb on intrinsic single wall carbon nanotubes surface by weak physisorption. Besides, the density of states changes little before and after typical lung cancer breath gases adsorption. Compared with single wall carbon nanotubes adsorption, single Ni atom doping significantly improves its adsorption properties to typical lung cancer breath gases by decreasing adsorption distance and increasing adsorption energy and charge transfer. The density of states presents different degrees of variation during the typical lung cancer breath gases adsorption, resulting in the specific change of conductivity of gas sensing material. Based on the different adsorption properties of Ni-SWCNTs to typical lung cancer breath gases, it provides an effective way to build a portable noninvasive portable device used to evaluate and diagnose lung cancer at early stage in time.

  19. Proteoglycan changes in the extracellular matrix of lung tissue from patients with pulmonary emphysema

    NARCIS (Netherlands)

    van Straaten, JFM; Coers, W; Noordhoek, JA; Flipsen, JTM; Kauffman, HF; Timens, W; Postma, DS

    1999-01-01

    To characterize the changes in the extracellular matrix in smoking-related pulmonary emphysema, we undertook immunohistochemical studies in lung tissues from controls (n = 7), from patients with mild (n = 11) and severe (n = 8) emphysema, and from patients with lung fibrosis (n = 6). We studied coll

  20. Iron supplementation at high altitudes induces inflammation and oxidative injury to lung tissues in rats

    Energy Technology Data Exchange (ETDEWEB)

    Salama, Samir A., E-mail: salama.3@buckeyemail.osu.edu [High Altitude Research Center, Taif University, Al-Haweiah, Taif 21974 (Saudi Arabia); Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University, Cairo 11751 (Egypt); Department of Pharmacology and GTMR Unit, College of Clinical Pharmacy, Taif University, Al-Haweiah, Taif 21974 (Saudi Arabia); Omar, Hany A. [Department of Pharmacology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514 (Egypt); Maghrabi, Ibrahim A. [Department of Clinical Pharmacy, College of Clinical Pharmacy, Taif University, Al-Haweiah, Taif 21974 (Saudi Arabia); AlSaeed, Mohammed S. [Department of Surgery, College of Medicine, Taif University, Al-Haweiah, Taif 21974 (Saudi Arabia); EL-Tarras, Adel E. [High Altitude Research Center, Taif University, Al-Haweiah, Taif 21974 (Saudi Arabia)

    2014-01-01

    Exposure to high altitudes is associated with hypoxia and increased vulnerability to oxidative stress. Polycythemia (increased number of circulating erythrocytes) develops to compensate the high altitude associated hypoxia. Iron supplementation is, thus, recommended to meet the demand for the physiological polycythemia. Iron is a major player in redox reactions and may exacerbate the high altitudes-associated oxidative stress. The aim of this study was to explore the potential iron-induced oxidative lung tissue injury in rats at high altitudes (6000 ft above the sea level). Iron supplementation (2 mg elemental iron/kg, once daily for 15 days) induced histopathological changes to lung tissues that include severe congestion, dilatation of the blood vessels, emphysema in the air alveoli, and peribronchial inflammatory cell infiltration. The levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), lipid peroxidation product and protein carbonyl content in lung tissues were significantly elevated. Moreover, the levels of reduced glutathione and total antioxidant capacity were significantly reduced. Co-administration of trolox, a water soluble vitamin E analog (25 mg/kg, once daily for the last 7 days of iron supplementation), alleviated the lung histological impairments, significantly decreased the pro-inflammatory cytokines, and restored the oxidative stress markers. Together, our findings indicate that iron supplementation at high altitudes induces lung tissue injury in rats. This injury could be mediated through excessive production of reactive oxygen species and induction of inflammatory responses. The study highlights the tissue injury induced by iron supplementation at high altitudes and suggests the co-administration of antioxidants such as trolox as protective measures. - Highlights: • Iron supplementation at high altitudes induced lung histological changes in rats. • Iron induced oxidative stress in lung tissues of rats at high altitudes. • Iron

  1. Improved correction for the tissue fraction effect in lung PET/CT imaging

    Science.gov (United States)

    Holman, Beverley F.; Cuplov, Vesna; Millner, Lynn; Hutton, Brian F.; Maher, Toby M.; Groves, Ashley M.; Thielemans, Kris

    2015-09-01

    Recently, there has been an increased interest in imaging different pulmonary disorders using PET techniques. Previous work has shown, for static PET/CT, that air content in the lung influences reconstructed image values and that it is vital to correct for this ‘tissue fraction effect’ (TFE). In this paper, we extend this work to include the blood component and also investigate the TFE in dynamic imaging. CT imaging and PET kinetic modelling are used to determine fractional air and blood voxel volumes in six patients with idiopathic pulmonary fibrosis. These values are used to illustrate best and worst case scenarios when interpreting images without correcting for the TFE. In addition, the fractional volumes were used to determine correction factors for the SUV and the kinetic parameters. These were then applied to the patient images. The kinetic parameters K1 and Ki along with the static parameter SUV were all found to be affected by the TFE with both air and blood providing a significant contribution to the errors. Without corrections, errors range from 34-80% in the best case and 29-96% in the worst case. In the patient data, without correcting for the TFE, regions of high density (fibrosis) appeared to have a higher uptake than lower density (normal appearing tissue), however this was reversed after air and blood correction. The proposed correction methods are vital for quantitative and relative accuracy. Without these corrections, images may be misinterpreted.

  2. Measurement of MMP-9 and -12 degraded elastin (ELM) provides unique information on lung tissue degradation

    DEFF Research Database (Denmark)

    Skjøt-Arkil, Helene; Clausen, Rikke E; Nguyen, Quoc Hai Trieu;

    2012-01-01

    Elastin is an essential component of selected connective tissues that provides a unique physiological elasticity. Elastin may be considered a signature protein of lungs where matrix metalloprotease (MMP) -9-and -12, may be considered the signature proteases of the macrophages, which in part...... are responsible for tissue damage during disease progression. Thus, we hypothesized that a MMP-9/-12 generated fragment of elastin may be a relevant biochemical maker for lung diseases....

  3. Nickel accumulation in lung tissues is associated with increased risk of p53 mutation in lung cancer patients.

    Science.gov (United States)

    Chiou, Yu-Hu; Wong, Ruey-Hong; Chao, Mu-Rong; Chen, Chih-Yi; Liou, Saou-Hsing; Lee, Huei

    2014-10-01

    Occupational exposure to nickel compounds has been associated with lung cancer. The correlation between high nickel levels and increased risk of lung cancer has been previously reported in a case-control study. This study assessed whether nickel exposure increased the occurrence of p53 mutations due to DNA repair inhibition by nickel. A total of 189 lung cancer patients were enrolled to determine nickel levels in tumor-adjacent normal lung tissues and p53 mutation status in lung tumors through atomic absorption spectrometry and direct sequencing, respectively. Nickel levels in p53 mutant patients were significantly higher than those in p53 wild-type patients. When patients were divided into high- and low-nickel subgroups by median nickel level, the high-nickel subgroup of patients had an odds ratio (OR) of 3.25 for p53 mutation risk relative to the low-nickel subgroup patients. The OR for p53 mutation risk of lifetime non-smokers, particularly females, in the high-nickel subgroup was greater than that in the low-nickel subgroup. To determine whether nickel affected DNA repair capacity, we conducted the host cell reactivation assay in A549 and H1975 lung cancer cells and showed that the DNA repair activity was reduced by nickel chloride in a dose-dependent manner. This was associated with elevated production of hydrogen peroxide-induced 8-oxo-deoxyguanosine. Therefore, increased risk of p53 mutation due to defective DNA repair caused by high nickel levels in lung tissues may be one mechanism by which nickel exposure contributes to lung cancer development, especially in lifetime female non-smokers.

  4. Up-regulation of ALG-2 in hepatomas and lung cancer tissue

    DEFF Research Database (Denmark)

    la Cour, Jonas Marstrand; Mollerup, Jens; Winding, Pernille

    2003-01-01

    , a result confirmed by immunohistochemical analysis. Staining of four different lung cancer tissue microarrays including specimens of 263 patients showed that ALG-2 is mainly localized to epithelial cells and significantly up-regulated in small-cell lung cancers and in non-small-cell lung cancers. Our...... using Western blot analysis and immunohistochemistry. Western blot analysis of 15 different adult mouse tissues demonstrated that ALG-2 is ubiquitously expressed. We found that ALG-2 was more than threefold overexpressed in rat liver hepatoma compared to normal rat liver using Western blot analysis...

  5. High and low mammographic density human breast tissues maintain histological differential in murine tissue engineering chambers.

    Science.gov (United States)

    Chew, G L; Huang, D; Lin, S J; Huo, C; Blick, T; Henderson, M A; Hill, P; Cawson, J; Morrison, W A; Campbell, I G; Hopper, J L; Southey, M C; Haviv, I; Thompson, E W

    2012-08-01

    Mammographic density (MD) is the area of breast tissue that appears radiologically white on mammography. Although high MD is a strong risk factor for breast cancer, independent of BRCA1/2 mutation status, the molecular basis of high MD and its associated breast cancer risk is poorly understood. MD studies will benefit from an animal model, where hormonal, gene and drug perturbations on MD can be measured in a preclinical context. High and low MD tissues were selectively sampled by stereotactic biopsy from operative specimens of high-risk women undergoing prophylactic mastectomy. The high and low MD tissues were transferred into separate vascularised biochambers in the groins of SCID mice. Chamber material was harvested after 6 weeks for histological analyses and immunohistochemistry for cytokeratins, vimentin and a human-specific mitochondrial antigen. Within-individual analysis was performed in replicate mice, eliminating confounding by age, body mass index and process-related factors, and comparisons were made to the parental human tissue. Maintenance of differential MD post-propagation was assessed radiographically. Immunohistochemical staining confirmed the preservation of human glandular and stromal components in the murine biochambers, with maintenance of radiographic MD differential. Propagated high MD regions had higher stromal (p = 0.0002) and lower adipose (p = 0.0006) composition, reflecting the findings in the original human breast tissue, although glands appeared small and non-complex in both high and low MD groups. No significant differences were observed in glandular area (p = 0.4) or count (p = 0.4) between high and low MD biochamber tissues. Human mammary glandular and stromal tissues were viably maintained in murine biochambers, with preservation of differential radiographic density and histological features. Our study provides a murine model for future studies into the biomolecular basis of MD as a risk factor for breast cancer.

  6. Cardiovascular Tissue Engineering Research Support at the National Heart, Lung, and Blood Institute

    OpenAIRE

    Lundberg, Martha Shauck

    2013-01-01

    Tissue engineering aims at building three-dimensional living substitutes that are equal to or better than the damaged tissue to be replaced. The development of such a tissue replacement requires a multidisciplinary approach and careful attention to the optimal cell source, the interactions of growth factors and extracellular milieu, and the scaffolding design. This article is a review of the National Heart, Lung, and Blood Institute's (NHLBI) tissue engineering programs, which support researc...

  7. Microstructural Analysis of Peripheral Lung Tissue through CPMG Inter-Echo Time R2 Dispersion.

    Directory of Open Access Journals (Sweden)

    Felix T Kurz

    Full Text Available Since changes in lung microstructure are important indicators for (early stage lung pathology, there is a need for quantifiable information of diagnostically challenging cases in a clinical setting, e.g. to evaluate early emphysematous changes in peripheral lung tissue. Considering alveoli as spherical air-spaces surrounded by a thin film of lung tissue allows deriving an expression for Carr-Purcell-Meiboom-Gill transverse relaxation rates R2 with a dependence on inter-echo time, local air-tissue volume fraction, diffusion coefficient and alveolar diameter, within a weak field approximation. The model relaxation rate exhibits the same hyperbolic tangent dependency as seen in the Luz-Meiboom model and limiting cases agree with Brooks et al. and Jensen et al. In addition, the model is tested against experimental data for passively deflated rat lungs: the resulting mean alveolar radius of RA = 31.46 ± 13.15 μm is very close to the literature value (∼34 μm. Also, modeled radii obtained from relaxometer measurements of ageing hydrogel foam (that mimics peripheral lung tissue are in good agreement with those obtained from μCT images of the same foam (mean relative error: 0.06 ± 0.01. The model's ability to determine the alveolar radius and/or air volume fraction will be useful in quantifying peripheral lung microstructure.

  8. Prediction of lung density changes after radiotherapy by cone beam computed tomography response markers and pre-treatment factors for non-small cell lung cancer patients

    DEFF Research Database (Denmark)

    Bernchou, Uffe; Hansen, Olfred; Schytte, Tine;

    2015-01-01

    BACKGROUND AND PURPOSE: This study investigates the ability of pre-treatment factors and response markers extracted from standard cone-beam computed tomography (CBCT) images to predict the lung density changes induced by radiotherapy for non-small cell lung cancer (NSCLC) patients. METHODS...... AND MATERIALS: Density changes in follow-up computed tomography scans were evaluated for 135 NSCLC patients treated with radiotherapy. Early response markers were obtained by analysing changes in lung density in CBCT images acquired during the treatment course. The ability of pre-treatment factors and CBCT...... markers to predict lung density changes induced by radiotherapy was investigated. RESULTS: Age and CBCT markers extracted at 10th, 20th, and 30th treatment fraction significantly predicted lung density changes in a multivariable analysis, and a set of response models based on these parameters were...

  9. The Expression and Significance of RKIP in Lung Squamous Cell Carcinoma Tissues

    Directory of Open Access Journals (Sweden)

    Haiyuan XU

    2011-03-01

    Full Text Available Background and objective Raf kinase inhibitory protein (RKIP belongs to the phosphatidylethanolamine binding protein (PEBP family. RKIP is an endogenous inhibitor of the Raf-1-MEK1/2-ERK1/2 signaling pathway, NFkappaB signaling pathway and G protein coupled receptors signaling pathway. The aim of this study is to explore the expression of RKIP in lung squamous cell carcinoma, and the relationship between RKIP expression and clinical pathology of lung squamous cell carcinoma. Methods The expression of RKIP mRNA was detected in 56 lung squamous cell carcinoma tissues and adjacent cancer tissues by RT-PCR. The expression level of RKIP protein was detected by Western blot. The positive rates of RKIP expression in cancer tissues and adjacent cancer tissues were analyzed. Results RKIP mRNA positive expression rate in cancer tissues was significantly lower than that in adjacent cancer tissues (P < 0.05. The positive rate of RKIP mRNA expression in the cancer tissues with lymph node metastasis was significantly lower than that without lymph node metastasis (P < 0.05. RKIP mRNA expression has no remarkable correlation with age, sex, tumor differentiation and size (P > 0.05. RKIP protein expression in the cancer tissues was significantly lower than that in adjacent cancer tissues (P < 0.05. Conclusion The deficiency of RKIP expression is positively correlated with carcinogenesis and invasion metastasis of lung squamous cell carcinoma.

  10. The Potential for Resident Lung Mesenchymal Stem Cells to Promote Functional Tissue Regeneration: Understanding Microenvironmental Cues

    Directory of Open Access Journals (Sweden)

    Susan M. Majka

    2012-10-01

    Full Text Available Tissue resident mesenchymal stem cells (MSCs are important regulators of tissue repair or regeneration, fibrosis, inflammation, angiogenesis and tumor formation. Bone marrow derived mesenchymal stem cells (BM-MSCs and endothelial progenitor cells (EPC are currently being considered and tested in clinical trials as a potential therapy in patients with such inflammatory lung diseases including, but not limited to, chronic lung disease, pulmonary arterial hypertension (PAH, pulmonary fibrosis (PF, chronic obstructive pulmonary disease (COPD/emphysema and asthma. However, our current understanding of tissue resident lung MSCs remains limited. This review addresses how environmental cues impact on the phenotype and function of this endogenous stem cell pool. In addition, it examines how these local factors influence the efficacy of cell-based treatments for lung diseases.

  11. The potential for resident lung mesenchymal stem cells to promote functional tissue regeneration: understanding microenvironmental cues.

    Science.gov (United States)

    Foronjy, Robert F; Majka, Susan M

    2012-12-01

    Tissue resident mesenchymal stem cells (MSCs) are important regulators of tissue repair or regeneration, fibrosis, inflammation, angiogenesis and tumor formation. Bone marrow derived mesenchymal stem cells (BM-MSCs) and endothelial progenitor cells (EPC) are currently being considered and tested in clinical trials as a potential therapy in patients with such inflammatory lung diseases including, but not limited to, chronic lung disease, pulmonary arterial hypertension (PAH), pulmonary fibrosis (PF), chronic obstructive pulmonary disease (COPD)/emphysema and asthma. However, our current understanding of tissue resident lung MSCs remains limited. This review addresses how environmental cues impact on the phenotype and function of this endogenous stem cell pool. In addition, it examines how these local factors influence the efficacy of cell-based treatments for lung diseases.

  12. Measurement of histamine release from human lung tissue ex vivo by microdialysis technique

    DEFF Research Database (Denmark)

    Nissen, Dan; Petersen, Lars Jelstrup; Nolte, H;

    1998-01-01

    OBJECTIVE AND DESIGN: Currently no method is available for measurement of mediator release from intact human lung. In this study, a microdialysis technique was used to measure histamine release from mast cells in human lung tissue ex vivo. MATERIAL: Microdialysis fibers of 216 microm were inserted...... into lung tissue and perfused with Krebs Ringer buffer at a rate of 3 microl/min. After a 15 min period of steady-state perfusion, anti-IgE and vehicle were injected into the lung tissue above individual fibers. Samples from each fibre were collected for 20 min at 2 min intervals. Histamine was assayed...... fluorometrically. RESULTS: Anti-IgE concentrations of 40-40,000 U/ml dose-dependently released histamine, significant histamine release being demonstrated with anti-IgE concentrations of 400 U/ml and greater. The kinetics of histamine release showed peak values 2-8 min after the injection. Great individual...

  13. Expression of IRAK1 in lung cancer tissues and its clinicopathological significance: a microarray study.

    Science.gov (United States)

    Zhang, Xiuling; Dang, Yiwu; Li, Ping; Rong, Minhua; Chen, Gang

    2014-01-01

    The interleukin-1 receptor associated kinases 1 (IRAK1) is a down stream effector molecule of the toll like receptor (TLR) signaling pathway, which is involved in inflammation, autoimmunity and cancer. However, the role of IRAK1 in lung cancer remains unclarified. Herein, we investigated the protein expression and the clinicopathological significance of IRAK1 in 3 formalin-fixed paraffin-embedded lung cancer tissue microarrays by using immunohistochemistry, which included 365 tumor and 30 normal lung tissues. We found that the expression of IRAK1 in lung cancer was significantly higher compared with that in normal lung tissues (P=0.002). Receiver operating characteristic (ROC) curves were generated to evaluate the power of IRAK1 to distinguish lung cancer from non-cancerous lung tissue. The area under curve (AUC) of ROC of IRAK1 was 0.643 (95% CI 0.550~0.735, P=0.009). Additionally, IRAK1 expression was related to clinical TNM stage (r=0.241, P tissues (P=0.003, P=0.002, respectively). Further spearman analysis showed that IRAK1 protein in NSCLC was positive correlated with clinical TNM stage (r=0.222, P < 0.001), lymph node metastasis (r=0.277, P < 0.001), tumor size (r=0.292, P < 0.001) and distal metastasis (r=0.110, P=0.043). In conclusion, the expression of IRAK1 protein might be valuable in identifying patients with increased risks of lung cancer and might act as a target for diagnosis and gene therapy for lung cancer.

  14. Tissue Carcinoembryonic Antigen, Calcium, Copper and Iron Levels in Cancerous Lung Patients

    Directory of Open Access Journals (Sweden)

    Nasar Yousuf ALWAHAIBI

    2011-01-01

    Full Text Available Background and objective The expression of various trace elements and markers in lung cancer is controversial. The aim of this study is to evaluate the presence of calcium (Ca, copper (Cu, iron (Fe and carcinoembryonic antigen (CEA in cancerous untreated lung tissues and to determine a possible association between these markers and lung cancer. Methods Fourty-eight cancerous lung tissue blocks, from Sultan Qaboos University Hospital, Sultanate of Oman, were studied. Fe, Ca, Cu, and CEA were demonstrated in the tissue blocks using Perl's Prussian blue, Von Kossa's, modified rhodanine and immunohistochemical staining methods, respectively. Results Twenty-three of 48 specimens showed positive Fe staining, 2 showed positive Ca staining and Cu was absent in all specimens. 93.7% expressed CEA in varying degree of positivity. 81.25% of these sections showed high expression of CEA. Conclusion Tissue concentrations of trace elements were not elevated in lung cancer and therefore cannot be considered as a potential marker. Despite the low sensitivity and specificity of CEA as previously reported, tissue CEA should be considered as a potential marker in the evaluation of lung cancer.

  15. Tissue Carcinoembryonic Antigen, Calcium, Copper and Iron Levels in Cancerous Lung Patients

    Institute of Scientific and Technical Information of China (English)

    Nasar Yousuf ALWAHAIBI; Jokha Sultan ALGHARIBI; Amna Salim ALSHUKAILI; Ahmed Khalifa ALSHUKAILI

    2011-01-01

    Background and objective The expression of various trace elements and markers in lung cancer is controversial. The aim of this study is to evaluate the presence of calcium (Ca), copper (Cu), iron (Fe) and carcinoembryonic antigen (CEA) in cancerous untreated lung tissues and to determine a possible association between these markers and lung cancer.Methods Fourty-eight cancerous lung tissue blocks, from Sultan Qaboos University Hospital, Sultanate of Oman, were studied. Fe, Ca, Cu, and CEA were demonstrated in the tissue blocks using Perl's Prussian blue, Von Kossa's, modified rhodanine and immunohistochemical staining methods, respectively.Results Twenty-three of 48 specimens showed positive Fe staining, 2 showed positive Ca staining and Cu was absent in all specimens. 93.7% expressed CEA in varying degree of positivity. 81.25% of these sections showed high expression of CEA. Conclusion Tissue concentrations of trace elements were not elevated in lung cancer and therefore cannot be considered as a potential marker. Despite the low sensitivity and specificity of CEA as previously reported, tissue CEA should be considered as a potential marker in the evaluation of lung cancer.

  16. Optical imaging of tissue mitochondrial redox state in intact rat lungs in two models of pulmonary oxidative stress.

    Science.gov (United States)

    Sepehr, Reyhaneh; Staniszewski, Kevin; Maleki, Sepideh; Jacobs, Elizabeth R; Audi, Said; Ranji, Mahsa

    2012-04-01

    Ventilation with enhanced fractions of O(2) (hyperoxia) is a common and necessary treatment for hypoxemia in patients with lung failure, but prolonged exposure to hyperoxia causes lung injury. Ischemia-reperfusion (IR) injury of lung tissue is common in lung transplant or crush injury to the chest. These conditions are associated with apoptosis and decreased survival of lung tissue. The objective of this work is to use cryoimaging to evaluate the effect of exposure to hyperoxia and IR injury on lung tissue mitochondrial redox state in rats. The autofluorescent mitochondrial metabolic coenzymes nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) are electron carriers in ATP generation. These intrinsic fluorophores were imaged for rat lungs using low-temperature fluorescence imaging (cryoimaging). Perfused lungs from four groups of rats were studied: normoxia (control), control perfused with an mitochondrial complex IV inhibitor (potassium cyanide, KCN), rats exposed to hyperoxia (85% O(2)) for seven days, and from rats subjected to lung IR in vivo 24 hours prior to study. Each lung was sectioned sequentially in the transverse direction, and the images were used to reconstruct a three-dimensional (3-D) rendering. In KCN perfused lungs the respiratory chain was more reduced, whereas hyperoxic and IR lung tissue have a more oxidized respiratory chain than control lung tissue, consistent with previously measured mitochondrial dysfunction in both hyperoxic and IR lungs.

  17. Optical imaging of tissue mitochondrial redox state in intact rat lungs in two models of pulmonary oxidative stress

    Science.gov (United States)

    Sepehr, Reyhaneh; Staniszewski, Kevin; Maleki, Sepideh; Jacobs, Elizabeth R.; Audi, Said

    2012-01-01

    Abstract. Ventilation with enhanced fractions of O2 (hyperoxia) is a common and necessary treatment for hypoxemia in patients with lung failure, but prolonged exposure to hyperoxia causes lung injury. Ischemia-reperfusion (IR) injury of lung tissue is common in lung transplant or crush injury to the chest. These conditions are associated with apoptosis and decreased survival of lung tissue. The objective of this work is to use cryoimaging to evaluate the effect of exposure to hyperoxia and IR injury on lung tissue mitochondrial redox state in rats. The autofluorescent mitochondrial metabolic coenzymes nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) are electron carriers in ATP generation. These intrinsic fluorophores were imaged for rat lungs using low-temperature fluorescence imaging (cryoimaging). Perfused lungs from four groups of rats were studied: normoxia (control), control perfused with an mitochondrial complex IV inhibitor (potassium cyanide, KCN), rats exposed to hyperoxia (85% O2) for seven days, and from rats subjected to lung IR in vivo 24 hours prior to study. Each lung was sectioned sequentially in the transverse direction, and the images were used to reconstruct a three-dimensional (3-D) rendering. In KCN perfused lungs the respiratory chain was more reduced, whereas hyperoxic and IR lung tissue have a more oxidized respiratory chain than control lung tissue, consistent with previously measured mitochondrial dysfunction in both hyperoxic and IR lungs. PMID:22559688

  18. Combination effects of tissue heterogeneity and geometric targeting error in stereotactic body radiotherapy for lung cancer using CyberKnife.

    Science.gov (United States)

    Kang, Ki Mun; Jeong, Bae Kwon; Choi, Hoon-Sik; Yoo, Seung Hoon; Hwang, Ui-Jung; Lim, Young Kyung; Jeong, Hojin

    2015-09-08

    We have investigated the combined effect of tissue heterogeneity and its variation associated with geometric error in stereotactic body radiotherapy (SBRT) for lung cancer. The treatment plans for eight lung cancer patients were calculated using effective path length (EPL) correction and Monte Carlo (MC) algorithms, with both having the same beam configuration for each patient. These two kinds of plans for individual patients were then subsequently recalculated with adding systematic and random geometric errors. In the ordinary treatment plans calculated with no geometric offset, the EPL calculations, compared with the MC calculations, largely overestimated the doses to PTV by ~ 21%, whereas the overestimation were markedly lower in GTV by ~ 12% due to relatively higher density of GTV than of PTV. When recalculating the plans for individual patients with assigning the systematic and random geometric errors, no significant changes in the relative dose distribution, except for overall shift, were observed in the EPL calculations, whereas largely altered in the MC calculations with a consistent increase in dose to GTV. Considering the better accuracy of MC than EPL algorithms, the present results demonstrated the strong coupling of tissue heterogeneity and geometric error, thereby emphasizing the essential need for simultaneous correction for tissue heterogeneity and geometric targeting error in SBRT of lung cancer.

  19. EXPRESSION AND SIGNIFICANCE OF C-erbB-2 IN THE TISSUES OF LUNG CANCER

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To elucidate the expression and clinical significance of C-erbB-2 in the tissue of lung cancer. Methods Immunohistochemistry method was used to detect the protein expression of C-erbB-2 in lung cancer tissue. Results The positive expression rate of C-erbB-2 protein in 38 cases of lung cancer was 53.3% (21/38),which was higher than those in lung benign control group (P<0. 001). The significant correlation were found between the protein level and tumor stage(r= +0. 64,P<0.02). The order was stage Ⅳ>stage Ⅲ >stage Ⅱ >stage Ⅰ . There was no correlation among protein expression of C-erbB-2 in various histological types of lung cancer (P>0.05 for all). Conclusion The positive expression rates of C-erbB-2 were significantly higher in lung cancer group than those in benign control group. There is significant correlation between C-erbB-2 expression and lung cancer stage. There is no correlation among protein expression of C-erbB-2 and histological types of lung cancer.

  20. Lung-resident tissue macrophages generate Foxp3+ regulatory T cells and promote airway tolerance.

    Science.gov (United States)

    Soroosh, Pejman; Doherty, Taylor A; Duan, Wei; Mehta, Amit Kumar; Choi, Heonsik; Adams, Yan Fei; Mikulski, Zbigniew; Khorram, Naseem; Rosenthal, Peter; Broide, David H; Croft, Michael

    2013-04-01

    Airway tolerance is the usual outcome of inhalation of harmless antigens. Although T cell deletion and anergy are likely components of tolerogenic mechanisms in the lung, increasing evidence indicates that antigen-specific regulatory T cells (inducible Treg cells [iTreg cells]) that express Foxp3 are also critical. Several lung antigen-presenting cells have been suggested to contribute to tolerance, including alveolar macrophages (MØs), classical dendritic cells (DCs), and plasmacytoid DCs, but whether these possess the attributes required to directly promote the development of Foxp3(+) iTreg cells is unclear. Here, we show that lung-resident tissue MØs coexpress TGF-β and retinal dehydrogenases (RALDH1 and RALDH 2) under steady-state conditions and that their sampling of harmless airborne antigen and presentation to antigen-specific CD4 T cells resulted in the generation of Foxp3(+) Treg cells. Treg cell induction in this model depended on both TGF-β and retinoic acid. Transfer of the antigen-pulsed tissue MØs into the airways correspondingly prevented the development of asthmatic lung inflammation upon subsequent challenge with antigen. Moreover, exposure of lung tissue MØs to allergens suppressed their ability to generate iTreg cells coincident with blocking airway tolerance. Suppression of Treg cell generation required proteases and TLR-mediated signals. Therefore, lung-resident tissue MØs have regulatory functions, and strategies to target these cells might hold promise for prevention or treatment of allergic asthma.

  1. Lung tissue flap repairs esophagus defection with an inner chitosan tube stent

    Institute of Scientific and Technical Information of China (English)

    Gang Chen; Wen-Jun Shi

    2009-01-01

    AIM:To repair the partial esophagus defect with a chitosan stent, a new esophageal prosthesis made of pulmonary tissue with vascular pedicle. METHODS:Fifteen Japanese big ear white rabbits were divided into experimental group ( n = 10) and control group ( n = 5). Esophagus defect in rabbits of experimental group was repaired using lung tissue flap with a chitosan tube stent, gross and histological appearance was observed at week 2, 4 and 8 after operation, and barium sulphate X-ray screen was performed at week 10 after operation. Esophagus defect of rabbits in control group was repaired using lung tissue flap with no chitosan tube stent, gross and histological appearance was observed at week 2, 4 and 8 after operation, and barium sulphate X-ray screen was performed at week 10 after operation. RESULTS:In the experimental group, 6 rabbits survived for over two weeks, the lung tissue flap healed esophageal defec t ion, and squamous metaplasia occurred on the surface of lung tissue flap. At week 10 after operation, barium sulphate examination found that barium was fluent through the esophagus with no stricture or back stream, the creeping was good. In the control group, 4 rabbits survived for two weeks, the lung tissue flap healed esophageal defection with fibrous tissue hyperplasia, barium sulphate examination found that barium was fluent through the esophagus with a slight stricture or back stream, and the creeping was not good at week 10 after operation.CONCLUSION:Esophagus defect can be repaired using lung tissue flap with an inner chitosan tube stent.

  2. Effect of lung and target density on small-field dose coverage and PTV definition

    Energy Technology Data Exchange (ETDEWEB)

    Higgins, Patrick D., E-mail: higgi010@umn.edu; Ehler, Eric D.; Cho, Lawrence C.; Dusenbery, Kathryn E.

    2015-04-01

    We have studied the effect of target and lung density on block margin for small stereotactic body radiotherapy (SBRT) targets. A phantom (50 × 50 × 50 cm{sup 3}) was created in the Pinnacle (V9.2) planning system with a 23-cm diameter lung region of interest insert. Diameter targets of 1.6, 2.0, 3.0, and 4.0 cm were placed in the lung region of interest and centered at a physical depth of 15 cm. Target densities evaluated were 0.1 to 1.0 g/cm{sup 3}, whereas the surrounding lung density was varied between 0.05 and 0.6 g/cm{sup 3}. A dose of 100 cGy was delivered to the isocenter via a single 6-MV field, and the ratio of the average dose to points defining the lateral edges of the target to the isocenter dose was recorded for each combination. Field margins were varied from none to 1.5 cm in 0.25-cm steps. Data obtained in the phantom study were used to predict planning treatment volume (PTV) margins that would match the clinical PTV and isodose prescription for a clinical set of 39 SBRT cases. The average internal target volume (ITV) density was 0.73 ± 0.17, average local lung density was 0.33 ± 0.16, and average ITV diameter was 2.16 ± 0.8 cm. The phantom results initially underpredicted PTV margins by 0.35 cm. With this offset included in the model, the ratio of predicted-to-clinical PTVs was 1.05 ± 0.32. For a given target and lung density, it was found that treatment margin was insensitive to target diameter, except for the smallest (1.6-cm diameter) target, for which the treatment margin was more sensitive to density changes than the larger targets. We have developed a graphical relationship for block margin as a function of target and lung density, which should save time in the planning phase by shortening the design of PTV margins that can satisfy Radiation Therapy Oncology Group mandated treatment volume ratios.

  3. Comprehensive Analysis of Transcriptome Sequencing Data in the Lung Tissues of COPD Subjects

    Directory of Open Access Journals (Sweden)

    Woo Jin Kim

    2015-01-01

    Full Text Available Background and Objectives. Chronic obstructive pulmonary disease (COPD is a complex disease characterized by airflow limitation. Although airway inflammation and oxidative stress are known to be important in the pathogenesis of COPD, the mechanism underlying airflow obstruction is not fully understood. Gene expression profiling of lung tissue was performed to define the molecular pathways that are dysregulated in COPD. Methods. RNA was isolated from lung tissues obtained from 98 subjects with COPD and 91 control subjects with normal spirometry. The RNA samples were processed with RNA-seq using the HiSeq 2000 system. Genes expressed differentially between the two groups were identified using Student’s t-test. Results. After filtering for genes with zero counts and noncoding genes, 16,676 genes were evaluated. A total of 2312 genes were differentially expressed between the lung tissues of COPD and control subjects (false discovery rate corrected q<0.01. The expression of genes related to oxidative phosphorylation and protein catabolism was reduced and genes related to chromatin modification were dysregulated in lung tissues of COPD subjects. Conclusions. Oxidative phosphorylation, protein degradation, and chromatin modification were the most dysregulated pathways in the lung tissues of COPD subjects. These findings may have clinical and mechanistic implications in COPD.

  4. EXPRESSION AND SIGNIFICANCE OF SURVIVIN mRNA IN LUNG CANCER TISSUE MICROARRAY DETECTED BY FISH

    Institute of Scientific and Technical Information of China (English)

    Xin-yun Wang; Xing-ye Wu; Zhi Yao; Yan Li; Ting Liu; Hai-yan Zheng; Cong-zhong Zhu; Cui-yun Sun; Ai-xiang Wang; Min Zhao

    2005-01-01

    Objective To investigate the expression of Survivin mRNA in lung cancer tissue microarray (TMA) by fluorescence in situ hybridization (FISH) method, and determine the role and significance of it in lung cancer genesis and progress. Methods The expression of Survivin mRNA was detected by FISH method and TMA technology. Fifty-four cases of lung cancer and 10 cases of normal lung tissue were examined. Results Survivin mRNA was expressed in 66.7% (36/54) of lung cancer; the positive ratio of lung cancer was significantly higher than that of normal lung tissue (0/10; x2= 15.238, P < 0.05). The positive ratio of Survivin mRNA was significantly higher in poor differentiated cancer (20/24, 83.3%) than moderate and well differentiated cancer (16/30, 53.3%; x2= 5.40, P <0.05). The positive ratio of Survivin mRNA was significantly higher in group with lymph node metastasis (27/32, 84.4%) than without lymph node metastasis (9/22, 40.9%; x2= 11.084, P < 0.05). The positive ratio of Survivin mRNA was significantly higher in stage Ⅲ-Ⅳ(12/13, 92.3%) than stage Ⅰ - Ⅱ (24/41, 58.5%; x2= 5.066, P < 0.05). Conclusion Survivin mRNA highly expresses in lung cancer, which is related to the progress and malignant behavior. Survivin may play a promoting role in lung cancer genesis and progress and provide a basis for estimating prognosis and treatment.

  5. Method for Obtaining Committed Adult Mesenchymal Precursors from Skin and Lung Tissue

    OpenAIRE

    Aurora Bernal; María Fernández; Pérez, Laura M.; Nuria San Martín; Gálvez, Beatriz G.

    2012-01-01

    AIMS: The present study reports an easy and efficient method for obtaining adult mesenchymal precursors from different adult mouse tissues. MATERIALS AND METHODS: We describe the isolation and expansion of mesenchymal precursors from skin and lung by a non-enzymatic method. Skin and lung mesenchymal precursors isolated by a modified explant technique were characterized in vitro by defined morphology and by a specific gene expression profile and surface markers. RESULTS AND CONCLUSIONS: Our re...

  6. Up-regulation of ALG-2 in hepatomas and lung cancer tissue

    DEFF Research Database (Denmark)

    la Cour, Jonas Marstrand; Mollerup, Jens; Winding, Pernille

    2003-01-01

    ALG-2 was isolated in a screen for proteins involved in programmed cell death and is the first Ca(2+)-binding protein found to be directly involved in apoptosis. We have generated polyclonal antibodies that are suitable for detecting ALG-2 using different immunological methods. Three commercial......, a result confirmed by immunohistochemical analysis. Staining of four different lung cancer tissue microarrays including specimens of 263 patients showed that ALG-2 is mainly localized to epithelial cells and significantly up-regulated in small-cell lung cancers and in non-small-cell lung cancers. Our...

  7. Three dimensional imaging of paraffin embedded human lung tissue samples by micro-computed tomography.

    Directory of Open Access Journals (Sweden)

    Anna E Scott

    Full Text Available Understanding the three-dimensional (3-D micro-architecture of lung tissue can provide insights into the pathology of lung disease. Micro computed tomography (µCT has previously been used to elucidate lung 3D histology and morphometry in fixed samples that have been stained with contrast agents or air inflated and dried. However, non-destructive microstructural 3D imaging of formalin-fixed paraffin embedded (FFPE tissues would facilitate retrospective analysis of extensive tissue archives of lung FFPE lung samples with linked clinical data.FFPE human lung tissue samples (n = 4 were scanned using a Nikon metrology µCT scanner. Semi-automatic techniques were used to segment the 3D structure of airways and blood vessels. Airspace size (mean linear intercept, Lm was measured on µCT images and on matched histological sections from the same FFPE samples imaged by light microscopy to validate µCT imaging.The µCT imaging protocol provided contrast between tissue and paraffin in FFPE samples (15 mm x 7 mm. Resolution (voxel size 6.7 µm in the reconstructed images was sufficient for semi-automatic image segmentation of airways and blood vessels as well as quantitative airspace analysis. The scans were also used to scout for regions of interest, enabling time-efficient preparation of conventional histological sections. The Lm measurements from µCT images were not significantly different to those from matched histological sections.We demonstrated how non-destructive imaging of routinely prepared FFPE samples by laboratory µCT can be used to visualize and assess the 3D morphology of the lung including by morphometric analysis.

  8. Fibrocytes and the tissue niche in lung repair

    Directory of Open Access Journals (Sweden)

    Bjermer Leif

    2011-06-01

    Full Text Available Abstract Human fibrocytes are bone marrow-derived mesenchymal progenitor cells that express a variety of markers related to leukocytes, hematopoietic stem cells and a diverse set of fibroblast phenotypes. Fibrocytes can be recruited from the circulation to the tissue where they further can differentiate and proliferate into various mesenchymal cell types depending on the tissue niche. This local tissue niche is important because it modulates the fibrocytes and coordinates their role in tissue behaviour and repair. However, plasticity of a niche may be co-opted in chronic airway diseases such as asthma, idiopathic pulmonary fibrosis and obliterative bronchiolitis. This review will therefore focus on a possible role of fibrocytes in pathological tissue repair processes in those diseases.

  9. Three-Dimensionally Engineered Normal Human Lung Tissue-Like Assemblies: Target Tissues for Human Respiratory Viral Infections

    Science.gov (United States)

    Goodwin, Thomas J.; McCarthy, M.; Lin, Y-H.; Deatly, A. M.

    2008-01-01

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

  10. Relationship between mass density, electron density, and elemental composition of body tissues for Monte Carlo simulation in radiation treatment planning

    CERN Document Server

    Kanematsu, Nobuyuki

    2015-01-01

    Purpose: For Monte Carlo simulation of radiotherapy, x-ray CT number of every system needs to be calibrated and converted to mass density and elemental composition. This study aims to formulate material properties of body tissues for practical two-step conversion from CT number. Methods: We used the latest compilation on body tissues that constitute reference adult male and female. We formulated the relations among mass, electron, and elemental densities into polylines to connect representative tissues, for which we took mass-weighted mean for the tissues in limited density regions. We compared the polyline functions of mass density with a bi-line for electron density and broken lines for elemental densities, which were derived from preceding studies. Results: There was generally high correlation between mass density and the other densities except of C, N, and O for light spongiosa tissues occupying 1% of body mass. The polylines fitted to the dominant tissues and were generally consistent with the bi-line an...

  11. Histopathology effects of nickel nanoparticles on lungs, liver, and spleen tissues in male mice

    Science.gov (United States)

    Ajdari, Marziyeh; Ziaee Ghahnavieh, Marziyeh

    2014-09-01

    Because of the classification of the nickel compounds as carcinogenic substances, there is a need for in vivo tests to nickel nanoparticles (NiNPs) for observing their effects on health experimentally. Spherical NiNPs with 10 nm in diameter and 75 ppm concentration were applied for investigating their toxicities within male albino mice as an in vivo model. We randomly made sham group, control group, and 75 ppm group (with five animals in each group). Then, the nanoparticles were injected into mice intraperitonealy for 7 days and after that their lungs, liver, and spleen were removed for histopathological observations. At the end of the test, section microscopic observations of liver, spleen, and lung in sham and control groups showed normal tissues but these tissues underwent significant abnormal effects in 75 ppm group. NiNPs can cause undesirable effects in lungs, liver, and spleen tissues with same condition of this study.

  12. Extraction and Quantification of Carbon Nanotubes in Biological Matrices with Application to Rat Lung Tissue

    Science.gov (United States)

    Doudrick, Kyle; Corson, Nancy; Oberdörster, Günter; Elder, Alison; Herckes, Pierre; Halden, Rolf U.; Westerhoff, Paul

    2013-01-01

    Extraction of carbon nanotubes (CNTs) from biological matrices such as rat lung tissue is integral to developing a quantification method for evaluating the environmental and human health exposure and toxicity of CNTs. The ability of various chemical treatment methods, including Solvable (2.5% sodium hydroxide/surfactant mixture), ammonium hydroxide, nitric acid, sulfuric acid, hydrochloric acid, hydrofluoric acid, hydrogen peroxide, and proteinase K, to extract CNTs from rat lung tissue was evaluated. CNTs were quantified using programmed thermal analysis (PTA). Two CNTs were used to represent the lower (500°C) and upper (800°C) PTA limit of CNT thermal stability. The recovery efficiency of each of the eight chemical reagents evaluated was found to depend on the ability to (1) minimize oxidation of CNTs, (2) remove interfering background carbon from the rat lung tissue, and (3) separate the solid-phase CNTs from the liquid-phase dissolved tissue via centrifugation. A two-step extraction method using Solvable and proteinase K emerged as the optimal approach, enabling a recovery of 98 ± 15% of a 2.9 ± 0.19 µg CNT loading that was spiked into whole rat lungs. Due to its high yield and applicability to low organ burdens of nanomaterials, this extraction method is particularly well suited for in vivo studies to quantify clearance rates and retained CNTs in lungs and other organs. PMID:23992048

  13. Modeling Mycobacterium tuberculosis early granuloma formation in experimental human lung tissue

    Directory of Open Access Journals (Sweden)

    Venkata Ramanarao Parasa

    2014-02-01

    Full Text Available The widely used animal models for tuberculosis (TB display fundamental differences from human TB. Therefore, a validated model that recapitulates human lung TB is attractive for TB research. Here, we describe a unique method for establishment of TB infection in an experimental human lung tissue model. The model is based on cell lines derived from human lungs and primary macrophages from peripheral blood, and displays characteristics of human lung tissue, including evenly integrated macrophages throughout the epithelium, production of extracellular matrix, stratified epithelia and mucus secretion. Establishment of experimental infection in the model tissue with Mycobacterium tuberculosis, the bacterium that causes TB, resulted in clustering of macrophages at the site of infection, reminiscent of early TB granuloma formation. We quantitated the extent of granuloma formation induced by different strains of mycobacteria and validated our model against findings in other TB models. We found that early granuloma formation is dependent on ESAT-6, which is secreted via the type VII secretion machinery of virulent mycobacteria. Our model, which can facilitate the discovery of the interactions between mycobacteria and host cells in a physiological environment, is the first lung tissue model described for TB.

  14. Classification of normal and cancerous lung tissues by electrical impendence tomography.

    Science.gov (United States)

    Gao, Jianling; Yue, Shihong; Chen, Jun; Wang, Huaxiang

    2014-01-01

    Biological tissue impedance spectroscopy can provide rich physiological and pathological information by measuring the variation of the complex impedance of biological tissues under various frequencies of driven current. Electrical Impedance Tomography (EIT) technique can measure the impedance spectroscopy of biological tissue in medical field. Before application, a key problem must be solved on how to generally distinguish normal tissues from the cancerous in terms of measurable EIT data. In this paper, the impedance spectroscopy characteristics of human lung tissue are studied. On the basis of the measured data of 109 lung cancer patients, Cole-Cole Circle radius (CCCR) and the complex modulus are extracted. In terms of the two characteristics, 71.6% and 66.4% samples of cancerous and normal tissues can be correctly classified, respectively. Furthermore, two characteristics of the measured EIT data of each patient consist of a two-dimensional vector and all such vectors comprise a set of vectors. When classifying the vector set, the rate of correctly partitioning normal and cancerous tissues can be raised to 78.2%. The main factors to affect the classification results on normal and cancerous tissues are generally analyzed. The proposed method will play an important role in further working out an efficient and feasible diagnostic method for potential lung cancer patients, and provide theoretical basis and reference data for electrical impedance tomography technology in monitoring pulmonary function.

  15. Measurement of lung tissue dynamics in artificially ventilated rats with optical coherence tomography

    Directory of Open Access Journals (Sweden)

    Schnabel Christian

    2017-09-01

    Full Text Available Diseases of lung tissue and the airways become a major task for medical care and health care systems in modern industrial countries in the future. Suitable treatment methods and strategies for lung support and artificial ventilation are of dare need. Besides the obvious importance as life-saving intervention, the effects of usually used over-pressure ventilation onto the sensitive alveolar tissue are insufficiently understood. Therefore, it is of great interest to characterize lung tissue during artificial ventilation at the alveolar level. Those measurements can be used to link micromechanics of alveolar structures to mechanical properties of the whole lung like compliance and resistance measured at the ventilator device. This can be done only in animal experiments due to the fact that imaging techniques used in human diagnostics like CT or MRT fail to resolve alveolar tissue structures. The disadvantage of high-resolution techniques like optical coherence tomography (OCT or intravital microscopy (IVM is the need of a surgical access to the lung due to the limitation in penetration depth of these techniques. Furthermore, imaging dynamic processes with high-resolution imaging techniques during uninterrupted artificial ventilation is a challenging task. In this study, we present a measurement setup for combined imaging of conventional pressure-controlled ventilated rats and the visualization of volume changes of alveolar structures during one cycle of breath. A custom-made OCT system in combination with a triggered scanning algorithm was used to acquire time-resolved 3D OCT image data. Furthermore, this system was combined with a self-adapting autofocus function for intravital microscopy to track the lung surface keeping the tissue in focal plane. The combination of new dynamic measurement modes for OCT and IVM allows new insights into alveolar tissue and will promote the understanding of mechanical behavior during artificial ventilation.

  16. Near-affine-invariant texture learning for lung tissue analysis using isotropic wavelet frames.

    Science.gov (United States)

    Depeursinge, Adrien; Van de Ville, Dimitri; Platon, Alexandra; Geissbuhler, Antoine; Poletti, Pierre-Alexandre; Müller, Henning

    2012-07-01

    We propose near-affine-invariant texture descriptors derived from isotropic wavelet frames for the characterization of lung tissue patterns in high-resolution computed tomography (HRCT) imaging. Affine invariance is desirable to enable learning of nondeterministic textures without a priori localizations, orientations, or sizes. When combined with complementary gray-level histograms, the proposed method allows a global classification accuracy of 76.9% with balanced precision among five classes of lung tissue using a leave-one-patient-out cross validation, in accordance with clinical practice.

  17. The effect of respiratory induced density variations on non-TOF PET quantitation in the lung

    Science.gov (United States)

    Holman, Beverley F.; Cuplov, Vesna; Hutton, Brian F.; Groves, Ashley M.; Thielemans, Kris

    2016-04-01

    Accurate PET quantitation requires a matched attenuation map. Obtaining matched CT attenuation maps in the thorax is difficult due to the respiratory cycle which causes both motion and density changes. Unlike with motion, little attention has been given to the effects of density changes in the lung on PET quantitation. This work aims to explore the extent of the errors caused by pulmonary density attenuation map mismatch on dynamic and static parameter estimates. Dynamic XCAT phantoms were utilised using clinically relevant 18F-FDG and 18F-FMISO time activity curves for all organs within the thorax to estimate the expected parameter errors. The simulations were then validated with PET data from 5 patients suffering from idiopathic pulmonary fibrosis who underwent PET/Cine-CT. The PET data were reconstructed with three gates obtained from the Cine-CT and the average Cine-CT. The lung TACs clearly displayed differences between true and measured curves with error depending on global activity distribution at the time of measurement. The density errors from using a mismatched attenuation map were found to have a considerable impact on PET quantitative accuracy. Maximum errors due to density mismatch were found to be as high as 25% in the XCAT simulation. Differences in patient derived kinetic parameter estimates and static concentration between the extreme gates were found to be as high as 31% and 14%, respectively. Overall our results show that respiratory associated density errors in the attenuation map affect quantitation throughout the lung, not just regions near boundaries. The extent of this error is dependent on the activity distribution in the thorax and hence on the tracer and time of acquisition. Consequently there may be a significant impact on estimated kinetic parameters throughout the lung.

  18. Expression and Clinical Significance of SHP2 in the Tumor Tissues of Smokers with Lung Cancer

    Directory of Open Access Journals (Sweden)

    Xuemei ZHAN

    2010-09-01

    Full Text Available Background and objective It has been proved that protein phosphorylation and dephosphorylation were important mechanisms in lung cancer development, and tobacco smoking is an important risk factor of lung cancer. The aim of this study is to investigate the expression and clinical significance of protein tyrosine phosphatase SHP2 in non-small cell lung cancer (NSCLC and small cell lung cancer (SCLC; the relationship between tobacco smoking and the expression of SHP2 is also studied. Methods Immunohistochemistry (Invision and fluorescence in situ hybridization (FISH were used to detect the expression of SHP2 and the augment of SHP2 mRNA in the 53 lung cancer specimens. Results The weak positive rate of SHP2 was 80% (which was also the total positive rate in normal bronchial epithelium. The weak, moderate and strong positive rates were 35.4%, 43.8% and 6.2% (total positive rate was 85.4% in 48 NSCLC patients, 0%, 80% and 20% (total positve rate was 100% in 5 SCLC patients, 40.7%, 37.4% and 3.7% (total positive rate was 81.5% in the tumor tissues of 27 NSCLC patients who didn’t smoke and 23.8%, 71.4% and 4.7% (total positive rate was 100% in the tumor tissues of 21 NSCLC patients whose smoking indexes were ≥400. Significant differences of SHP2 expression were observed between tumor tissues and normal bronchial epithelium, NSCLC and SCLC, and between different smoking indexes (P < 0.05. Conclusion The enhancement of SHP2 expression in the tumor tissues of NSCLC patients who smoke may be correlated with tobacco smoking; SHP2 may play certain role in the development of lung cancer; SHP2 prospectively provides new ideas for the drug research and development of lung cancer treatment.

  19. [The effectiveness of care bundles in maintaining the skin integrity and reducing the incidence density of pressure ulcers in lung cancer inpatients].

    Science.gov (United States)

    Lin, Wen-Ling; Tseng, Chien-Hua; Chung, Yi-Jen; Chuang, Hsin-Chu; Lin, Yun-Lan; Chang, Pi-Hua

    2014-04-01

    Pressure ulcers are tissue defects that form on the skin as a result of progressive skin damage. Pressure ulcers are a skin-integrity-related care issue and an important clinical indicator of care quality, especially for lung cancer inpatients who face rapidly deteriorating health conditions due to multiple symptoms and the side effects of treatment. Treating severe pressure ulcers may consume considerable manpower, time, and medical resources. Pressure ulcers may be avoided or effectively treated when nurses conduct proper skin assessments and care for wounds properly. This project evaluates the efficacy of skin care bundles in terms of reducing the incidence density of pressure ulcers in lung cancer inpatients. Data gathered between January 2010 and March 2011 showed unstable incidence density for pressure ulcers. The average pressure-ulcer incidence density in lung cancer inpatients was 2.09%, which was 8-times higher than the average for all patients. Using evidence-based care bundles for pressure ulcer prevention, we trained nurse staffs to incorporate these bundles into their clinical daily care of lung cancer patients in our hospital. During the study period between November 2011 and January 2012, the pressure-ulcer incidence density gradually fell to 0.55%. The incidence density continued to fall to 0.33% over the subsequent 8 months. We used the concept of "care bundles" to establish a standard skin-care protocol for advanced lung cancer inpatients. This protocol improved the clinical ability of nursing staffs and effectively maintained skin care quality in lung cancer patients.

  20. The effects of iterative reconstruction and kernel selection on quantitative computed tomography measures of lung density.

    Science.gov (United States)

    Rodriguez, Alfonso; Ranallo, Frank N; Judy, Philip F; Fain, Sean B

    2017-06-01

    To determine the effects of iterative reconstruction (IR) and high-frequency kernels on quantitative computed tomography (qCT) density measures at reduced X-ray dose. The COPDGene 2 Phantom (CTP 698, The Phantom Laboratory, Salem, NY) with four embedded lung mimicking foam densities (12lb, 20lb, and 4lb), as well as water, air, and acrylic reference inserts, was imaged using a GE 64 slice CT750 HD scanner in helical mode with four current-time products ranging from 12 to 100 mAs. The raw acquired data were reconstructed using standard (STD - low frequency) and Bone (high frequency) kernels with filtered back projection (FBP), 100% ASiR, and Veo reconstruction algorithms. The reference density inserts were manually segmented using Slicer3D (www.slicer.org), and the mean, standard deviation, and histograms of the segmented regions were generated using Fiji (http://fiji.sc/Fiji) for each reconstruction. Measurements of threshold values placed on the cumulative frequency distribution of voxels determined by these measured histograms at 5%, PD5phant , and 15%, PD15phant , (analogous to the relative area below -950 HU (RA-950) and percent density 15 (PD15) in human lung emphysema quantification, respectively), were also performed. The use of high-resolution kernels in conjunction with ASiR and Veo did not significantly affect the mean Hounsfield units (HU) of each of the density standards (density regions. The density histogram became more sharply peaked, and standard deviation was reduced for IR, directly effecting density thresholds, PD5phant and PD15phant, placed on the cumulative frequency distribution of each region in the phantom, which serve as analogs to RA-950 and PD15 typically used in lung density quantitation. The combination of high-frequency kernels (Bone) with ASiR mitigates this effect and preserves density measures derived from the image histogram. Moreover, previous studies have shown improved accuracy of qCT airway measures of wall thickness (WT) and

  1. Experimental evaluation of a new system for laser tissue welding applied on damaged lungs.

    Science.gov (United States)

    Schiavon, Marco; Marulli, Giuseppe; Zuin, Andrea; Lunardi, Francesca; Villoresi, Paolo; Bonora, Stefano; Calabrese, Fiorella; Rea, Federico

    2013-05-01

    Alveolar air leaks represent a challenging problem in thoracic surgery, leading to increased patient morbidity and prolonged hospitalization. Several methods have been used, but no ideal technique exists yet. We investigated the lung-sealing capacity of an experimental kit for laser tissue welding. The kit is composed of a semiconductor laser system applied on a protein substrate associated with a chromophore that increases absorption. In vitro tests on porcine lung tissue were done to define ideal laser parameters (power 100 Å, frequency 50 Hz, pulse duration 400 µs) and protein substrate dilution (50%). For in vivo tests, through a left thoracotomy, 14 pigs received two different lung damages: a linear incision and a circular incision. Protein substrate applied on damaged areas was treated with laser to obtain a layer that reconstituted the integrity of the visceral pleura. Air leaks were intraoperatively evaluated by water submersion test with an airway pressure of 20 cmH2O. Animals were sacrificed at postoperative days 0 and 7 to study early and late pathological features. After applying laser treatment, no air leaks were seen in all proofs except in 2 cases in which a second application was required. At time 0, pathological damage mostly consisted of superficial alveolar necrotic tissue covered by protein membrane. At time 7, a complete recovery of lung lesions by fibrous scar with slight inflammatory reaction of adjacent lung tissue was seen. This experimental study demonstrated the effectiveness of laser tissue welding applied to seal air leaks after lung surgery. Further studies are needed to verify acceptability for human application.

  2. ENO1 Protein Levels in the Tumor Tissues and Circulating Plasma Samples of Non-small Cell Lung Cancer Patients

    Directory of Open Access Journals (Sweden)

    Ying ZHANG

    2010-12-01

    Full Text Available Background and objective Proper tumor markers are useful to diagnosis, prognosis and treatment for lung cancer. The aim of this study is to examine the levels of alpha-enolase (ENO1 protein in the tumor tissues and peripheral plasma samples obtained from non-small cell lung cancer (NSCLC patients, and evaluate its potential clinical significance. Methods The ENO1 protein levels in the tumor tissues and corresponding normal tissues from 16 cases of lung squamous cell carcinoma were analyzed by Western blot. The ENO1 protein levels in the plasma samples from 42 healthy individuals, 34 patients with lung benign disease and 84 patients with NSCLC were measured by double antibody sandwich enzyme-linked immunosorbent assay. Results For 87.5% (14/16 of the patients with lung squamous cell carcinoma, the ENO1 protein level in the tumor tissues was higher than that in the corresponding normal lung tissues. The ENO1 protein level in the plasma of NSCLC patients was significantly higher than that in the plasma of healthy individuals (P=0.031 and patients with lung benign disease (P=0.019. Furthermore, the ENO1 protein level was significantly higher in the plasma of patients with lung adenocarcinoma than that of patients with lung squamous cell carcinoma. Conclusion The elevated levels of ENO1 protein in the tumor tissues and the plasma samples from NSCLC patients indicate ENO1 may be a candidate biomarker of lung cancer.

  3. Beryllium detection in human lung tissue using electron probe X-ray microanalysis.

    Science.gov (United States)

    Butnor, Kelly J; Sporn, Thomas A; Ingram, Peter; Gunasegaram, Sue; Pinto, John F; Roggli, Victor L

    2003-11-01

    Chronic berylliosis is an uncommon disease that is caused by the inhalation of beryllium particles, dust, or fumes. The distinction between chronic berylliosis and sarcoidosis can be difficult both clinically and histologically, as both entities can have similar presentations and exhibit nonnecrotizing granulomatous inflammation of the lungs. The diagnosis of chronic berylliosis relies on a history of exposure to beryllium, roentgenographic evidence of diffuse nodular disease, and demonstration of beryllium hypersensitivity by ancillary studies, such as lymphocyte proliferation testing. Additional support may be gained by the demonstration of beryllium in lung tissue. Unlike other exogenous particulates, such as asbestos, detection of beryllium in human lung tissue is problematic. The low atomic number of beryllium usually makes it unsuitable for conventional microprobe analysis. We describe a case of chronic berylliosis in which beryllium was detected in lung tissue using atmospheric thin-window energy-dispersive X-ray analysis (ATW EDXA). A woman with a history of occupational exposure to beryllium at a nuclear weapons testing facility presented with progressive cough and dyspnea and a nodular pattern on chest roentgenograph. Open lung biopsy showed nonnecrotizing granulomatous inflammation that was histologically indistinguishable from sarcoidosis. Scanning electron microscopy and ATW EDXA demonstrated particulates containing beryllium within the granulomas. This application of EDXA offers significant advantages over existing methods of beryllium detection in that it is nondestructive, more widely available, and can be performed using routine paraffin sections.

  4. Reliability of a Tissue Microarray in Detecting Thyroid Transcription Factor-1 Protein in Lung Carcinomas

    Institute of Scientific and Technical Information of China (English)

    Xiaoyan Bai; Hong Shen

    2007-01-01

    OBJECTIVE To compare the expression of the thyroid transcription factor-1 (TTF-1) in human normal adult type Ⅱ alveolar epithelial cells,embryonic pneumocytes and cancer cells of lung carcinoma and metastatic lymph nodes using a tissue microarray (TMA) along with paired conventional full sections.and to jnvestigate the reliability of tissue microarrays in detecting protein expression in lung carcinoma.METHODS A lung carcinoma TMA including 765 cores was constructed.TTF-1 protein expression in both TMA and paired conventional full sections were detected by yhe immunohistochemical SP method using a monoclonal antibody to TTF-1.A PU (Positive Unit) of TTF-1 protein was assessed quantitatively by the Leica Q500MC image analysis system with results from the paired conventional full sections as controls.RESULTS There was no signifcance between TMA and paired conven tional full sections in TTF-1 expression in difierent nuclei of the lung tissue.CONCLUSION TTF-1 protein expression in lung carcinoma detected by TMA was highly concordanl with that of paired full sections.TMA is a reliable method in detecting protein expression.

  5. Effects of ozone on lung tissue of E-supplemented rats

    Energy Technology Data Exchange (ETDEWEB)

    Coleman, R.D.; Abedin, M.Z.; Alfin-Slater, R.B.

    1986-01-01

    The effects of dietary vitamin E (E) in protecting lung tissue of rats exposed to ozone were studied in male, pathogen-free Sprague-Dawley rats fed synthetic diets containing 0, 10 and 50 IU E/Kg for 6 wks. Thereafter, half of the animals in each group were exposed to 0.8 ppm ozone for 4 days, the other half to filtered air, then all animals were killed. Plasma E levels increased with increasing dietary E in both ozone-exposed and air-breathing rats; values in both groups were 12 times higher at 50 IU than what was observed in E-free dietary controls. Even greater increases were seen in lung and liver. Ozone enhanced the observed increased levels in the lung but diminished those in the liver. Ozone produced lipid oxidation in the lung at 0 and 10 IU E as measured by a modified TBA test whereas 50 IU was protective. In the lung, mean organ weight, cytosolic protein content, and activities of NADPH-generating and sulfhydryl-metabolizing enzymes were not affected by the level of dietary E in air-breathing controls. Ozone exposure, however, increased these indices but the extent of increase varied inversely with the E level in the tissue. It is suggested that the enhanced enzyme activity and lipid oxidation in the lung reflects injury from ozone exposure. Reduction in the extent of these changes with increased tissue E suggests that dietary vitamin E may offer protection against the oxidant-induced lung injury.

  6. Mechanics, hydrodynamics and energetics of blue whale lunge feeding: efficiency dependence on krill density.

    Science.gov (United States)

    Goldbogen, J A; Calambokidis, J; Oleson, E; Potvin, J; Pyenson, N D; Schorr, G; Shadwick, R E

    2011-01-01

    Lunge feeding by rorqual whales (Balaenopteridae) is associated with a high energetic cost that decreases diving capacity, thereby limiting access to dense prey patches at depth. Despite this cost, rorquals exhibit high rates of lipid deposition and extremely large maximum body size. To address this paradox, we integrated kinematic data from digital tags with unsteady hydrodynamic models to estimate the energy budget for lunges and foraging dives of blue whales (Balaenoptera musculus), the largest rorqual and living mammal. Our analysis suggests that, despite the large amount of mechanical work required to lunge feed, a large amount of prey and, therefore, energy is obtained during engulfment. Furthermore, we suggest that foraging efficiency for blue whales is significantly higher than for other marine mammals by nearly an order of magnitude, but only if lunges target extremely high densities of krill. The high predicted efficiency is attributed to the enhanced engulfment capacity, rapid filter rate and low mass-specific metabolic rate associated with large body size in blue whales. These results highlight the importance of high prey density, regardless of prey patch depth, for efficient bulk filter feeding in baleen whales and may explain some diel changes in foraging behavior in rorqual whales.

  7. Comparative characterization of pulmonary surfactant aggregates and alkaline phosphatase isozymes in human lung carcinoma tissue.

    Science.gov (United States)

    Iino, Nozomi; Matsunaga, Toshiyuki; Harada, Tsuyoshi; Igarashi, Seiji; Koyama, Iwao; Komoda, Tsugikazu

    2007-05-01

    Alkaline phosphatase (AP) isozymes are surfactant-associated proteins (SPs). Since several different AP isozymes have been detected in the pneumocytes of lung cancer patients, we attempted to identify the relationship between pulmonary surfactant aggregate subtypes and AP isozymes. Pulmonary surfactant aggregates were isolated from carcinoma and non-carcinoma tissues of patients with non-small cell carcinoma of the lung. Upon analysis, ultraheavy, heavy, and light surfactant aggregates were detected in the non-carcinoma tissues, but no ultraheavy surfactant aggregates were found in the carcinoma tissues. Surfactant-associated protein A (SP-A) was detected as two bands (a 27-kDa band and a 54-kDa band) in the ultraheavy, heavy, and light surfactant aggregates found in the non-carcinoma tissues. Although both SP-A bands were detected in the heavy and light surfactant aggregates from adenocarcinoma tissues, the 54-kDa band was not detected in squamous cell carcinoma tissues. Liver AP (LAP) was detected in the heavy and light surfactant aggregates from both non-carcinoma and squamous carcinoma tissues, but not in heavy surfactant aggregates from adenocarcinoma tissues. A larger amount of bone type AP (BAP) was found in light surfactant aggregate fractions from squamous cell carcinomas than those from adenocarcinoma tissues or non-carcinoma tissues from patients with either type of cancer. LAP, BAP, and SP-A were identified immunohistochemically in type II pneumocytes from non-carcinoma tissues and adenocarcinoma cells, but no distinct SP-A staining was observed in squamous cell carcinoma tissues. The present study has thus revealed several differences in pulmonary surfactant aggregates and AP isozymes between adenocarcinoma tissue and squamous cell carcinoma tissue.

  8. TISSUE REMODELING IN THE HUMAN LUNG IN RELATION TO PARTICLE CONCENTRATION AND METAL CONTENT

    Science.gov (United States)

    TISSUE REMODELING IN THE HUMAN LUNG IN RELATION TO PARTICLE CONCENTRATION AND METAL CONTENT. J Gallagher1, J Inmon1, S Schlaegle2, A Levine2, T Rogers3, J Scott1, F Green4, M Schenker5, K Pinkerton5 1NHEERL, US-EPA, RTP, NC, USA; 2RJ Lee Group Inc, Monroeville, Pa, USA; ...

  9. The Use of CT Perfusion to Determine Microvessel Density in Lung Cancer: Comparison with FDG-PET and Pathology

    Institute of Scientific and Technical Information of China (English)

    Ning Xing; Zu-long Cai; Shao-hong Zhao; Li Yang; Bai-xuan Xu; Fu-lin Wang

    2011-01-01

    Objective: To investigate the validity of CT perfusion in assessing angiogenic activity of lung cancer. Methods: Fifty-six patients with lung cancer scheduled for elective surgical resection received 16-slice helical CT perfusion imaging. Time-density curve (TDC), blood flow (BF), blood volume (BV), mean transmit time (MTT) and permeability surface area product (PS) were calculated. 18F-deoxyglucose-positron emission tomography (FGD-PET)was carried out in 14 out of the 56 patients to calculate standardized uptake values (SUVs). Tumor microvessel density (MVD) was examined using CD34 immunohistochemical staining of the resected tumor tissue. Pearson's correlation analysis was used to evaluate potential correlation between CT perfusion parameters and MVD or SUV. Results: Average time to peak height (TPH) of the TDCs (including two types of TDC) was 24.38±5.69 seconds.Average BF, BV, MTT and PS were 93.42±53.45 ml/100g/min, 93.42±53.45 ml/100g, 6.83±4.51 s and 31.92±18.73ml/100g/rnin, respectively. Average MVD was 62.04±29.06/HPF. The mean SUV was 6.33±3.26. BF was positively correlated with MVD (r=0.620, P<0.01) and SUV (r=0.891, P<O.01). PS was also positively correlated with SUV (r=0.720, P<0.05). A positive correlation was also observed between tumor MVD and SUV (r=0.915, P<0.01). Conclusions: CT perfusion imaging is a reliable tool to evaluate the tumor neovascularity of lung cancer.

  10. Global Gene Expression Profiling in Lung Tissues of Rat Exposed to Lunar Dust Particles

    Science.gov (United States)

    Yeshitla, Samrawit A.; Lam, Chiu-Wing; Kidane, Yared H.; Feiveson, Alan H.; Ploutz-Snyder, Robert; Wu, Honglu; James, John T.; Meyers, Valerie E.; Zhang, Ye

    2014-01-01

    The Moon's surface is covered by a layer of fine, potential reactive dust. Lunar dust contain about 1-2% respirable very fine dust (less than 3 micrometers). The habitable area of any lunar landing vehicle and outpost would inevitably be contaminated with lunar dust that could pose a health risk. The purpose of the study is to analyze the dynamics of global gene expression changes in lung tissues of rats exposed to lunar dust particles. F344 rats were exposed for 4 weeks (6h/d; 5d/wk) in nose-only inhalation chambers to concentrations of 0 (control air), 2.1, 6.8, 21, and 61 mg/m3 of lunar dust. Animals were euthanized at 1 day and 13 weeks after the last inhalation exposure. After being lavaged, lung tissue from each animal was collected and total RNA was isolated. Four samples of each dose group were analyzed using Agilent Rat GE v3 microarray to profile global gene expression of 44K transcripts. After background subtraction, normalization, and log transformation, t tests were used to compare the mean expression levels of each exposed group to the control group. Correction for multiple testing was made using the method of Benjamini, Krieger, and Yekuteli (1) to control the false discovery rate. Genes with significant changes of at least 1.75 fold were identified as genes of interest. Both low and high doses of lunar dust caused dramatic, dose-dependent global gene expression changes in the lung tissues. However, the responses of lung tissue to low dose lunar dust are distinguished from those of high doses, especially those associated with 61mg/m3 dust exposure. The data were further integrated into the Ingenuity system to analyze the gene ontology (GO), pathway distribution and putative upstream regulators and gene targets. Multiple pathways, functions, and upstream regulators have been identified in response to lunar dust induced damage in the lung tissue.

  11. [Distribution of compact bone mesenchymal stem cells in lung tissue and bone marrow of mouse].

    Science.gov (United States)

    Wang, Rui-Ping; Wu, Ren-Na; Guo, Yu-Qing; Zhang, Bin; Chen, Hu

    2014-02-01

    This study was aimed to investigate the distribution of compact bone mesenchymal stem cells(MSC) marked with lentiviral plasmid pGC FU-RFP-LV in lung tissue and bone marrow of mouse. The MSC were infected by lentivirus with infection efficiency 78%, the infected MSC were injected into BALB/c mice via tail veins in concentration of 1×10(6) /mouse. The mice were randomly divided into 4 group according to 4 time points as 1, 2, 5 and 7 days. The lung tissue and bone marrow were taken and made of frozen sections and smears respectively in order to observed the distributions of MSC. The results indicated that the lentiviral infected MSC displayed phenotypes and biological characteristics which conformed to MSC by immunophenotyping analysis and induction differentiation detection. After the MSC were infected with optimal viral titer MOI = 50, the cell growth no significantly changed; the fluorescent microscopy revealed that the distributions of MSC in bone marrow on day 1, 2, 5 and 7 were 0.50 ± 0.20, 0.67 ± 0.23, 0.53 ± 0.14, 0.33 ± 0.16; those in lung tissue were 0.55 ± 0.15, 0.47 ± 0.13, 0.29 ± 0.13, 0.26 ± 0.08. It is concluded that the distribution of MSC in lung tissue reaches a peak on day 1, while distribution of MSC in bone marrow reaches a peak on day 2. The distribution of mouse MSC relates with RFP gene expression and implantation of MSC in lung tissue and bone marrow.

  12. Cytonuclear Epistasis Controls the Density of Symbiont Wolbachia pipientis in Nongonadal Tissues of Mosquito Culex quinquefasciatus.

    Science.gov (United States)

    Emerson, Kevin J; Glaser, Robert L

    2017-08-07

    Wolbachia pipientis, a bacterial symbiont infecting arthropods and nematodes, is vertically transmitted through the female germline and manipulates its host's reproduction to favor infected females. Wolbachia also infects somatic tissues where it can cause nonreproductive phenotypes in its host, including resistance to viral pathogens. Wolbachia-mediated phenotypes are strongly associated with the density of Wolbachia in host tissues. Little is known, however, about how Wolbachia density is regulated in native or heterologous hosts. Here, we measure the broad-sense heritability of Wolbachia density among families in field populations of the mosquito Culex pipiens, and show that densities in ovary and nongonadal tissues of females in the same family are not correlated, suggesting that Wolbachia density is determined by distinct mechanisms in the two tissues. Using introgression analysis between two different strains of the closely related species C. quinquefasciatus, we show that Wolbachia densities in ovary tissues are determined primarily by cytoplasmic genotype, while densities in nongonadal tissues are determined by both cytoplasmic and nuclear genotypes and their epistatic interactions. Quantitative-trait-locus mapping identified two major-effect quantitative-trait loci in the C. quinquefasciatus genome explaining a combined 23% of variance in Wolbachia density, specifically in nongonadal tissues. A better understanding of how Wolbachia density is regulated will provide insights into how Wolbachia density can vary spatiotemporally in insect populations, leading to changes in Wolbachia-mediated phenotypes such as viral pathogen resistance. Copyright © 2017 Emerson, Glaser.

  13. [Lung tissue in intratracheal exposure to mine dust].

    Science.gov (United States)

    Mikhaĭlova, A; Vodenicharov, E

    1984-01-01

    The experiment was performed 64 albino female rats by a single, intretracheal treatment with 50 mg mine dust. Dynamic biochemical studies were carried out - by 3th and 6th months of the experiment. The data obtained were compared with the changes observed in the positive controls - DQ12 and Ti02 The activity of the oxidation-reduction enzymes and hydrolytic ones was enhanced, the content of sulphhydryl groups and soluble proteins was increased. The results obtained are an evidence of the advancing metabolic disturbances in pulmonary tissue, being better manifested by 6th month of the experiment.

  14. Rapid detection of Mannheimia haemolytica in lung tissues of sheep and from bacterial culture

    Directory of Open Access Journals (Sweden)

    Jyoti Kumar

    2015-09-01

    Full Text Available Aim: This study was aimed to detect Mannheimia haemolytica in lung tissues of sheep and from a bacterial culture. Introduction: M. haemolytica is one of the most important and well-established etiological agents of pneumonia in sheep and other ruminants throughout the world. Accurate diagnosis of M. haemolytica primarily relies on bacteriological examination, biochemical characteristics and, biotyping and serotyping of the isolates. In an effort to facilitate rapid M. haemolytica detection, polymerase chain reaction assay targeting Pasteurella haemolytica serotype-1 specific antigens (PHSSA, Rpt2 and 12S ribosomal RNA (rRNA genes were used to detect M. haemolytica directly from lung tissues and from bacterial culture. Materials and Methods: A total of 12 archived lung tissues from sheep that died of pneumonia on an organized farm were used. A multiplex polymerase chain reaction (mPCR based on two-amplicons targeted PHSSA and Rpt2 genes of M. haemolytica were used for identification of M. haemolytica isolates in culture from the lung samples. All the 12 lung tissue samples were tested for the presence M. haemolytica by PHSSA and Rpt2 genes based PCR and its confirmation by sequencing of the amplicons. Results: All the 12 lung tissue samples tested for the presence of PHSSA and Rpt2 genes of M. haemolytica by mPCR were found to be positive. Amplification of 12S rRNA gene fragment as internal amplification control was obtained with each mPCR reaction performed from DNA extracted directly from lung tissue samples. All the M. haemolytica were also positive for mPCR. No amplified DNA bands were observed for negative control reactions. All the three nucleotide sequences were deposited in NCBI GenBank (Accession No. KJ534629, KJ534630 and KJ534631. Sequencing of the amplified products revealed the identity of 99-100%, with published sequence of PHSSA and Rpt2 genes of M. haemolytica available in the NCBI database. Sheep specific mitochondrial 12S r

  15. Surface fluorescence studies of tissue mitochondrial redox state in isolated perfused rat lungs.

    Science.gov (United States)

    Staniszewski, Kevin; Audi, Said H; Sepehr, Reyhaneh; Jacobs, Elizabeth R; Ranji, Mahsa

    2013-04-01

    We designed a fiber-optic-based optoelectronic fluorometer to measure emitted fluorescence from the auto-fluorescent electron carriers NADH and FAD of the mitochondrial electron transport chain (ETC). The ratio of NADH to FAD is called the redox ratio (RR = NADH/FAD) and is an indicator of the oxidoreductive state of tissue. We evaluated the fluorometer by measuring the fluorescence intensities of NADH and FAD at the surface of isolated, perfused rat lungs. Alterations of lung mitochondrial metabolic state were achieved by the addition of rotenone (complex I inhibitor), potassium cyanide (KCN, complex IV inhibitor) and/or pentachlorophenol (PCP, uncoupler) into the perfusate recirculating through the lung. Rotenone- or KCN-containing perfusate increased RR by 21 and 30%, respectively. In contrast, PCP-containing perfusate decreased RR by 27%. These changes are consistent with the established effects of rotenone, KCN, and PCP on the redox status of the ETC. Addition of blood to perfusate quenched NADH and FAD signal, but had no effect on RR. This study demonstrates the capacity of fluorometry to detect a change in mitochondrial redox state in isolated perfused lungs, and suggests the potential of fluorometry for use in in vivo experiments to extract a sensitive measure of lung tissue health in real-time.

  16. Effect of polydatin on phospholipase A2 in lung tissues in rats with endotoxic shock

    Institute of Scientific and Technical Information of China (English)

    舒仕瑜; 王兴勇; 凌智瑜; 卢仲毅

    2004-01-01

    Objective: To study the effect of polydatin on phospholipase A2 in lung tissues in rats with endotoxic shock.Methods: Thirty-two healthy male Wistar rats were employed in this study. A total of 8 rats received normal saline intravenously (control group ), 8 rats received 10 mg/kg of endotoxin ( endotoxic shock group), 8 rats received 1 mg/kg of polydatin after endotoxin injection (polydatin treatment group), and 8 rats received 1 mg/kg of polydatin (polydatin prevention group ) 30 minutes before endotoxin injection. Mean arterial pressure was measured once half an hour. Lung tissues were collected 6 hours later. Phospholipase A2 activity was measured with acid titration. The gene expression of secretory phospholipase A2 type IIA was detected with reverse transcription polymerase chain reaction. Meanwhile, the histological changes of the lungs among four groups were compared through microscopic examination. Results: Phospholipase A2 activity and the gene expression of secretory phospholipase A2 type ⅡA increased after endotoxin injection, but polydatin could inhibit these effects of endotoxin. Obvious morphological evidence could be found in the lung pathological sections and the protective effect of polydatin was most significant in the polydatin prevention group.Conclusions: Polydatin has prophylactic and therapeutic effects (the former is more distinct than the latter) on acutely injured lungs in rats with endotoxic shock and which suggests that polydatin may be a phospholipase A2 inhibitor.

  17. Endothelial Cells Expressing Endothelial and Mesenchymal Cell Gene Products in Lung Tissue From Patients With Systemic Sclerosis-Associated Interstitial Lung Disease.

    Science.gov (United States)

    Mendoza, Fabian A; Piera-Velazquez, Sonsoles; Farber, John L; Feghali-Bostwick, Carol; Jiménez, Sergio A

    2016-01-01

    To examine whether lung endothelial cells (ECs) from patients with systemic sclerosis (SSc)-associated interstitial lung disease (ILD) express mesenchymal cell-specific proteins and gene transcripts, indicative of the occurrence of endothelial-to-mesenchymal phenotypic transition (EndoMT). Lung tissue from 6 patients with SSc-associated pulmonary fibrosis was examined by histopathology and immunohistochemistry. Confocal laser microscopy was utilized to assess the simultaneous expression of EC and myofibroblast molecular markers. CD31+CD102+ ECs were isolated from the lung tissue of 2 patients with SSc-associated ILD and 2 normal control subjects, and the expression of EC and mesenchymal cell markers and other relevant genes was analyzed by quantitative polymerase chain reaction, immunofluorescence microscopy, and Western blotting. Immunohistochemical staining revealed cells expressing the EC-specific marker CD31 in the subendothelial, perivascular, and parenchymal regions of the lungs from all SSc patients. Confocal microscopy identified cells displaying simultaneous expression of von Willebrand factor and α-smooth muscle actin in small and medium-sized arterioles in the SSc lung tissue but not in normal control lungs. CD31+CD102+ ECs isolated from SSc lungs expressed high levels of mesenchymal cell-specific genes (type I collagen, type III collagen, and fibronectin), EC-specific genes (type IV collagen and VE-cadherin), profibrotic genes (transforming growth factor β1 and connective tissue growth factor), and genes encoding EndoMT-related transcription factors (TWIST1 and SNAI2). Cells coexpressing EC- and mesenchymal cell-specific molecules are present in the lungs of patients with SSc-associated ILD. CD31+CD102+ ECs isolated from SSc lungs simultaneously expressed mesenchymal cell- and EC-specific transcripts and proteins. Collectively, these observations demonstrate the occurrence of EndoMT in the lungs of patients with SSc-associated ILD. © 2016, American

  18. Expression of Interleukin-17A in Lung Tissues of Irradiated Mice and the Influence of Dexamethasone

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    Li-Ping Wang

    2014-01-01

    Full Text Available Purpose. To investigate the expressions of IL-17A in different phases of radiation-induced lung injury and the effect of dexamethasone. Methods. The thorax of C57BL/6 mice was irradiated with 15 Gy rays. Mice from dexamethasone-treated group were injected intraperitoneally with dexamethasone (0.42 mg/kg/day every day for the first month after irradiation. IL-17A in lung tissues was detected by immunohistochemistry. IL-17A, TGF-β1, and IL-6 in bronchoalveolar lavage fluid were detected by ELISA. Lung inflammation and collagen deposition were observed by H&E and Masson methods. The degree of alveolitis and fibrosis was judged according to scoring. Results. IL-17A expression was appreciable at 1 week, peaked at 4 weeks, and subsequently declined at 8 weeks after irradiation. IL-17A was reduced after dexamethasone application at all the observation periods. Dexamethasone also inhibited expressions of TGF-β, IL-6, and TNF-α in bronchoalveolar lavage fluid. Moreover, dexamethasone attenuated the severity of lung injury by reducing the infiltration of inflammatory cells and collagen deposition. Terms of survival and the time of death in mice of treatment group were postponed and survival rate was improved. Conclusions. IL-17A plays an important role in the process of radiation-induced lung injury. And dexamethasone may provide a protective role in lung injury induced by radiation.

  19. High-Density Spot Seeding for Tissue Model Formation

    Science.gov (United States)

    Marquette, Michele L. (Inventor); Sognier, Marguerite A. (Inventor)

    2016-01-01

    A model of tissue is produced by steps comprising seeding cells at a selected concentration on a support to form a cell spot, incubating the cells to allow the cells to partially attach, rinsing the cells to remove any cells that have not partially attached, adding culture medium to enable the cells to proliferate at a periphery of the cell spot and to differentiate toward a center of the cell spot, and further incubating the cells to form the tissue. The cells may be C2C12 cells or other subclones of the C2 cell line, H9c2(2-1) cells, L6 cells, L8 cells, QM7 cells, Sol8 cells, G-7 cells, G-8 cells, other myoblast cells, cells from other tissues, or stem cells. The selected concentration is in a range from about 1 x 10(exp 5) cells/ml to about 1 x 10(exp 6) cells/ml. The tissue formed may be a muscle tissue or other tissue depending on the cells seeded.

  20. MicroRNA expression in lung tissue and blood isolated from pigs suffering from bacterial pneumonia

    DEFF Research Database (Denmark)

    Skovgaard, Kerstin; Wendt, Karin Tarp; Heegaard, Peter M. H.

    MicroRNAs (miRNAs) are a highly evolutionarily conserved group of small non-coding RNA molecules, which regulate the activity of other genes at the post-transcriptional level. Recently it has become evident that miRNA plays an important role in modulating and fine tuning of the innate and adaptive...... immune responses. Still, little is known about the impact of miRNAs in the development and pathogenesis of lung infections. Expression of miRNA, known to be induced by bacterial (i.e., LPS) ligands and thus supposed to play a role in the regulation of antimicrobial defence, were studied in lung tissue...

  1. Decay-Accelerating Factor Mitigates Controlled Hemorrhage-Instigated Intestinal and Lung Tissue Damage and Hyperkalemia in Swine

    Science.gov (United States)

    2011-07-01

    Decay-Accelerating Factor Mitigates Controlled Hemorrhage- Instigated Intestinal and Lung Tissue Damage and Hyperkalemia in Swine Jurandir J. Dalle...DAF treatment improved hemorrhage- induced hyperkalemia . The protective effects of DAF appear to be related to its ability to reduce tissue complement...Decay-accelerating factor mitigates controlled hemorrhage-instigated intestinal and lung tissue damage and hyperkalemia in swine 5a. CONTRACT NUMBER

  2. Profiling microRNAs in lung tissue from pigs infected with Actinobacillus pleuropneumoniae

    DEFF Research Database (Denmark)

    Podolska, Agnieszka; Anthon, Christian; Bak, Mads

    2012-01-01

    Background: MicroRNAs (miRNAs) are a class of non-protein-coding genes that play a crucial regulatory role in mammalian development and disease. Whereas a large number of miRNAs have been annotated at the structural level during the latest years, functional annotation is sparse. Actinobacillus...... pleuropneumoniae (APP) causes serious lung infections in pigs. Severe damage to the lungs, in many cases deadly, is caused by toxins released by the bacterium and to some degree by host mediated tissue damage. However, understanding of the role of microRNAs in the course of this infectious disease in porcine......R-451 and miR-15a appear as very promising candidates for microRNAs involved in response to pathogen infection. Conclusions: This is the first study revealing significant differences in composition and expression profiles of miRNAs in lungs infected with a bacterial pathogen. Our results extend...

  3. Lung Cancer Signature Biomarkers: tissue specific semantic similarity based clustering of Digital Differential Display (DDD data

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    Srivastava Mousami

    2012-11-01

    Full Text Available Abstract Background The tissue-specific Unigene Sets derived from more than one million expressed sequence tags (ESTs in the NCBI, GenBank database offers a platform for identifying significantly and differentially expressed tissue-specific genes by in-silico methods. Digital differential display (DDD rapidly creates transcription profiles based on EST comparisons and numerically calculates, as a fraction of the pool of ESTs, the relative sequence abundance of known and novel genes. However, the process of identifying the most likely tissue for a specific disease in which to search for candidate genes from the pool of differentially expressed genes remains difficult. Therefore, we have used ‘Gene Ontology semantic similarity score’ to measure the GO similarity between gene products of lung tissue-specific candidate genes from control (normal and disease (cancer sets. This semantic similarity score matrix based on hierarchical clustering represents in the form of a dendrogram. The dendrogram cluster stability was assessed by multiple bootstrapping. Multiple bootstrapping also computes a p-value for each cluster and corrects the bias of the bootstrap probability. Results Subsequent hierarchical clustering by the multiple bootstrapping method (α = 0.95 identified seven clusters. The comparative, as well as subtractive, approach revealed a set of 38 biomarkers comprising four distinct lung cancer signature biomarker clusters (panel 1–4. Further gene enrichment analysis of the four panels revealed that each panel represents a set of lung cancer linked metastasis diagnostic biomarkers (panel 1, chemotherapy/drug resistance biomarkers (panel 2, hypoxia regulated biomarkers (panel 3 and lung extra cellular matrix biomarkers (panel 4. Conclusions Expression analysis reveals that hypoxia induced lung cancer related biomarkers (panel 3, HIF and its modulating proteins (TGM2, CSNK1A1, CTNNA1, NAMPT/Visfatin, TNFRSF1A, ETS1, SRC-1, FN1, APLP2, DMBT1

  4. Lung cancer signature biomarkers: tissue specific semantic similarity based clustering of digital differential display (DDD) data.

    Science.gov (United States)

    Srivastava, Mousami; Khurana, Pankaj; Sugadev, Ragumani

    2012-11-02

    The tissue-specific Unigene Sets derived from more than one million expressed sequence tags (ESTs) in the NCBI, GenBank database offers a platform for identifying significantly and differentially expressed tissue-specific genes by in-silico methods. Digital differential display (DDD) rapidly creates transcription profiles based on EST comparisons and numerically calculates, as a fraction of the pool of ESTs, the relative sequence abundance of known and novel genes. However, the process of identifying the most likely tissue for a specific disease in which to search for candidate genes from the pool of differentially expressed genes remains difficult. Therefore, we have used 'Gene Ontology semantic similarity score' to measure the GO similarity between gene products of lung tissue-specific candidate genes from control (normal) and disease (cancer) sets. This semantic similarity score matrix based on hierarchical clustering represents in the form of a dendrogram. The dendrogram cluster stability was assessed by multiple bootstrapping. Multiple bootstrapping also computes a p-value for each cluster and corrects the bias of the bootstrap probability. Subsequent hierarchical clustering by the multiple bootstrapping method (α = 0.95) identified seven clusters. The comparative, as well as subtractive, approach revealed a set of 38 biomarkers comprising four distinct lung cancer signature biomarker clusters (panel 1-4). Further gene enrichment analysis of the four panels revealed that each panel represents a set of lung cancer linked metastasis diagnostic biomarkers (panel 1), chemotherapy/drug resistance biomarkers (panel 2), hypoxia regulated biomarkers (panel 3) and lung extra cellular matrix biomarkers (panel 4). Expression analysis reveals that hypoxia induced lung cancer related biomarkers (panel 3), HIF and its modulating proteins (TGM2, CSNK1A1, CTNNA1, NAMPT/Visfatin, TNFRSF1A, ETS1, SRC-1, FN1, APLP2, DMBT1/SAG, AIB1 and AZIN1) are significantly down regulated

  5. Angiogenesis and mast cell density as predictors of patient survival in squamous cell carcinoma of lung

    Directory of Open Access Journals (Sweden)

    Ehsan Ullah

    2013-01-01

    Full Text Available Background: Measuring the microvascular and mast cell density in squamous cell carcinoma of lung and correlating them with the patient survival may be helpful to guide the use of cancer chemotherapeutic agents which target molecular mechanisms of tumour angiogenesis and mast cells. Materials and Methods: It was an observational study. It included 39 newly diagnosed, adult patients of pulmonary squamous cell carcinoma. Angiogenesis was determined by Chalkley′s method after immunohistochemical staining of micro-vessels with CD34. Mast cells per HPF were counted in Tolouidine blue stained sections. Results: Mean age of the patients was 58.33 ± 9.14 years. Male to female ratio was 9:1. Most (92.3% patients were current smokers. Majority of tumours (71.8% were localised to major bronchi and/or near to hilum and many of them (74.4% were poorly differentiated. Mean micro-vascular density was 11.80 ± 3.66 per HPF which showed strong negative correlation (r = -0.481, p =0.002 between microvascular density (MVD and tumour grade. Mean mast cell density was 1.60 ± 2.04 which showed strong negative correlation (r=-.683, p =0.0001 with grade. Angiogenesis and mast cell density were found to be positively correlated (r=0.439, p =0.005. High MVD, but not the MCD was associated with poor survival. Conclusion: Angiogenesis and mast cell density are positively correlated with each other however; only high MVD is associated with decreased survival. Thus, the anti-angiogenic agents may be useful in squamous cell carcinoma lung, especially the well differentiated tumours.

  6. Results of total lung irradiation and chemotherapy in comparison with partial lung irradiation in metastatic undifferentiated soft tissue sarcomas

    Energy Technology Data Exchange (ETDEWEB)

    Zamboglou, N.; Fuerst, G.; Pape, H.; Bannach, B.; Schmitt, G.; Molls, M.

    1988-07-01

    The poor prognosis of patients with unresectable pulmonary metastases of soft tissue sarcoma is well known. In order to evaluate the beneficial effect of radiotherapy, we have treated 44 patients with pulmonary metastases of grade 3 soft tissue sarcoma from 1980 to 1986. In 36 patients the treatment volume was restricted to the single metastases up to a dose of 50 to 60 (9 to 10 Gy/week). The survival rate at one year was 18% and at two years 6%. Eight patients were treated with a combined regimen, consisting of cisplatin and ifosfamide with simultaneous whole lung irradiation. Irradiation was performed with 8 or 16 MV photons at a hyperfractionation of 2x0,8 Gy/day (8 Gy/week). After a dose of 12 Gy, the single metastases were boosted up to 50 to 60 Gy, with a second course of chemotherapy. In six of eight patients complete remissions were achieved, one patient showed a partial remission. The survival rate at 27 months was 50%. The patients with partial remission died from pulmonary progression at 23 months. One patient died after twelve months from a loco-regional recurrence in the tonsillar fossa without evidence of pulmonary disease. Side effects included alopecia and moderate bone marrow suppression approximately twelve days after each chemotherapy cycle. Pulmonary fibrosis was observed only at the high dose volume without impairment of respiratory function. From these observations the conclusion is drawn that whole lung irradiation simultaneously with cisplatin and ifosfamide chemotherapy provides good palliative results without relevant morbidity in patients with high grade unresectable pulmonary metastases of soft tissue sarcomas.

  7. Molecular and histological changes in cerebral cortex and lung tissues under the effect of tramadol treatment.

    Science.gov (United States)

    Awadalla, Eatemad A; Salah-Eldin, Alaa-Eldin

    2016-08-01

    Tramadol abuse is one of the most frequent health problems in Egypt and worldwide. In most cases, tramadol abused by men face a problem with premature ejaculation. Tramadol like other opioids induces a decrease in plasma antioxidant levels, which may reflect a failure of the antioxidant defense mechanism against oxidative damage. The present work aimed to study the possible deleterious effects of oral administration of tramadol on brain and lung tissues in rats. Twenty adult male albino rats were divided into two groups; a control administered with normal saline and tramadol-treated (40mg/kg b.w.) group for 20 successive days. At the end of experimental period, blood was collected and specimens from brains and lungs were taken for histopathological and molecular studies. Malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) activities were measured in serum of control and tramadol-treated groups. Brain and lung specimens were histopathological evaluated using light microscopy. The expression levels of apoptotic related genes; Bcl-2, Bax and Caspase-3 were study in brain and lung tissues using RT-PCR analysis. We recorded a significant increase MDA level, while antioxidant enzymes; GSH, SOD and CAT were significantly decreased after tramadol-treatment. The obtained results revealed that tramadol induced a remarkable histomorphological changes in rats' brains (cerebral cortex and hippocampus) and severe histopathological changes in rats' lung when compared to that of control. On molecular level, the expression of the pro-apoptotic Bax and Caspase-3 showed a significant increase whereas the anti-apoptotic Bcl-2 decreased markedly indicating that tramadol is harmful at cellular level and can induce apoptotic changes in brain tissues. Our data confirmed the risk of increased oxidative stress, neuronal and pulmonary damage due to tramadol abuse. Although tramadol is reported to be effective in pain management, its toxicity should

  8. Expression of transcription factor Klf8 in lung cancer tissue and the biological effect of downregulation of Klf8 expression in lung cancer cell lines

    Institute of Scientific and Technical Information of China (English)

    Xuan-Hong Yi; Jing Wang

    2016-01-01

    Objective:To study the expression of transcription factor Klf8 in lung cancer tissue and the biological effect of downregulation of Klf8 expression in lung cancer cell lines.Methods:Cancer tissue and adjacent normal lung tissue were collected and mRNA contents of Klf8 were detected; lung cancer A549 cell lines were cultured, and after transfection of Klf8 siRNA, cell cycle, cell invasion and epithelial-mesenchymal transition were detected.Results:mRNA contents of Klf8 in lung cancer tissue were higher than those in adjacent normal lung tissue; after transfection of Klf8 siRNA, Klf8 mRNA inhibition rate was 74.31%; G0/G1 phase ratio of Klf8 siRNA group was higher than that of negative control siRNA group; ratios of S-phase and G2/M phase cells, mRNA contents of Cyclin D1 and number of cells invading to the outer side of the transwell microporous membrane were lower than those of negative control siRNA group; mRNA contents of CDH1 and CK18 as well as Snail and Slug of Klf8 siRNA group were higher than those of negative control siRNA group; mRNA contents of VIM and N-cadherin were lower than those of negative control siRNA group.Conclusion:The expression of Klf8 in lung cancer tissue abnormally elevates; downregulation of Klf8 expression in lung cancer cell lines can inhibit malignant biological effect of cells, manifested as cell cycle arrest as well as the inhibition of cell invasion and epithelial-mesenchymal transition processes.

  9. Measurement of lung density in congestive heart failure by computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Nomura, Masanori; Miyagi, Yutaka; Tachi, Keiji; Sakabe, Yoshiyuki; Sakai, Yasuhiko; Hishida, Hitoshi; Mizuno, Yasushi; Sasaki, Fumio; Koga, Sukehiko (Fujita-Gakuen Health Univ., Toyoake, Aichi (Japan))

    1984-11-01

    The computed tomography (CT) number within the region of interest (ROI) was used as a parameter to assess lung density in patients with congestive heart failure. Thirty-eight patients with valvular heart disease (VHD) and 34 patients with ischemic heart disease (IHD) were studied. Based on the New York Heart Association (NYHA) classification, 24 VHD patients were in class I or II (VHD I-II) and the other 14 were in NYHA class III or IV (VHD III-IV). Eighteen patients with IHD were in NYHA class I or II (IHD I-II) and 16 were in class III or IV (IHD III-IV). The CT number was measured bilaterally at the upper, middle and lower levels of the chest and compared with the corresponding value in 21 normal subjects (Group N). In a preliminary study on Group N, the CT numbers were insensitive to the size of the ROI, but were closely related to its location. In clinical applications, the mean values of the CT numbers in all six lung fields increased in the order of IHD I-II, to VHD I-II, IHD III-IV and VHD III-IV. Except for patients in IHD I-II, they were significantly larger than in Group N. The relationship between the CT number and the systolic and mean pulmonary arterial pressures and the pulmonary capillary wedge pressure were evaluated in 36 patients. Significant correlations were obtained in all six lung fields (r=0.65-0.78, p < 0.001). The results suggest that measurement of lung density by CT is useful for the quantitative evaluation of the severity of disease in patients with congestive heart failure.

  10. Conditional overexpression of connective tissue growth factor disrupts postnatal lung development.

    Science.gov (United States)

    Wu, Shu; Platteau, Astrid; Chen, Shaoyi; McNamara, George; Whitsett, Jeffrey; Bancalari, Eduardo

    2010-05-01

    Connective tissue growth factor (CTGF) is a member of an emerging family of immediate-early gene products that coordinates complex biological processes during development, differentiation, and tissue repair. Overexpression of CTGF is associated with mechanical ventilation with high tidal volume and oxygen exposure in newborn lungs. However, the role of CTGF in postnatal lung development and remodeling is not well understood. In the present study, a double-transgenic mouse model was generated with doxycycline-inducible overexpression of CTGF in respiratory epithelial cells. Overexpression of CTGF from Postnatal Days 1-14 resulted in thicker alveolar septa and decreased secondary septal formation. This is correlated with increased myofibroblast differentiation and disorganized elastic fiber deposition in alveolar septa. Overexpression of CTGF also decreased alveolar capillary network formation. There were increased alpha-smooth muscle actin expression and collagen deposition, and dramatic thickening in the peribronchial/peribronchiolar and perivascular regions in the double-transgenic lungs. Furthermore, overexpression of CTGF increased integrin-linked kinase expression, activated its downstream signaling target, Akt, as well as increased mRNA expression of fibronectin. These data demonstrate that overexpression of CTGF disrupts alveologenesis and capillary formation, and induces fibrosis during the critical period of alveolar development. These histologic changes are similar to those observed in lungs of infants with bronchopulmonary dysplasia.

  11. Serum biomarkers reflecting specific tumor tissue remodeling processes are valuable diagnostic tools for lung cancer.

    Science.gov (United States)

    Willumsen, Nicholas; Bager, Cecilie L; Leeming, Diana J; Smith, Victoria; Christiansen, Claus; Karsdal, Morten A; Dornan, David; Bay-Jensen, Anne-Christine

    2014-10-01

    Extracellular matrix (ECM) proteins, such as collagen type I and elastin, and intermediate filament (IMF) proteins, such as vimentin are modified and dysregulated as part of the malignant changes leading to disruption of tissue homeostasis. Noninvasive biomarkers that reflect such changes may have a great potential for cancer. Levels of matrix metalloproteinase (MMP) generated fragments of type I collagen (C1M), of elastin (ELM), and of citrullinated vimentin (VICM) were measured in serum from patients with lung cancer (n = 40), gastrointestinal cancer (n = 25), prostate cancer (n = 14), malignant melanoma (n = 7), chronic obstructive pulmonary disease (COPD) (n = 13), and idiopathic pulmonary fibrosis (IPF) (n = 10), as well as in age-matched controls (n = 33). The area under the receiver operating characteristics (AUROC) was calculated and a diagnostic decision tree generated from specific cutoff values. C1M and VICM were significantly elevated in lung cancer patients as compared with healthy controls (AUROC = 0.98, P < 0.0001) and other cancers (AUROC = 0.83 P < 0.0001). A trend was detected when comparing lung cancer with COPD+IPF. No difference could be seen for ELM. Interestingly, C1M and VICM were able to identify patients with lung cancer with a positive predictive value of 0.9 and an odds ratio of 40 (95% CI = 8.7-186, P < 0.0001). Biomarkers specifically reflecting degradation of collagen type I and citrullinated vimentin are applicable for lung cancer patients. Our data indicate that biomarkers reflecting ECM and IMF protein dysregulation are highly applicable in the lung cancer setting. We speculate that these markers may aid in diagnosing and characterizing patients with lung cancer.

  12. Interstitial lung disease in connective tissue disease--mechanisms and management.

    Science.gov (United States)

    Wells, Athol U; Denton, Christopher P

    2014-12-01

    Pulmonary complications are an important extra-articular feature of autoimmune rheumatic diseases and a major cause of mortality. The underlying pathogenesis probably involves multiple cellular compartments, including the epithelium, lung fibroblasts, and the innate and adaptive immune system. Heterogeneity in the extent and progression of lung fibrosis probably reflects differences in underlying pathogenic mechanisms. Growing understanding of the key pathogenic drivers of lung fibrosis might lead to the development of more effective targeted therapies to replicate the treatment advances in other aspects of these diseases. Interstitial lung disease (ILD) in connective tissue disease (CTD) is characterized using the classification of the idiopathic interstitial pneumonias. Systemic sclerosis is most frequently associated with ILD and, in most of these patients, ILD manifests as a histological pattern of nonspecific interstitial pneumonia. Conversely, in rheumatoid arthritis, the pattern of ILD is most often usual interstitial pneumonia. The key goals of clinical assessment of patients with both ILD and CTD are the detection of ILD and prognostic evaluation to determine which patients should be treated. Data from treatment trials in systemic sclerosis support the use of immunosuppressive therapy, with the treatment benefit largely relating to the prevention of progression of lung disease.

  13. Lung involvement in connective tissue diseases: a comprehensive review and a focus on rheumatoid arthritis.

    Science.gov (United States)

    Marigliano, Benedetta; Soriano, Alessandra; Margiotta, Domenico; Vadacca, Marta; Afeltra, Antonella

    2013-09-01

    The lungs are frequently involved in Connective Tissue Diseases (CTDs). Interstitial lung disease (ILD) is one of the most common pleuropulmonary manifestations that affects prognosis significantly. In practice, rheumatologists and other physicians tend to underestimate the impact of CTD-ILDs and diagnose respiratory impairment when it has reached an irreversible fibrotic stage. Early investigation, through clinical evidence, imaging and - in certain cases - lung biopsy, is therefore warranted in order to detect a possible ILD at a reversible initial inflammatory stage. In this review, we focus on lung injury during CTDs, with particular attention to ILDs, and examine their prevalence, clinical manifestations and histological patterns, as well as therapeutic approaches and known complications till date. Although several therapeutic agents have been approved, the best treatment is still not certain and additional trials are required, which demand more knowledge of pulmonary involvement in CTDs. Our central aim is therefore to document the impact that lung damage has on CTDs. We will mainly focus on Rheumatoid Arthritis (RA), which - unlike other rheumatic disorders - resembles Idiopathic Pulmonary Fibrosis (IPF) in numerous aspects.

  14. Expression of SHP2 and related markers in non-small cell lung cancer: a tissue microarray study of 80 cases.

    Science.gov (United States)

    Tang, Chunlan; Luo, Dan; Yang, Heping; Wang, Qingliang; Zhang, Rong; Liu, Guoxiang; Zhou, Xiangdong

    2013-10-01

    The purpose of this study was to assess the relationships between the expression of SHP2 and VEGF, VEGFR-1, VEGFR-2, MMP-2, MMP-9, TIMP-1, TIMP-2, and microvessel density (MVD), as well as the clinicopathologic parameters of these markers in non-small cell lung cancer (NSCLC). Using a tissue microarray, the expression of these 8 markers in 80 NSCLC cases was detected by immunohistochemistry. The expression of the markers was higher in cancer tissues when compared with the surrounding tissues. The MVD was lower in the CD34-positive cancer tissues than in the surrounding tissues. Significantly higher positive rates of expression for SHP2, MMP-9, and MMP-2 were observed in patients with lymph node metastases. The later the clinical stage was, the higher the expression of MMP-9 and MMP-2. The expression of VEGF in patients with lung squamous cell carcinomas was significantly higher than in patients with lung adenocarcinomas. The positive expression of SHP2 correlated significantly with that of VEGFR-2 and the MVD and a survival disadvantage was noted in the patients with SHP2-positive tumors. Therefore, our data suggest that the expression of SHP2 in NSCLC has high specificity and sensitivity and is closely related to lymph node metastasis and the expression of VEGFR-2 and the MVD in patients with NSCLC. SHP2 expression may promote the invasion and metastasis of NSCLC through angiogenesis and the lymphatic system.

  15. Bioimpedance for the spot measurement of tissue density

    Science.gov (United States)

    Dylke, E. S.; Ward, L. C.; Stannard, C.; Leigh, A.; Kilbreath, S. L.

    2013-04-01

    Long-standing lymphoedema is characterised by tissues changes which are currently not detectable using bioimpedance spectroscopy. It has been suggested that a combination of bipolar and tetrapolar measurements may be used to detect these tissues changes for a single site in the transverse direction. This was technique was trialled in a group of control participants with no history of lymphoedema or recent upper limb trauma. Repeated spot measurements were done without removal of electrodes to determine biological variability as well as with removal of electrodes to determine technical reproducibility. The inter-limb spot ratio of the controls was then compared to that of a number of women previously diagnosed with secondary lymphoedema in the forearm. Biological variability was not found to greatly influence repeated measures but only moderate technical reliability was found despite excellent co-efficient of variation for the majority of the measurements. A difference was seen between those with more severe swelling and the controls. This novel technique shows promise in detecting tissue changes associated with long-standing lymphoedema.

  16. Microarray expression profiles of genes in lung tissues of rats subjected to focal cerebral ischemia-induced lung injury following bone marrow-derived mesenchymal stem cell transplantation.

    Science.gov (United States)

    Hu, Yue; Xiong, Liu-Lin; Zhang, Piao; Wang, Ting-Hua

    2017-01-01

    Ischemia-induced stroke is the most common disease of the nervous system and is associated with a high mortality rate worldwide. Cerebral ischemia may lead to remote organ dysfunction, particular in the lungs, resulting in lung injury. Nowadays, bone marrow-derived mesenchymal stem cells (BMSCs) are widely studied in clinical trials as they may provide an effective solution to the treatment of neurological and cardiac diseases; however, the underlying molecular mechanisms remain unknown. In this study, a model of permanent focal cerebral ischemia-induced lung injury was successfully established and confirmed by neurological evaluation and lung injury scores. We demonstrated that the transplantation of BMSCs (passage 3) via the tail vein into the lung tissues attenuated lung injury. In order to elucidate the underlying molecular mechanisms, we analyzed the gene expression profiles in lung tissues from the rats with focal cerebral ischemia and transplanted with BMSCs using a Gene microarray. Moreover, the Gene Ontology database was employed to determine gene function. We found that the phosphoinositide 3-kinase (PI3K)-AKT signaling pathway, transforming growth factor-β (TGF-β) and platelet-derived growth factor (PDGF) were downregulated in the BMSC transplantation groups, compared with the control group. These results suggested that BMSC transplantation may attenuate lung injury following focal cerebral ischemia and that this effect is associated with the downregulation of TGF-β, PDGF and the PI3K-AKT pathway.

  17. Hair Growth Promoting Potential of Phospholipids Purified from Porcine Lung Tissues

    OpenAIRE

    Choi, Seong-Hyun; Moon, Jeong-Su; Jeon, Byung-suk; Jeon, Yeon-Jeong; Yoon, Byung-IL; Lim, Chang-Jin

    2015-01-01

    BP201, porcine lung tissue-derived phospholipids, consists of phosphatidylcholine as a major phospholipid species. BP201 promoted hair growth after application onto the shaved backs of BALB/c and C3H mice. Its effect was enhanced when applied together with minoxidil (MNX) in C3H mice. When the tissue specimens prepared from the shaved skins of BP201-treated and control mice were microscopically examined, the total numbers of hair follicles in both anagen and telogen phases of BP201-treated mi...

  18. Microarray analysis of long non-coding RNAs in COPD lung tissue.

    Science.gov (United States)

    Bi, Hui; Zhou, Ji; Wu, Dandan; Gao, Wei; Li, Lingling; Yu, Like; Liu, Feng; Huang, Mao; Adcock, Ian M; Barnes, Peter J; Yao, Xin

    2015-02-01

    Long noncoding RNAs (lncRNAs) play an important role in the pathogenesis of many human diseases. In this study, we provide the description of genome-wide lncRNA expression in the lung tissue of non-smokers without Chronic obstructive pulmonary disease (COPD), of smokers without COPD and of smokers with COPD. RNA was extracted from human lung tissue and analysed using an Agilent Human lncRNA + mRNA Array v2.0 system. 39,253 distinct lncRNA transcripts were detected in the lung tissues of all subjects. In smokers without COPD 87 lncRNAs were significantly up-regulated and 244 down-regulated compared to non-smokers without COPD with RNA50010|UCSC-9199-1005 and RNA58351| CombinedLit_316_550, the most over- and under-regulated, respectively. In contrast, in COPD patients 120 lncRNAs were over-expressed and 43 under-expressed compared with smokers without COPD with RNA44121|UCSC-2000-3182 and RNA43510|UCSC-1260-3754 being the most over- and under-regulated, respectively. Gene Ontology (GO) and pathway analysis indicated that cigarette smoking was associated with activation of metabolic pathways, whereas COPD transcripts were associated with 'hematopoietic cell lineage', intermediary metabolism and immune system processes. We conclude that the altered expression of lncRNAs might play partial role in pathways implicated in COPD onset and progression such as intermediary metabolism and the immune response.

  19. Fusing visual and clinical information for lung tissue classification in high-resolution computed tomography.

    Science.gov (United States)

    Depeursinge, Adrien; Racoceanu, Daniel; Iavindrasana, Jimison; Cohen, Gilles; Platon, Alexandra; Poletti, Pierre-Alexandre; Müller, Henning

    2010-09-01

    We investigate the influence of the clinical context of high-resolution computed tomography (HRCT) images of the chest on tissue classification. 2D regions of interest in HRCT axial slices from patients affected with an interstitial lung disease are automatically classified into five classes of lung tissue. Relevance of the clinical parameters is studied before fusing them with visual attributes. Two multimedia fusion techniques are compared: early versus late fusion. Early fusion concatenates features in one single vector, yielding a true multimedia feature space. Late fusion consisting of the combination of the probability outputs of two support vector machines. The late fusion scheme allowed a maximum of 84% correct predictions of testing instances among the five classes of lung tissue. This represents a significant improvement of 10% compared to a pure visual-based classification. Moreover, the late fusion scheme showed high robustness to the number of clinical parameters used, which suggests that it is appropriate for mining clinical attributes with missing values in clinical routine. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  20. Comparative performance analysis of state-of-the-art classification algorithms applied to lung tissue categorization.

    Science.gov (United States)

    Depeursinge, Adrien; Iavindrasana, Jimison; Hidki, Asmâa; Cohen, Gilles; Geissbuhler, Antoine; Platon, Alexandra; Poletti, Pierre-Alexandre; Müller, Henning

    2010-02-01

    In this paper, we compare five common classifier families in their ability to categorize six lung tissue patterns in high-resolution computed tomography (HRCT) images of patients affected with interstitial lung diseases (ILD) and with healthy tissue. The evaluated classifiers are naive Bayes, k-nearest neighbor, J48 decision trees, multilayer perceptron, and support vector machines (SVM). The dataset used contains 843 regions of interest (ROI) of healthy and five pathologic lung tissue patterns identified by two radiologists at the University Hospitals of Geneva. Correlation of the feature space composed of 39 texture attributes is studied. A grid search for optimal parameters is carried out for each classifier family. Two complementary metrics are used to characterize the performances of classification. These are based on McNemar's statistical tests and global accuracy. SVM reached best values for each metric and allowed a mean correct prediction rate of 88.3% with high class-specific precision on testing sets of 423 ROIs.

  1. Differential effects of chronic cyanide intoxication on heart, lung and pancreatic tissues.

    Science.gov (United States)

    Okolie, N P; Osagie, A U

    2000-06-01

    The histotoxic effects of chronic cyanide insult on heart, lung and pancreatic tissues, and some corroborative enzyme and metabolite changes were studied in New Zealand White rabbits using colorimetric, enzymatic and histochemical methods. Two groups of rabbits were fed for 10 months on either pure growers mash or grower mash +702 ppm inorganic cyanide. There were no significant differences in time-course profiles of serum amylase and fasting blood glucose between the cyanide-fed group and control. Pancreatic islet and heart histologies showed no pathological changes, and there were no significant differences in both serum and heart aspartate transaminase activities between the two groups. However, there were significant decreases (Pactivity in the lungs of the cyanide-fed group, with corresponding significant (Pactivity of the enzyme. Histological examination of lung tissue of the cyanide-treated rabbits revealed focal areas of pulmonary oedema and necrosis. These results suggest the existence of variabilities in tissue susceptibilities to the toxic effect of chronic cyanide exposure. It would appear that chronic cyanide exposure may not predispose to diabetes in the presence of adequate protein intake.

  2. Modeling the lung: Design and development of tissue engineered macro- and micro-physiologic lung models for research use.

    Science.gov (United States)

    Nichols, Joan E; Niles, Jean A; Vega, Stephanie P; Argueta, Lissenya B; Eastaway, Adriene; Cortiella, Joaquin

    2014-09-01

    Respiratory tract specific cell populations, or tissue engineered in vitro grown human lung, have the potential to be used as research tools to mimic physiology, toxicology, pathology, as well as infectious diseases responses of cells or tissues. Studies related to respiratory tract pathogenesis or drug toxicity testing in the past made use of basic systems where single cell populations were exposed to test agents followed by evaluations of simple cellular responses. Although these simple single-cell-type systems provided good basic information related to cellular responses, much more can be learned from cells grown in fabricated microenvironments which mimic in vivo conditions in specialized microfabricated chambers or by human tissue engineered three-dimensional (3D) models which allow for more natural interactions between cells. Recent advances in microengineering technology, microfluidics, and tissue engineering have provided a new approach to the development of 2D and 3D cell culture models which enable production of more robust human in vitro respiratory tract models. Complex models containing multiple cell phenotypes also provide a more reasonable approximation of what occurs in vivo without the confounding elements in the dynamic in vivo environment. The goal of engineering good 3D human models is the formation of physiologically functional respiratory tissue surrogates which can be used as pathogenesis models or in the case of 2D screening systems for drug therapy evaluation as well as human toxicity testing. We hope that this manuscript will serve as a guide for development of future respiratory tract model systems as well as a review of conventional models. © 2014 by the Society for Experimental Biology and Medicine.

  3. Intravenous augmentation treatment and lung density in severe α1 antitrypsin deficiency (RAPID)

    DEFF Research Database (Denmark)

    Chapman, Kenneth R; Burdon, Jonathan G W; Piitulainen, Eeva

    2015-01-01

    BACKGROUND: The efficacy of α1 proteinase inhibitor (A1PI) augmentation treatment for α1 antitrypsin deficiency has not been substantiated by a randomised, placebo-controlled trial. CT-measured lung density is a more sensitive measure of disease progression in α1 antitrypsin deficiency emphysema...... than spirometry is, so we aimed to assess the efficacy of augmentation treatment with this measure. METHODS: The RAPID study was a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial of A1PI treatment in patients with α1 antitrypsin deficiency. We recruited eligible non...

  4. Expression of aquaporin-1 and aquaporin-3 in lung tissue of rat model with ischemia-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    ZHAO Song; LI Xiang-nan

    2010-01-01

    @@ End-stage lung diseases are common and frequentlyoccurring diseases which are difficult for clinical treatment. In recent years, lung transplantation has become a widely accepted and effective therapeutic option for patients with the end-stage pulmonary diseases. Early pulmonary edema resulting from ischemia-reperfusion injury accounts for the major part of mortality and morbidity after lung transplantation. The water channel proteins in lung injury have been little studied, and their impact on the formation of pulmonary edema remains unclear. In this study, we established a rat lung ischemia-reperfusion model to study its impact on the expressions of water channel proteins in lung tissue and explore a new approach to lung transplantation in pulmonary edema pathogenesis.

  5. Lung-dominant connective tissue disease among patients with interstitial lung disease: prevalence, functional stability, and common extrathoracic features

    Directory of Open Access Journals (Sweden)

    Daniel Antunes Silva Pereira

    2015-04-01

    Full Text Available OBJECTIVE: To describe the characteristics of a cohort of patients with lung-dominant connective tissue disease (LD-CTD. METHODS: This was a retrospective study of patients with interstitial lung disease (ILD, positive antinuclear antibody (ANA results (≥ 1/320, with or without specific autoantibodies, and at least one clinical feature suggestive of connective tissue disease (CTD. RESULTS: Of the 1,998 patients screened, 52 initially met the criteria for a diagnosis of LD-CTD: 37% were male; the mean age at diagnosis was 56 years; and the median follow-up period was 48 months. During follow-up, 8 patients met the criteria for a definitive diagnosis of a CTD. The remaining 44 patients comprised the LD-CTD group, in which the most prevalent extrathoracic features were arthralgia, gastroesophageal reflux disease, and Raynaud's phenomenon. The most prevalent autoantibodies in this group were ANA (89% and anti-SSA (anti-Ro, 27%. The mean baseline and final FVC was 69.5% and 74.0% of the predicted values, respectively (p > 0.05. Nonspecific interstitial pneumonia and usual interstitial pneumonia patterns were found in 45% and 9% of HRCT scans, respectively; 36% of the scans were unclassifiable. A similar prevalence was noted in histological samples. Diffuse esophageal dilatation was identified in 52% of HRCT scans. Nailfold capillaroscopy was performed in 22 patients; 17 showed a scleroderma pattern. CONCLUSIONS: In our LD-CTD group, there was predominance of females and the patients showed mild spirometric abnormalities at diagnosis, with differing underlying ILD patterns that were mostly unclassifiable on HRCT and by histology. We found functional stability on follow-up. Esophageal dilatation on HRCT and scleroderma pattern on nailfold capillaroscopy were frequent findings and might come to serve as diagnostic criteria.

  6. Post-mortem detection of gasoline residues in lung tissue and heart blood of fire victims.

    Science.gov (United States)

    Pahor, Kevin; Olson, Greg; Forbes, Shari L

    2013-09-01

    The purpose of this study was to determine whether gasoline residues could be detected post-mortem in lung tissue and heart blood of fire victims. The lungs and heart blood were investigated to determine whether they were suitable samples for collection and could be collected without contamination during an autopsy. Three sets of test subjects (pig carcasses) were investigated under two different fire scenarios. Test subjects 1 were anaesthetized following animal ethics approval, inhaled gasoline vapours for a short period and then euthanized. The carcasses were clothed and placed in a house where additional gasoline was poured onto the carcass post-mortem in one fire, but not in the other. Test subjects 2 did not inhale gasoline, were clothed and placed in the house and had gasoline poured onto them in both fires. Test subjects 3 were clothed but had no exposure to gasoline either ante- or post-mortem. Following controlled burns and suppression with water, the carcasses were collected, and their lungs and heart blood were excised at a necropsy. The headspace from the samples was analysed using thermal desorption-gas chromatography-mass spectroscopy. Gasoline was identified in the lungs and heart blood from the subjects that were exposed to gasoline vapours prior to death (test subjects 1). All other samples were negative for gasoline residues. These results suggest that it is useful to analyse for volatile ignitable liquids in lung tissue and blood as it may help to determine whether a victim was alive and inhaling gases at the time of a fire.

  7. Association of Inorganics Accumulation with the Activation of NF-κB Signaling Pathway and the iNOS Expression of Lung Tissue in Xuanwei Lung Cancer Patients

    Directory of Open Access Journals (Sweden)

    Jiapeng YANG

    2016-01-01

    Full Text Available Background and objective Indoor air pollution induces asthma, leads to chronic obstructive pulmonary disease, and may promote lung cancer. Our previous studies found that the accumulation of inorganic particulate matter that is due to indoor air pollution can lead to damage to alveolar cells and activation of signaling pathway, and ultimately provoke tumorigenesis. The aim of this study is to explore the accumulation of inorganics and activation of nuclear factor κB (NF-κB-inducible nitric oxide synthase (iNOS signaling pathway of lung tissue in Xuanwei lung cancer patients. Methods From December 2013 to November 2014, 48 cases Xuanwei patients with lung cancer who underwent surgical treatment from the Third Affiliated Hospital of Kunming Medical University were enrolled in this study and compared with lung cancer patients from other regions. The ultrastructure of postoperative specimens was observed by transmission electron microscopy (TEM to explore the occurrence of inorganic particles. Serum cytokines were analyzed. Then, the expression levels of NF-κB-p65 protein and iNOS protein in postoperative specimens was explored by immunohistochemistry and Western blot. Finally, 8-OHdG accumulation in lung cancer tissues and urine was measured. Results A large number of nanoscale inorganics were observed in alveolar type II cells and macrophages located in adjacent tissues of lung cancer with Xuanwei patients. Silicon (Si content was found in inorganic elemental analysis. The serum interleukin (IL-1β levels (31.50±19.16 pg/mL of Xuanwei lung-cancer patients were remarkably higher than those from other regions (11.33±6.94 pg/mL (P<0.01, with statistically significant difference. The pathological tissues of Xuanwei lung-cancer patients express NF-κB-p65, and iNOS expression were significantly higher than those of patients from non-Xuanwei regions. No significant difference was found between cancerous and normal adjacent tissues. Xuanwei lung

  8. Reproducible isolation of type II pneumocytes from fetal and adult rat lung using nycodenz density gradients.

    Science.gov (United States)

    Viscardi, R M; Ullsperger, S; Resau, J H

    1992-01-01

    Isolating fresh, relatively pure type II pneumocytes from the lung, particularly of fetal origin, is a difficult process. Separation by buoyant density gradient centrifugation has been used successfully to isolate adult type II cells. There is concern, however, that Percoll, a gradient medium that is commonly used for type II cell isolation, may be toxic to cells. We evaluated a new gradient medium, Nycodenz, that is (1) a true solution, (2) transparent, (3) not metabolized by cells, and (4) nontoxic to cells. Type II pneumocytes were isolated from 19- and 21-day gestation fetal and adult rat lung by elastase digestion and separated on preformed isotonic Nycodenz gradients (2 mL each of 27.6, 20.7, 13.8, and 4.6 (w/v) solutions). Type II pneumocytes were recovered from the density range 1.057-1.061 and identified by binding of FITC-conjugated and gold-complexed Maclura pomifera lectin. Cells derived from 19-day fetal lung contained abundant glycogen and reacted with a monoclonal antibody to the cytokeratins 8 and 18, which are markers of the fetal type II cell. Adult type II cells reacted with antibodies to cytokeratins 8, 18, and 19. Type II cell purity was 79.7 +/- 2.4%, 83.8 +/- 2.8%, and 82.6 +/- 1.8% (means +/- SEM) for 19- and 21-day gestation fetal and adult lung preparations, respectively. Cell viability was greater than 95%. The final cell yield for adult preparations was 17.8 +/- 2.7 x 10(6)/rat (means +/- SEM). To determine if the freshly isolated type II pneumocytes were functionally active, the incorporation of [3H]choline into phosphatidylcholine was measured. The percent saturation of phosphatidylcholine was high for both populations of freshly isolated cells. However, adult type II pneumocytes incorporated [3H]choline into phosphatidylcholine more rapidly than 21-day gestation fetal cells (5.97 x 10(-3) dpm/10(6) cells/h vs. 0.32 x 10(-3) dpm/10(6) cells/h, P less than .005). We have demonstrated that, using the Nycodenz isolation method, it is

  9. Histological Changes in the Lung and Liver Tissues in Mice Exposed to Pyrethroid Inhalation

    Directory of Open Access Journals (Sweden)

    Nadeem SHEIKH

    2013-12-01

    Full Text Available Cypermethrin, a type II pyrethroid, is one of the most widely used insecticides in Pakistan. It is considered to be a safe pesticide; however, the possible health hazards of this pyrethroid have been ignored. Cypermethrin may become an air pollutant and adversely affect the health of non-target organisms, leading to acute or chronic disorders. The present work aims to investigate the effects of cypermethrin on lung and liver tissues due to inhalation exposure. The study is performed on 16 mature Swiss albino mice, including controls. The animals are divided into 4 groups (4 mice each and exposed to 0.5 % dilution of cypermethrin in an inhalation chamber (40×35×25 cm3 for different time periods, whereas control animals are not exposed to any insecticide. The histopathological changes in lungs and liver tissues reveal that cypermethrin exposure induces time dependent changes in the liver and in the lungs. It damages the normal organization of liver tissues, causing liver injury due to necrosis, significant decrease in number of cells, and widening of sinusoids and fibrosis. Inhalation exposure of cypermethrin results in significant hyperplasia, clumping of cells and necrosis in the lungs. It also induces pulmonary edema, alveolitis, and pulmonary fibrosis by the deposition of collagen. Taking these findings together, it may be concluded that cypermethrin and other pyrethroids cause hazardous effects in non-target organisms through inhalation exposure. Serious efforts and awareness are required to monitor and reduce the insecticide induced health hazards in third world countries.doi:10.14456/WJST.2014.67

  10. Changes of myocardial capillary density in progression of experimental lung emphysema.

    Science.gov (United States)

    Sulkowski, S; Musiatowicz, B; Sulkowska, M; Sobaniec-Lotowska, M; Dziechiol, J; Sulik, M; Szynaka, B

    1996-01-01

    A morphometrical analysis of changes in the heart of rats with experimental lung emphysema due to single intratracheal administration of papain solution has been done. Special attention has been paid to quantitative changes of capillaries and to the cardiomyocyte diameter in respective regions of the myocardium after one, three and six months following the administration of papain. A histological and morphometrical analysis of changes in the lungs has also been carried out and partial pressures of oxygen and carbon dioxide in the arterial blood of the examined animals have been marked. It has been found that a single administration of papain caused emphysematous changes in the lungs, growing more intense until the third month of the experiment. The progression of these changes corresponded to a capillary density increase in the right ventricle, interventricular septum and in the subendocardial layer of the left ventricle. The increase in the number of capillaries was interpreted as the first adaptive stage of cor pulmonale development and explained by the occurrence of angiogenesis. The changes co-existed with a decrease in partial pressure of oxygen in the arterial blood. After six months of the experiment, a reduction in capillary density in the heart regions mentioned above and a simultaneous increase in the cardiomycyte transversal diameter were observed, being the exponents of evident myocardial hypertrophy. Development of ultrastructural changes in the hearts of rats has been analysed too. Simultaneous development of changes in the right ventricle muscle and in the subendocardial layer of the heart left ventricle myocardium was observed. The role of hypoxia as a one of essential factors responsible for the observed morphologic changes has been discussed.

  11. Method for obtaining committed adult mesenchymal precursors from skin and lung tissue.

    Directory of Open Access Journals (Sweden)

    Aurora Bernal

    Full Text Available AIMS: The present study reports an easy and efficient method for obtaining adult mesenchymal precursors from different adult mouse tissues. MATERIALS AND METHODS: We describe the isolation and expansion of mesenchymal precursors from skin and lung by a non-enzymatic method. Skin and lung mesenchymal precursors isolated by a modified explant technique were characterized in vitro by defined morphology and by a specific gene expression profile and surface markers. RESULTS AND CONCLUSIONS: Our results show that these precursors express stem cell and mesenchymal surface markers as well as epithelial markers. However, they are negative for markers of endothelium, cardiac and skeletal muscle or adipose tissue, indicating that they have initiated commitment to the tissues from which were isolated. These precursors can migrate without any stimulus and in response to stimuli as SDF1, MCP1 and TNFα and can be differentiated into epithelial lineages. Based on the properties of these precursors from adult tissues, we propose their use as tools for regenerative biomedicine.

  12. HOPE-fixation of lung tissue allows retrospective proteome and phosphoproteome studies.

    Science.gov (United States)

    Shevchuk, Olga; Abidi, Nada; Klawonn, Frank; Wissing, Josef; Nimtz, Manfred; Kugler, Christian; Steinert, Michael; Goldmann, Torsten; Jänsch, Lothar

    2014-11-07

    Hepes-glutamic acid buffer-mediated organic solvent protection effect (HOPE)-fixation has been introduced as an alternative to formalin fixation of clinical samples. Beyond preservation of morphological structures for histology, HOPE-fixation was demonstrated to be compatible with recent methods for RNA and DNA sequencing. However, the suitability of HOPE-fixed materials for the inspection of proteomes by mass spectrometry so far remained undefined. This is of particular interest, since proteins constitute a prime resource for drug research and can give valuable insights into the activity status of signaling pathways. In this study, we extracted proteins from human lung tissue and tested HOPE-treated and snap-frozen tissues comparatively by proteome and phosphoproteome analyses. High confident data from accurate mass spectrometry allowed the identification of 2603 proteins and 3036 phosphorylation sites. HOPE-fixation did not hinder the representative extraction of proteins, and investigating their biochemical properties, covered subcellular localizations, and cellular processes revealed no bias caused by the type of fixation. In conclusion, proteome as well as phosphoproteome data of HOPE lung samples were qualitatively equivalent to results obtained from snap-frozen tissues. Thus, HOPE-treated tissues match clinical demands in both histology and retrospective proteome analyses of patient samples by proteomics.

  13. Benefit of adjunctive tacrolimus in connective tissue disease-interstitial lung disease.

    Science.gov (United States)

    Witt, Leah J; Demchuk, Carley; Curran, James J; Strek, Mary E

    2016-02-01

    We evaluated the safety and effectiveness of adjunctive tacrolimus therapy with conventional immunosuppression in patients with severe connective tissue disease-related interstitial lung disease (CTD-ILD). We included patients from our interstitial lung disease (ILD) registry with CTD-ILD, in whom tacrolimus was added to corticosteroids and an additional immunosuppressive agent. Demographic data, clinical features, lung function, radiographic images, and pathologic findings were reviewed. Effectiveness was assessed by comparing pulmonary function tests (PFTs) closest to tacrolimus initiation to PFTs approximately 6-12 months later. Corticosteroid dose at these time points was also evaluated. We report adverse events attributed to tacrolimus. Seventeen patients with CTD-ILD were included in adverse event analysis; twelve were included in efficacy analysis. Length of tacrolimus therapy ranged from 6 to 110 months (mean 38.8 months ± 31.4). The mean improvement in percent predicted total lung capacity was 7.5% ± 11.7 (p = 0.02). Forced vital capacity mean improvement was 7.4% ± 12.5 (p = 0.06). The average decrease in corticosteroid dose at follow-up was 20.3 mg ± 25.2 (p = 0.02) with complete discontinuation in six patients. No patients experienced a life-threatening adverse event attributed to tacrolimus. Tacrolimus can be effective and is well tolerated as an adjunctive therapy and allows tapering of corticosteroids.

  14. Morphological and immunohistochemical features of the lung tissue in Sudden Infant Death Syndrome (SIDS

    Directory of Open Access Journals (Sweden)

    Kadir Tukhtaev

    2013-04-01

    Full Text Available Morphological and immunohistochemical features of the lung tissue from 50 corpses of infants aged 1 month to 1 year were studied to determine their place in the structure of causes of death. Immunohistochemistry revealed decreased expression of surfactant protein B in most cases of sudden infant death syndrome (SIDS, which is probably due to qualitative changes in pulmonary surfactant. The data obtained suggest that the comprehensive studies of lung tissue of infants may contribute to clarifying the degree of risk and more accurately determining the causes of death in some cases of sudden infant death. This will help reduce the risk of diagnostic errors, i.e., hypo- or over-diagnosis SIDS and is of practical importance for forensic examination. This is especially true for those cases that require the need for differential diagnosis of SIDS with different types of pneumonia or mechanical asphyxia. Further investigations in this area should focus on the study of the molecular and genetic mechanisms of synthesis and transport of surfactant proteins, and to develop simple inexpensive methods for detection of the lungs surfactant deficiency in infants.

  15. Arsenic Species in Scute (Shell Plate) and Lung Tissues of Desert Tortoises

    Science.gov (United States)

    Foster, A. L.; Berry, K.; Jacobson, E. R.; Rytuba, J. J.

    2009-12-01

    The desert tortoise (Gopherus agassizii) is federally listed as a threatened species, and its numbers have been in decline for at least two decades. Portions of protected desert tortoise habitats coincide with anthropogenic features such as historic mines and military bases that are potential sources of ingested or inhaled arsenic. Previous studies of necropsied desert tortoise specimens collected from the Mojave Desert have shown a statistically significant link between elevated tissue levels of arsenic (As) and the occurrence of clinical disease states. Synchrotron-based, microbeam X-ray absorption fine structure spectroscopy (XAFS) and X-ray fluorescence mapping (XRF) were the primary techniques used to identify As species in these tissues. Specimens have been analyzed from a mining-impacted area (Kelly-Rand Mining district, Kern County), and from sites on or adjacent to military bases (National Training Center, Ft Irwin, and Edwards AFB). XRF maps showed that scute sections sliced perpendicular to the exposed surface contain one or more diffuse bands of As(III) coordinated by oxygen instead of sulfur. This As(III) species is identical in all individuals, suggesting that it represents metabolized As. In contrast, the exterior surface and edges of scute sections contained As-rich particles of varying oxidation state and species, suggesting an exogenous origin. Particles contained reduced As in sulfides (Cu sulfide or arsenide) and As(V) in ferric sulfates and/or ferric arsenates. XAFS spectra of many As(V)-rich particles were close visual matches to spectra of known arsenic-bearing minerals or phases such as scorodite, jarosite, and arsenic adsorbed to iron (hydr)oxides. At least one, and more commonly 3-5 exogeneous As-rich particles were found in the formalin-preserved lung tissue sections examined, suggesting that such particles were relatively common. Pentavalent As was observed in forms similar to those encountered on scute sections. As(III) was observed in

  16. FIB-SEM imaging of carbon nanotubes in mouse lung tissue.

    Science.gov (United States)

    Købler, Carsten; Saber, Anne Thoustrup; Jacobsen, Nicklas Raun; Wallin, Håkan; Vogel, Ulla; Qvortrup, Klaus; Mølhave, Kristian

    2014-06-01

    Ultrastructural characterisation is important for understanding carbon nanotube (CNT) toxicity and how the CNTs interact with cells and tissues. The standard method for this involves using transmission electron microscopy (TEM). However, in particular, the sample preparation, using a microtome to cut thin sample sections for TEM, can be challenging for investigation of regions with agglomerations of large and stiff CNTs because the CNTs cut with difficulty. As a consequence, the sectioning diamond knife may be damaged and the uncut CNTs are left protruding from the embedded block surface excluding them from TEM analysis. To provide an alternative to ultramicrotomy and subsequent TEM imaging, we studied focused ion beam scanning electron microscopy (FIB-SEM) of CNTs in the lungs of mice, and we evaluated the applicability of the method compared to TEM. FIB-SEM can provide serial section volume imaging not easily obtained with TEM, but it is time-consuming to locate CNTs in the tissue. We demonstrate that protruding CNTs after ultramicrotomy can be used to locate the region of interest, and we present FIB-SEM images of CNTs in lung tissue. FIB-SEM imaging was applied to lung tissue from mice which had been intratracheally instilled with two different multiwalled CNTs; one being short and thin, and the other longer and thicker. FIB-SEM was found to be most suitable for detection of the large CNTs (Ø ca. 70 nm), and to be well suited for studying CNT agglomerates in biological samples which is challenging using standard TEM techniques.

  17. 非小细胞肺癌组织中肝再生磷酸酶-2和-3表达及微血管密度相关性分析%Expressions of phosphatase of regenerating liver-2 and-3 and their correlation with microvessel density in non-small cell lung cancer tissues

    Institute of Scientific and Technical Information of China (English)

    郭延林; 朱彦君; 伍青; 刘颖汇; 李彩伟

    2013-01-01

    目的 探讨非小细胞肺癌(non-small cell lung cancer,NSCLC)组织中肝再生磷酸酶(phosphatase of regenerating liver,PRL)-2、PRL-3表达情况及与微血管密度(microvessel density,MVD)的相关性,分析其表达与临床病理指标间的相关性.方法 采用免疫组织化学法检测40例NSCLC患者癌组织及癌旁正常组织中PRL-2、PRL-3表达情况,并检测癌组织中MVD值,分析PRL-2、PRL-3表达水平与MVD值间相关性及其与临床病理参数间关系.结果 PRL-2、PRL-3在癌组织中阳性表达率分别为65%、70%,其表达在肿瘤分化程度、淋巴结转移情况及TNM分期上差异有统计学意义(P<0.05),在癌旁组织中均未发现阳性表达;NSCLC患者癌组织MVD值在年龄、肿瘤淋巴结转移情况及TNM分期上差异有统计学意义(P<0.05);PRL-2与PRL-3 (r=0.452,P=0.008)、PRL-2与MVD(r=0.536,P=0.000)、PRL-3与MVD(r=0.452,P=0.004)呈明显正相关;PRL-2、PRL-3阳性表达者及MVD值>40者出现疾病进展例数明显高于PRL-2、PRL-3阴性者及MVD值≤40者(P<0.05).结论 PRL-2、PRL-3异常表达时可能通过影响肿瘤新生血管的形成而促进肺癌的形成、增殖及侵袭,对临床诊疗及判定预后有一定价值.

  18. Effect of zinc on the content of chemical elements in the lung tissue during obesity in the experiment.

    Science.gov (United States)

    Churin, B V; Trunova, V A; Sidorina, A V; Zvereva, V V; Astashov, V V

    2015-02-01

    We found no deviations from normalcy in the content of chemical elements (K, Ca, Mn, Fe, Cu, Zn, Se, Br, Rb, and Sr) in the lungs of rats with mild alimentary obesity, but revealed redistribution of correlations between the elements indicating impaired metabolism in this organ. Zinc supplementation had no effect on the body weight and content of chemical elements (including zinc) in the lung tissue in rats fed high fat diet, but led to significant changes in the correlations between the elements. Bromine, rubidium, and strontium are actively involved in interelement interactions in the lung tissue. These elements should be given more attention in considering biological processes including alimentary obesity.

  19. Comparison between concentrations of amphotericin B in infected lung lesion and in uninfected lung tissue in a patient treated with liposomal amphotericin B (AmBisome).

    Science.gov (United States)

    Watanabe, Akira; Matsumoto, Kana; Igari, Hidetoshi; Uesato, Masaya; Yoshida, Shigetoshi; Nakamura, Yasutaka; Morita, Kunihiko; Shibuya, Kazutoshi; Matsubara, Hisahiro; Yoshino, Ichiro; Kamei, Katsuhiko

    2010-09-01

    Generally, the primary lesion of a mold infection is in the airway, an extravascular site. Therefore, the antifungal drug concentration at the actual tissue lesion of a mold infection is as important as in the blood compartment. Although our antifungal armamentarium has expanded recently, polyenes are still often needed in clinical practice because of their potent fungicidal activity and the rarity of resistance. Nevertheless, the distribution of amphotericin B (AmB) in infected lung tissue has not yet been evaluated. Using high-performance liquid chromatography analysis, we determined the concentrations of AmB in plasma and infected and uninfected tissues of resected lung simultaneously, in a patient with pulmonary aspergillosis treated with liposomal amphotericin B (L-AmB). The AmB concentration in the infected lesion of the lung was approximately 5.2 times higher than that in plasma and 3.7 times higher than in uninfected lung tissue. L-AmB accumulated in the infected lesion of the lung at a higher concentration. Although our data are from only one patient, they may be useful in helping to develop better strategies for the use of L-AmB against pulmonary fungal infections.

  20. Effects of Tamoxifen and oestrogen on histology and radiographic density in high and low mammographic density human breast tissues maintained in murine tissue engineering chambers.

    Science.gov (United States)

    Chew, G L; Huo, C W; Huang, D; Blick, T; Hill, P; Cawson, J; Frazer, H; Southey, M C; Hopper, J L; Britt, K; Henderson, M A; Haviv, I; Thompson, E W

    2014-11-01

    Mammographic density (MD) is a strong risk factor for breast cancer. It is altered by exogenous endocrine treatments, including hormone replacement therapy and Tamoxifen. Such agents also modify breast cancer (BC) risk. However, the biomolecular basis of how systemic endocrine therapy modifies MD and MD-associated BC risk is poorly understood. This study aims to determine whether our xenograft biochamber model can be used to study the effectiveness of therapies aimed at modulating MD, by examine the effects of Tamoxifen and oestrogen on histologic and radiographic changes in high and low MD tissues maintained within the biochamber model. High and low MD human tissues were precisely sampled under radiographic guidance from prophylactic mastectomy fresh specimens of high-risk women, then inserted into separate vascularized murine biochambers. The murine hosts were concurrently implanted with Tamoxifen, oestrogen or placebo pellets, and the high and low MD biochamber tissues maintained in the murine host environment for 3 months, before the high and low MD biochamber tissues were harvested for histologic and radiographic analyses. The radiographic density of high MD tissue maintained in murine biochambers was decreased in Tamoxifen-treated mice compared to oestrogen-treated mice (p = 0.02). Tamoxifen treatment of high MD tissue in SCID mice led to a decrease in stromal (p = 0.009), and an increase in adipose (p = 0.023) percent areas, compared to placebo-treated mice. No histologic or radiographic differences were observed in low MD biochamber tissue with any treatment. High MD biochamber tissues maintained in mice implanted with Tamoxifen, oestrogen or placebo pellets had dynamic and measurable histologic compositional and radiographic changes. This further validates the dynamic nature of the MD xenograft model, and suggests the biochamber model may be useful for assessing the underlying molecular pathways of Tamoxifen-reduced MD, and in testing of other

  1. Allosteric Modulation of Beta1 Integrin Function Induces Lung Tissue Repair

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    Rehab AlJamal-Naylor

    2012-01-01

    Full Text Available The cellular cytoskeleton, adhesion receptors, extracellular matrix composition, and their spatial distribution are together fundamental in a cell's balanced mechanical sensing of its environment. We show that, in lung injury, extracellular matrix-integrin interactions are altered and this leads to signalling alteration and mechanical missensing. The missensing, secondary to matrix alteration and cell surface receptor alterations, leads to increased cellular stiffness, injury, and death. We have identified a monoclonal antibody against β1 integrin which caused matrix remodelling and enhancement of cell survival. The antibody acts as an allosteric dual agonist/antagonist modulator of β1 integrin. Intriguingly, this antibody reversed both functional and structural tissue injury in an animal model of degenerative disease in lung.

  2. Paraquat increases connective tissue growth factor expression and impairs lung fibroblast proliferation and viscoelasticity.

    Science.gov (United States)

    Zhang, N; Xie, Y-P; Pang, L; Zang, X-X; Wang, J; Shi, D; Wu, Y; Liu, X-L; Wang, G-H

    2014-12-01

    This in vitro study was designed to investigate the molecular mechanisms of paraquat-induced damage using cultured human fetal lung fibroblasts (MRC-5 cells), in order to promote the development of improved therapies for paraquat poisoning. Paraquat's effects on proliferation were examined by flow cytometry, on viscoelasticity by the micropipette aspiration technique, and on connective tissue growth factor (CTGF) expression by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Paraquat was found to significantly reduce the proliferation index of MRC-5 cells in a concentration-dependent manner (p paraquat led to a significant and time-dependent increase in CTGF expression (p paraquat-induced lung fibrosis but may represent useful targets of improved molecular-based therapies for paraquat poisoning.

  3. Evaluating the significance of density, localization, and PD-1/PD-L1 immunopositivity of mononuclear cells in the clinical course of lung adenocarcinoma patients with brain metastasis

    DEFF Research Database (Denmark)

    Téglási, Vanda; Reiniger, Lilla; Fabian, Katalin

    2017-01-01

    therapeutic strategies with these agents. The aim of this study was to characterize the distribution of ICs and determine the expression of the checkpoint molecules programmed death protein 1 (PD-1) and its ligand, PD-L1, in brain metastasis of lung adenocarcinoma (LUAD) patients and to analyze......Background. Management of lung cancer patients who suffer from brain metastases represents a major challenge. Considering the promising results with immune checkpoint inhibitor treatment, evaluating the status of immune cell (IC) infiltrates in the prognosis of brain metastasis may lead to better...... their clinicopathological correlations. Methods. We determined the presence of peritumoral mononuclear cells (mononuclear ring) and the density of intratumoral stromal mononuclear cells on brain metastasis tissue sections of 208 LUAD patients. PD-L1/PD-1 expressions were analyzed by immunohistochemistry. Results...

  4. SU-E-J-64: Evaluation of a Commercial EPID-Based in Vivo Dosimetric System in the Presence of Lung Tissue Heterogeneity

    Energy Technology Data Exchange (ETDEWEB)

    Gimeno-Olmos, J; Palomo-Llinares, R; Candela-Juan, C; Carmona Meseguer, V; Lliso-Valverde, F [Hospital Universitari i Politecnic La Fe, Valencia, Valencia (Spain); Garcia-Martinez, T [Hospital de la Ribera, Alzira, Valencia (Spain); Richart-Sancho, J [Clinica Benidorm, Benidorm, Alicante (Spain); Ballester, F [University of Valencia, Burjassot (Spain); Perez-Calatayud, J [Hospital Universitari i Politecnic La Fe, Valencia, Valencia (Spain); Clinica Benidorm, Benidorm, Alicante (Spain)

    2014-06-01

    Purpose: To study the performance of Dosimetry Check (DC), an EPID-based dosimetry software, which allows performing transit dosimetry, in low density medium, by comparing calculations in-phantom, and analysing results for 15 lung patients. Methods: DC software (v.3.8, pencil beam-based algorithm) has been tested, for plans (Eclipse v.10.0 TPS) delivered in two Varian Clinac iX equipped with aS1000 EPIDs.In the CIRS lung phantom, comparisons between DC and Eclipse (Acuros) were performed for several plans: (1) four field box; (2) square field delivered in arc mode; (3) RapidArc lung patient plan medially centred; (4) RapidArc lung patient plan centred in one lung. Reference points analysed: P1 (medial point, plans 1–3) and P2 (located inside one lung, plan 4).For fifteen lung patients treated with RapidArc, the isocentre and 9 additional points inside the PTV as well as the gamma passing rate (3%/3mm) for the PTV and at the main planes were studied. Results: In-phantom:P1: Per-field differences in plan 1: good agreement for AP-PA fields; discrepancy of 7% for the lateral fields. Global differences (plans 1–3): about 4%, showing a compensating effect of the individual differences.P2: Global difference (plan 4): 15 %. This represents the worst case situation as it is a point surrounded by lung tissue, where the DC pencil beam algorithm is expected to give the greater difference against Acuros.Lung patients: Mean point difference inside the PTV:(5.4±4.2) %. Gamma passing rate inside the PTV:(45±12) %. Conclusion: The performance of DC in heterogeneous lung medium was studied with a special phantom and the results for 15 patients were analysed. The found deviations show that even though DC is a highly promising in vivo dosimetry tool, there is a need of incorporating a more accurate algorithm mainly for plans with low density regions involved.

  5. Profiling microRNAs in lung tissue from pigs infected with Actinobacillus pleuropneumoniae

    Directory of Open Access Journals (Sweden)

    Podolska Agnieszka

    2012-09-01

    Full Text Available Abstract Background MicroRNAs (miRNAs are a class of non-protein-coding genes that play a crucial regulatory role in mammalian development and disease. Whereas a large number of miRNAs have been annotated at the structural level during the latest years, functional annotation is sparse. Actinobacillus pleuropneumoniae (APP causes serious lung infections in pigs. Severe damage to the lungs, in many cases deadly, is caused by toxins released by the bacterium and to some degree by host mediated tissue damage. However, understanding of the role of microRNAs in the course of this infectious disease in porcine is still very limited. Results In this study, the RNA extracted from visually unaffected and necrotic tissue from pigs infected with Actinobacillus pleuropneumoniae was subjected to small RNA deep sequencing. We identified 169 conserved and 11 candidate novel microRNAs in the pig. Of these, 17 were significantly up-regulated in the necrotic sample and 12 were down-regulated. The expression analysis of a number of candidates revealed microRNAs of potential importance in the innate immune response. MiR-155, a known key player in inflammation, was found expressed in both samples. Moreover, miR-664-5p, miR-451 and miR-15a appear as very promising candidates for microRNAs involved in response to pathogen infection. Conclusions This is the first study revealing significant differences in composition and expression profiles of miRNAs in lungs infected with a bacterial pathogen. Our results extend annotation of microRNA in pig and provide insight into the role of a number of microRNAs in regulation of bacteria induced immune and inflammatory response in porcine lung.

  6. Serum B cell-activating factor (BAFF) level in connective tissue disease associated interstitial lung disease.

    Science.gov (United States)

    Hamada, Tsutomu; Samukawa, Takuya; Kumamoto, Tomohiro; Hatanaka, Kazuhito; Tsukuya, Go; Yamamoto, Masuki; Machida, Kentaro; Watanabe, Masaki; Mizuno, Keiko; Higashimoto, Ikkou; Inoue, Yoshikazu; Inoue, Hiromasa

    2015-09-30

    Interstitial lung diseases (ILDs) are common in patients with connective tissue diseases (CTDs). Although the diagnosis of an underlying CTD in ILD (CTD-ILD) affects both prognosis and treatment, it is sometimes difficult to distinguish CTD-ILD from chronic fibrosing interstitial pneumonia (CFIP). B cell-activating factor belonging to the tumour necrosis factor family (BAFF) plays a crucial role in B cell development, survival, and antibody production. We examined serum levels of BAFF, surfactant protein D (SP-D), and Krebs von den Lungen-6 (KL-6) in 33 patients with CTD-ILD, 16 patients with undifferentiated CTD-ILD, 19 patients with CFIP, and 26 healthy volunteers. And we analysed the relationship between serum BAFF levels and pulmonary function, as well as the expression of BAFF in the lung tissue of patients with CTD-ILD. Serum levels of BAFF were significantly higher in CTD-ILD patients compared to healthy subjects and CFIP patients. However, there were no significant differences in serum levels of SP-D and KL-6. Furthermore, serum BAFF levels in CTD-ILD patients were inversely correlated with pulmonary function. BAFF was strongly expressed in the lungs of CTD-ILD patients, but weakly in normal lungs. This is the first study to demonstrate that serum BAFF levels were significantly higher in CTD-ILD patients compared to healthy subjects and CFIP patients. Furthermore, serum BAFF levels were correlated with pulmonary function. We consider that serum BAFF levels in patients with CTD-ILD reflect the presence of ILDs disease activity and severity. These finding suggest that BAFF may be a useful marker for distinguishing CTD-ILD from CFIP.

  7. Small interference RNA targeting tissue factor inhibits human lung adenocarcinoma growth in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Wang Jianing

    2011-05-01

    Full Text Available Abstract Background The human coagulation trigger tissue factor (TF is overexpressed in several types of cancer and involved in tumor growth, vascularization, and metastasis. To explore the role of TF in biological processes of lung adenocarcinoma, we used RNA interference (RNAi technology to silence TF in a lung adenocarcinoma cell line A549 with high-level expression of TF and evaluate its antitumor effects in vitro and in vivo. Methods The specific small interfering RNA (siRNA designed for targeting human TF was transfected into A549 cells. The expression of TF was detected by reverse transcription-PCR and Western blot. Cell proliferation was measured by MTT and clonogenic assays. Cell apoptosis was assessed by flow cytometry. The metastatic potential of A549 cells was determined by wound healing, the mobility and Matrigel invasion assays. Expressions of PI3K/Akt, Erk1/2, VEGF and MMP-2/-9 in transfected cells were detected by Western blot. In vivo, the effect of TF-siRNA on the growth of A549 lung adenocarcinoma xenografts in nude mice was investigated. Results TF -siRNA significantly reduced the expression of TF in the mRNA and protein levels. The down-regulation of TF in A549 cells resulted in the suppression of cell proliferation, invasion and metastasis and induced cell apoptosis in dose-dependent manner. Erk MAPK, PI3K/Akt pathways as well as VEGF and MMP-2/-9 expressions were inhibited in TF-siRNA transfected cells. Moreover, intratumoral injection of siRNA targeting TF suppressed the tumor growth of A549 cells in vivo model of lung adenocarcinoma. Conclusions Down-regulation of TF using siRNA could provide a potential approach for gene therapy against lung adenocarcinoma, and the antitumor effects may be associated with inhibition of Erk MAPK, PI3K/Akt pathways.

  8. Interaction between fragile histamine triad and protein kinase C alpha in human non-small cell lung cancer tissues

    Institute of Scientific and Technical Information of China (English)

    Peng-hui Zhuang; Zhao-hui Liu; Xiao-gang Jiang; Cheng-en Pan

    2009-01-01

    Objective To investigate the interaction between fragile histamine triad (FHIT) and protein kinase C alpha (PKCα) in human non-small cell lung cancer tissues. Methods FHIT and PKC伪 double positive samples were screened by immunohistochemical staining from 13 human non-small cell lung cancer tissues. Co-immunoprecipitation was performed by using anti-FHIT and anti-PKCα. The immune precipitate was analyzed by SDS-PAGE and Western blot. Results Immune precipitate staining detection showed that 3 samples out of the 13 cases were double positive for FHIT and PKCα. FHIT protein was present in the immune precipitate of anti-PKCα while there was PKCα in the immune precipitate of anti-FHITmAb. Conclusion FHIT and PKCα exist as a complex in human non-small cell lung cancer tissues, which will provide a new route for studying the pathogenesis and immunotherapy of human non-small cell lung cancer.

  9. Neutrophil elastase causes tissue damage that decreases host tolerance to lung infection with burkholderia species.

    Directory of Open Access Journals (Sweden)

    Manoranjan Sahoo

    2014-08-01

    Full Text Available Two distinct defense strategies can protect the host from infection: resistance is the ability to destroy the infectious agent, and tolerance is the ability to withstand infection by minimizing the negative impact it has on the host's health without directly affecting pathogen burden. Burkholderia pseudomallei is a Gram-negative bacterium that infects macrophages and causes melioidosis. We have recently shown that inflammasome-triggered pyroptosis and IL-18 are equally important for resistance to B. pseudomallei, whereas IL-1β is deleterious. Here we show that the detrimental role of IL-1β during infection with B. pseudomallei (and closely related B. thailandensis is due to excessive recruitment of neutrophils to the lung and consequent tissue damage. Mice deficient in the potentially damaging enzyme neutrophil elastase were less susceptible than the wild type C57BL/6J mice to infection, although the bacterial burdens in organs and the extent of inflammation were comparable between C57BL/6J and elastase-deficient mice. In contrast, lung tissue damage and vascular leakage were drastically reduced in elastase-deficient mice compared to controls. Bradykinin levels were higher in C57BL/6 than in elastase-deficient mice; administration of a bradykinin antagonist protected mice from infection, suggesting that increased vascular permeability mediated by bradykinin is one of the mechanisms through which elastase decreases host tolerance to melioidosis. Collectively, these results demonstrate that absence of neutrophil elastase increases host tolerance, rather than resistance, to infection by minimizing host tissue damage.

  10. Optimization of CT image reconstruction algorithms for the lung tissue research consortium (LTRC)

    Science.gov (United States)

    McCollough, Cynthia; Zhang, Jie; Bruesewitz, Michael; Bartholmai, Brian

    2006-03-01

    To create a repository of clinical data, CT images and tissue samples and to more clearly understand the pathogenetic features of pulmonary fibrosis and emphysema, the National Heart, Lung, and Blood Institute (NHLBI) launched a cooperative effort known as the Lung Tissue Resource Consortium (LTRC). The CT images for the LTRC effort must contain accurate CT numbers in order to characterize tissues, and must have high-spatial resolution to show fine anatomic structures. This study was performed to optimize the CT image reconstruction algorithms to achieve these criteria. Quantitative analyses of phantom and clinical images were conducted. The ACR CT accreditation phantom containing five regions of distinct CT attenuations (CT numbers of approximately -1000 HU, -80 HU, 0 HU, 130 HU and 900 HU), and a high-contrast spatial resolution test pattern, was scanned using CT systems from two manufacturers (General Electric (GE) Healthcare and Siemens Medical Solutions). Phantom images were reconstructed using all relevant reconstruction algorithms. Mean CT numbers and image noise (standard deviation) were measured and compared for the five materials. Clinical high-resolution chest CT images acquired on a GE CT system for a patient with diffuse lung disease were reconstructed using BONE and STANDARD algorithms and evaluated by a thoracic radiologist in terms of image quality and disease extent. The clinical BONE images were processed with a 3 x 3 x 3 median filter to simulate a thicker slice reconstructed in smoother algorithms, which have traditionally been proven to provide an accurate estimation of emphysema extent in the lungs. Using a threshold technique, the volume of emphysema (defined as the percentage of lung voxels having a CT number lower than -950 HU) was computed for the STANDARD, BONE, and BONE filtered. The CT numbers measured in the ACR CT Phantom images were accurate for all reconstruction kernels for both manufacturers. As expected, visual evaluation of the

  11. Resolvin D1 prevents smoking-induced emphysema and promotes lung tissue regeneration

    Directory of Open Access Journals (Sweden)

    Kim KH

    2016-05-01

    Full Text Available Kang-Hyun Kim,1 Tai Sun Park,2,3 You-Sun Kim,1,3 Jae Seung Lee,2,3 Yeon-Mok Oh,2,3 Sang-Do Lee,2,3 Sei Won Lee2,3 1Asan Institute for Life Sciences, 2Department of Pulmonology and Critical Care Medicine, Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, 3Department of Pulmonology and Critical Care Medicine, University of Ulsan College of Medicine, Seoul, Republic of Korea Purpose: Emphysema is an irreversible disease that is characterized by destruction of lung tissue as a result of inflammation caused by smoking. Resolvin D1 (RvD1, derived from docosahexaenoic acid, is a novel lipid that resolves inflammation. The present study tested whether RvD1 prevents smoking-induced emphysema and promotes lung tissue regeneration.Materials and methods: C57BL/6 mice, 8 weeks of age, were randomly divided into four groups: control, RvD1 only, smoking only, and smoking with RvD1 administration. Four different protocols were used to induce emphysema and administer RvD1: mice were exposed to smoking for 4 weeks with poly(I:C or to smoking only for 24 weeks, and RvD1 was injected within the smoking exposure period to prevent regeneration or after completion of smoking exposure to assess regeneration. The mean linear intercept and inflammation scores were measured in the lung tissue, and inflammatory cells and cytokines were measured in the bronchoalveolar lavage fluid.Results: Measurements of mean linear intercept showed that RvD1 significantly attenuated smoking-induced lung destruction in all emphysema models. RvD1 also reduced smoking-induced inflammatory cell infiltration, which causes the structural derangements observed in emphysema. In the 4-week prevention model, RvD1 reduced the smoking-induced increase in eosinophils and interleukin-6 in the bronchoalveolar lavage fluid. In the 24-week prevention model, RvD1 also reduced the increased neutrophils and total cell counts induced by smoking.Conclusion: RvD1

  12. Cryopreservation and in vitro culture of primary cell types from lung tissue of a stranded pygmy sperm whale (Kogia breviceps).

    Science.gov (United States)

    Annalaura Mancia; Spyropoulos, Demetri D; McFee, Wayne E; Newton, Danforth A; Baatz, John E

    2012-01-01

    Current models for in vitro studies of tissue function and physiology, including responses to hypoxia or environmental toxins, are limited and rely heavily on standard 2-dimensional (2-D) cultures with immortalized murine or human cell lines. To develop a new more powerful model system, we have pursued methods to establish and expand cultures of primary lung cell types and reconstituted tissues from marine mammals. What little is known about the physiology of the deep-sea diving pygmy sperm whale (PSW), Kogia breviceps, comes primarily from stranding events that occur along the coast of the southeastern United States. Thus, development of a method for preserving live tissues and retrieving live cells from deceased stranded individuals was initiated. This report documents successful cryopreservation of PSW lung tissue. We established in vitro cultures of primary lung cell types from tissue fragments that had been cryopreserved several months earlier at the stranding event. Dissociation of cryopreserved lung tissues readily provides a variety of primary cell types that, to varying degrees, can be expanded and further studied/manipulated in cell culture. In addition, PSW-specific molecular markers have been developed that permitted the monitoring of fibroblast, alveolar type II, and vascular endothelial cell types. Reconstitution of 3-D cultures of lung tissues with these cell types is now underway. This novel system may facilitate the development of rare or disease-specific lung tissue models (e.g., to test causes of PSW stranding events and lead to improved treatments for pulmonary hypertension or reperfusion injury in humans). Also, the establishment of a "living" tissue bank biorepository for rare/endangered species could serve multiple purposes as surrogates for freshly isolated samples.

  13. Real-time in vivo tissue characterization with diffuse reflectance spectroscopy during transthoracic lung biopsy: a clinical feasibility study

    NARCIS (Netherlands)

    Spliethoff, Jarich; Prevoo, Warner; Meier, Mark A.J.; de Jong, Jeroen; Evers, Daniel; Evers, Daniel J.; Sterenborg, Hendricus J.C.M.; Lucassen, Gerald; Lucassen, Gerald W.; Hendriks, Benno H.W.; Ruers, Theo J.M.

    2016-01-01

    Purpose: This study presents the first in vivo real-time tissue characterization during image-guided percutaneous lung biopsies using diffuse reflectance spectroscopy (DRS) sensing at the tip of a biopsy needle with integrated optical fibers. Experimental Design: Tissues from 21 consented patients

  14. Abnormal expression of vascular endothelial growth factor (VEGF) and its clinical features in tissues of human lung cancer

    Institute of Scientific and Technical Information of China (English)

    Xinhua Wu; Dengfu Yao; Gongshen Shi; Liwei Qiu; Wei Wu; Songshi Ni; Xueguang Zhang

    2005-01-01

    Objective: Angiogennesis, the formation of new blood vessels from the existing vascular bed, is essential step for growth and invasion of primary tumor. Vascular endothelial growth-factor (VEGF) is known to play crucial role in tumor angiogenesis. In the present study, we investigate the expression of VEGF and VEGF-mRNA in the angiogennesis, metastasis and prognosis of lung cancer.Methods: The VEGF cellular distributions and expression in 38 specimens of patients with lung cancer were investigated with immunohistochemistry stain technology. The total RNAs in 38 tissues of lung cancer was measured, then the levels of VEGF-mRNA expression were analyzed by a reverse-transcription polymerase chain reaction (RT-PCR) assay. The levels of VEGF in sera of patients with lung cancer, benign lung diseases and healthy controls were detected through Enzyme linked immunosorbent assay (ELISA) method. Results: The VEGF positive stain was 76% in 38 cases of lung cancer specimens. The 89% rate of VEGF stain was found for clinical stage Ⅲ cases and 92%for stage Ⅳ lung cancers. The significantly higher expression of VEGF was evidenced in patients with lymph node metastasis (84 % ), distant metastasis (90%), and lung cancers with lower histological differentiation (89%), respectively. The expression level of total RNA was significantly higher in patients with lung cancers than that in their paracancerous or distant lung tissues. The VEGF expressions were tightly correlated with total RNA concentration of lung carcinoma ( P < 0.01 ). The predominant expressions of VEGF121 and VEGF165 gene fragments were found in lung cancer specimens by RT-PCR analysis. No significant difference of serum VEGF levels was detected between cases with lung cancer and patients with benign diseases. However, the VEGF level of cases with benign diseases was decreased significantly after patients with anti-inflammation medication. Conclusion: The present data suggested that the tumor tissue VEGF

  15. Relationship between frequency, length, and treatment outcome of exacerbations to baseline lung function and lung density in alpha-1 antitrypsin-deficient COPD

    Directory of Open Access Journals (Sweden)

    Vijayasaratha K

    2012-11-01

    Full Text Available Kesavaperumal Vijayasaratha,1 Robert A Stockley21Lung Investigation Unit, 2Research and Development, University Hospital Birmingham NHS Trust, Birmingham, UKBackground: Diary cards are useful for analyzing exacerbations in chronic obstructive pulmonary disease (COPD, although factors influencing the length and frequency of each episode are poorly understood. This study investigated factors that influence the features of exacerbations in patients with alpha-1 antitrypsin (AAT deficiency (PiZ phenotype and COPD.Methods: Daily diary cards were collected over 2 years. Patients had emphysema visualized and quantified by computed tomography scan, and had at least one documented exacerbation in the previous year.Results: The patients (n = 23 had a mean age of 52.5 years, forced expiratory volume in one second (FEV1 of 1.2 L (38.4% predicted, corrected gas transfer (KCO of 0.90 mmol/min/kPa/L (59.7% predicted, and 15th percentile lung density of 44.55 g/L. Two hundred and sixty-three exacerbations (164 treated were identified. The frequency of treated exacerbations correlated negatively with KCO% predicted (r = −0.432; P = 0.022. Exacerbation length (determined for 17 of the patients for whom diary card data through the episode were available correlated negatively with baseline 15th percentile lung density (r = −0.361; P = 0.003, and increased the longer treatment was delayed (r = 0.503; P < 0.001. Treatment delay was shorter with higher day 1 symptom score, lower baseline FEV1, FEV1/forced vital capacity, and lower 15th percentile lung density (r = −0.368, 0.272, 0.461, and 0.786; P = 0.004, 0.036, <0.001, and <0.001, respectively. Time to resolution of exacerbation after treatment initiation was not affected by treatment delay, but correlated negatively with KCO% predicted (r = −0.647; P = 0.007.Conclusion: In alpha-1 antitrypsin deficiency, the frequency and length of resolution of exacerbation were related to baseline gas transfer. Treatment

  16. Serotype 1 and 8 Pneumococci Evade Sensing by Inflammasomes in Human Lung Tissue.

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    Diana Fatykhova

    Full Text Available Streptococcus pneumoniae is a major cause of pneumonia, sepsis and meningitis. The pore-forming toxin pneumolysin is a key virulence factor of S. pneumoniae, which can be sensed by the NLRP3 inflammasome. Among the over 90 serotypes, serotype 1 pneumococci (particularly MLST306 have emerged across the globe as a major cause of invasive disease. The cause for its particularity is, however, incompletely understood. We therefore examined pneumococcal infection in human cells and a human lung organ culture system mimicking infection of the lower respiratory tract. We demonstrate that different pneumococcal serotypes differentially activate inflammasome-dependent IL-1β production in human lung tissue and cells. Whereas serotype 2, 3, 6B, 9N pneumococci expressing fully haemolytic pneumolysins activate NLRP3 inflammasome-dependent responses, serotype 1 and 8 strains expressing non-haemolytic toxins are poor activators of IL-1β production. Accordingly, purified haemolytic pneumolysin but not serotype 1-associated non-haemolytic toxin activates strong IL-1β production in human lungs. Our data suggest that the evasion of inflammasome-dependent innate immune responses by serotype 1 pneumococci might contribute to their ability to cause invasive diseases in humans.

  17. Lung disease

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000066.htm Lung disease To use the sharing features on this page, ... fibrosis and sarcoidosis are examples of lung tissue disease. Lung circulation diseases -- These diseases affect the blood vessels ...

  18. Binding of 1-nitro(/sup 14/C)pyrene to DNA and protein in cultured lung macrophages and respiratory tissues

    Energy Technology Data Exchange (ETDEWEB)

    King, L.C.; Ball, L.M.; Lewtas, J. (Envrironmental Protection Agency, Research Triangle Park, Genetic Toxicology Division); Jackson, M. (Environmental Protection Agency, Research Triangle Park, Cellular Pathology and Biochemistry Section)

    1983-07-01

    Binding of 1-nitro(/sup 14/C)pyrene(1-NP) or its metabolites to cellular DNA and protein in cultures of rabbit alveolar macrophages and lung and tracheal tissues was examined. DNA binding was highest in tracheal tissue (136.9 +- 18.3 pmol 1-NP/mg DNA). DNA binding in macrophages and lung tissue was one-fifth of the level observed in tracheal tissue. Also, 1-NP was bound to cellular protein in tracheal and lung tissues, and at a lower level in macrophages. Co-cultivation of the macrophages with lung and tracheal tissues decreased the DNA binding in tracheal tissue and increased the protein binding in macrophages. This study shows that lung cells and tissue are capable of binding 1-NP or its metabolites to DNA and protein.

  19. Lung cancer in uranium miners: A tissue resource and pilot study. Final performance report

    Energy Technology Data Exchange (ETDEWEB)

    Samet, J.; Gilliland, F.D.

    1998-08-13

    This project incorporates two related research projects directed toward understanding respiratory carcinogenesis in radon-exposed former uranium miners. The first project involved a continuation of the tissue resource of lung cancer cases from former underground uranium miners and comparison cases from non-miners. The second project was a pilot study for a proposed longitudinal study of respiratory carcinogenesis in former uranium miners. The objectives including facilitating the investigation of molecular changes in radon exposed lung cancer cases, developing methods for prospectively studying clinical, cytologic, cytogenetic, and molecular changes in the multi-event process of respiratory carcinogenesis, and assessing the feasibility of recruiting former uranium miners into a longitudinal study that collected multiple biological specimens. A pilot study was conducted to determine whether blood collection, induced sputum, bronchial brushing, washings, and mucosal biopsies from participants at two of the hospitals could be included efficiently. A questionnaire was developed for the extended study and all protocols for specimen collection and tissue handling were completed. Resource utilization is in progress at ITRI and the methods have been developed to study molecular and cellular changes in exfoliated cells contained in sputum as well as susceptibility factors.

  20. Undifferentiated connective tissue disease presenting with prevalent interstitial lung disease: Case report and review of literature

    Directory of Open Access Journals (Sweden)

    Sfriso Paolo

    2011-06-01

    Full Text Available Abstract Undifferentiated connective tissue diseases (UCTDs are clinical entities characterised by signs and symptoms suggestive of a systemic autoimmune disease, which do not fulfil the diagnostic criteria for a defined connective tissue disease. Lung involvement can complicate the course and management of the disease, often determining a worse outcome. Respiratory dysfunction as the first clinical manifestation has seldom been reported. We describe a case of a female patient who developed significant respiratory dysfunction as the principal clinical sign. Video-assisted thoracoscopy was performed and a histological pattern of nonspecific interstitial pneumonia (NSIP was found. A pathological diagnosis suggested careful follow-up with extensive immunological screening which then detected Raynaud's phenomenon and positivity of antinuclear antibodies. After a multidisciplinary discussion (pneumologist, radiologist, pathologist and rheumatologist a final diagnosis of NSIP associated with UCTD was made. The diagnosis of UCTD should be considered when NSIP is diagnosed even in cases with evident first clinical manifestations of severe respiratory dysfunction. A multidisciplinary approach in the field of interstitial lung disease with NSIP, also including rheumatologic expertise, is fundamental to achieve a prompt and correct diagnosis.

  1. Bone tissue density modification in treatment of shin pseudoarthrosis by transosseous compressive osteosynthesis

    Directory of Open Access Journals (Sweden)

    Tishkov N.V.

    2011-12-01

    Full Text Available Objective is to detect bone mineral density along the shin according to «Esperanto» levels by Hounsfield's scale. Materials and methods. The analysis of density modification in 25 patients with pseudoarthrosis of tibia with predominant localization in a lower one-third of bone has been carried out. Results. By means of computed tomography it has been revealed that the bone tissue density of the tibia in the process of false joint union when using the compressive variant of combined transosseous osteosynthesis has changed according to the regularity reproducing phase character of the accumulation of mineral substances in the bone. Conclution. The growth of mineral density of the bone tissue during treatment spreads in the directions from proximal and distal metaepiphyses to the zone of pseudoarthrosis knitting

  2. Effects of tissue heterogeneity on the optical estimate of breast density

    Science.gov (United States)

    Taroni, Paola; Pifferi, Antonio; Quarto, Giovanna; Spinelli, Lorenzo; Torricelli, Alessandro; Abbate, Francesca; Balestreri, Nicola; Ganino, Serena; Menna, Simona; Cassano, Enrico; Cubeddu, Rinaldo

    2012-01-01

    Breast density is a recognized strong and independent risk factor for developing breast cancer. At present, breast density is assessed based on the radiological appearance of breast tissue, thus relying on the use of ionizing radiation. We have previously obtained encouraging preliminary results with our portable instrument for time domain optical mammography performed at 7 wavelengths (635–1060 nm). In that case, information was averaged over four images (cranio-caudal and oblique views of both breasts) available for each subject. In the present work, we tested the effectiveness of just one or few point measurements, to investigate if tissue heterogeneity significantly affects the correlation between optically derived parameters and mammographic density. Data show that parameters estimated through a single optical measurement correlate strongly with mammographic density estimated by using BIRADS categories. A central position is optimal for the measurement, but its exact location is not critical. PMID:23082283

  3. Demonstration of non-degraded Aleutian disease virus (ADV) proteins in lung tissue from experimentally infected mink kits

    DEFF Research Database (Denmark)

    Alexandersen, Søren; Uttenthal, Åse; Aasted, B.

    1986-01-01

    Isolates of ADV replicate to rather high quantities in lungs from neonatally infected mink kits. The virus was analysed for polypeptide composition, and for the first time high molecular weight polypeptides have been observed inin vivo produced ADVs. These polypeptides are analogous to those ofin...... described forin vitro produced ADV-G. Presence of the ADV coded, non-structural polypeptide with the molecular weight of 71kD (p71) was also demonstrated in the lung tissue from mink kits....

  4. Procoagulant, tissue factor-bearing microparticles in bronchoalveolar lavage of interstitial lung disease patients: an observational study.

    Directory of Open Access Journals (Sweden)

    Federica Novelli

    Full Text Available Coagulation factor Xa appears involved in the pathogenesis of pulmonary fibrosis. Through its interaction with protease activated receptor-1, this protease signals myofibroblast differentiation in lung fibroblasts. Although fibrogenic stimuli induce factor X synthesis by alveolar cells, the mechanisms of local posttranslational factor X activation are not fully understood. Cell-derived microparticles are submicron vesicles involved in different physiological processes, including blood coagulation; they potentially activate factor X due to the exposure on their outer membrane of both phosphatidylserine and tissue factor. We postulated a role for procoagulant microparticles in the pathogenesis of interstitial lung diseases. Nineteen patients with interstitial lung diseases and 11 controls were studied. All subjects underwent bronchoalveolar lavage; interstitial lung disease patients also underwent pulmonary function tests and high resolution CT scan. Microparticles were enumerated in the bronchoalveolar lavage fluid with a solid-phase assay based on thrombin generation. Microparticles were also tested for tissue factor activity. In vitro shedding of microparticles upon incubation with H₂O₂ was assessed in the human alveolar cell line, A549 and in normal bronchial epithelial cells. Tissue factor synthesis was quantitated by real-time PCR. Total microparticle number and microparticle-associated tissue factor activity were increased in interstitial lung disease patients compared to controls (84±8 vs. 39±3 nM phosphatidylserine; 293±37 vs. 105±21 arbitrary units of tissue factor activity; mean±SEM; p<.05 for both comparisons. Microparticle-bound tissue factor activity was inversely correlated with lung function as assessed by both diffusion capacity and forced vital capacity (r² = .27 and .31, respectively; p<.05 for both correlations. Exposure of lung epithelial cells to H₂O₂ caused an increase in microparticle-bound tissue factor

  5. NOTCH1, HIF1A and other cancer-related proteins in lung tissue from uranium miners--variation by occupational exposure and subtype of lung cancer.

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    Beate Pesch

    Full Text Available BACKGROUND: Radon and arsenic are established pulmonary carcinogens. We investigated the association of cumulative exposure to these carcinogens with NOTCH1, HIF1A and other cancer-specific proteins in lung tissue from uranium miners. METHODOLOGY/PRINCIPAL FINDINGS: Paraffin-embedded tissue of 147 miners was randomly selected from an autopsy repository by type of lung tissue, comprising adenocarcinoma (AdCa, squamous cell carcinoma (SqCC, small cell lung cancer (SCLC, and cancer-free tissue. Within each stratum, we additionally stratified by low or high level of exposure to radon or arsenic. Lifetime exposure to radon and arsenic was estimated using a quantitative job-exposure matrix developed for uranium mining. For 22 cancer-related proteins, immunohistochemical scores were calculated from the intensity and percentage of stained cells. We explored the associations of these scores with cumulative exposure to radon and arsenic with Spearman rank correlation coefficients (r(s. Occupational exposure was associated with an up-regulation of NOTCH1 (radon r(s = 0.18, 95% CI 0.02-0.33; arsenic: r(s = 0.23, 95% CI 0.07-0.38. Moreover, we investigated whether these cancer-related proteins can classify lung cancer using supervised and unsupervised classification. MUC1 classified lung cancer from cancer-free tissue with a failure rate of 2.1%. A two-protein signature discriminated SCLC (HIF1A low, AdCa (NKX2-1 high, and SqCC (NKX2-1 low with a failure rate of 8.4%. CONCLUSIONS/SIGNIFICANCE: These results suggest that the radiation-sensitive protein NOTCH1 can be up-regulated in lung tissue from uranium miners by level of exposure to pulmonary carcinogens. We evaluated a three-protein signature consisting of a physiological protein (MUC1, a cancer-specific protein (HIF1A, and a lineage-specific protein (NKX2-1 that could discriminate lung cancer and its major subtypes with a low failure rate.

  6. Effect of high tidal volume ventilation and lipopolysaccharide on mitogen-activated protein kinase in rat lung tissue

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ Mechanical ventilation, a crucial therapy to acute respiratory distress syndrome (ARDS), could exacerbate lung injury, and even result in ventilator-induced lung injury (VILI) if misused in some condition1. Over-activating inflammatory cells and expanding inflammatory responses, which are induced by infection, are fundamental reasons for ARDS. Among them, mitogen-activated protein kinase (MAPK) intracellular signal transduction pathways are key processes. This study aimed to investigate the time course of MAPK activation in rat lung tissue after high tidal volume (VT) ventilation and the role of lipopolysaccharide (LPS) in high-sensitivity, and to elucidate the effect of the pathway on VILI.

  7. Hydrogen sulfide regulates lung tissue-oxidized glutathione and total antioxidant capacity in hypoxic pulmonary hypertensive rats

    Institute of Scientific and Technical Information of China (English)

    Hong-ling WEI; Chun-yu ZHANG; Hong-fang JIN; Chao-shu TANG; Jun-bao DU

    2008-01-01

    Aim: To investigate the modulatory effect of sudium hydrosulfide on lung tissue-oxidized glutathione and total antioxidant capacity in the development of hypoxic pulmonary hypertension (HPH). Methods: After 21 d of hypoxia, the mean pulmo-nary artery pressure was measured by cardiac catheterization. The plasma H2S level and production of H2S in the lung tissues were determined by using a spectrophotometer. The lung homogenates were assayed for total antioxidant capacity (T-AOC), superoxide dismutase (SOD), oxidized glutathione (GSSG), re-duced glutathione and malonaldehyde by colorimetry. The mRNA level of SOD was analyzed by real-time PCR, and the SOD expression was detected by Western blotting. Results: In the hypoxia group, the plasma H2S concentration and H2S production in the lung was significantly decreased compared with the control P<0.01). The administration of sodium hydrosulfide could reduce the mean pul-monary artery pressure by 31.2% compared with the hypoxia group (P<0.01). Treat-ment with sodium hydrosulfide decreased GSSG, and the T-AOC level of the lung tissues was enhanced compared with the hypoxia group (P<0.05). There were no significant changes in the lung tissue SOD mRNA level, protein level, and its activity among the 3 groups. Conclusion: Oxidative stress occurred in the development of HPH and was accompanied by a decrease in the endogenous production of H2S in the lung tissues. H2S acted as an antioxidant during the oxidative stress of HPH partly as a result of the attenuated GSSG content.

  8. Effect of gas density and ventilatory pattern of steady-state co uptake by the lung.

    Science.gov (United States)

    Kvale, P A; Davis, J; Schroter, R C

    1975-09-01

    The steady-state uptake of carbon monoxide was measured in five normal subjects to study stratified inhomogeneity of gases in the pulmonary airways. An attempt was made to assess the effect of stratified inhomogeneity by varying the physical properties of the inspired gases and the depth and rate of ventilation by the subjects. Twelve different controlled patterns of breathing were followed by each subject on each of three gas mixtures (20% O2 with N2, He and SF6 plus 0.04% CO in each case). The experimental results show that CO uptake was significantly different when breathing the different density gases but that it was always greatest from the most dense gas SF6 and least from He. If the uptake of CO from the inspired gas across the alveolar membrane were controlled by simple molecular diffusion then as gas density decreases uptake would increase. As inspiratory flow rate was increased there was an almost linear increase in CO uptake for each gas mixture with a difference in uptake between the different-density gases which became most marked at the higher flow rates. Flow rate was increased in two ways: by maintaining tidal volume and altering breathing frequency or by maintaining frequency and altering tidal volume. The results for the two extremes, helium and SF6, indicated a difference between these methods of increasing flow rate. In the case of SF6, doubling the flow rate by increasing breathing frequency gave an uptake only marginally lower than doubling the depth of penetration. With helium, however, it was necessary to treble the frequency to obtain the increment of CO uptake achieved by doubling the depth of penetration. The experimental observations are explained by the use of a model based on Taylor dispersion in the conducting airways. The conclusion is that the results confirm the presence of significant stratified inhomogeneity in the airways of the lung.

  9. Proteomic Analysis of Lung Tissue in a Rat Acute Lung Injury Model: Identification of PRDX1 as a Promoter of Inflammation

    Directory of Open Access Journals (Sweden)

    Dongdong Liu

    2014-01-01

    Full Text Available Acute respiratory distress syndrome (ARDS remains a high morbidity and mortality disease entity in critically ill patients, despite decades of numerous investigations into its pathogenesis. To obtain global protein expression changes in acute lung injury (ALI lung tissues, we employed a high-throughput proteomics method to identify key components which may be involved in the pathogenesis of ALI. In the present study, we analyzed lung tissue proteomes of Pseudomonas aeruginosa-induced ALI rats and identified eighteen proteins whose expression levels changed more than twofold as compared to normal controls. In particular, we found that PRDX1 expression in culture medium was elevated by a lipopolysaccharide (LPS challenge in airway epithelial cells in vitro. Furthermore, overexpression of PRDX1 increased the expression of proinflammatory cytokines interleukin-6 (IL-6, interleukin-8 (IL-8, and tumor necrosis factor-α (TNF-α, whereas knockdown of PRDX1 led to downregulated expression of cytokines induced by LPS. In conclusion, our findings provide a global alteration in the proteome of lung tissues in the ALI rat model and indicate that PRDX1 may play a critical role in the pathogenesis of ARDS by promoting inflammation and represent a novel strategy for the development of new therapies against ALI.

  10. Anti-human tissue factor antibody ameliorated intestinal ischemia reperfusion-induced acute lung injury in human tissue factor knock-in mice.

    Science.gov (United States)

    He, Xiaolin; Han, Bing; Mura, Marco; Li, Li; Cypel, Marcelo; Soderman, Avery; Picha, Kristen; Yang, Jing; Liu, Mingyao

    2008-01-30

    Interaction between the coagulation and inflammation systems plays an important role in the development of acute respiratory distress syndrome (ARDS). Anti-coagulation is an attractive option for ARDS treatment, and this has promoted development of new antibodies. However, preclinical trials for these antibodies are often limited by the high cost and availability of non-human primates. In the present study, we developed a novel alternative method to test the role of a humanized anti-tissue factor mAb in acute lung injury with transgenic mice. Human tissue factor knock-in (hTF-KI) transgenic mice and a novel humanized anti-human tissue factor mAb (anti-hTF mAb, CNTO859) were developed. The hTF-KI mice showed a normal and functional expression of hTF. The anti-hTF mAb specifically blocked the pro-coagulation activity of brain extracts from the hTF-KI mice and human, but not from wild type mice. An extrapulmonary ARDS model was used by intestinal ischemia-reperfusion. Significant lung tissue damage in hTF-KI mice was observed after 2 h reperfusion. Administration of CNTO859 (5 mg/kg, i.v.) attenuated the severity of lung tissue injury, decreased the total cell counts and protein concentration in bronchoalveolar lavage fluid, and reduced Evans blue leakage. In addition, the treatment significantly reduced alveolar fibrin deposition, and decreased tissue factor and plasminogen activator inhibitor-1 activity in the serum. This treatment also down-regulated cytokine expression and reduced cell death in the lung. This novel anti-hTF antibody showed beneficial effects on intestinal ischemia-reperfusion induced acute lung injury, which merits further investigation for clinical usage. In addition, the use of knock-in transgenic mice to test the efficacy of antibodies against human-specific proteins is a novel strategy for preclinical studies.

  11. The use of the compound probability density function in ultrasonic tissue characterization

    Energy Technology Data Exchange (ETDEWEB)

    Shankar, P M [Department of Electrical and Computer Engineering, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104 (United States)

    2004-03-21

    Recently, a compound probability density function (pdf) was proposed to model the envelope of the ultrasonic backscattered echo from tissues. This pdf will allow local and global variations in scattering cross sections and even multiple scattering in tissue. It approximates to the Nakagami, K or Rayleigh distributions under different limiting conditions, thus making it very versatile. In this work, a new parameter associated with compound pdf, speckle factor, has been introduced to characterize the scattering conditions. The usefulness of this parameter for tissue characterization has been explored through computer simulation of ultrasonic A scans and analyses of the data collected from tissue-mimicking phantoms. Results suggest the potential applications of the compound pdf and its parameters in ultrasonic tissue characterization.

  12. Connective tissue growth factor stimulates the proliferation, migration and differentiation of lung fibroblasts during paraquat-induced pulmonary fibrosis.

    Science.gov (United States)

    Yang, Zhizhou; Sun, Zhaorui; Liu, Hongmei; Ren, Yi; Shao, Danbing; Zhang, Wei; Lin, Jinfeng; Wolfram, Joy; Wang, Feng; Nie, Shinan

    2015-07-01

    It is well established that paraquat (PQ) poisoning can cause severe lung injury during the early stages of exposure, finally leading to irreversible pulmonary fibrosis. Connective tissue growth factor (CTGF) is an essential growth factor that is involved in tissue repair and pulmonary fibrogenesis. In the present study, the role of CTGF was examined in a rat model of pulmonary fibrosis induced by PQ poisoning. Histological examination revealed interstitial edema and extensive cellular thickening of interalveolar septa at the early stages of poisoning. At 2 weeks after PQ administration, lung tissue sections exhibited a marked thickening of the alveolar walls with an accumulation of interstitial cells with a fibroblastic appearance. Masson's trichrome staining revealed a patchy distribution of collagen deposition, indicating pulmonary fibrogenesis. Western blot analysis and immunohistochemical staining of tissue samples demonstrated that CTGF expression was significantly upregulated in the PQ-treated group. Similarly, PQ treatment of MRC-5 human lung fibroblast cells caused an increase in CTGF in a dose-dependent manner. Furthermore, the addition of CTGF to MRC-5 cells triggered cellular proliferation and migration. In addition, CTGF induced the differentiation of fibroblasts to myofibroblasts, as was evident from increased expression of α-smooth muscle actin (α-SMA) and collagen. These findings demonstrate that PQ causes increased CTGF expression, which triggers proliferation, migration and differentiation of lung fibroblasts. Therefore, CTGF may be important in PQ-induced pulmonary fibrogenesis, rendering this growth factor a potential pharmacological target for reducing lung injury.

  13. Proteomic Comparison of Two-Dimensional Gel Electrophoresis Pro files from Human Lung Squamous Carcinoma and Normal Bronchial Epithelial Tissues

    Institute of Scientific and Technical Information of China (English)

    Cui Li; Ping Chen; Jingyun Xie; Songping Liang; Xianquan Zhan; Maoyu Li; Xiaoying Wu; Feng Li; Jianling Li; Zhiqiang Xiao; Zhuchu Chen; Xueping Feng

    2003-01-01

    Differential proteome profiles of human lung squamous carcinoma tissue compared to paired tumor-adjacent normal bronchial epithelial tissue were established and analyzed by means of immobilized pH gradient-based two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). The results showed that well-resolved, reproducible 2-DE patterns of human lung squamous carcinoma and adjacent normal bronchial epithelial tissues were obtained under the condition of 0.75-ug protein-load. The average deviation of spot position was 0.733+0.101 mm in IEF direction, and 0.925+0.207 mm in SDS-PAGE direction. For tumor tissue, a total of 1241±88 spots were detected, 987±65 spots were matched with an average matching rate of 79.5%. For control, a total of 1190+72 spots were detected, and 875±48 spots were matched with an average matching rate of 73.5%. A total of 864±34 spots were matched between tumors and controls.Forty-three differential proteins were characterized: some proteins were related to oncogenes, and others involved in the regulation of cell cycle and signal transduction. It is suggested that the differential proteomic approach is valuable for mass identification of differentially expressed proteins involved in lung carcinogenesis.These data will be used to establish human lung cancer proteome database to further study human lung squamous carcinoma.

  14. Interaction between fragile histamine triad and protein kinase C alpha in human non-small cell lung cancer tissues

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Objective To investigate the interaction between fragile histamine triad (FHIT) and protein kinase C alpha (PKCα) in human non-small cell lung cancer tissues. Methods FHIT and PKCα double positive samples were screened by immunohistochemical staining from 13 human non-small cell lung cancer tissues. Co-immunoprecipitation was performed by using anti-FHIT and anti-PKCα. The immune precipitate was analyzed by SDS-PAGE and Western blot. Results Immune precipitate staining detection showed that 3 samples out of...

  15. Effective atomic numbers and electron densities of some human tissues and dosimetric materials for mean energies of various radiation sources relevant to radiotherapy and medical applications

    Science.gov (United States)

    Kurudirek, Murat

    2014-09-01

    Effective atomic numbers, Zeff, and electron densities, neff, are convenient parameters used to characterise the radiation response of a multi-element material in many technical and medical applications. Accurate values of these physical parameters provide essential data in medical physics. In the present study, the effective atomic numbers and electron densities have been calculated for some human tissues and dosimetric materials such as Adipose Tissue (ICRU-44), Bone Cortical (ICRU-44), Brain Grey/White Matter (ICRU-44), Breast Tissue (ICRU-44), Lung Tissue (ICRU-44), Soft Tissue (ICRU-44), LiF TLD-100H, TLD-100, Water, Borosilicate Glass, PAG (Gel Dosimeter), Fricke (Gel Dosimeter) and OSL (Aluminium Oxide) using mean photon energies, Em, of various radiation sources. The used radiation sources are Pd-103, Tc-99, Ra-226, I-131, Ir-192, Co-60, 30 kVp, 40 kVp, 50 kVp (Intrabeam, Carl Zeiss Meditec) and 6 MV (Mohan-6 MV) sources. The Em values were then used to calculate Zeff and neff of the tissues and dosimetric materials for various radiation sources. Different calculation methods for Zeff such as the direct method, the interpolation method and Auto-Zeff computer program were used and agreements and disagreements between the used methods have been presented and discussed. It has been observed that at higher Em values agreement is quite satisfactory (Dif.<5%) between the adopted methods.

  16. Cigarette smoke promotes dendritic cell accumulation in COPD; a Lung Tissue Research Consortium study

    Directory of Open Access Journals (Sweden)

    Yi Eunhee S

    2010-04-01

    Full Text Available Abstract Background Abnormal immune responses are believed to be highly relevant in the pathogenesis of chronic obstructive pulmonary disease (COPD. Dendritic cells provide a critical checkpoint for immunity by their capacity to both induce and suppress immunity. Although evident that cigarette smoke, the primary cause of COPD, significantly influences dendritic cell functions, little is known about the roles of dendritic cells in the pathogenesis of COPD. Methods The extent of dendritic cell infiltration in COPD tissue specimens was determined using immunohistochemical localization of CD83+ cells (marker of matured myeloid dendritic cells, and CD1a+ cells (Langerhans cells. The extent of tissue infiltration with Langerhans cells was also determined by the relative expression of the CD207 gene in COPD versus control tissues. To determine mechanisms by which dendritic cells accumulate in COPD, complimentary studies were conducted using monocyte-derived human dendritic cells exposed to cigarette smoke extract (CSE, and dendritic cells extracted from mice chronically exposed to cigarette smoke. Results In human COPD lung tissue, we detected a significant increase in the total number of CD83+ cells, and significantly higher amounts of CD207 mRNA when compared with control tissue. Human monocyte-derived dendritic cells exposed to CSE (0.1-2% exhibited enhanced survival in vitro when compared with control dendritic cells. Murine dendritic cells extracted from mice exposed to cigarette smoke for 4 weeks, also demonstrated enhanced survival compared to dendritic cells extracted from control mice. Acute exposure of human dendritic cells to CSE induced the cellular pro-survival proteins heme-oxygenase-1 (HO-1, and B cell lymphoma leukemia-x(L (Bcl-xL, predominantly through oxidative stress. Although activated human dendritic cells conditioned with CSE expressed diminished migratory CCR7 expression, their migration towards the CCR7 ligand CCL21 was not

  17. High-density Lipoproteins and Apolipoprotein A-I: Potential New Players in the Prevention and Treatment of Lung Disease

    Directory of Open Access Journals (Sweden)

    Elizabeth M. Gordon

    2016-09-01

    Full Text Available Apolipoprotein A-I (apoA-I and high-density lipoproteins (HDL mediate reverse cholesterol transport out of cells. Furthermore, HDL has additional protective functions, which include anti-oxidative, anti-inflammatory, anti-apoptotic, and vasoprotective effects. In contrast, HDL can become dysfunctional with a reduction in both cholesterol efflux and anti-inflammatory properties in the setting of disease or the acute phase response. These paradigms are increasingly being recognized to be active in the pulmonary system, where apoA-I and HDL have protective effects in normal lung health, as well as in a variety of disease states, including acute lung injury, asthma, chronic obstructive pulmonary disease, lung cancer, pulmonary arterial hypertension, pulmonary fibrosis, and viral pneumonia. Similar to observations in cardiovascular disease, however, HDL may become dysfunctional and contribute to disease pathogenesis in respiratory disorders. Furthermore, synthetic apoA-I mimetic peptides have been shown to have protective effects in animal models of acute lung injury, asthma, pulmonary hypertension, and influenza pneumonia. These findings provide evidence to support the concept that apoA-I mimetic peptides might be developed into a new treatment that can either prevent or attenuate the manifestations of lung diseases, such as asthma. Thus, the lung is positioned to take a page from the cardiovascular disease playbook and utilize the protective properties of HDL and apoA-I as a novel therapeutic approach.

  18. Tissue Platinum Concentration and Tumor Response in Non–Small-Cell Lung Cancer

    Science.gov (United States)

    Kim, Eric S.; Lee, J. Jack; He, Guangan; Chow, Chi-Wan; Fujimoto, Junya; Kalhor, Neda; Swisher, Stephen G.; Wistuba, Ignacio I.; Stewart, David J.; Siddik, Zahid H.

    2012-01-01

    Purpose Platinum resistance is a major limitation in the treatment of advanced non–small-cell lung cancer (NSCLC). Reduced intracellular drug accumulation is one of the most consistently identified features of platinum-resistant cell lines, but clinical data are limited. We assessed the effects of tissue platinum concentrations on response and survival in NSCLC. Patients and Methods We measured total platinum concentrations by flameless atomic absorption spectrophotometry in 44 archived fresh-frozen NSCLC specimens from patients who underwent surgical resection after neoadjuvant platinum-based chemotherapy. Tissue platinum concentration was correlated with percent reduction in tumor size on post- versus prechemotherapy computed tomography scans. The relationship between tissue platinum concentration and survival was assessed by univariate and multicovariate Cox proportional hazards regression model analysis and Kaplan-Meier analysis. Results Tissue platinum concentration correlated significantly with percent reduction in tumor size (P < .001). The same correlations were seen with cisplatin, carboplatin, and all histology subgroups. Furthermore, there was no significant impact of potential variables such as number of cycles and time lapse from last chemotherapy on platinum concentration. Patients with higher platinum concentration had longer time to recurrence (P = .034), progression-free survival (P = .018), and overall survival (P = .005) in the multicovariate Cox model analysis after adjusting for number of cycles. Conclusion This clinical study established a relationship between tissue platinum concentration and response in NSCLC. It suggests that reduced platinum accumulation might be an important mechanism of platinum resistance in the clinical setting. Further studies investigating factors that modulate intracellular platinum concentration are warranted. PMID:22891266

  19. Are there characteristic alterations in lung tissue associated with Crohn's disease?

    Science.gov (United States)

    Kayser, K; Probst, F; Gabius, H J; Müller, K M

    1990-08-01

    Two male patients aged 12 and 31 years suffered from Crohn's disease for more than six years and were treated with Cortison for more than four years. Surgical excision of parts of the terminal ileum was performed in both patients. They suffered from pulmonary symptoms as dyspnoea, shortness of breath and ventilation disturbances two years after operation. Wedge biopsies of the lungs revealed the following histomorphological findings: 1. Granulomatous interstitial lymphocyte infiltrates 2. Acute alveolitis with severe dysplasia of pneumocytes 3. Moderate interstitial fibrosis. Immunohistology performed in one case showed predominantly lambda chains expressed by lymphocytes associated with IgA and IgM. IgG was missing, furthermore kappa chains could not be detected. Macrophages contained endogenous lectins (sugar receptors) for fucose, maltose, and N-acetyl-D-glucosamine (glcNAc). No receptors specific for mannose, lactose, and heparin could be found. Pneumocytes did not bind the neoglycoproteins but were found to express HLA-DR receptors detectable by the monoclonal antibody LN 3 in dysplastic pneumocytes only. The histomorphological and immunohistochemical findings suggest that the analyzed alterations of lung tissue are related to the underlying disease of enteritis regionalis.

  20. Interobserver variability in visual evaluation of thoracic CT scans and comparison with automatic computer measurements of CT lung density

    DEFF Research Database (Denmark)

    Winkler Wille, Mathilde Marie; Thomsen, Laura Hohwü; Dirksen, Asger;

    2012-01-01

    information. The lung was segmented automatically by in-house developed computer software, and the percentage of pixels below -950 HU was used as a surrogate marker for emphysema. The observer variability, as well as the correlation with the lung density measurements, was analysed using Spearman’s rank......Introduction – Emphysema is defined by pathology, but is most precisely evaluated in vivo by computed tomography (CT). Aims – were to determine the reproducibility of visual evaluation of emphysema, i.e. the observer variability, and furthermore to compare the visual evaluations to automatic CT...

  1. BMP-2 Dependent Increase of Soft Tissue Density in Arthrofibrotic TKA.

    Science.gov (United States)

    Pfitzner, Tilman; Röhner, Eric; Krenn, Veit; Perka, Carsten; Matziolis, Georg

    2012-01-01

    Arthrofibrosis after total knee arthroplasty (TKA) is difficult to treat, as its aetiology remains unclear. In a previous study, we established a connection between the BMP-2 concentration in the synovial fluid and arthrofibrosis after TKA. The hypothesis of the present study was, therefore, that the limited range of motion in arthrofibrosis is caused by BMP-2 induced heterotopic ossifications, the quantity of which is dependent on the BMP-2 concentration in the synovial fluid.Eight patients with arthrofibrosis after TKA were included. The concentration of BMP-2 in the synovial fluid from each patient was determined by ELISA. Radiologically, digital radiographs were evaluated and the grey scale values were determined as a measure of the tissue density of defined areas. Apart from air, cutis, subcutis and muscle, the soft-tissue density in the area of the capsule of the suprapatellar pouch was determined. The connection between the BMP-2 concentration and the soft-tissue density was then investigated.The average BMP-2 concentration in the synovial fluid was 24.3 ± 6.9 pg/ml. The density of the anterior knee capsule was on average 136 ± 35 grey scale values. A linear correlation was shown between the BMP-2 concentration in the synovial fluid and the radiological density of the anterior joint capsule (R=0.84, p = 0.009).We were able to show that there is a connection between BMP-2 concentration and soft-tissue density in arthrofibrosis after TKA. This opens up the possibility of conducting a prophylaxis against arthrofibrosis in risk patients by influencing the BMP-2 pathway.

  2. Nonspecific interstitial pneumonia overlaps organizing pneumonia in lung-dominant connective tissue disease.

    Science.gov (United States)

    Li, Xue-Ren; Peng, Shou-Chun; Wei, Lu-Qing

    2015-01-01

    Here, we reported two cases of nonspecific interstitial pneumonia overlap organizing pneumonia (NSIP/OP) with lung-dominant connective tissue disease (LD-ILD). The first case is a patient with hands of chapped skin, right-sided pleuritic chest discomfort, weakness, positive ANA and antibodies to Ro/SS-A (+++) and Ro-52 (++). In the second case, there were Reynaud's disease, and nucleolus-ANA increased (1:800). Chest high resolution CT scan in both cases showed ground-glass opacifications, predominantly in basal and subpleural region and the pathologic manifestation were correlated with NSIP/OP, which were previously discovered in Sjogren syndrome, PM/DM and other rheumatic diseases. The two cases of NSIP/OP with LD-CTD we reported expand disease spectrum of NSIP/OP pathological types in ILD. However, it is necessary to process large-scale studies.

  3. Modelling staphylococcal pneumonia in a human 3D lung tissue model system delineates toxin-mediated pathology

    Directory of Open Access Journals (Sweden)

    Srikanth Mairpady Shambat

    2015-11-01

    Full Text Available Staphylococcus aureus necrotizing pneumonia is recognized as a toxin-mediated disease, yet the tissue-destructive events remain elusive, partly as a result of lack of mechanistic studies in human lung tissue. In this study, a three-dimensional (3D tissue model composed of human lung epithelial cells and fibroblasts was used to delineate the role of specific staphylococcal exotoxins in tissue pathology associated with severe pneumonia. To this end, the models were exposed to the mixture of exotoxins produced by S. aureus strains isolated from patients with varying severity of lung infection, namely necrotizing pneumonia or lung empyema, or to purified toxins. The necrotizing pneumonia strains secreted high levels of α-toxin and Panton-Valentine leukocidin (PVL, and triggered high cytotoxicity, inflammation, necrosis and loss of E-cadherin from the lung epithelium. In contrast, the lung empyema strain produced moderate levels of PVL, but negligible amounts of α-toxin, and triggered limited tissue damage. α-toxin had a direct damaging effect on the epithelium, as verified using toxin-deficient mutants and pure α-toxin. Moreover, PVL contributed to pathology through the lysis of neutrophils. A combination of α-toxin and PVL resulted in the most severe epithelial injury. In addition, toxin-induced release of pro-inflammatory mediators from lung tissue models resulted in enhanced neutrophil migration. Using a collection of 31 strains from patients with staphylococcal pneumonia revealed that strains producing high levels of α-toxin and PVL were cytotoxic and associated with fatal outcome. Also, the strains that produced the highest toxin levels induced significantly greater epithelial disruption. Of importance, toxin-mediated lung epithelium destruction could be inhibited by polyspecific intravenous immunoglobulin containing antibodies against α-toxin and PVL. This study introduces a novel model system for study of staphylococcal pneumonia in a

  4. Modelling staphylococcal pneumonia in a human 3D lung tissue model system delineates toxin-mediated pathology.

    Science.gov (United States)

    Mairpady Shambat, Srikanth; Chen, Puran; Nguyen Hoang, Anh Thu; Bergsten, Helena; Vandenesch, Francois; Siemens, Nikolai; Lina, Gerard; Monk, Ian R; Foster, Timothy J; Arakere, Gayathri; Svensson, Mattias; Norrby-Teglund, Anna

    2015-11-01

    Staphylococcus aureus necrotizing pneumonia is recognized as a toxin-mediated disease, yet the tissue-destructive events remain elusive, partly as a result of lack of mechanistic studies in human lung tissue. In this study, a three-dimensional (3D) tissue model composed of human lung epithelial cells and fibroblasts was used to delineate the role of specific staphylococcal exotoxins in tissue pathology associated with severe pneumonia. To this end, the models were exposed to the mixture of exotoxins produced by S. aureus strains isolated from patients with varying severity of lung infection, namely necrotizing pneumonia or lung empyema, or to purified toxins. The necrotizing pneumonia strains secreted high levels of α-toxin and Panton-Valentine leukocidin (PVL), and triggered high cytotoxicity, inflammation, necrosis and loss of E-cadherin from the lung epithelium. In contrast, the lung empyema strain produced moderate levels of PVL, but negligible amounts of α-toxin, and triggered limited tissue damage. α-toxin had a direct damaging effect on the epithelium, as verified using toxin-deficient mutants and pure α-toxin. Moreover, PVL contributed to pathology through the lysis of neutrophils. A combination of α-toxin and PVL resulted in the most severe epithelial injury. In addition, toxin-induced release of pro-inflammatory mediators from lung tissue models resulted in enhanced neutrophil migration. Using a collection of 31 strains from patients with staphylococcal pneumonia revealed that strains producing high levels of α-toxin and PVL were cytotoxic and associated with fatal outcome. Also, the strains that produced the highest toxin levels induced significantly greater epithelial disruption. Of importance, toxin-mediated lung epithelium destruction could be inhibited by polyspecific intravenous immunoglobulin containing antibodies against α-toxin and PVL. This study introduces a novel model system for study of staphylococcal pneumonia in a human setting. The

  5. [Comparison of 51 element contents in normal human lung tissue over twenty years].

    Science.gov (United States)

    Zeng, Jing; Ouyang, Li; Wang, Xiao-Yan; Liu, Ya-Qiong; Xie, Qing; Chu, Hong-Da; Wu, Quan; Fan, Ti-Qiang; Wang, Jing-Yu

    2008-05-01

    Changes in content and distribution of elements in human tissues may reflect changes in environmental backgrounds, and are closely related to human health. To investigate the change in element background in normal lung tissue in different stage, we used ICP-MS, ICP-AES and GFAAS to determine 51 element contents in normal human lung samples of 1982-83 year (n = 7) and compare with those of 2004-05 year (n = 16). Samples were from healthy male adults who died suddenly, and were treated with microwave digestion and wet digestion method. The results show that the contents of 23 elements (Na, Mg, P, K, As, Mo, Ag, Ba, Bi, Y, La, Ce, Pr, Nd, Sm, Gd, Tb, Dy, Ho, Er, Tm, Yb and Lu) are significantly higher, and 6 elements (Zn, Ga, Ge, Se, Au and Zr) are significantly lower in the 2004-05 samples than those in the 1982-83 samples. This difference would be related to the changes in environmental backgrounds and people's living habit during twenty years. The distinctive decrease in contents of the 2004-05 samples for most measured rare earth elements (REEs) may be due to more rational usage of REEs in present, while were the soil and corps were largely abused in 1980s in China. The significant increase in contents of some useful micro-elements (Zn and Se ) in the present samples maybe because of the increased intake of these elements as people own more health consciousness. Besides, the increased contents of heavy metal Pb, Cd, Cr and Ni in the present samples may be related to the deterioration of air quality as industrialization course. More than half of measured elements have been significantly changed over twenty years, indicating that some normal value ranges of element contents should be adjusted according to the difference.

  6. Quantitative digital subtraction radiography for assessment of bone density changes following periodontal guided tissue regeneration.

    Science.gov (United States)

    Christgau, M; Wenzel, A; Hiller, K A; Schmalz, G

    1996-01-01

    The quantitative assessment of alveolar bone density changes in periodontal defects following guided tissue regeneration (GTR). Twelve patients with 30 intrabony lesions and 16 furcation defects took part. Standardized radiographic and clinical examinations were carried out immediately before and then 5 and 13 months after surgery. Intra-oral radiographs were evaluated by means of digital subtraction radiography (DSR). Within the subtraction images, a window ('experimental region') was defined covering the visible density changes in the defect area. Background noise was measured by using a similarly sized window ('control region') located in an area not affected by GTR. Bone density changes were quantitatively evaluated by calculation of the mean, standard deviation and maximum and minimum values of the grey-level histogram within these windows. DSR revealed significant bone density gain after GTR in intrabony and furcation defects. While a continuous increase was observed over the 13 month period in intrabony defects, changes in furcation defects occurred mostly in the 5-13 month period. Clinically, a distinct vertical and horizontal attachment gain was found. The correlation coefficients between changes in radiographic density and clinical parameters were low, indicating a difference in the information obtained by the two diagnostic methods. Quantitative DSR is a valuable, non-invasive, objective method to obtain information on density changes in intrabony and furcation defects treated by GTR. However, a full assessment of soft and hard tissue changes requires both clinical evaluation and DSR.

  7. The Effects of Aerobic Exercise on NF-κB and TNF-α in Lung Tissue of Male Rat

    Directory of Open Access Journals (Sweden)

    Mohamad Fashi

    2015-07-01

    Full Text Available Background:Regular aerobic exercise improves theBackground: Regular aerobic exercise improves the inflammatory status in different lung diseases. However, the effects of long-term aerobic exercise on the lung response have not been investigated. The present study evaluated the effect of aerobic exercise on the lung inflammatory.Materials and Methods: 12 adult male Wistar rats were divided to 2 groups: A: control (n=6, B: aerobic exercise (five times per week for 4 week; n=6. The gene expression of NF-κB and TNF-α were analyzed in lung tissue by Real time–PCR. In order to determine the significant differences between groups independent t-test were used.Results: Aerobic exercise inhibited the gene expression of NF-κB and TNF-α. But there was no significant difference between A and B groups for TNF-α and NF-κB.Conclusion: We conclude that four week aerobic exercise decrease inflammatory status in lung tissue. Our results indicate a need for human studies that evaluate the lung responses to aerobic exercise.

  8. Promotion of MAG-1 on Metastasis of Lung Cancer Cells in vitro and Its Expression in Lung Cancer Tissue of 24 Cases

    Directory of Open Access Journals (Sweden)

    Jinqiang ZHANG

    2009-02-01

    Full Text Available Background and objective Tumor metastasis is a multistep process with many genes involved in. A novel gene MAG-1 , identified by suppression subtractive hybridization from lung cancer cells was found to be associated with tumor metastasis. The aims of this work are to investigate the metastasis related effects of MAG-1 on human lunggiant-cell line PLA801, and to compare the expression rate of MAG-1 in cancer tissue from lung cancer patients with different metastatic status. Methods Sense and anti-sense expressing vectors of MAG-1 were constructed and transfected into PLA801C and PLA801D respectively. Colony forming, adherence assay, MTT assay and Transwell experiments were used to evaluate the alterations of clone forming, cell-matrix adherence, proliferating and invasion of the stable transfected cell strains. Western blot was employed to detect the proteins levels of CD44, and MMP-2 in cell strains and mRNAstate of MAG-1 in lung cancer tissue from patients with or without pathological metastasis were also analyzed by RTPCR. Results MAG-1 could increase cell-ECM (Extracellular Matrix adhesive capacity, promote invasion, enhance cell proliferation and had no effects on clone forming ability of PLA801 cells in soft agar. MAG-1 was also found have positive effects on the protein level of CD44 and MMP-2 in PLA801 cells, and the detection rate of MAG-1 mRNA was much higher in cancer tissue from metastatic patients (7/12 than that in non-metastatic patients (2/12. Conclusion MAG-1 could promote lung cancer metastasis and might be a metastasis associated gene of lung cancer.

  9. 组织工程肺支架的选择%The choice of the lung scaffold in tissue engineering

    Institute of Scientific and Technical Information of China (English)

    赵政政; 吴镜湘; 徐美英

    2015-01-01

    Background End-stage pulmonary disease is one of the major healthcare challenges in the world,and lung transplantation is the only choice for survival.Yet,the donor organ shortage,needed and infective transmission limit the application of lung transplantation.The engineered lung tissue could theoretically overcome these hurdles.Objective This review will discuss recent advances of scaffolds in the tissue engineering.Content Narrating the scaffold of the lung in tissue engineering from performance,materials,preparation and prospect.Trend to provide new ideas and method for thetreatment on the therapy of endstage lung diseases.%背景 肺移植手术在终末期肺疾病的有效治疗中已被广泛接受,但供源短缺、免疫抑制、潜在疾病传播等现象日益突出,组织工程肺的构建和应用有望解决以上难题. 目的 总结组织工程肺支架的研究进展. 内容 就组织工程肺支架的性能、材料、制备和展望等方面进行综述. 趋向 为终末期肺疾病的治疗提供新思路.

  10. Pharmacokinetics of tildipirosin in bovine plasma, lung tissue, and bronchial fluid (from live, nonanesthetized cattle).

    Science.gov (United States)

    Menge, M; Rose, M; Bohland, C; Zschiesche, E; Kilp, S; Metz, W; Allan, M; Röpke, R; Nürnberger, M

    2012-12-01

    The pharmacokinetics of tildipirosin (Zuprevo(®) 180 mg/mL solution for injection for cattle), a novel 16-membered macrolide for treatment, control, and prevention of bovine respiratory disease, were investigated in studies collecting blood plasma, lung tissue, and in vivo samples of bronchial fluid (BF) from cattle. After single subcutaneous (s.c.) injection at 4 mg/kg body weight, maximum plasma concentration (C(max)) was 0.7 μg/mL. T(max) was 23 min. Mean residence time from the time of dosing to the time of last measurable concentration (MRT(last)) and terminal half-life (T(1/2) ) was 6 and 9 days, respectively. A strong dose-response relationship with no significant sex effect was shown for both C(max) and area under the plasma concentration-time curve from time 0 to the last sampling time with a quantifiable drug concentration (AUC(last) ) over the range of doses up to 6 mg/kg. Absolute bioavailability was 78.9%. The volume of distribution based on the terminal phase (V(z)) was 49.4 L/kg, and the plasma clearance was 144 mL/h/kg. The time-concentration profile of tildipirosin in BF and lung far exceeded those in blood plasma. In lung, tildipirosin concentrations reached 9.2 μg/g at 4 h, peaked at 14.8 μg/g at day 1, and slowly declined to 2.0 μg/g at day 28. In BF, the concentration of tildipirosin reached 1.5 and 3.0 μg/g at 4 and 10 h, maintained a plateau of about 3.5 μg/g between day 1 and 3, and slowly declined to 1.0 at day 21. T(1/2) in lung and BF was approximately 10 and 11 days. Tildipirosin is rapidly and extensively distributed to the respiratory tract followed by slow elimination.

  11. Measurement of hard tissue density of head phantom based on the HU by using CBCT

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Moon Sun; Kang, Dong Wan; Kim, Jae Duk [School of Dentistry, Chosun University, Gwangju (Korea, Republic of)

    2009-09-15

    The purpose of this study was to determine a conversion coefficient for Hounsfield Units(HU) to material density (g cm{sup -3}) obtained from cone-beam computed tomography (CBMercuRay{sup TM}) data and to measure the hard tissue density based on the Hounsfield scale on dental head phantom. CT Scanner Phantom (AAPM) equipped with CT Number Insert consists of five cylindrical pins of materials with different densities and teflon ring was scanned by using the CBMercuRay{sup TM} (Hitachi, Tokyo, Japan) volume scanner. The raw data were converted into DICOM format and the HU of different areas of CT number insert measured by using CBWorks{sup TM}. Linear regression analysis and Student t-test were performed statistically. There was no significant difference (P>0.54) between real densities and measured densities. A linear regression was performed using the density, {rho} (g cm{sup -3}), as the dependent variable in terms of the HU (H). The regression equation obtained was {rho}=0.00072 H-0.01588 with an R2 value of 0.9968. Density values based on the Hounsfield scale was 1697.1 {+-} 24.9 HU in cortical bone, 526.5 {+-} 44.4 HU in trabecular bone, 2639.1 {+-} 48.7 HU in enamel, 1246.1 {+-} 39.4 HU in dentin of dental head phantom. CBCT provides an effective option for determination of material density expressed as Hounsfield Units.

  12. Improved calibration of mass stopping power in low density tissue for a proton pencil beam algorithm.

    Science.gov (United States)

    Warren, Daniel R; Partridge, Mike; Hill, Mark A; Peach, Ken

    2015-06-07

    Dose distributions for proton therapy treatments are almost exclusively calculated using pencil beam algorithms. An essential input to these algorithms is the patient model, derived from x-ray computed tomography (CT), which is used to estimate proton stopping power along the pencil beam paths. This study highlights a potential inaccuracy in the mapping between mass density and proton stopping power used by a clinical pencil beam algorithm in materials less dense than water. It proposes an alternative physically-motivated function (the mass average, or MA, formula) for use in this region. Comparisons are made between dose-depth curves calculated by the pencil beam method and those calculated by the Monte Carlo particle transport code MCNPX in a one-dimensional lung model. Proton range differences of up to 3% are observed between the methods, reduced to  stopping power calculation methodology results in relatively minor differences in dose when plans use three fields, but differences are observed at the 2%-2 mm level when a single field uniform dose technique is adopted. It is therefore suggested that the MA formula is adopted by users of the pencil beam algorithm for optimal dose calculation in lung, and that a similar approach is considered when beams traverse other low density regions such as the paranasal sinuses and mastoid process.

  13. Improved calibration of mass stopping power in low density tissue for a proton pencil beam algorithm

    Science.gov (United States)

    Warren, Daniel R.; Partridge, Mike; Hill, Mark A.; Peach, Ken

    2015-06-01

    Dose distributions for proton therapy treatments are almost exclusively calculated using pencil beam algorithms. An essential input to these algorithms is the patient model, derived from x-ray computed tomography (CT), which is used to estimate proton stopping power along the pencil beam paths. This study highlights a potential inaccuracy in the mapping between mass density and proton stopping power used by a clinical pencil beam algorithm in materials less dense than water. It proposes an alternative physically-motivated function (the mass average, or MA, formula) for use in this region. Comparisons are made between dose-depth curves calculated by the pencil beam method and those calculated by the Monte Carlo particle transport code MCNPX in a one-dimensional lung model. Proton range differences of up to 3% are observed between the methods, reduced to  calculation methodology results in relatively minor differences in dose when plans use three fields, but differences are observed at the 2%-2 mm level when a single field uniform dose technique is adopted. It is therefore suggested that the MA formula is adopted by users of the pencil beam algorithm for optimal dose calculation in lung, and that a similar approach is considered when beams traverse other low density regions such as the paranasal sinuses and mastoid process.

  14. Lung Ultrasonography in the Evaluation of Interstitial Lung Disease in Systemic Connective Tissue Diseases: Criteria and Severity of Pulmonary Fibrosis - Analysis of 52 Patients.

    Science.gov (United States)

    Buda, N; Piskunowicz, M; Porzezińska, M; Kosiak, W; Zdrojewski, Z

    2016-08-01

    Patients with a diagnosed systemic connective tissue disease require regular monitoring from the point of view of interstitial lung disease. The main aim of this work is a description of the criteria for pulmonary fibrosis and the degree of the severity of the fibrosis during the course of interstitial lung disease through the TLU (transthoracic lung ultrasound). 52 patients with diagnosed diffuse interstitial lung disease were qualified for this research, together with 50 volunteers in the control group. The patients in both groups were over 18 years of age and were of both sexes. The results of the TLU of the patients underwent statistical analysis and were compared to High-Resolution Computed Tomography (HRCT) results. As a consequence of the statistical analysis, we defined our own criteria for pulmonary fibrosis in TLU: irregularity of the pleura line, tightening of the pleura line, the fragmentary nature of the pleura line, blurring of the pleura line, thickening of the pleura line, artifacts of line B ≤ 3 and ≥ 4, artifacts of Am line and subpleural consolidations Lung Ultrasonography (TLU) gives a new outlook on the diagnostic possibilities, non-invasive and devoid of ionising radiation, of pulmonary fibrosis. This research work has allowed to discover two new ultrasound symptoms of pulmonary fibrosis (blurred pleural line and Am lines). © Georg Thieme Verlag KG Stuttgart · New York.

  15. A new therapeutic strategy for lung tissue injury induced by influenza with CR2 targeting complement inhibitior

    Directory of Open Access Journals (Sweden)

    Tomlinson Stephen

    2010-02-01

    Full Text Available Abstract Background Influenza is a respiratory disease that seriously threatens human health. In fact, influenza virus itself does not make critical contribution to mortality induced by influenza, but "cytokine storm" produced by the excessive immune response triggered by the virus can result in inflammatory reaction of lung tissues and fatal lung tissue injury, and thus increase influenza mortality. Therefore, besides antiviral drugs, immunosuppression drugs should also be included in infection treatment. Presentation of the hypothesis Complement is the center of inflammatory reaction. If complement system is over activated, the body will have strong inflammatory reaction or tissue injury, resulting in pathological process. Many studies have proved that, inflammatory injury of lung tissues caused by influenza virus is closely related to complement activation. Therefore, inhibiting complement activation can significantly reduce inflammatory injury in lung tissues. As complement is both a physiological defense and pathological damage medium, systematic inhibition may result in side effects including infection. Therefore, we design targeting complement inhibitors for complement activation sites, i.e. with CR2 as targeting vector, complement inhibitors like CD59 and Crry are targeted to inflammatory sites to specially inhibit the complement activation in local injury, thus local inflammatory reaction is inhibited. Testing the hypothesis CR2-CD59 and CR2-Crry targeting complement inhibitors are fusion-expressed, and their biological activity is examined via in vivo and in vitro tests. CR2 targeting complement inhibitors are used to treat mouse influenza viral pneumonia model, with PBS treatment group as the control. The survival and lung tissue injury of the mice is observed and the effect of CR2 targeting complement inhibitors on pneumonia induced by influenza virus is evaluated. Implications of the hypothesis CR2 targeting complement inhibitors

  16. Relationship between the level of interleukin-9 expression in serum of connective tissue disease patients with interstitial lung disease

    Institute of Scientific and Technical Information of China (English)

    欧阳涵

    2013-01-01

    Objective To investigate the level of interleukin (IL) -9 in patients with connective tissue disease (CTD) and connective tissue disease with interstitial lung disease (CTD-ILD) ,and explore the role of IL-9 in the pathogenesis of CTD and CTD-ILD.Methods Sixty-one hospitalized untreated CTD patients were recruited and 20healthy volunteers were enrolled as healthy controls.Patients in the CTD group included 19 systemic sclerosis (SSc) patients,15 rheumatoid arthritis (RA) patients,

  17. Macrophages in lung tissue from patients with pulmonary emphysema express both inducible and endothelial nitric oxide synthase

    NARCIS (Netherlands)

    van Straaten, JFM; Postma, DS; Coers, W; Noordhoek, JA; Kauffman, HF; Timens, W

    1998-01-01

    To provide information concerning a possible biologic role of nitric oxide (NO) in smoking-related emphysema, we performed immunohistochemical studies in lung tissue from control subjects and patients with mild and severe emphysema We studied the presence of inducible and endothelial NO synthases (i

  18. Primary mesenchymal stem cells in human transplanted lungs are CD90/CD105 perivascularly located tissue-resident cells

    DEFF Research Database (Denmark)

    Rolandsson, Sara; Andersson Sjöland, Annika; Brune, Jan C

    2014-01-01

    in vitro MSC properties; however, xenotransplantation into non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice showed that lung MSC readily differentiated into adipocytes and stromal tissues, but lacked significant in vivo bone formation. CONCLUSIONS: These data clearly demonstrate...

  19. Two-color widefield fluorescence microendoscopy enables multiplexed molecular imaging in the alveolar space of human lung tissue

    Science.gov (United States)

    Krstajić, Nikola; Akram, Ahsan R.; Choudhary, Tushar R.; McDonald, Neil; Tanner, Michael G.; Pedretti, Ettore; Dalgarno, Paul A.; Scholefield, Emma; Girkin, John M.; Moore, Anne; Bradley, Mark; Dhaliwal, Kevin

    2016-04-01

    We demonstrate a fast two-color widefield fluorescence microendoscopy system capable of simultaneously detecting several disease targets in intact human ex vivo lung tissue. We characterize the system for light throughput from the excitation light emitting diodes, fluorescence collection efficiency, and chromatic focal shifts. We demonstrate the effectiveness of the instrument by imaging bacteria (Pseudomonas aeruginosa) in ex vivo human lung tissue. We describe a mechanism of bacterial detection through the fiber bundle that uses blinking effects of bacteria as they move in front of the fiber core providing detection of objects smaller than the fiber core and cladding (˜3 μm). This effectively increases the measured spatial resolution of 4 μm. We show simultaneous imaging of neutrophils, monocytes, and fungus (Aspergillus fumigatus) in ex vivo human lung tissue. The instrument has 10 nM and 50 nM sensitivity for fluorescein and Cy5 solutions, respectively. Lung tissue autofluorescence remains visible at up to 200 fps camera acquisition rate. The optical system lends itself to clinical translation due to high-fluorescence sensitivity, simplicity, and the ability to multiplex several pathological molecular imaging targets simultaneously.

  20. Hair growth promoting potential of phospholipids purified from porcine lung tissues.

    Science.gov (United States)

    Choi, Seong-Hyun; Moon, Jeong-Su; Jeon, Byung-Suk; Jeon, Yeon-Jeong; Yoon, Byung-Il; Lim, Chang-Jin

    2015-03-01

    BP201, porcine lung tissue-derived phospholipids, consists of phosphatidylcholine as a major phospholipid species. BP201 promoted hair growth after application onto the shaved backs of BALB/c and C3H mice. Its effect was enhanced when applied together with minoxidil (MNX) in C3H mice. When the tissue specimens prepared from the shaved skins of BP201-treated and control mice were microscopically examined, the total numbers of hair follicles in both anagen and telogen phases of BP201-treated mice were significantly higher than those of control mice. The numbers of hair follicles in the anagen phase of BP201-treated mice were also higher than those of control mice. In combination with MNX, BP201 further increased the total number of hair follicles, but did not alter the percentage of hair follicles in the anagenic phase. BP201 also increased the proliferation of human hair follicle dermal papilla cells. Collectively, BP201 possesses hair growth promoting potential, which would suggest its use singly or in combination for hair growth products.

  1. Low or undetectable TPO receptor expression in malignant tissue and cell lines derived from breast, lung, and ovarian tumors

    Directory of Open Access Journals (Sweden)

    Erickson-Miller Connie L

    2012-09-01

    Full Text Available Abstract Background Numerous efficacious chemotherapy regimens may cause thrombocytopenia. Thrombopoietin receptor (TPO-R agonists, such as eltrombopag, represent a novel approach for the treatment of chemotherapy-induced thrombocytopenia. The TPO-R MPL is expressed on megakaryocytes and megakaryocyte precursors, although little is known about its expression on other tissues. Methods Breast, lung, and ovarian tumor samples were analyzed for MPL expression by microarray and/or quantitative reverse transcription-polymerase chain reaction (qRT-PCR, and for TPO-R protein expression by immunohistochemistry (IHC. Cell line proliferation assays were used to analyze the in vitro effect of eltrombopag on breast, lung, and ovarian tumor cell proliferation. The lung carcinoma cell lines were also analyzed for TPO-R protein expression by Western blot. Results MPL mRNA was not detectable in 118 breast tumors and was detectable at only very low levels in 48% of 29 lung tumors studied by microarray analysis. By qRT-PCR, low but detectable levels of MPL mRNA were detectable in some normal (14-43% and malignant (3-17% breast, lung, and ovarian tissues. A comparison of MPL to EPOR, ERBB2, and IGF1R mRNA demonstrates that MPL mRNA levels were far lower than those of EPOR and ERBB2 mRNA in the same tissues. IHC analysis showed negligible TPO-R protein expression in tumor tissues, confirming mRNA analysis. Culture of breast, lung, and ovarian carcinoma cell lines showed no increase, and in fact, showed a decrease in proliferation following incubation with eltrombopag. Western blot analyses revealed no detectable TPO-R protein expression in the lung carcinoma cell lines. Conclusions Multiple analyses of breast, lung, and ovarian tumor samples and/or cell lines show no evidence of MPL mRNA or TPO-R protein expression. Eltrombopag does not stimulate growth of breast, lung, or ovarian tumor cell lines at doses likely to exert their actions on megakaryocytes and

  2. In vitro metabolism of beclomethasone dipropionate, budesonide, ciclesonide, and fluticasone propionate in human lung precision-cut tissue slices

    Directory of Open Access Journals (Sweden)

    Fisher Robyn

    2007-09-01

    Full Text Available Abstract Background The therapeutic effect of inhaled corticosteroids (ICS may be affected by the metabolism of the drug in the target organ. We investigated the in vitro metabolism of beclomethasone dipropionate (BDP, budesonide (BUD, ciclesonide (CIC, and fluticasone propionate (FP in human lung precision-cut tissue slices. CIC, a new generation ICS, is hydrolyzed by esterases in the upper and lower airways to its pharmacologically active metabolite desisobutyryl-ciclesonide (des-CIC. Methods Lung tissue slices were incubated with BDP, BUD, CIC, and FP (initial target concentration of 25 μM for 2, 6, and 24 h. Cellular viability was assessed using adenosine 5'-triphosphate content and protein synthesis in lung slices. Metabolites and remaining parent compounds in the tissue samples were analyzed by HPLC with UV detection. Results BDP was hydrolyzed to the pharmacologically active metabolite beclomethasone-17-monopropionate (BMP and, predominantly, to inactive beclomethasone (BOH. CIC was hydrolyzed initially to des-CIC with a slower rate compared to BDP. A distinctly smaller amount (approximately 10-fold less of fatty acid esters were formed by BMP (and/or BOH than by BUD or des-CIC. The highest relative amounts of fatty acid esters were detected for BUD. For FP, no metabolites were detected at any time point. The amount of drug-related material in lung tissue (based on initial concentrations at 24 h was highest for CIC, followed by BUD and FP; the smallest amount was detected for BDP. Conclusion The in vitro metabolic pathways of the tested ICS in human lung tissue were differing. While FP was metabolically stable, the majority of BDP was converted to inactive polar metabolites. The formation of fatty acid conjugates was confirmed for BMP (and/or BOH, BUD, and des-CIC.

  3. Transcriptional Profiling of Swine Lung Tissue after Experimental Infection with Actinobacillus pleuropneumoniae

    Directory of Open Access Journals (Sweden)

    Xuewei Li

    2013-05-01

    Full Text Available Porcine pleuropneumonia is a highly contagious respiratory disease that causes great economic losses worldwide. In this study, we aimed to explore the underlying relationship between infection and injury by investigation of the whole porcine genome expression profiles of swine lung tissues post-inoculated with experimentally Actinobacillus pleuropneumoniae. Expression profiling experiments of the control group and the treatment group were conducted using a commercially available Agilent Porcine Genechip including 43,603 probe sets. Microarray analysis was conducted on profiles of lung from challenged versus non-challenged swine. We found 11,929 transcripts, identified as differentially expressed at the p ≤0.01 level. There were 1188 genes annotated as swine genes in the GenBank Data Base. GO term analysis identified a total of 89 biological process categories, 82 cellular components and 182 molecular functions that were significantly affected, and at least 27 biological process categories that were related to the host immune response. Gene set enrichment analysis identified 13 pathways that were significantly associated with host response. Many proinflammatory-inflammatory cytokines were activated and involved in the regulation of the host defense response at the site of inflammation; while the cytokines involved in regulation of the host immune response were suppressed. All changes of genes and pathways of induced or repressed expression not only led to a decrease in antigenic peptides presented to T lymphocytes by APCs via the MHC and alleviated immune response injury induced by infection, but also stimulated stem cells to produce granulocytes (neutrophils, eosinophils, and basophils and monocyte, and promote neutrophils and macrophages to phagocytose bacterial and foreign antigen at the site of inflammation. The defense function of swine infection with Actinobacillus pleuropneumoniae was improved, while its immune function was decreased.

  4. Age influence on mice lung tissue response to [i]Aspergillus fumigatus[/i] chronic exposure

    Directory of Open Access Journals (Sweden)

    Marta Kinga Lemieszek

    2015-02-01

    Full Text Available [b]Introduction and objective[/b]. Exposure to conidia of [i]Aspergillus fumigatus[/i] was described as a causative factor of a number of the respiratory system diseases, including asthma, chronic eosinophilic pneumonia, hypersensitivity pneumonitis and bronchopulmonary aspergillosis. The study investigates the effects of the repeated exposure to [i]A. fumigatus[/i] in mice pulmonary compartment. Our work tackles two, so far insufficiently addressed, important aspects of interaction between affected organism and[i] A. fumigatus[/i]: 1 recurrent character of exposure (characteristic for pathomechanism of the abovementioned disease states and 2 impact of aging, potentially important for the differentiation response to an antigen. [b]Materials and methods[/b]. In order to dissect alterations of the immune system involved with both aging and chronic exposure to [i]A. fumigatus[/i], we used 3- and 18-month-old C57BL/6J mice exposed to repeated[i] A. fumigatus[/i] inhalations for 7 and 28 days. Changes in lung tissue were monitored by histological and biochemical evaluation. Concentration of pro- and anti-inflammatory cytokines in lung homogenates was assessed by ELISA tests. [b]Results and conclusions. [/b]Our study demonstrated that chronic inflammation in pulmonary compartment, characterized by the significant increase of proinflammatory cytokines (IL1, IL6, IL10 levels, was the dominant feature of mice response to repeated [i]A. fumigatus[/i] inhalations. The pattern of cytokines’ profile in the course of exposure was similar in both age groups, however in old mice the growth of the cytokines’ levels was more pronounced (especially in case of IL1.

  5. Study of the Effect of Breast Tissue Density on Detection of Masses in Mammograms

    Directory of Open Access Journals (Sweden)

    A. García-Manso

    2013-01-01

    Full Text Available One of the parameters that are usually stored for mammograms is the BI-RADS density, which gives an idea of the breast tissue composition. In this work, we study the effect of BI-RADS density in our ongoing project for developing an image-based CAD system to detect masses in mammograms. This system consists of two stages. First, a blind feature extraction is performed for regions of interest (ROIs, using Independent Component Analysis (ICA. Next, in the second stage, those features form the input vectors to a classifier, neural network, or SVM classifier. To train and test our system, the Digital Database for Screening Mammography (DDSM was used. The results obtained show that the maximum variation in the performance of our system considering only prototypes obtained from mammograms with a concrete value of density (both for training and test is about 7%, yielding the best values for density equal to 1, and the worst for density equal to 4, for both classifiers. Finally, with the overall results (i.e., using prototypes from mammograms with all the possible values of densities, we obtained a difference in performance that is only 2% lower than the maximum, also for both classifiers.

  6. Buffer optimization for high resolution of human lung cancer tissue proteins by two-dimensional gel electrophoresis.

    Science.gov (United States)

    Lee, Kibeom; Pi, Kyungbae; Lee, Keeman

    2009-01-01

    A problem in proteomic analysis of lung cancer tissue is the presence of complex components of different histological backgrounds (squamous cell carcinoma, small cell lung carcinoma, and adenocarcinoma). The efficient solubilization of protein components before two-dimensional electrophoresis (2-DE) is a very critical. Poor solubilization has been associated with a failure to detect proteins and diffuse, streaked and/or trailing protein spots. Here, we have optimized the solubilization of human lung cancer tissue to increase protein resolution. Isoelectric focusing (IEF) rehydration buffer containing a thiourea-urea mixture provided superior resolution, whereas a buffer without thiourea yielded consistently poor results. In addition, IEF rehydration buffers containing CHAPS and DTT gave superior resolution, whereas buffers containing Nonidet P-40 (NP-40) and/or Triton X-100 did not. A tributylphosphine-containing buffer gave consistently poor results. Using optimized conditions, we used 2-D gel analysis of human lung cancer tissue to identify 11 differentially-expressed protein spots by MALDI-mass spectrometry. This study provides a methodological tool to study the complex mammalian proteomes.

  7. Analysis of factors causing signal loss in the measurement of lung tissue water by nuclear magnetic resonance

    Energy Technology Data Exchange (ETDEWEB)

    Fukuzaki, Minoru [Tokai Univ. Junior Coll., Tokyo (Japan); Shioya, Sumie; Haida, Munetaka

    1997-05-01

    The water content of lung, brain, and muscle tissue was measured by nuclear magnetic resonance (NMR) and compared with gravimetric determinations. The NMR signal intensity of water was measured by a single 90 degree pulse and by a spin-echo sequence. The absolute water content was determined by the difference in the sample`s weight before and after desiccation. The NMR detectable water in each tissue was expressed as a percentage of the signal intensity for an equal weight of distilled water. Using the single pulse measurement, 67% of the gravimetrically-measured water was detected in collapsed lung samples (consisting of about 47% retained air), in contrast to 96% for brain and 98% for muscle. For degassed lung samples, the NMR detectability of water increased to 87% with the single pulse measurement and to 90% with the spin-echo measurement, but the values remained significantly less than those of brain or muscle. Factors that caused the NMR signal loss of 33% in collapsed lung samples were: air-tissue interfaces (20%), microscopic field inhomogeneity (3%), and a water component with an extremely short magnetization decay time constant (10%). (author)

  8. Dihydropyrimidine dehydrogenase (DPD) expression is negatively regulated by certain microRNAs in human lung tissues.

    Science.gov (United States)

    Hirota, Takeshi; Date, Yuko; Nishibatake, Yu; Takane, Hiroshi; Fukuoka, Yasushi; Taniguchi, Yuuji; Burioka, Naoto; Shimizu, Eiji; Nakamura, Hiroshige; Otsubo, Kenji; Ieiri, Ichiro

    2012-07-01

    Dihydropyrimidine dehydrogenase (DPD) is important to the antitumor effect of 5-fluorouracil (5-FU). DPD gene (DPYD) expression in tumors is correlated with sensitivity to 5-FU. Because the 5-FU accumulated in cancer cells is also rapidly converted into inactivated metabolites through catabolic pathways mediated by DPD, high DPD activity in cancer cells is an important determinant of the response to 5-FU. DPD activity is highly variable and reduced activity causes a high risk of 5-FU toxicity. Genetic variation in DPYD has been proposed as the main factor responsible for the variation in DPD activity. However, only a small proportion of the activity of DPD can be explained by DPYD mutations. In this study, we found that DPYD is a target of the following microRNAs (miRNA): miR-27a, miR-27b, miR-134, and miR-582-5p. In luciferase assays with HepG2 cells, the overexpression of these miRNAs was associated with significantly decreased reporter activity in a plasmid containing the 3'-UTR of DYPD mRNA. The level of DPD protein in MIAPaca-2 cells was also significantly decreased by the overexpression of these four miRNAs. The results suggest that miR-27a, miR-27b, miR-134, and miR-582-5p post-transcriptionally regulate DPD protein expression. The levels of miRNAs in normal lung tissue and lung tumors were compared; miR-27b and miR-134 levels were significantly lower in the tumors than normal tissue (3.64 ± 4.02 versus 9.75 ± 6.58 and 0.64 ± 0.75 versus 1.48 ± 1.39). DPD protein levels were significantly higher in the tumors. Thus, the decreased expression of miR-27b would be responsible for the high levels of DPD protein. This study is the first to show that miRNAs regulate the DPD protein, and provides new insight into 5-FU-based chemotherapy.

  9. Tea polyphenols prevent lung from preneoplastic lesions and effect p53 and bcl-2 gene expression in rat lung tissues.

    Science.gov (United States)

    Gu, Qihua; Hu, Chengping; Chen, Qiong; Xia, Ying

    2013-01-01

    Lung cancer is one of the cancers that have the highest incidence and the highest mortality rate, and it is of great interest to identify ways to prevent its occurrence. We had established an animal model by using 3,4-benzopyrene intra-pulmonary injection in our previous study, and had observed that the rats lung carcinoma incidence and multiplicity were significantly reduced by green tea administration. This study further investigated the effect of tea polyphenols on rat lung preneoplastic lesions using the lung carcinoma model established by 3,4-benzopyrene intra-pulmonary injection. Sprague-Dawley rats of the same age were randomly divided into 10 groups and treated with 3,4-benzopyrene by intra-pulmonary injection. Five groups were given 0.3% solution of tea polyphenols (equivalent to 1.2% of green tea) in drinking water, while the other 5 groups were given pure drinking water. The rats were sacrificed at 0, 1, 4, 8 and 16 weeks after carcinogen treatment. In the control groups of rats, local bronchial inflammation were observed at 1 week after 3,4-benzopyrene treatment. From 4 weeks to 16 weeks after carcinogen treatment, hyperplasia, cell hyperproliferation, heterogeneity were observed in the bronchial epithelium. Meanwhile, the expression of p53 mRNA and protein, as well as the level of bcl-2, increased in the bronchial epithelial lesion. Tea polyphenols treatment significantly alleviated the bronchial epithelial lesions. At the same time, tea polyphenols treatment enhanced p53 expression, but reduced bcl-2 expression. These results indicated that tea polyphenols may have preventive effect against lung preneoplasm lesions, possibly through regulating the expression of some critical genes such as p53 and bcl-2.

  10. Proteomic Comparison of Two—Dimensional Gel Electrophoresis Profiles from Human Lung Squamous Carcinoma and Normal Bronchial Epithelial Tissues

    Institute of Scientific and Technical Information of China (English)

    CuiLi; XianquanZhan; MaoyuLi; XiaoyingWu; FengLi; JianlingLi; ZhiqiangXiao; ZhuchuChen; XuepingFeng; PingChen; JingyunXie; SongpingLiang

    2003-01-01

    Differential proteome profiles of human lung squamous carcinoma tissue compared to paired tumor-adjacent normal bronchial epithelial tissue were established and analyzed by means of immobilized pH gradient-based two-dimensional polyacrylamide gel electrophoresis(2-D PAGE)and matrix-assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF-MS).The results showed that well-resolved,reproducible 2-DE patterns of human lung squamous carcinoma and adjacent normal bronchial epithelial tissues were obtained under the condition of 0.75-mg protein-load.The average deviation of spot position was 0.733±0.101 mm in IEF direction,and 0.925±0.207mm in SDS-PAGE direction.For tumor tissue,a total of 1241±88 spots were detected,987±65 spots were matched with an average matching rate of 79.5%.For control,a total of 1190±72 spots were detected,and 875±48 spots were matched with an average matching rate of 73.5%.A total of 864±34 spots were matched between tumors and controls.Forth-three differential proteins were characterized:some proteins were related to oncogenes,and others involved in the regulation of cell cycle and signal transduction.It is suggested that the differential proteomic approach is valuable for mass identification of differentially expressed proteins involved in lung carcinogenesis.These data will be used to establish human lung cancer proteome database to further study human lung squamous carcinoma.

  11. KLC1-ALK: a novel fusion in lung cancer identified using a formalin-fixed paraffin-embedded tissue only.

    Directory of Open Access Journals (Sweden)

    Yuki Togashi

    Full Text Available The promising results of anaplastic lymphoma kinase (ALK inhibitors have changed the significance of ALK fusions in several types of cancer. These fusions are no longer mere research targets or diagnostic markers, but they are now directly linked to the therapeutic benefit of patients. However, most available tumor tissues in clinical settings are formalin-fixed and paraffin-embedded (FFPE, and this significantly limits detailed genetic studies in many clinical cases. Although recent technical improvements have allowed the analysis of some known mutations in FFPE tissues, identifying unknown fusion genes by using only FFPE tissues remains difficult. We developed a 5'-rapid amplification of cDNA ends-based system optimized for FFPE tissues and evaluated this system on a lung cancer tissue with ALK rearrangement and without the 2 known ALK fusions EML4-ALK and KIF5B-ALK. With this system, we successfully identified a novel ALK fusion, KLC1-ALK. The result was confirmed by reverse transcription-polymerase chain reaction and fluorescence in situ hybridization. Then, we synthesized the putative full-length cDNA of KLC1-ALK and demonstrated the transforming potential of the fusion kinase with assays using mouse 3T3 cells. To the best of our knowledge, KLC1-ALK is the first novel oncogenic fusion identified using only FFPE tissues. This finding will broaden the potential value of archival FFPE tissues and provide further biological and clinical insights into ALK-positive lung cancer.

  12. Anti-human tissue factor antibody ameliorated intestinal ischemia reperfusion-induced acute lung injury in human tissue factor knock-in mice.

    Directory of Open Access Journals (Sweden)

    Xiaolin He

    Full Text Available BACKGROUND: Interaction between the coagulation and inflammation systems plays an important role in the development of acute respiratory distress syndrome (ARDS. Anti-coagulation is an attractive option for ARDS treatment, and this has promoted development of new antibodies. However, preclinical trials for these antibodies are often limited by the high cost and availability of non-human primates. In the present study, we developed a novel alternative method to test the role of a humanized anti-tissue factor mAb in acute lung injury with transgenic mice. METHODOLOGY/PRINCIPAL FINDINGS: Human tissue factor knock-in (hTF-KI transgenic mice and a novel humanized anti-human tissue factor mAb (anti-hTF mAb, CNTO859 were developed. The hTF-KI mice showed a normal and functional expression of hTF. The anti-hTF mAb specifically blocked the pro-coagulation activity of brain extracts from the hTF-KI mice and human, but not from wild type mice. An extrapulmonary ARDS model was used by intestinal ischemia-reperfusion. Significant lung tissue damage in hTF-KI mice was observed after 2 h reperfusion. Administration of CNTO859 (5 mg/kg, i.v. attenuated the severity of lung tissue injury, decreased the total cell counts and protein concentration in bronchoalveolar lavage fluid, and reduced Evans blue leakage. In addition, the treatment significantly reduced alveolar fibrin deposition, and decreased tissue factor and plasminogen activator inhibitor-1 activity in the serum. This treatment also down-regulated cytokine expression and reduced cell death in the lung. CONCLUSIONS: This novel anti-hTF antibody showed beneficial effects on intestinal ischemia-reperfusion induced acute lung injury, which merits further investigation for clinical usage. In addition, the use of knock-in transgenic mice to test the efficacy of antibodies against human-specific proteins is a novel strategy for preclinical studies.

  13. Cell culture density affects the stemness gene expression of adipose tissue-derived mesenchymal stem cells.

    Science.gov (United States)

    Kim, Dae Seong; Lee, Myoung Woo; Lee, Tae-Hee; Sung, Ki Woong; Koo, Hong Hoe; Yoo, Keon Hee

    2017-03-01

    The results of clinical trials using mesenchymal stem cells (MSCs) are controversial due to the heterogeneity of human MSCs and differences in culture conditions. In this regard, it is important to identify gene expression patterns according to culture conditions, and to determine how the cells are expanded and when they should be clinically used. In the current study, stemness gene expression was investigated in adipose tissue-derived MSCs (AT-MSCs) harvested following culture at different densities. AT-MSCs were plated at a density of 200 or 5,000 cells/cm(2). After 7 days of culture, stemness gene expression was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. The proliferation rate of AT-MSCs harvested at a low density (~50% confluent) was higher than that of AT-MSCs harvested at a high density (~90% confluent). Although there were differences in the expression levels of stemness gene, such as octamer-binding transcription factor 4, nanog homeobox (Nanog), SRY-box 2, Kruppel like factor 4, v-myc avian myelocytomatosis viral oncogene homolog (c-Myc), and lin-28 homolog A, in the AT-MSCs obtained from different donors, RT-qPCR analysis demonstrated differential gene expression patterns according to the cell culture density. Expression levels of stemness genes, particularly Nanog and c-Myc, were upregulated in AT-MSCs harvested at a low density (~50% confluent) in comparison to AT-MSCs from the same donor harvested at a high density (~90% confluent). These results imply that culture conditions, such as the cell density at harvesting, modulate the stemness gene expression and proliferation of MSCs.

  14. Human lung density is not altered following normoxic and hypoxic moderate-intensity exercise: implications for transient edema.

    Science.gov (United States)

    Hodges, Alastair N H; Sheel, A William; Mayo, John R; McKenzie, Donald C

    2007-07-01

    The purpose of this study was to examine the effects of exercise on extravascular lung water as it may relate to pulmonary gas exchange. Ten male humans underwent measures of maximal oxygen uptake (Vo2 max) in two conditions: normoxia (N) and normobaric hypoxia of 15% O2 (H). Lung density was measured by quantified MRI before and 48.0 +/- 7.4 and 100.7 +/- 15.1 min following 60 min of cycling exercise in N (intensity = 61.6 +/- 9.5% Vo2 max) and 55.5 +/- 9.8 and 104.3 +/- 9.1 min following 60 min cycling exercise in H (intensity = 65.4 +/- 7.1% hypoxic Vo2 max), where Vo2 max = 65.0 +/- 7.5 ml x kg(-1) x min(-1) (N) and 54.1 +/- 7.0 ml x kg(-1) x min(-1) (H). Two subjects demonstrated mild exercise-induced arterial hypoxemia (EIAH) [minimum arterial oxygen saturation (SaO2 min) = 94.5% and 93.8%], and seven subjects demonstrated moderate EIAH (SaO2 min = 91.4 +/- 1.1%) as measured noninvasively during the Vo2 max test in N. Mean lung densities, measured once preexercise and twice postexercise, were 0.177 +/- 0.019, 0.181 +/- 0.019, and 0.173 +/- 0.019 g/ml (N) and 0.178 +/- 0.021, 0.174 +/- 0.022, and 0.176 +/- 0.019 g/ml (H), respectively. No significant differences (P > 0.05) were found in lung density following exercise in either condition or between conditions. Transient interstitial pulmonary edema did not occur following sustained steady-state cycling exercise in N or H, indicating that transient edema does not result from pulmonary capillary leakage during sustained submaximal exercise.

  15. Dynamic dual-energy chest radiography: a potential tool for lung tissue motion monitoring and kinetic study.

    Science.gov (United States)

    Xu, Tong; Ducote, Justin L; Wong, Jerry T; Molloi, Sabee

    2011-02-21

    Dual-energy chest radiography has the potential to provide better diagnosis of lung disease by removing the bone signal from the image. Dynamic dual-energy radiography is now possible with the introduction of digital flat-panel detectors. The purpose of this study is to evaluate the feasibility of using dynamic dual-energy chest radiography for functional lung imaging and tumor motion assessment. The dual-energy system used in this study can acquire up to 15 frames of dual-energy images per second. A swine animal model was mechanically ventilated and imaged using the dual-energy system. Sequences of soft-tissue images were obtained using dual-energy subtraction. Time subtracted soft-tissue images were shown to be able to provide information on regional ventilation. Motion tracking of a lung anatomic feature (a branch of pulmonary artery) was performed based on an image cross-correlation algorithm. The tracking precision was found to be better than 1 mm. An adaptive correlation model was established between the above tracked motion and an external surrogate signal (temperature within the tracheal tube). This model is used to predict lung feature motion using the continuous surrogate signal and low frame rate dual-energy images (0.1-3.0 frames per second). The average RMS error of the prediction was (1.1 ± 0.3) mm. The dynamic dual energy was shown to be potentially useful for lung functional imaging such as regional ventilation and kinetic studies. It can also be used for lung tumor motion assessment and prediction during radiation therapy.

  16. DETECTING EXPRESSION OF MRP-1/CD9 mRNA IN LUNG CANCERS USING TISSUE MICROARRAYS AND FLUORESCENCE IN SITU HYBRIDIZATION METHODS

    Institute of Scientific and Technical Information of China (English)

    WANG Xin-yun; LIU Ting; LI Yan; ZHAO Feng-yun; SUN Cui-yun; WANG Ai-xiang

    2005-01-01

    Objective: The aim of this study was to investigate the MRP-1/CD9mRNA expression in lung cancer and normal lung tissues and the relationship between its expression and pathologic grades, clinical stages, metastasis and prognosis.Methods: To observe MRP-1/C9mRNA expression, tissue microarray (TMA) containing 54 lung cancers and 10 normal lung tissues was prepared and Fluorescence in situ hybridization was used. Results: The positive rate of MRP-1/CD9 expression was 48.1% in lung cancer, lower than that of normal lung tissues. The statistical difference was significant (P<0.05). Its protein expression had no relationship with the patients' ages, sex and the macroscopic type of tumor, but had relationships with the histological type, clinical stage, differentiated degree and metastasis. The expression in non-small cell lung cancer (NSCLC) was higher than that in small cell lung cancer (SCLC); in well-moderately differentiated group was higher than that in poorly differentiated group; Earlier period group (Ⅰ+Ⅱ) was higher than in later period group (Ⅲ+Ⅳ); and in group without lymphoid metastasis was higher than in patients with lymphoid metastasis. Conclusion: The progression of the lung cancer maybe related with the descended MRP-1/Cd9 expression, which may be useful in evaluating the prognosis of cancer patients.

  17. SU-E-T-572: Normal Lung Tissue Sparing in Radiation Therapy for Locally Advanced Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hong, C; Ju, S; Ahn, Y [Samsung Medical Center, Seoul (Korea, Republic of)

    2015-06-15

    Purpose: To compare normal lung-sparing capabilities of three advanced radiation therapy techniques for locally advanced non-small cell lung cancer (LA-NSCLC). Methods: Four-dimensional computed tomography (4DCT) was performed in 10 patients with stage IIIb LA-NSCLC. The internal target volume (ITV); planning target volume (PTV); and organs at risks (OARs) such as spinal cord, total normal lung, heart, and esophagus were delineated for each CT data set. Intensity-modulated radiation therapy (IMRT), Tomohelical-IMRT (TH-IMRT), and TomoDirect-IMRT (TD-IMRT) plans were generated (total prescribed dose, 66 Gy in 33 fractions to the PTV) for each patient. To reduce the normal lung dose, complete and directional block function was applied outside the normal lung far from the target for both TH-IMRT and TD-IMRT, while pseudo- OAR was set in the same region for IMRT. Dosimetric characteristics of the three plans were compared in terms of target coverage, the sparing capability for the OAR, and the normal tissue complication probability (NTCP). Beam delivery efficiency was also compared. Results: TH-IMRT and TD-IMRT provided better target coverage than IMRT plans. Lung volume receiving ≥–30 Gy, mean dose, and NTCP were significant with TH-IMRT than with IMRT (p=0.006), and volume receiving ≥20–30 Gy was lower in TD-IMRT than in IMRT (p<0.05). Compared with IMRT, TH-IMRT had better sparing effect on the spinal cord (Dmax, NTCP) and heart (V45) (p<0.05). NTCP for the spinal cord, V45 and V60 for the heart, and Dmax for the esophagus were significantly lower in TD-IMRT than in IMRT. The monitor units per fraction were clearly smaller for IMRT than for TH-IMRT and TD-IMRT (p=0.006). Conclusion: In LA-NSCLC, TH-IMRT gave superior PTV coverage and OAR sparing compared to IMRT. TH-IMRT provided better control of the lung volume receiving ≥5–30 Gy. The delivery time and monitor units were lower in TD-IMRT than in TH-IMRT.

  18. Amount of stroma is associated with mammographic density and stromal expression of oestrogen receptor in normal breast tissues.

    Science.gov (United States)

    Gabrielson, Marike; Chiesa, Flaminia; Paulsson, Janna; Strell, Carina; Behmer, Catharina; Rönnow, Katarina; Czene, Kamila; Östman, Arne; Hall, Per

    2016-07-01

    Following female sex and age, mammographic density is considered one of the strongest risk factors for breast cancer. Despite the association between mammographic density and breast cancer risk, little is known about the underlying histology and biological basis of breast density. To better understand the mechanisms behind mammographic density we assessed morphology, proliferation and hormone receptor status in relation to mammographic density in breast tissues from healthy women. Tissues were obtained from 2012-2013 by ultrasound-guided core needle biopsy from 160 women as part of the Karma (Karolinska mammography project for risk prediction for breast cancer) project. Mammograms were collected through routine mammography screening and mammographic density was calculated using STRATUS. The histological composition, epithelial and stromal proliferation status and hormone receptor status were assessed through immunohistochemical staining. Higher mammographic density was significantly associated with a greater proportion of stromal and epithelial tissue and a lower proportion of adipose tissue. Epithelial expression levels of Ki-67, oestrogen receptor (ER) and progesterone receptor (PR) were not associated with mammographic density. Epithelial Ki-67 was associated with a greater proportion of epithelial tissue, and epithelial PR was associated with a greater proportion of stromal and a lower proportion of adipose tissue. Epithelial ER was not associated with any tissues. In contrast, expression of ER in the stroma was significantly associated with a greater proportion of stroma, and negatively associated with the amount of adipose tissue. High mammographic density is associated with higher amount of stroma and epithelium and less amount of fat, but is not associated with a change in epithelial proliferation or receptor status. Increased expressions of both epithelial PR and stromal ER are associated with a greater proportion of stroma, suggesting hormonal involvement

  19. Integrative proteomics and tissue microarray profiling indicate the association between overexpressed serum proteins and non-small cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Yansheng Liu

    Full Text Available Lung cancer is the leading cause of cancer deaths worldwide. Clinically, the treatment of non-small cell lung cancer (NSCLC can be improved by the early detection and risk screening among population. To meet this need, here we describe the application of extensive peptide level fractionation coupled with label free quantitative proteomics for the discovery of potential serum biomarkers for lung cancer, and the usage of Tissue microarray analysis (TMA and Multiple reaction monitoring (MRM assays for the following up validations in the verification phase. Using these state-of-art, currently available clinical proteomic approaches, in the discovery phase we confidently identified 647 serum proteins, and 101 proteins showed a statistically significant association with NSCLC in our 18 discovery samples. This serum proteomic dataset allowed us to discern the differential patterns and abnormal biological processes in the lung cancer blood. Of these proteins, Alpha-1B-glycoprotein (A1BG and Leucine-rich alpha-2-glycoprotein (LRG1, two plasma glycoproteins with previously unknown function were selected as examples for which TMA and MRM verification were performed in a large sample set consisting about 100 patients. We revealed that A1BG and LRG1 were overexpressed in both the blood level and tumor sections, which can be referred to separate lung cancer patients from healthy cases.

  20. Clinicopathological and Prognostic Significance of a Panel of Tumor Biomarkers 
in Lung Adenocarcinoma: a Tissue Microarray Study

    Directory of Open Access Journals (Sweden)

    Xin YANG

    2014-03-01

    Full Text Available Background and objective Lung adenocarcinoma is one of the most common histological subtypes of lung cancer. The incidence of this disease was continuously increased. This study aims to detect the expressions of Napsin A, TTF-1, ERCC1, RRM1, EGFR, HER2, ERα, ERβ, PR, and Bcl-2 in lung adenocarcinoma and to explore their correlations with clinicopathological characteristics and prognosis. Methods A total of 227 lung adenocarcinoma specimens were constructed in tissue microarrays. The expressions of the 10 tumor biomarkers were analyzed by immunohistochemistry on paraffin-embedded sections. Results Among the 10 markers, Napsin A was gender-related (P=0.049. Napsin A, PR, and EGFR were significantly associated with smoking. TTF-1 and ERCC1 were closely associated with tumor size. Napsin A, TTF-1, ERα, and PR were remarkably associated with tumor differentiation. TTF-1, Bcl-2, and ERCC1 were closely associated with tumor stage (P0.05. Univariate analysis results showed that Napsin A, TTF-1, and ERCC1 were significantly associated with overall survival. TTF-1 was remarkably associated with disease-free survival (P0.05. Multivariate analysis results showed that pathological staging was significantly associated with overall survival and disease-free survival (P0.05. Conclusion Napsin A, TTF-1, and ERCC1 are the markers indicating good prognosis of lung adenocarcinoma.

  1. The interaction of asbestos and iron in lung tissue revealed by synchrotron-based scanning X-ray microscopy

    Science.gov (United States)

    Pascolo, Lorella; Gianoncelli, Alessandra; Schneider, Giulia; Salomé, Murielle; Schneider, Manuela; Calligaro, Carla; Kiskinova, Maya; Melato, Mauro; Rizzardi, Clara

    2013-01-01

    Asbestos is a potent carcinogen associated with malignant mesothelioma and lung cancer but its carcinogenic mechanisms are still poorly understood. Asbestos toxicity is ascribed to its particular physico-chemical characteristics, and one of them is the presence of and ability to adsorb iron, which may cause an alteration of iron homeostasis in the tissue. This observational study reports a combination of advanced synchrotron-based X-ray imaging and micro-spectroscopic methods that provide correlative morphological and chemical information for shedding light on iron mobilization features during asbestos permanence in lung tissue. The results show that the processes responsible for the unusual distribution of iron at different stages of interaction with the fibres also involve calcium, phosphorus and magnesium. It has been confirmed that the dominant iron form present in asbestos bodies is ferritin, while the concurrent presence of haematite suggests alteration of iron chemistry during asbestos body permanence. PMID:23350030

  2. Controlling activation site density by low-energy far-field stimulation in cardiac tissue

    Science.gov (United States)

    Hörning, Marcel; Takagi, Seiji; Yoshikawa, Kenichi

    2012-06-01

    Tachycardia and fibrillation are potentially fatal arrhythmias associated with the formation of rotating spiral waves in the heart. Presently, the termination of these types of arrhythmia is achieved by use of antitachycardia pacing or cardioversion. However, these techniques have serious drawbacks, in that they either have limited application or produce undesirable side effects. Low-energy far-field stimulation has recently been proposed as a superior therapy. This proposed therapeutic method would exploit the phenomenon in which the application of low-energy far-field shocks induces a large number of activation sites (“virtual electrodes”) in tissue. It has been found that the formation of such sites can lead to the termination of undesired states in the heart and the restoration of normal beating. In this study we investigate a particular aspect of this method. Here we seek to determine how the activation site density depends on the applied electric field through in vitro experiments carried out on neonatal rat cardiac tissue cultures. The results indicate that the activation site density increases exponentially as a function of the intracellular conductivity and the level of cell isotropy. Additionally, we report numerical results obtained from bidomain simulations of the Beeler-Reuter model that are quantitatively consistent with our experimental results. Also, we derive an intuitive analytical framework that describes the activation site density and provides useful information for determining the ratio of longitudinal to transverse conductivity in a cardiac tissue culture. The results obtained here should be useful in the development of an actual therapeutic method based on low-energy far-field pacing. In addition, they provide a deeper understanding of the intrinsic properties of cardiac cells.

  3. High-density cell systems incorporating polymer microspheres as microenvironmental regulators in engineered cartilage tissues.

    Science.gov (United States)

    Solorio, Loran D; Vieregge, Eran L; Dhami, Chirag D; Alsberg, Eben

    2013-06-01

    To address the significant clinical need for tissue-engineered therapies for the repair and regeneration of articular cartilage, many systems have recently been developed using bioactive polymer microspheres as regulators of the chondrogenic microenvironment within high-density cell cultures. In this review, we highlight various densely cellular systems utilizing polymer microspheres as three-dimensional (3D) structural elements within developing engineered cartilage tissue, carriers for cell expansion and delivery, vehicles for spatiotemporally controlled growth factor delivery, and directors of cell behavior via regulation of cell-biomaterial interactions. The diverse systems described herein represent a shift from the more traditional tissue engineering approach of combining cells and growth factors within a biomaterial scaffold, to the design of modular systems that rely on the assembly of cells and bioactive polymer microspheres as building blocks to guide the creation of articular cartilage. Cell-based assembly of 3D microsphere-incorporated structures represents a promising avenue for the future of tissue engineering.

  4. Obstructive jaundice leads to accumulation of oxidized low density lipoprotein in human liver tissue

    Institute of Scientific and Technical Information of China (English)

    Mustafa Comert; Yucel Ustundag; Ishak Ozel Tekin; Banu Dogan Gun; Figen Barut

    2006-01-01

    Oxidized low density lipoprotein (ox-LDL) molecule is one of the most important modified lipoproteins produced during the oxidative stress. Modified lipoproteins have been defined as being part of the immune inflammatory mechanisms in association with oxidant stress. We have reported the accumulation of ox-LDL in Balb/c mice liver after bile duct ligation previously. Here, we investigated this finding in human beings with obstructive jaundice.Our study demonstrates that obstructive jaundice results in tremendous accumulation of ox-LDL in the liver tissue of patients.

  5. SU-E-T-573: Normal Tissue Dose Effect of Prescription Isodose Level Selection in Lung Stereotactic Body Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Q; Lei, Y; Zheng, D; Zhu, X; Wahl, A; Lin, C; Zhou, S; Zhen, W [University of Nebraska Medical Center, Omaha, NE (United States)

    2015-06-15

    Purpose: To evaluate dose fall-off in normal tissue for lung stereotactic body radiation therapy (SBRT) cases planned with different prescription isodose levels (IDLs), by calculating the dose dropping speed (DDS) in normal tissue on plans computed with both Pencil Beam (PB) and Monte-Carlo (MC) algorithms. Methods: The DDS was calculated on 32 plans for 8 lung SBRT patients. For each patient, 4 dynamic conformal arc plans were individually optimized for prescription isodose levels (IDL) ranging from 60% to 90% of the maximum dose with 10% increments to conformally cover the PTV. Eighty non-overlapping rind structures each of 1mm thickness were created layer by layer from each PTV surface. The average dose in each rind was calculated and fitted with a double exponential function (DEF) of the distance from the PTV surface, which models the steep- and moderate-slope portions of the average dose curve in normal tissue. The parameter characterizing the steep portion of the average dose curve in the DEF quantifies the DDS in the immediate normal tissue receiving high dose. Provided that the prescription dose covers the whole PTV, a greater DDS indicates better normal tissue sparing. The DDS were compared among plans with different prescription IDLs, for plans computed with both PB and MC algorithms. Results: For all patients, the DDS was found to be the lowest for 90% prescription IDL and reached a highest plateau region for 60% or 70% prescription. The trend was the same for both PB and MC plans. Conclusion: Among the range of prescription IDLs accepted by lung SBRT RTOG protocols, prescriptions to 60% and 70% IDLs were found to provide best normal tissue sparing.

  6. Dexmedetomidine Inhibits Inflammatory Reaction in Lung Tissues of Septic Rats by Suppressing TLR4/NF-κB Pathway

    Directory of Open Access Journals (Sweden)

    Yuqing Wu

    2013-01-01

    and 20 μg/kg significantly decreased mortality and pulmonary inflammation of septic rats, as well as suppressed CLP-induced elevation of TNF-α and IL-6 and inhibited TLR4/MyD88 expression and NF-κB activation. These results suggest that dexmedetomidine may decrease mortality and inhibit inflammatory reaction in lung tissues of septic rats by suppressing TLR4/MyD88/NF-κB pathway.

  7. Rapamycin regulates connective tissue growth factor expression of lung epithelial cells via phosphoinositide 3-kinase.

    Science.gov (United States)

    Xu, Xuefeng; Wan, Xuan; Geng, Jing; Li, Fei; Yang, Ting; Dai, Huaping

    2013-09-01

    The pathogenesis of idiopathic pulmonary fibrosis (IPF) remains largely unknown. It is believed that IPF is mainly driven by activated alveolar epithelial cells that have a compromised migration capacity, and that also produce substances (such as connective tissue growth factor, CTGF) that contribute to fibroblast activation and matrix protein accumulation. Because the mechanisms regulating these processes are unclear, the aim of this study was to determine the role of rapamycin in regulating epithelial cell migration and CTGF expression. Transformed epithelial cell line A549 and normal human pulmonary alveolar or bronchial epithelial cells were cultured in regular medium or medium containing rapamycin. Real time reverse transcriptase polymerase chain reaction was employed to determine CTGF mRNA expression. Western blotting and an enzyme-linked immunosorbent assay were used for detecting CTGF protein. Wound healing and migration assays were used to determine the cell migration potential. Transforming growth factor (TGF)-β type I receptor (TβRI) inhibitor, SB431542 and phosphoinositide 3-kinase (PI3K) inhibitor, LY294002 were used to determine rapamycin's mechanism of action. It was found that treatment of A549 and normal human alveolar or bronchial epithelial cells with rapamycin significantly promoted basal or TGF-β1 induced CTGF expression. LY294002, not SB431542 attenuated the promotional effect of rapamycin on CTGF expression. Cell mobility was not affected by rapamycin in wound healing and migration assays. These data suggest rapamycin has a profibrotic effect in vitro and underscore the potential of combined therapeutic approach with PI3K and mammalian target of rapamycin inhibitors for the treatment of animal or human lung fibrosis.

  8. When is pneumonia not pneumonia: a clinicopathologic study of the utility of lung tissue biopsies in determining the suitability of cadaveric tissue for donation.

    Science.gov (United States)

    Kubilay, Zeynep; Layon, A Joseph; Baer, Herman; Archibald, Lennox K

    2016-06-01

    Healthcare-associated pneumonia (HCAP) represents a major diagnostic challenge because of the relatively low sensitivity and specificity of clinical criteria, radiological findings, and microbiologic culture results. It is often difficult to distinguish between pneumonia, underlying pulmonary disease, or conditions with pulmonary complications; this is compounded by the often-subjective clinical diagnosis of pneumonia. We conducted this study to determine the utility of post-mortem lung biopsies for diagnosing pneumonia in tissue donors diagnosed with pneumonia prior to death. Subjects were deceased patients who had been hospitalized at death and diagnosed with pneumonia. Post-mortem lung biopsies were obtained from the anatomic portion of the cadaveric lung corresponding to chest radiograph abnormalities. Specimens were fixed, stained with hematoxylin and eosin, and read by a single board-certified pathologist. Histological criteria for acute pneumonia included intense neutrophilic infiltration, fibrinous exudates, cellular debris, necrosis, or bacteria in the interstitium and intra-alveolar spaces. Of 143 subjects with a diagnosis of pneumonia at time of death, 14 (9.8 %) had histological evidence consistent with acute pneumonia. The most common histological diagnoses were emphysema (53 %), interstitial fibrosis (40 %), chronic atelectasis (36 %), acute and chronic passive congestion consistent with underlying cardiomyopathy (25 %), fibro-bullous disease (12 %), and acute bronchitis (11 %). HCAP represents a major diagnostic challenge because of the relatively low sensitivity and specificity of clinical criteria, radiological findings, and microbiologic testing. We found that attending physician-diagnosed pneumonia did not correlate with post-mortem pathological diagnosis. We conclude that histological examination of cadaveric lung tissue biopsies enables ascertainment or rule out of underlying pneumonia and prevents erroneous donor deferrals.

  9. Inhibition of connective tissue growth factor attenuates paraquat-induced lung fibrosis in a human MRC-5 cell line.

    Science.gov (United States)

    Huang, Min; Yang, Huifang; Zhu, Lingqin; Li, Honghui; Zhou, Jian; Zhou, Zhijun

    2016-11-01

    Chronic exposure to Paraquat (PQ) may result in progressive pulmonary fibrosis and subsequent chronic obstructive pulmonary malfunction. Connective tissue growth factor (CTGF) has been proposed as a key determinant in the development of lung fibrosis. We investigated thus whether knock down of CTGF can prevent human lung fibroblasts (MRC-5) activation and proliferation with the subsequent inhibition of PQ-induced fibrosis. MRC-5 was transfected with CTGF-siRNAs and exposed to different concentrations of PQ. The siRNA-silencing efficacy was evaluated using western blotting analyses, qRT-PCR and flow cytometry. Next, the viability and migration of MRC-5 was determined. MMP-2, MMP-9, and TIMP-1 accumulation were quantified to evaluate the lung fibrosis exposure to PQ. Over expression of CTGF mRNA was observed in human MRC-5 cell as early as 6 h following PQ stimulation. CTGF gene expression in MRC-5 cells was substantially reduced by RNAi, which significantly suppressed the expression of the lung fibrosis markers such as tissue inhibitor of metalloproteinase-2 (TIMP-2), Matrix metalloproteinase-2 (MMP-2) and Matrix metalloproteinase-9 (MMP-9) that were stimulated by PQ. Inhibition of CTGF expression suppressed impeded the proliferation and migration ability of MRC-5 cells and resulted in cell-extracellular matrix (ECM) protein accumulation in cells. Our results suggest that CTGF promoted the development of PQ-induced lung fibrosis in collaboration with transforming growth factor β1 (TGFβ1). Furthermore, the observed arresting effects of CTGF knock down during this process suggested that CTGF is the potential target site for preventing PQ-induced pulmonary fibrosis. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1620-1626, 2016.

  10. Detection of EGFR and COX-2 Expression by Immunohistochemical Method on a Tissue Microarray Section in Lung Cancer and Biological Significance

    Directory of Open Access Journals (Sweden)

    Xinyun WANG

    2010-02-01

    Full Text Available Background and objective Epidermal growth factor receptor (EGFR and cyclooxygenase-2 (COX-2, which can regulate growth, invasion and metastasis of tumor through relevant signaling pathway, have been detected in a variety of solid tumors. The aim of this study is to investigate the biological significance of EGFR and COX-2 expression in lung cancer and the relationship between them. Methods The expression of EGFR and COX-2 was detected in 89 primary lung cancer tissues, 12 premaliganant lesions, 12 lymph node metastases, and 10 normal lung tissues as the control by immunohistochemical method on a tissue microarray section. Results EGFR protein was detectable in 59.6%, 41.7%, and 66.7% of primary lung cancer tissues, premalignant lesions and lymph node metastases, respectively; COX-2 protein was detectable in 52.8%, 41.7%, and 66.7% of primary lung cancer tissues, premalignant lesions and lymph node metastases, respectively, which were significantly higher than those of the control (P 0.05. COX-2 expression was related to gross type (P < 0.05. A highly positive correlation was observed between EGFR and COX-2 expression (P < 0.01. Conclusion Overexpression of EGFR and COX-2 may play an important role in the tumorgenesis, progression and malignancy of lung cancer. Detection of EGFR and COX-2 expression might be helpful to diagnosis and prognosis of lung cancer.

  11. Cell culture density affects the proliferation activity of human adipose tissue stem cells.

    Science.gov (United States)

    Kim, Dae Seong; Lee, Myoung Woo; Ko, Young Jong; Chun, Yong Hoon; Kim, Hyung Joon; Sung, Ki Woong; Koo, Hong Hoe; Yoo, Keon Hee

    2016-01-01

    In this study, we investigated the effect of cell density on the proliferation activity of human mesenchymal stem cells (MSCs) derived from adipose tissue (AT-MSCs) over time in culture. Passage #4 (P4) and #12 (P12) AT-MSCs from two donors were plated at a density of 200 (culture condition 1, CC1) or 5000 (culture condition 2, CC2) cells cm(-2) . After 7 days of incubation, P4 and P12 AT-MSCs cultured in CC1 were thin and spindle-shaped, whereas those cultured in CC2 had extensive cell-to-cell contacts and an expanded cell volume. In addition, P4 and P12 AT-MSCs in CC1 divided more than three times, while those in CC2 divided less than once on average. Flow cytometric analysis using 5(6)-carboxyfluorescein diacetate N-succinimidyl ester dye showed that the fluorescence intensity of AT-MSCs was lower in CC1 than in CC2. Furthermore, expression of proliferation-associated genes, such as CDC45L, CDC20A and KIF20A, in P4 AT-MSCs was higher in CC1 than in CC2, and this difference was also observed in P12 AT-MSCs. These data demonstrated that cell culture density affects the proliferation activity of MSCs, suggesting that it is feasible to design a strategy to prepare suitable MSCs using specific culture conditions.

  12. Study of electron densities of normal and neoplastic human breast tissues by Compton scattering using synchrotron radiation

    Energy Technology Data Exchange (ETDEWEB)

    Antoniassi, M.; Conceicao, A.L.C. [Departamento de Fisica-Faculdade de Filosofia Ciencias e Letras de Ribeirao Preto-Universidade de Sao Paulo, Ribeirao Preto, Sao Paulo (Brazil); Poletti, M.E., E-mail: poletti@ffclrp.usp.br [Departamento de Fisica-Faculdade de Filosofia Ciencias e Letras de Ribeirao Preto-Universidade de Sao Paulo, Ribeirao Preto, Sao Paulo (Brazil)

    2012-07-15

    Electron densities of 33 samples of normal (adipose and fibroglangular) and neoplastic (benign and malignant) human breast tissues were determined through Compton scattering data using a monochromatic synchrotron radiation source and an energy dispersive detector. The area of Compton peaks was used to determine the electron densities of the samples. Adipose tissue exhibits the lowest values of electron density whereas malignant tissue the highest. The relationship with their histology was discussed. Comparison with previous results showed differences smaller than 4%. - Highlights: Black-Right-Pointing-Pointer Electron density of normal and neoplastic breast tissues was measured using Compton scattering. Black-Right-Pointing-Pointer Monochromatic synchrotron radiation was used to obtain the Compton scattering data. Black-Right-Pointing-Pointer The area of Compton peaks was used to determine the electron densities of samples. Black-Right-Pointing-Pointer Adipose tissue shows the lowest electron density values whereas the malignant tissue the highest. Black-Right-Pointing-Pointer Comparison with previous results showed differences smaller than 4%.

  13. Relationship between electron density and effective densities of body tissues for stopping, scattering and nuclear interaction of proton and ion beams

    CERN Document Server

    Kanematsu, Nobuyuki

    2011-01-01

    In treatment planning of charged-particle radiotherapy, patient heterogeneity is normally modeled as variable-density water to best reproduce the stopping power. This water-based model would cause substantial errors in multiple scattering and nuclear interaction as body tissues may deviate from water in elemental compositions. In this study, we physically defined distinctive effective densities for stopping, scattering, and nuclear interactions of proton and ions and constructed their conversion functions to correct the water-based model, using the standard elemental composition data for body tissues. As we took the electron density for the reference in the formulation, these conversion functions are generally valid for treatment planning systems that normally have a function to convert CT number to electron density or stopping-power ratio. The proposed extension in heterogeneity correction will enable accurate beam dose calculation without seriously sacrificing simplicity or efficiency of the water-based mod...

  14. Bone tissue stiffness in the mandibular condyle is dependent on the direction and density of the cancellous structure.

    NARCIS (Netherlands)

    Eijden, T.M. van; Ruijven, L.J. van; Giesen, E.B.W.

    2004-01-01

    Variation in the apparent stiffness of cancellous bone is generally ascribed to variation in cancellous structure and density, while the bone tissue stiffness is assumed to be constant. The purpose of the present study was to examine whether the bone tissue stiffness is dependent on the direction an

  15. The effect of extremely low frequency magnetic field on heart tissue iron density

    Directory of Open Access Journals (Sweden)

    Yusuf Nergiz

    2011-06-01

    Full Text Available The aim of this histological study was to investigate the effects of extremely low frequency, low intensity magnetic field on the heart muscle ıron density.Materials and methods: In this study, 45 male Spraque Dawley rats were introduced and were divided into three groups as sham, control and experiment group. The experimental group was exposed to a 0.25 mT to Extremely Low Frequency Magnetic Field (ELF-MF for 14 days, 3h a day in metacrylate boxes. The sham group was treated like the experimental group, except for ELF-MF exposure. For control, nothing applied to rats in this group and they completed their life cycle in the cage during the study period. After exposure period, the rats were sacrificed under ketalar anesthesia (50 mg / kg, intramuscularly. Heart tissues were immediately fixed in 10% neutral formaldehyde and embedded in paraffin blocks. Histological sections from cardiac tissue stained by hematoxylin-eosin, Perls’ Prussian blue for iron pigments. Histological slides were photographed under a Nikon DS-2MV photomicroscope.Results: The architecture and histology of the control, sham and experimental group were observed as normal. No differences were observed between the control, sham and experimental rat groups in the iron stain of heart tissues.Conclusion: As a result of our study, we did not observe differences between the control and ELF-MF (experimental group. In this investigation we demonstrated that the exposure of cardiac tissue of rats to the ELF-MF did not change in the iron stain study. J Clin Exp Invest 2011;2(2:144-8

  16. Is There a Regulatory Role of Immunoglobulins on Tissue Forming Cells Relevant in Chronic Inflammatory Lung Diseases?

    Directory of Open Access Journals (Sweden)

    Michael Roth

    2011-01-01

    Full Text Available Epithelial cells, fibroblasts and smooth muscle cells together form and give structure to the airway wall. These three tissue forming cell types are structure giving elements and participate in the immune response to inhaled particles including allergens and dust. All three cell types actively contribute to the pathogenesis of chronic inflammatory lung diseases such as asthma and chronic obstructive pulmonary disease (COPD. Tissue forming cells respond directly to allergens through activated immunoglobulins which then bind to their corresponding cell surface receptors. It was only recently reported that allergens and particles traffic through epithelial cells without modification and bind to the immunoglobulin receptors on the surface of sub-epithelial mesenchymal cells. In consequence, these cells secrete pro-inflammatory cytokines, thereby extending the local inflammation. Furthermore, activation of the immunoglobulin receptors can induce proliferation and tissue remodeling of the tissue forming cells. New studies using anti-IgE antibody therapy indicate that the inhibition of immunoglobulins reduces the response of tissue forming cells. The unmeasured questions are: (i why do tissue forming cells express immunoglobulin receptors and (ii do tissue forming cells process immunoglobulin receptor bound particles? The focus of this review is to provide an overview of the expression and function of various immunoglobulin receptors.

  17. Investigation of the signature of lung tissue in X-ray grating-based phase-contrast imaging

    CERN Document Server

    Weber, Thomas; Haas, Wilhelm; Pelzer, Georg; Rieger, Jens; Ritter, André; Wucherer, Lukas; Braun, Jan Matthias; Durst, Jürgen; Michel, Thilo; Anton, Gisela

    2012-01-01

    Purpose: Grating-based X-ray phase-contrast imaging is a promising modality increasing the soft tissue contrast in medical imaging. In this work, the signature of lung tissue in X-ray grating-based physe-contrast imaging is investigated. Methods: We used a Talbot-Lau interferometer for our investigations of two C57BL/6 mice. Both underwent projection imaging and computed tomography. Results: The results show that the three images obtained by X-ray phase-contrast imaging show complementary anatomical structures. Especially the dark field image allows a more-exact determination of the position of the lung in the chest cavity. Conclusion: Due to its sensitivity to granular structures, the dark field image may be used for the diagnosis of lung diseases in earlier stages or without a CT scan. Furthermore, X-ray phase-contrast imaging may also have great potential in the application of animal laboratory sciences to reduce the number of required animals used in long-term translational, toxicity, and regenerative med...

  18. ELISA for complexes between urokinase-type plasminogen activator and its receptor in lung cancer tissue extracts

    DEFF Research Database (Denmark)

    de Witte, H; Pappot, H; Brünner, N

    1997-01-01

    A sandwich-type ELISA has been developed for the assessment of complexes between urokinase-type plasminogen activator (uPA) and its receptor (uPAR) in extracts of squamous cell lung carcinomas. The assay is based on a combination of rabbit polyclonal anti-uPA antibodies and a biotinylated mouse a......PA:uPAR complexes in lung tumor tissue as well as other types of cancer.......A sandwich-type ELISA has been developed for the assessment of complexes between urokinase-type plasminogen activator (uPA) and its receptor (uPAR) in extracts of squamous cell lung carcinomas. The assay is based on a combination of rabbit polyclonal anti-uPA antibodies and a biotinylated mouse...... indicate that de novo complex formation is a major factor to consider and that complexes analyzed in the presence of this antagonist represent original uPA:uPAR complexes present prior to tumor tissue processing. The present ELISA appears suitable for studying the potential prognostic impact of u...

  19. Perinatal Exposure to Insecticide Methamidophos Suppressed Production of Proinflammatory Cytokines Responding to Virus Infection in Lung Tissues in Mice

    Directory of Open Access Journals (Sweden)

    Wataru Watanabe

    2013-01-01

    Full Text Available Methamidophos, a representative organophosphate insecticide, is regulated because of its severe neurotoxicity, but it is suspected of contaminating agricultural foods in many countries due to illicit use. To reveal unknown effects of methamidophos on human health, we evaluated the developmental immunotoxicity of methamidophos using a respiratory syncytial virus (RSV infection mouse model. Pregnant mice were exposed to methamidophos (10 or 20 ppm in their drinking water from gestation day 10 to weaning on postnatal day 21. Offsprings born to these dams were intranasally infected with RSV. The levels of interleukin-6 (IL-6 and interferon-gamma in the bronchoalveolar lavage fluids after infection were significantly decreased in offspring mice exposed to methamidophos. Treatment with methamidophos did not affect the pulmonary viral titers but suppressed moderately the inflammation of lung tissues of RSV-infected offspring, histopathologically. DNA microarray analysis revealed that gene expression of the cytokines in the lungs of offspring mice exposed to 20 ppm of methamidophos was apparently suppressed compared with the control. Methamidophos did not suppress IL-6 production in RSV-infected J774.1 cell cultures. Thus, exposure of the mother to methamidophos during pregnancy and nursing was suggested to cause an irregular immune response in the lung tissues in the offspring mice.

  20. On the impact of low power density microwaves in some living tissues

    Energy Technology Data Exchange (ETDEWEB)

    Creanga, M.; Tufescu, D.E. [Univ. Al. I. Cuza, Faculty of Physics, Iasi (Romania)

    2006-07-01

    The biomedical and ecological interest for the microwave impact on the Earth biosphere is continuously increased since the industrial, military and communication activities strongly contribute to the electromagnetic stress of living bodies. In the next the authors present some of the main results obtained regarding the microwave exposure of various types of biological material: bacteria, fungi, young plant seedlings, dry seeds, animal tissues. The electromagnetic exposure was carried out in open space in well controlled environmental conditions by using 10.75 GHz/1 m W cm{sup -2} microwaves. Biochemical assays and cytogenetic tests have been carried out to reveal the changes induced post irradiation. The response of some pathogen bacteria, have been emphasized by means of turbidimetric measurements - the stimulatory effect being noticed at the level of the microbial population density (the stimulation of the human body microbial flora seems to be one of the side effects of microwave exposures). The behavior of some fungus species was investigated by spectrophotometric assay of various enzyme systems: either inhibitor y or stimulatory effects have been revealed, depending on the species and enzyme peculiarities (certain biotechnological tools could be developed based on fungi exposure to microwaves). The genetic effects of seed exposure have been studied by applying cytogenetic tests to meristem tissues provided by freshly germinated cereal plantlets. Significant rate of chromosomal aberrations has been observed following the microwave exposure as well as stimulatory influence on the proliferation rate (the possibility of plant growth stimulation is suggested). The vegetal tissue cultures (in vitro micro propagated pharmaceutical plants) exposed to low power density microwaves presented increased levels of assimilatory pigments (the controlled development of technical plants for medical uses is proposed). The chlorophyll ratio in young tree seedlings after

  1. Rapamycin attenuates bleomycin-induced pulmonary fibrosis in rats and the expression of metalloproteinase-9 and tissue inhibitors of metalloproteinase-1 in lung tissue

    Institute of Scientific and Technical Information of China (English)

    Jin Xiaoguang; Dai Huaping; Ding Ke; Xu Xuefeng; Pang Baosen; Wang Chen

    2014-01-01

    Background Idiopathic pulmonary fibrosis (IPF) is the most common and devastating form of interstitial lung disease (ILD) in the clinic.There is no effective therapy except for lung transplantation.Rapamycin is an immunosuppressive drug with potent antifibrotic activity.The purpose of this study was to examine the effects of rapamycin on bleomycininduced pulmonary fibrosis in rats and the relation to the expression of metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1).Methods Sprague-Dawley rats were treated with intratracheal injection of 0.3 ml of bleomycin (5 mg/kg) in sterile 0.9% saline to make the pulmonary fibrosis model.Rapamycin was given at a dose of 0.5 mg/kg per gavage,beginning one day before bleomycin instillation and once daily until animal sacrifice.Ten rats in each group were sacrificed at 3,7,14,28 and 56 days after bleomycin administration.Alveolitis and pulmonary fibrosis were semi-quantitatively assessed after HE staining and Masson staining under an Olympus BX40 microscope with an IDA-2000 Image Analysis System.Type Ⅰ and Ⅲ collagen fibers were identified by Picro-sirius-polarization.Hydroxyproline content in lung tissue was quantified by a colorimetric-based spectrophotometric assay,MMP-9 and TIMP-1 were detected by immunohistochemistry and by realtime quantitative reverse transcriptase polymerase chain reaction (RT-PCR).Results Bleomycin induced alveolitis and pulmonary fibrosis of rats was inhibited by rapamycin.Significant inhibition of alveolitis and hydroxyproline product were demonstrated when daily administration of rapamycin lasted for at least 14 days.The inhibitory efficacy on pulmonary fibrosis was unremarkable until rapamycin treatment lasted for at least 28 days (P <0.05).It was also demonstrated that rapamycin treatment reduced the expression of MMP-9 and TIMP-1 in lung tissue that was increased by bleomycin.Conclusion These results highlight the significance of rapamycin in alleviating

  2. Repeated intratracheal instillation of PM10 induces lipid reshaping in lung parenchyma and in extra-pulmonary tissues.

    Directory of Open Access Journals (Sweden)

    Angela Maria Rizzo

    Full Text Available Adverse health effects of air pollution attributed mainly to airborne particulate matter have been well documented in the last couple of decades. Short term exposure, referring to a few hours exposure, to high ambient PM10 concentration is linked to increased hospitalization rates for cardiovascular events, typically 24 h after air pollution peaks. Particulate matter exposure is related to pulmonary and cardiovascular diseases, with increased oxidative stress and inflammatory status. Previously, we have demonstrated that repeated intratracheal instillation of PM10sum in BALB/c mice leads to respiratory tract inflammation, creating in lung a condition which could potentially evolve in a systemic toxic reaction. Additionally, plasma membrane and tissue lipids are easily affected by oxidative stress and directly correlated with inflammatory products. With this aim, in the present investigation using the same model, we analyzed the toxic potential of PM10sum exposure on lipid plasma membrane composition, lipid peroxidation and the mechanisms of cells protection in multiple organs such as lung, heart, liver and brain. Obtained results indicated that PM10 exposure led to lung lipid reshaping, in particular phospholipid and cholesterol content increases; concomitantly, the generation of oxidative stress caused lipid peroxidation. In liver we found significant changes in lipid content, mainly due to an increase of phosphatidylcholine, and in total fatty acid composition with a more pronounced level of docosahexaenoic acid; these changes were statistically correlated to lung molecular markers. Heart and brain were similarly affected; heart was significantly enriched in triglycerides in half of the PM10sum treated mice. These results demonstrated a direct involvement of PM10sum in affecting lipid metabolism and oxidative stress in peripheral tissues that might be related to the serious systemic air-pollution effects on human health.

  3. Repeated intratracheal instillation of PM10 induces lipid reshaping in lung parenchyma and in extra-pulmonary tissues.

    Science.gov (United States)

    Rizzo, Angela Maria; Corsetto, Paola Antonia; Farina, Francesca; Montorfano, Gigliola; Pani, Giuseppe; Battaglia, Cristina; Sancini, Giulio; Palestini, Paola

    2014-01-01

    Adverse health effects of air pollution attributed mainly to airborne particulate matter have been well documented in the last couple of decades. Short term exposure, referring to a few hours exposure, to high ambient PM10 concentration is linked to increased hospitalization rates for cardiovascular events, typically 24 h after air pollution peaks. Particulate matter exposure is related to pulmonary and cardiovascular diseases, with increased oxidative stress and inflammatory status. Previously, we have demonstrated that repeated intratracheal instillation of PM10sum in BALB/c mice leads to respiratory tract inflammation, creating in lung a condition which could potentially evolve in a systemic toxic reaction. Additionally, plasma membrane and tissue lipids are easily affected by oxidative stress and directly correlated with inflammatory products. With this aim, in the present investigation using the same model, we analyzed the toxic potential of PM10sum exposure on lipid plasma membrane composition, lipid peroxidation and the mechanisms of cells protection in multiple organs such as lung, heart, liver and brain. Obtained results indicated that PM10 exposure led to lung lipid reshaping, in particular phospholipid and cholesterol content increases; concomitantly, the generation of oxidative stress caused lipid peroxidation. In liver we found significant changes in lipid content, mainly due to an increase of phosphatidylcholine, and in total fatty acid composition with a more pronounced level of docosahexaenoic acid; these changes were statistically correlated to lung molecular markers. Heart and brain were similarly affected; heart was significantly enriched in triglycerides in half of the PM10sum treated mice. These results demonstrated a direct involvement of PM10sum in affecting lipid metabolism and oxidative stress in peripheral tissues that might be related to the serious systemic air-pollution effects on human health.

  4. Technical Note: Is bulk electron density assignment appropriate for MRI-only based treatment planning for lung cancer?

    Science.gov (United States)

    Prior, Phil; Chen, Xinfeng; Gore, Elizabeth; Johnstone, Candice; Li, X Allen

    2017-07-01

    MRI-based treatment planning in radiation therapy (RT) is prohibitive, in part, due to the lack of electron density (ED) information within the image. The dosimetric differences between MRI- and CT-based planning for intensity modulated RT (IMRT) of lung cancer were investigated to assess the appropriateness of bulk ED assignment. Planning CTs acquired for six representative lung cancer patients were used to generate bulk ED IMRT plans. To avoid the effect of anatomic differences between CT and MRI, "simulated MRI-based plans" were generated by forcing the relative ED (rED) to water on CT-delineated structures using organ specific values from the ICRU Report 46 and using the mean rED value of the internal target volume (ITV) from the planning CT. The "simulated MRI-based plans" were generated using a research planning system (Monaco v5.09.07a, Elekta, AB) and employing Monte Carlo dose calculation. The following dose-volume-parameters (DVPs) were collected from both the "simulated MRI-based plans" and the original planning CT: D95 , the dose delivered to 95% of the ITV & planning target volume (PTV), D5 and V5 , the volume of normal lung irradiated ≥5 Gy. The percent point difference and relative dose difference were used for comparison with the CT based plan for V5 and D95 respectively. A total of five plans per patient were generated; three with the ITV rED (rEDITV ) = 1.06, 1.0 and the mean value from the planning CT while the lung rED (rEDlung ) was fixed at the ICRU value of 0.26 and two with rEDlung = 0.1 and 0.5 while the rEDITV was fixed to the mean value from the planning CT. Noticeable differences in the ITV and PTV DVPs were observed. Variations of the normal lung V5 can be as large as 9.6%. In some instances, varying the rEDITV between rEDmean and 1.06 resulted in D95 increases ranging from 3.9% to 6.3%. Bulk rED assignment on normal lung affected the DVPs of the ITV and PTV by 4.0-9.8% and 0.3-19.6% respectively. Dose volume histograms were presented

  5. Relation of Visceral and Subcutaneous Adipose Tissue to Bone Mineral Density in Chinese Women

    Directory of Open Access Journals (Sweden)

    Ling Wang

    2013-01-01

    Full Text Available The relationship between adipose and bone tissues is still being debated. The purpose of our study was to evaluate whether the distribution and volume of abdomen adipose tissue are correlated to trabecular bone mineral density in the lumbar spine. In this cross-sectional study, 320 Chinese women, being divided into two groups according to age ≥55 years and <55 years, were evaluated with quantitative computed tomography (QCT of the spine to simultaneously evaluate the average trabecular BMD of L2–L4, VAT, and SAT. Possible covariates of height, weight, age, and comorbidities were considered. In the <55-year-old sample, multiple linear regression analyses indicated that VAT volume was negatively correlated to trabecular BMD (P value = 0.0003 and SAT volume had no correlation to trabecular BMD. In contrast, there was no significant correlation between VAT or SAT and BMD in the ≥55-year-old sample. Our results indicate that high VAT volume is associated with low BMD in Chinese women aged <55 years and SAT has no relation with BMD.

  6. Combination of body mass index and oxidized low density lipoprotein receptor 1 in prognosis prediction of patients with squamous non-small cell lung cancer

    OpenAIRE

    Jiang, Long; Jiang, Shanshan; Lin, Yongbin; Yang, Han; Zhao, Zerui; Xie, Zehua; Lin, Yaobin; Long, Hao

    2015-01-01

    Lung cancer, especially non-small cell lung cancer (NSCLC), represents enormous challenges in continuously achieving treatment improvements. Besides cancer, obesity is becoming ever more prevalent. Obesity is increasingly acknowledged as a major risk factor for several types of common cancers. Significant mechanisms overlap in the pathobiology of obesity and tumorigenesis. One of these mechanisms involves oxidized low density lipoprotein receptor 1 (OLR1), as a link between obesity and cancer...

  7. Effects of alginate hydrogel cross-linking density on mechanical and biological behaviors for tissue engineering.

    Science.gov (United States)

    Jang, Jinah; Seol, Young-Joon; Kim, Hyeon Ji; Kundu, Joydip; Kim, Sung Won; Cho, Dong-Woo

    2014-09-01

    An effective cross-linking of alginate gel was made through reaction with calcium carbonate (CaCO3). We used human chondrocytes as a model cell to study the effects of cross-linking density. Three different pore size ranges of cross-linked alginate hydrogels were fabricated. The morphological, mechanical, and rheological properties of various alginate hydrogels were characterized and responses of biosynthesis of cells encapsulated in each gel to the variation in cross-linking density were investigated. Desired outer shape of structure was maintained when the alginate solution was cross-linked with the applied method. The properties of alginate hydrogel could be tailored through applying various concentrations of CaCO3. The rate of synthesized GAGs and collagens was significantly higher in human chondrocytes encapsulated in the smaller pore structure than that in the larger pore structure. The expression of chondrogenic markers, including collagen type II and aggrecan, was enhanced in the smaller pore structure. It was found that proper structural morphology is a critical factor to enhance the performance and tissue regeneration.

  8. Quantification of extracellular matrix proteins from a rat lung scaffold to provide a molecular readout for tissue engineering.

    Science.gov (United States)

    Hill, Ryan C; Calle, Elizabeth A; Dzieciatkowska, Monika; Niklason, Laura E; Hansen, Kirk C

    2015-04-01

    The use of extracellular matrix (ECM) scaffolds, derived from decellularized tissues for engineered organ generation, holds enormous potential in the field of regenerative medicine. To support organ engineering efforts, we developed a targeted proteomics method to extract and quantify extracellular matrix components from tissues. Our method provides more complete and accurate protein characterization than traditional approaches. This is accomplished through the analysis of both the chaotrope-soluble and -insoluble protein fractions and using recombinantly generated stable isotope labeled peptides for endogenous protein quantification. Using this approach, we have generated 74 peptides, representing 56 proteins to quantify protein in native (nondecellularized) and decellularized lung matrices. We have focused on proteins of the ECM and additional intracellular proteins that are challenging to remove during the decellularization procedure. Results indicate that the acellular lung scaffold is predominantly composed of structural collagens, with the majority of these proteins found in the insoluble ECM, a fraction that is often discarded using widely accepted proteomic methods. The decellularization procedure removes over 98% of intracellular proteins evaluated and retains, to varying degrees, proteoglycans and glycoproteins of the ECM. Accurate characterization of ECM proteins from tissue samples will help advance organ engineering efforts by generating a molecular readout that can be correlated with functional outcome to drive the next generation of engineered organs.

  9. PCR assay detects Mannheimia haemolytica in culture-negative pneumonic lung tissues of bighorn sheep (Ovis canadensis) from outbreaks in the western USA, 2009-2010.

    Science.gov (United States)

    Shanthalingam, Sudarvili; Goldy, Andrea; Bavananthasivam, Jegarubee; Subramaniam, Renuka; Batra, Sai Arun; Kugadas, Abirami; Raghavan, Bindu; Dassanayake, Rohana P; Jennings-Gaines, Jessica E; Killion, Halcyon J; Edwards, William H; Ramsey, Jennifer M; Anderson, Neil J; Wolff, Peregrine L; Mansfield, Kristin; Bruning, Darren; Srikumaran, Subramaniam

    2014-01-01

    Mannheimia haemolytica consistently causes severe bronchopneumonia and rapid death of bighorn sheep (Ovis canadensis) under experimental conditions. However, Bibersteinia trehalosi and Pasteurella multocida have been isolated from pneumonic bighorn lung tissues more frequently than M. haemolytica by culture-based methods. We hypothesized that assays more sensitive than culture would detect M. haemolytica in pneumonic lung tissues more accurately. Therefore, our first objective was to develop a PCR assay specific for M. haemolytica and use it to determine if this organism was present in the pneumonic lungs of bighorns during the 2009-2010 outbreaks in Montana, Nevada, and Washington, USA. Mannheimia haemolytica was detected by the species-specific PCR assay in 77% of archived pneumonic lung tissues that were negative by culture. Leukotoxin-negative M. haemolytica does not cause fatal pneumonia in bighorns. Therefore, our second objective was to determine if the leukotoxin gene was also present in the lung tissues as a means of determining the leukotoxicity of M. haemolytica that were present in the lungs. The leukotoxin-specific PCR assay detected leukotoxin gene in 91% of lung tissues that were negative for M. haemolytica by culture. Mycoplasma ovipneumoniae, an organism associated with bighorn pneumonia, was detected in 65% of pneumonic bighorn lung tissues by PCR or culture. A PCR assessment of distribution of these pathogens in the nasopharynx of healthy bighorns from populations that did not experience an all-age die-off in the past 20 yr revealed that M. ovipneumoniae was present in 31% of the animals whereas leukotoxin-positive M. haemolytica was present in only 4%. Taken together, these results indicate that culture-based methods are not reliable for detection of M. haemolytica and that leukotoxin-positive M. haemolytica was a predominant etiologic agent of the pneumonia outbreaks of 2009-2010.

  10. Mechanics, Hydrodynamics and Energetics of Blue Whale Lunge Feeding: Efficiency Dependence on Krill Density

    Science.gov (United States)

    2011-01-01

    Ascent speed (m s–1) Lunge angle, type A (deg) Lunge angle, type B (deg) 6/30/2002 LJ 24 10.1 154 1.6 1.0 2.3 n/a n/a n/a 2.7 n/a n/a – n/a 7/24/2003 SNI ...5 11.0 261 2.8 3.5 2.3 –58 n/a 26 3.4 56 n/a –6 67 7/24/2003 SNI 3 10.7 261 3.7 3.7 2.0 n/a n/a n/a 2.8 n/a n/a – n/a 8/22/2003 TCB 1 12.1 259 5.0 4.0...CA; MB, Monterey Bay; SBC, Santa Barbara Channel; SC, Sea of Cortez; SNI , San Nicholas Island; TCB, Tanner-Cortez Banks. –, did not occur; n/a, not

  11. Dynamic changes in high and low mammographic density human breast tissues maintained in murine tissue engineering chambers during various murine peripartum states and over time.

    Science.gov (United States)

    Chew, G L; Huang, D; Huo, C W; Blick, T; Hill, P; Cawson, J; Frazer, H; Southey, M D; Hopper, J L; Henderson, M A; Haviv, I; Thompson, E W

    2013-07-01

    Mammographic density (MD) is a strong heritable risk factor for breast cancer, and may decrease with increasing parity. However, the biomolecular basis for MD-associated breast cancer remains unclear, and systemic hormonal effects on MD-associated risk is poorly understood. This study assessed the effect of murine peripartum states on high and low MD tissue maintained in a xenograft model of human MD. Method High and low MD human breast tissues were precisely sampled under radiographic guidance from prophylactic mastectomy specimens of women. The high and low MD tissues were maintained in separate vascularised biochambers in nulliparous or pregnant SCID mice for 4 weeks, or mice undergoing postpartum involution or lactation for three additional weeks. High and low MD biochamber material was harvested for histologic and radiographic comparisons during various murine peripartum states. High and low MD biochamber tissues in nulliparous mice were harvested at different timepoints for histologic and radiographic comparisons. Results High MD biochamber tissues had decreased stromal (p = 0.0027), increased adipose (p = 0.0003) and a trend to increased glandular tissue areas (p = 0.076) after murine postpartum involution. Stromal areas decreased (p = 0.042), while glandular (p = 0.001) and adipose areas (p = 0.009) increased in high MD biochamber tissues during lactation. A difference in radiographic density was observed in high (p = 0.0021) or low MD biochamber tissues (p = 0.004) between nulliparous, pregnant and involution groups. No differences in tissue composition were observed in high or low MD biochamber tissues maintained for different durations, although radiographic density increased over time. Conclusion High MD biochamber tissues had measurable histologic changes after postpartum involution or lactation. Alterations in radiographic density occurred in biochamber tissues between different peripartum states and over time. These findings

  12. Isolation, in vitro culture and identification of a new type of mesenchymal stem cell derived from fetal bovine lung tissues.

    Science.gov (United States)

    Hu, Pengfei; Pu, Yabin; Li, Xiayun; Zhu, Zhiqiang; Zhao, Yuhua; Guan, Weijun; Ma, Yuehui

    2015-09-01

    Lung‑derived mesenchymal stem cells (LMSCs) are considered to be important in lung tissue repair and regenerative processes. However, the biological characteristics and differentiation potential of LMSCs remain to be elucidated. In the present study, fetal lung‑derived mesenchymal stem cells (FLMSCs) were isolated from fetal bovine lung tissues by collagenase digestion. The in vitro culture conditions were optimized and stabilized and the self‑renewal ability and differentiation potential were evaluated. The results demonstrated that the FLMSCs were morphologically consistent with fibroblasts, were able to be cultured and passaged for at least 33 passages and the cell morphology and proliferative ability were stable during the first 10 passages. In addition, FLMSCs were found to express CD29, CD44, CD73 and CD166, however, they did not express hematopoietic cell specific markers, including CD34, CD45 and BOLA‑DRα. The growth kinetics of FLMSCs consisted of a lag phase, a logarithmic phase and a plateau phase, and as the passages increased, the proliferative ability of cells gradually decreased. The majority of FLMSCs were in G0/G1 phase. Following osteogenic induction, FLMSCs were positive for the expression of osteopontin and collagen type I α2. Following neurogenic differentiation, the cells were morphologically consistent with neuronal cells and positive for microtubule‑associated protein 2 and nestin expression. It was concluded that the isolated FLMSCs exhibited typical characteristics of mesenchymal stem cells and that the culture conditions were suitable for their proliferation and the maintenance of stemness. The present study illustrated the potential application of lung tissue as an adult stem cell source for regenerative therapies.

  13. Isolation of human β-defensin-4 in lung tissue and its increase in lower respiratory tract infection

    Directory of Open Access Journals (Sweden)

    Mukae Hiroshi

    2005-11-01

    Full Text Available Abstract Background Human β-defensin-4 (hBD-4, a new member of the β-defensin family, was discovered by an analysis of the genomic sequence. The objective of this study was to clarify hBD-4 expression in human lung tissue, along with the inducible expression in response to infectious stimuli, localization, and antimicrobial activities of hBD-4 peptides. We also investigated the participation of hBD-4 in chronic lower respiratory tract infections (LRTI by measuring the concentrations of hBD-4 peptides in human bronchial epithelial lining fluid (ELF. Methods The antimicrobial activity of synthetic hBD-4 peptides against E. coli and P. aeruginosa was measured by radial diffusion and colony count assays. We identified hBD-4 in homogenated human lung tissue by reverse-phase high-performance liquid chromatography coupled with a radioimmunoassay (RIA. Localization of hBD-4 was studied through immunohistochemical analysis (IHC. We investigated the effects of lipopolysaccharide (LPS on hBD-4 expression and its release from small airway epithelial cells (SAEC. We collected ELF from patients with chronic LRTI using bronchoscopic microsampling to measure hBD-4 concentrations by RIA. Results hBD-4 exhibited salt-sensitive antimicrobial activity against P. aeruginosa. We detected the presence of hBD-4 peptides in human lung tissue. IHC demonstrated the localization of hBD-4-producing cells in bronchial and bronchiolar epithelium. The levels of hBD-4 peptides released from LPS-treated SAECs were higher than those of untreated control cells. ELF hBD-4 was detectable in 4 of 6 patients with chronic LRTI, while the amounts in controls were all below the detectable level. Conclusion This study suggested that hBD-4 plays a significant role in the innate immunity of the lower respiratory tract.

  14. Increased COX-2 expression in epithelial and stromal cells of high mammographic density tissues and in a xenograft model of mammographic density.

    Science.gov (United States)

    Chew, G L; Huo, C W; Huang, D; Hill, P; Cawson, J; Frazer, H; Hopper, J L; Haviv, I; Henderson, M A; Britt, K; Thompson, E W

    2015-08-01

    Mammographic density (MD) adjusted for age and body mass index is one of the strongest known risk factors for breast cancer. Given the high attributable risk of MD for breast cancer, chemoprevention with a safe and available agent that reduces MD and breast cancer risk would be beneficial. Cox-2 has been implicated in MD-related breast cancer risk, and was increased in stromal cells in high MD tissues in one study. Our study assessed differential Cox-2 expression in epithelial and stromal cells in paired samples of high and low MD human breast tissue, and in a validated xenograft biochamber model of MD. We also examined the effects of endocrine treatment upon Cox-2 expression in high and low MD tissues in the MD xenograft model. Paired high and low MD human breast tissue samples were immunostained for Cox-2, then assessed for differential expression and staining intensity in epithelial and stromal cells. High and low MD human breast tissues were separately maintained in biochambers in mice treated with Tamoxifen, oestrogen or placebo implants, then assessed for percentage Cox-2 staining in epithelial and stromal cells. Percentage Cox-2 staining was greater for both epithelial (p = 0.01) and stromal cells (p tissues. In high MD biochamber tissues, percentage Cox-2 staining was greater in stromal cells of oestrogen-treated versus placebo-treated tissues (p = 0.05).

  15. Proteomic patterns analysis with multivariate calculations as a promising tool for prompt differentiation of early stage lung tissue with cancer and unchanged tissue material

    Directory of Open Access Journals (Sweden)

    Grodzki Tomasz

    2011-03-01

    Full Text Available Abstract Background Lung cancer diagnosis in tissue material with commonly used histological techniques is sometimes inconvenient and in a number of cases leads to ambiguous conclusions. Frequently advanced immunostaining techniques have to be employed, yet they are both time consuming and limited. In this study a proteomic approach is presented which may help provide unambiguous pathologic diagnosis of tissue material. Methods Lung tissue material found to be pathologically changed was prepared to isolate proteome with fast and non selective procedure. Isolated peptides and proteins in ranging from 3.5 to 20 kDa were analysed directly using high resolution mass spectrometer (MALDI-TOF/TOF with sinapic acid as a matrix. Recorded complex spectra of a single run were then analyzed with multivariate statistical analysis algorithms (principle component analysis, classification methods. In the applied protocol we focused on obtaining the spectra richest in protein signals constituting a pattern of change within the sample containing detailed information about its protein composition. Advanced statistical methods were to indicate differences between examined groups. Results Obtained results indicate changes in proteome profiles of changed tissues in comparison to physiologically unchanged material (control group which were reflected in the result of principle component analysis (PCA. Points representing spectra of control group were located in different areas of multidimensional space and were less diffused in comparison to cancer tissues. Three different classification algorithms showed recognition capability of 100% regarding classification of examined material into an appropriate group. Conclusion The application of the presented protocol and method enabled finding pathological changes in tissue material regardless of localization and size of abnormalities in the sample volume. Proteomic profile as a complex, rich in signals spectrum of proteins

  16. Prognostic impact of average iodine density assessed by dual-energy spectral imaging for predicting lung tumor recurrence after stereotactic body radiotherapy.

    Science.gov (United States)

    Aoki, Masahiko; Hirose, Katsumi; Sato, Mariko; Akimoto, Hiroyoshi; Kawaguchi, Hideo; Hatayama, Yoshiomi; Fujioka, Ichitaro; Tanaka, Mitsuki; Ono, Shuichi; Takai, Yoshihiro

    2016-07-01

    The purpose of this study was to investigate the prognostic significance of average iodine density as assessed by dual-energy computed tomography (DE-CT) for lung tumors treated with stereotactic body radiotherapy (SBRT). From March 2011 to August 2014, 93 medically inoperable patients with 74 primary lung cancers and 19 lung metastases underwent DE-CT prior to SBRT of a total dose of 45-60 Gy in 5-10 fractions. Of these 93 patients, nine patients had two lung tumors. Thus, 102 lung tumors were included in this study. DE-CT was performed for pretreatment evaluation. Regions of interest were set for the entire tumor, and average iodine density was obtained using a dedicated imaging software and evaluated with regard to local control. The median follow-up period was 23.4 months (range, 1.5-54.5 months). The median value of the average iodine density was 1.86 mg/cm(3) (range, 0.40-9.27 mg/cm(3)). Two-year local control rates for the high and low average iodine density groups divided by the median value of the average iodine density were 96.9% and 75.7% (P = 0.006), respectively. Tumors with lower average iodine density showed a worse prognosis, possibly reflecting a hypoxic cell population in the tumor. The average iodine density exhibited a significant impact on local control. Our preliminary results indicate that iodine density evaluated using dual-energy spectral CT may be a useful, noninvasive and quantitative assessment of radio-resistance caused by presumably hypoxic cell populations in tumors.

  17. Specific detection of Pasteurella multocida in chickens with fowl cholera and in pig lung tissues using fluorescent rRNA in situ hybridization

    DEFF Research Database (Denmark)

    Mbuthia, P.G.; Christensen, H.; Boye, Mette

    2001-01-01

    in formalin-fixed paraffin-embedded lung tissues from experimental fowl cholera in chickens and infections in pigs. In chicken lung tissues P. multocida cells were detected singly, in pairs, as microcolonies, and as massive colonies within air capillaries (septa and lumen), parabronchial septa, and blood...... and fast method for specific detection of P. multocida in histological formalin-fixed tissues. The test was replicable and reproducible and is recommended as a supplementary test for diagnosis and as a tool in pathogenesis studies of fowl cholera and respiratory tract infections in pigs due to P. multocida....

  18. An experimental study of interstitial lung tissue classification in HRCT images using ANN and role of cost functions

    Science.gov (United States)

    Dash, Jatindra K.; Kale, Mandar; Mukhopadhyay, Sudipta; Khandelwal, Niranjan; Prabhakar, Nidhi; Garg, Mandeep; Kalra, Naveen

    2017-03-01

    In this paper, we investigate the effect of the error criteria used during a training phase of the artificial neural network (ANN) on the accuracy of the classifier for classification of lung tissues affected with Interstitial Lung Diseases (ILD). Mean square error (MSE) and the cross-entropy (CE) criteria are chosen being most popular choice in state-of-the-art implementations. The classification experiment performed on the six interstitial lung disease (ILD) patterns viz. Consolidation, Emphysema, Ground Glass Opacity, Micronodules, Fibrosis and Healthy from MedGIFT database. The texture features from an arbitrary region of interest (AROI) are extracted using Gabor filter. Two different neural networks are trained with the scaled conjugate gradient back propagation algorithm with MSE and CE error criteria function respectively for weight updation. Performance is evaluated in terms of average accuracy of these classifiers using 4 fold cross-validation. Each network is trained for five times for each fold with randomly initialized weight vectors and accuracies are computed. Significant improvement in classification accuracy is observed when ANN is trained by using CE (67.27%) as error function compared to MSE (63.60%). Moreover, standard deviation of the classification accuracy for the network trained with CE (6.69) error criteria is found less as compared to network trained with MSE (10.32) criteria.

  19. Identification of differentially expressed genes in lung tissues of nickel-exposed rats using suppression subtractive hybridization.

    Science.gov (United States)

    Zhang, Jing; Zhang, Jun; Fan, Yingying; Liu, Lihong; Li, Mengjie; Zhou, Yang; Shao, Zhihua; Shi, Hongjun; Wang, Ying

    2011-11-01

    Occupational exposure to nickel compound, such as nickel refining, electroplating, and in conjunction with other metals, is harmful to the health, causing respiratory distress, and lung and nasal cancer. In this work, the different gene expression patterns of lung tissues from nickel-exposed rats and controls were investigated. The suppression subtractive hybridization (SSH) method was used to generate two subtracted cDNA libraries with gene transcripts differentially expressed after nickel inducing. Dot-blot hybridizations were used to confirm differential ratios of expression of obtained SSH clones. Out of 768 unique SSH clones, which were chosen randomly from the two subtraction libraries (384 of each), 319 could be verified as differentially expressed. According to blast screening and functional annotation, 28% genes in nickel-induced cDNA library were related to cell differentiation, whereas 21% in driver library were related to oxygen transport. Two novel expressed sequence tags (ESTs; NCBI Accession No. FC809414 and No. FC809411) in nickel-induced cDNA library were obtained. The genes detected in the present study are probably important genes associated with nickel-induced lung cancer.

  20. Airways, vasculature, and interstitial tissue: anatomically informed computational modeling of human lungs for virtual clinical trials

    Science.gov (United States)

    Abadi, Ehsan; Sturgeon, Gregory M.; Agasthya, Greeshma; Harrawood, Brian; Hoeschen, Christoph; Kapadia, Anuj; Segars, W. P.; Samei, Ehsan

    2017-03-01

    This study aimed to model virtual human lung phantoms including both non-parenchymal and parenchymal structures. Initial branches of the non-parenchymal structures (airways, arteries, and veins) were segmented from anatomical data in each lobe separately. A volume-filling branching algorithm was utilized to grow the higher generations of the airways and vessels to the level of terminal branches. The diameters of the airways and vessels were estimated using established relationships between flow rates and diameters. The parenchyma was modeled based on secondary pulmonary lobule units. Polyhedral shapes with variable sizes were modeled, and the borders were assigned to interlobular septa. A heterogeneous background was added inside these units using a non-parametric texture synthesis algorithm which was informed by a high-resolution CT lung specimen dataset. A voxelized based CT simulator was developed to create synthetic helical CT images of the phantom with different pitch values. Results showed the progressive degradation in depiction of lung details with increased pitch. Overall, the enhanced lung models combined with the XCAT phantoms prove to provide a powerful toolset to perform virtual clinical trials in the context of thoracic imaging. Such trials, not practical using clinical datasets or simplistic phantoms, can quantitatively evaluate and optimize advanced imaging techniques towards patient-based care.

  1. Primary thymic mucosa-associated lymphoid tissue lymphoma with multiple thin walled lung cysts: case report and literature review

    Institute of Scientific and Technical Information of China (English)

    Lung-Yun Kang; Szu-Pei Ho; Yi-Pin Chou

    2013-01-01

    Mucosa-associated lymphoid tissue (MALT) lymphoma of the thymus is rare.We reported a case of a 37-year-old Chinese female with Sj(o)gren's syndrome and hyperglobulinemia.She suffered from chronic cough for 3 weeks.Chest computed tomography (CT) demonstrated a multiloculated cystic mass in mediastinum prevascular space and multiple lung cysts.Laboratory exam of autoimmune markers showed positive of antinuclear antibody (ANA),Sj(o)gren's syndrome A (SSA),Sj(o)gren's syndrome B (SSB),and rheumatoid factors (RF).Thymectomy with lymph node dissection was performed.The pathology report revealed thymic extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue.Under immunohistochemical stains,CD20 and Bcl-2 were positive.No evidence of recurrence of disease was found.

  2. Matrix metalloproteinases-2, -9 and tissue inhibitor of metallo-proteinase-1 in lung cancer invasion and metastasis

    Institute of Scientific and Technical Information of China (English)

    MING Shu-hong; SUN Tie-ying; XIAO Wei; XU Xiao-mao

    2005-01-01

    @@ Lung cancer is a major cause of death from malignant disease due to its high incidence, malignant behavior and lack of major advancements in treatment strategies. The ability to invade tissues and establish colonies at remote sites is a defining characteristic of malignant neoplasms. Matrix metalloproteinases (MMPs) are zinc proteinases that degrade compounds of extracellular matrix (ECM). These enzymes have been implicated in tumour invasion and metastasis through degrading many extracellular matrix proteins especially MMP-2 and MMP-9, which are regarded as markers of tumour invasion and metastasis.1 The purpose of this study is to examine the role of MMP-9, MMP-2, tissue inhibitor of metalloproteinase-1 (TIMP-1) and MMP-9/TIMP-1 in tumour invasion and metastasis as well as the relationships between the mRNA expression of MMP-9 in white blood cells and MMP-9 levels in the plasma.

  3. Systematic comparison of RNA extraction techniques from frozen and fresh lung tissues: checkpoint towards gene expression studies

    Directory of Open Access Journals (Sweden)

    Seifart Carola

    2009-03-01

    Full Text Available Abstract Background The reliability of gene expression profiling-based technologies to detect transcriptional differences representative of the original samples is affected by the quality of the extracted RNA. It strictly depends upon the technique that has been employed. Hence, the present study aimed at systematically comparing silica-gel column (SGC and guanidine isothiocyanate (GTC techniques of RNA isolation to answer the question which technique is preferable when frozen, long-term stored or fresh lung tissues have to be evaluated for the downstream molecular analysis. Methods Frozen lungs (n = 3 were prepared by long-term storage (2.5 yrs in -80°C while fresh lungs (n = 3 were harvested and processed immediately. The purity and quantification of RNA was determined with a spectrophotometer whereas the total amounted copy numbers of target sequences were determined with iCycler detection system for assessment of RNA intactness (28S and 18S and fragment sizes, i.e. short (GAPDH-3' UTR, medium (GAPDH, and long (PBGD with 200 bp, 700 bp, and 1400 bp distance to the 3'ends of mRNA motif, respectively. Results Total yield of RNA was higher with GTC than SGC technique in frozen as well as fresh tissues while the purity of RNA remained comparable. The quantitative reverse transcriptase-polymerase chain reaction data revealed that higher mean copy numbers of 28S and a longer fragment (1400 bp were obtained from RNA isolated with SGC than GTC technique using fresh as well as frozen tissues. Additionally, a high mean copy number of 18S and medium fragment (700 bp were obtained in RNA isolated with SGC technique from fresh tissues, only. For the shorter fragment, no significant differences between both techniques were noticed. Conclusion Our data demonstrated that although the GTC technique has yielded a higher amount of RNA, the SGC technique was much more superior with respect to the reliable generation of an intact RNA and effectively amplified

  4. Expression of hENTl and ERCC1 genes in tumor tissues non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Jia-Jia Wu; Shun-Chang Jiao

    2013-01-01

    Objective:To investigate the expression of hENTl andERCC1 genes in tumor tissues non-small cell lung cancer(NSCLC).Methods:Fresh non-small lung cancer specimens were transplanted into nude mice.Twenty mice were randomized into two groups: experimental group receiving gemcitabine plus cisplatin and control group receiving0.9% physiological saline.The expressions of hENTl andERCC1 mRNA in tumor tissue were detected by real-time fluorescent quantitative PCR.The volume of tumor, the weight of nude mice and tumor volume were respectively measured and calculated2-3 times per week.Tissue samples were collected fromNSCLC mice treated with gemcitabine plus carboplatin.Results:The histological examination showed that many tumor cells were well preserved in nude mice.The rate of transplanted tumor cells was 86.7%.The concomitant treatment study showed that the rate ofTV,RTV,T/C inGEM+DDP group was the lowest.LBP+DOC,DDP+DOC obviously influenced the body weight.Compared with NS group,DDP group,GEM group, the survival period and the level of hENTl ofDDP+GEM group increased obviously, the level ofERCC1 decreased significantly(P<0.05).Conclusions:The expression of hENT1 andERCC1 genes in tumor tissues were closely correlated with the response to chemotherapy and prognosis of patients withNSCLC treated with gemcitabine plus cisplatin.

  5. Expression of Nitric Oxide Synthase Isoenzyme in Lung Tissue of Smokers with and without Chronic Obstructive Pulmonary Disease

    Directory of Open Access Journals (Sweden)

    Wen-Ting Jiang

    2015-01-01

    Full Text Available Background: It has been demonstrated that only 10%-20% cigarette smokers finally suffer chronic obstructive pulmonary disease (COPD. The underlying mechanism of development remains uncertain so far. Nitric oxide (NO has been found to be closely associated with the pathogenesis of COPD, the alteration of NO synthase (NOS expression need to be revealed. The study aimed to investigate the alterations of NOS isoforms expressions between smokers with and without COPD, which might be helpful for identifying the susceptibility of smokers developing into COPD. Methods: Peripheral lung tissues were obtained from 10 nonsmoker control subjects, 15 non-COPD smokers, and 15 smokers with COPD. Neuronal NOS (nNOS, inducible NOS (iNOS, and endothelial NOS (eNOS mRNA and protein levels were measured in each sample by using real-time polymerase chain reaction and Western blotting. Results: INOS mRNA was significantly increased in patients with COPD compared with nonsmokers and smokers with normal lung function (P < 0.001, P = 0.001, respectively. iNOS protein was also higher in COPD patients than nonsmokers and smokers with normal lung function (P < 0.01 and P = 0.01, respectively. However, expressions of nNOS and eNOS did not differ among nonsmokers, smokers with and without COPD. Furthermore, there was a negative correlation between iNOS protein level and lung function parameters forced expiratory volume in 1 s (FEV 1 (% predicted (r = −0.549, P = 0.001 and FEV 1 /forced vital capacity (%, r = −0.535, P = 0.001. Conclusions: The expression of iNOS significantly increased in smokers with COPD compared with that in nonsmokers or smokers without COPD. The results suggest that iNOS might be involved in the pathogenesis of COPD, and may be a potential marker to identify the smokers who have more liability to suffer COPD.

  6. A study of effective atomic number and electron density of gel dosimeters and human tissues for scattering of gamma rays: momentum transfer, energy and scattering angle dependence.

    Science.gov (United States)

    Kurudirek, Murat

    2016-11-01

    The objective of this work was to study water- and tissue-equivalent properties of some gel dosimeters, human tissues and water, for scattering of photons using the effective atomic number (Z eff). The Rayleigh to Compton scattering ratio (R/C) was used to obtain Z eff and electron density (N e ) of gel dosimeters, human tissues and water considering a 10(-2)-10(9) momentum transfer, q (Å(-1)). In the present work, a logarithmic interpolation procedure was used to estimate R/C as well as Z eff of the chosen materials in a wide scattering angle (1°-180°) and energy range (0.001-100 MeV). The Z eff of the chosen materials was found to increase as momentum transfer increases, for q > ~1 Å(-1). At fixed scattering angle and energy, Z eff of the material first increases and then becomes constant for high momentum transfers (q ≥ 3 Å(-1)), which indicates that Z eff is almost independent of energy and scattering angle for the chosen materials. Based on the Z eff data and the continuous momentum transfer range (10(-2)-10(9) Å(-1)), MAGIC, PAGAT and soft tissue were found to be water-equivalent materials, since their differences (%) relative to water are significantly low (≤3.2 % for MAGIC up to 10(3) Å(-1), ≤2.9 % for PAGAT up to 10(9) Å(-1), and ≤3.8 % for soft tissue up to 10(9) Å(-1)), while the Fricke gel was not found to be water equivalent. PAGAT was found to be a soft tissue-equivalent material in the entire momentum transfer range (<4.3 %), while MAGAT has shown to be tissue equivalent for brain (≤8.1 % up to 10 Å(-1)) and lung (<8.2 % up to 10 Å(-1)) tissues. The Fricke gel dosimeter has shown to be adipose tissue equivalent for most of the momentum range considered (<10 %).

  7. Lungs, bone marrow, and adipose tissue. A network approach to the pathobiology of chronic obstructive pulmonary disease.

    Science.gov (United States)

    Agustí, Alvar; Barberà, Joan A; Wouters, Emiel F M; Peinado, Victor I; Jeffery, Peter K

    2013-12-15

    Patients with chronic obstructive pulmonary disease (COPD) often suffer other concomitant disorders, such as cardiovascular diseases and metabolic disorders, that influence significantly (and independently of lung function) their health status and prognosis. Thus, COPD is not a single organ condition, and disturbances of a complex network of interorgan connected responses occur and modulate the natural history of the disease. Here, we propose a novel hypothesis that considers a vascularly connected network with (1) the lungs as the main external sensor of the system and a major source of "danger signals"; (2) the endothelium as an internal sensor of the system (also a potential target tissue); and (3) two key responding elements, bone marrow and adipose tissue, which produce both inflammatory and repair signals. According to the model, the development of COPD, and associated multimorbidities (here we focus on cardiovascular disease as an important example), depend on the manner in which the vascular connected network responds, adapts, or fails to adapt (dictated by the genetic and epigenetic background of the individual) to the inhalation of particles and gases, mainly in cigarette smoke. The caveats and limitations of the hypothesis, as well as the experimental and clinical research needed to test and explore the proposed model, are also briefly discussed.

  8. Assessment of Control Tissue for Gene and Protein Expression Studies: A Comparison of Three Alternative Lung Sources

    Directory of Open Access Journals (Sweden)

    Margaret R. Passmore

    2012-01-01

    Full Text Available The use of an appropriate control group in human research is essential in investigating the level of a pathological disorder. This study aimed to compare three alternative sources of control lung tissue and to determine their suitability for gene and protein expression studies. Gene and protein expression levels of the vascular endothelial growth factor (VEGF and gelatinase families and their receptors were measured using real-time reverse transcription polymerase chain reaction (RT-PCR and immunohistochemistry. The gene expression levels of VEGFA, placental growth factor (PGF, and their receptors, fms-related tyrosine kinase 1 (FLT1, and kinase insert domain receptor (KDR as well as matrix metalloproteinase-2 (MMP-2 and the inhibitors, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1 and TIMP-2 were significantly higher in lung cancer resections. The gene expression level of MMP-9 was significantly lower in the corresponding samples. Altered protein expression was also detected, depending on the area assessed. The results of this study show that none of the three control groups studied are completely suitable for gene and protein studies associated with the VEGF and gelatinase families, highlighting the need for researchers to be selective in which controls they opt for.

  9. Swarm rat chondrosarcoma cells as an in vivo model: lung colonization and effects of tissue environment on tumor growth.

    Science.gov (United States)

    Morcuende, Jose A; Stevens, Jeff W; Scheetz, Todd E; de Fatima Bonaldoc, Maria; Casavant, Thomas L; Otero, Jesse E; Soares, Marcelo B

    2012-01-01

    Swarm rat chondrosarcoma cells have been used extensively for biochemical studies of extra-cellular matrix metabolism in cartilage. However, these cells also possess tumor-like behavior in vivo and are useful in investigation of chondrosarcoma biology. the current study was designed to develop a metastatic model using swarm rat chondrosarcoma cells, and to assess the effect of tissue-environment on tumor behavior in vivo. Tumors were implanted subcutaneously or into bone, and animals were assessed radiographically and microscopically for tumor growth and metastasis. The subcutaneous tumor grew to an average mass of 35 g, while tumor implanted into bone grew 75 mg. Transplantation of the cells into the bone led to extensive bone remodeling with invasion of the medullary cavity and destruction of the bone cortex. Light microscopy demonstrated no significant differences in the number of mitoses, cellular atypia or extracellular matrix staining between the two sites of tumor implantation. Interestingly, lung colonization was observed in none of the animals in the subcutaneous tumor injection group, while tumors colonized the lungs in 95% of the rats with tumor injected into bone. Analysis of cDNA libraries from subcutaneous and bone-transplanted tumors demonstrated a complex and diverse array of expressed transcripts, and there were significant differences in gene expression between tumors at different sites. The results of this study suggest swarm rat chondrosarcoma is a model that resembles human chondrosarcoma mimicking its ability to infiltrate and remodel local bone and to colonize the lungs. Furthermore, the interaction between host-tissue and tumor cells plays a major role in the tumor behavior in this model. Identifying these interactions will lead to further understanding of chondrosarcoma and contribute to therapeutic targets in the future.

  10. Study of Different Tissue Density Effects on the Dose Distribution of a 103Pd Brachytherapy Source Model MED3633

    Directory of Open Access Journals (Sweden)

    Ali Asghar Mowlavi

    2010-09-01

    Full Text Available Introduction: Clinical application of encapsulated radioactive brachytherapy sources has a major role in cancer treatment. In the present research, the effects of different tissue densities on the dose distribution of a 103Pd brachytherapy source in a spherical phantom of 50 cm radius have been studied. Material and Methods: As is well known, absorbed dose in tissue depends to its density, but this difference is not clear in measurements. Therefore, we applied the MCNP code to evaluate the effect of density on the dose distribution. 103Pd brachytherapy sources are used to treat prostate, breast and other cancers. Results: Absorbed dose has been calculated and presented around a source placed in the center of the phantom for different tissue densities. Also, we derived anisotropy and radial dose functions and compared our Monte Carlo results with experimental results of Rivard and Li et al. for F(1, θ and g(r in 1.040 g/cm3 tissue. Conclusion: The results of this study show that relative dose variations around the source center are very considerable at different densities, because of the presence of a photoabsorber (Au-Cu alloy in the source core. Dose variation exceeds 80% at the point (Z = 2.4 mm, Y = 0 mm. Computed values of anisotropy and radial dose functions are in good agreement with the experimental results of Rivard and Li et al.

  11. Weight preserving image registration for monitoring disease progression in lung CT

    DEFF Research Database (Denmark)

    Gorbunova, Vladlena; Lo, Pechin Chien Pau; Haseem, Ashraf

    2008-01-01

    the density of lung tissue with respect to local expansion or compression such that the total weight of the lungs is preserved during deformation. Our method provides a good estimation of regional destruction of lung tissue for subjects with a significant difference in inspiration level between CT scans...... compared with intensities in the deformed baseline image indicate local loss of lung tissue that is associated with progression of emphysema. To account for differences in lung intensity owing to differences in the inspiration level in the two scans rather than disease progression, we propose to adjust...

  12. Magnesium intake mediates the association between bone mineral density and lean soft tissue in elite swimmers.

    Science.gov (United States)

    Matias, Catarina N; Santos, Diana A; Monteiro, Cristina P; Vasco, Ana M; Baptista, Fátima; Sardinha, Luís B; Laires, Maria J; Silva, Analiza M

    2012-01-01

    Magnesium (Mg) deficiency has been associated with bone disorders. Physical activity is also crucial for bone mineralization. Bone mass loss has been observed to be accelerated in subjects with low Mg intake. We aim to understand if Mg intake mediates the association between bone mineral density (BMD) and lean soft tissue (LST) in elite swimmers. Seventeen elite swimmers (eight males; nine females) were evaluated. Bone mineral content, BMD, LST, and fat mass were assessed using dual energy X-ray absorptiometry. Energy and nutrient intake were assessed during a seven-day period and analyzed with Food Processor SQL. Males presented lower values than the normative data for BMD. Mg, phosphorus (P) and vitamin D intake were significantly lower than the recommended daily allowance. A linear regression model demonstrated a significant association between LST and BMD. When Mg intake was included, we observed that this was a significant, independent predictor of BMD, with a significant increase of 24% in the R(2) of the initial predictive model. When adjusted for energy, vitamin D, calcium, and P intake, Mg remained a significant predictor of BMD. In conclusion, young athletes engaged in low impact sports, should pay special attention to Mg intake, given its potential role in bone mineral mass acquisition during growth.

  13. Detection of soft tissue densities from digital breast tomosynthesis: comparison of conventional and deep learning approaches

    Science.gov (United States)

    Fotin, Sergei V.; Yin, Yin; Haldankar, Hrishikesh; Hoffmeister, Jeffrey W.; Periaswamy, Senthil

    2016-03-01

    Computer-aided detection (CAD) has been used in screening mammography for many years and is likely to be utilized for digital breast tomosynthesis (DBT). Higher detection performance is desirable as it may have an impact on radiologist's decisions and clinical outcomes. Recently the algorithms based on deep convolutional architectures have been shown to achieve state of the art performance in object classification and detection. Similarly, we trained a deep convolutional neural network directly on patches sampled from two-dimensional mammography and reconstructed DBT volumes and compared its performance to a conventional CAD algorithm that is based on computation and classification of hand-engineered features. The detection performance was evaluated on the independent test set of 344 DBT reconstructions (GE SenoClaire 3D, iterative reconstruction algorithm) containing 328 suspicious and 115 malignant soft tissue densities including masses and architectural distortions. Detection sensitivity was measured on a region of interest (ROI) basis at the rate of five detection marks per volume. Moving from conventional to deep learning approach resulted in increase of ROI sensitivity from 0:832 +/- 0:040 to 0:893 +/- 0:033 for suspicious ROIs; and from 0:852 +/- 0:065 to 0:930 +/- 0:046 for malignant ROIs. These results indicate the high utility of deep feature learning in the analysis of DBT data and high potential of the method for broader medical image analysis tasks.

  14. [The receptor-mediated endocytosis of influenza viruses and low-density lipoproteins by tissue cells].

    Science.gov (United States)

    Pleskov, V M; Bannikov, A I; Zaĭtsev, Iu V

    1994-01-01

    The experimental data obtained by immunological, immunomorphological, biochemical, and virological methods are presented which substantiate a concept that various strains of influenza virus under study may penetrate tissue cells at sites of high affinity usually meant for low-density lipoproteins (LDLP) providing the cells with cholesterol for construction of outer and inner membranes. A computer analysis of a bank of data on the primary structure of proteins (the package of GENBER programme) revealed significant similarity of amino acid sequences between the area of viral hemagglutinin site attachment to cells and corresponding amino acids comprising apoB LDLP. The presented proofs are a convincing example of virus particles mimicry realized at the molecular level and give new concepts concerning the mechanisms of virus penetration into body cells which are important for the development of a principally new approach to creation of highly effective antiviral compounds. Moreover, the observed phenomenon may serve for explanation of the nature and mechanism of action of the so-called thermostable virus-neutralizing blood serum inhibitor.

  15. Evaluation of low density array technology for quantitative parallel measurement of multiple genes in human tissue

    Directory of Open Access Journals (Sweden)

    Harmer Daniel W

    2006-02-01

    Full Text Available Abstract Background Low density arrays (LDAs have recently been introduced as a novel approach to gene expression profiling. Based on real time quantitative RT-PCR (QRT-PCR, these arrays enable a more focused and sensitive approach to the study of gene expression than gene chips, while offering higher throughput than more established approaches to QRT-PCR. We have now evaluated LDAs as a means of determining the expression of multiple genes simultaneously in human tissues and cells. Results Comparisons between LDAs reveal low variability, with correlation coefficients close to 1. By performing 2-fold and 10-fold serial dilutions of cDNA samples in the LDAs we determined a clear linear relationship between the gene expression data points over 5 orders of magnitude. We also showed that it is possible to use LDAs to accurately and quantitatively detect 2-fold changes in target copy number as well as measuring genes that are expressed with low and high copy numbers in the range of 1 × 102 – 1 × 106 copies. Furthermore, the data generated by the LDA from a cell based pharmacological study were comparable to data generated by conventional QRT-PCR. Conclusion LDAs represent a valuable new approach for sensitive and quantitative gene expression profiling.

  16. Effects of quorum sensing system lasR/rhlR gene on the expression of Foxp3, TGF-β1 and IL-10 of lung tissue in tracheal intubation model rat with Pseudomonas aeruginosa biofilm infection

    Directory of Open Access Journals (Sweden)

    Qing-qing XIANG

    2016-03-01

    Full Text Available Objective  To investigate the effects of lasR/rhlR gene on Foxp3, TGF-β1 and IL-10 of lung tissue in rat tracheal intubation model with biofilm infection of Pseudomonas aeruginosa (Ps. aer wild strain (PAO1 and quorum sensing (QS deficient strain (ΔlasRΔrhlR. Methods  Twenty-one SD rats were randomly assigned into 3 groups (7 each: ΔlasRΔrhlR-treated group, PAO1-treated group and sterile control group. Biofilms (BF were cultured in vitro, and the BF coated tube (infected respectively with Ps. aer PAO1 strain, ΔlasRΔrhlR strain, or with asepsis was inserted into the trachea to establish the rat model. The rats were sacrificed on the 7th day after intubation. Colony count of lung tissue homogenate (cfu and lung HE staining were performed, and IL-10 content in bronchoalveolar lavage fluid (BALF, TGF-β1 in lung tissue, and the expression of Foxp3 mRNA in lung cells were determined. Results  The bacterial counts were significantly higher in PAO1 and ΔlasRΔrhlR groups than that in sterile control group, and the counts were obviously higher in PAO1 group (10 400.00±6313.70/g lung tissue than that in ΔlasRΔrhlR group (975.00±559.97/g lung tissue, P<0.05. There was no significant pathological changes in lung tissue in sterile control group, while the bronchi and blood vessels in PAO1 group were infiltrated by a large number of inflammatory cells and complicated with alveolar septum thickening and local abscess and necrosis. The pathological changes were milder in ΔlasRΔrhlR group than in PAO1 group; the expression of Foxp3 mRNA was higher in the two Ps. aer infected groups than that in sterile control group (0.65±0.32, and it was significantly higher in PAO1 group (4.62±1.07 than in ΔlasRΔrhlR group (2.15±1.43, P<0.05. The accumulated optical density value of TGF-β1 was significantly higher in the two Ps. aer infected groups than in sterile control group (3721.66±1412.95, and significantly higher in PAO1 group (65 090.56±33

  17. Tailoring treatment of nonsmall cell lung cancer by tissue type: role of pemetrexed

    Directory of Open Access Journals (Sweden)

    Steven F Powell

    2009-06-01

    Full Text Available Steven F Powell1, Arkadiusz Z Dudek21Department of Medicine, University of Minnesota, Minneapolis, MN, USA; 2Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, USAAbstract: Pemetrexed (ALIMTA, LY231514, MTA is a novel multitargeted antifolate that is currently approved for the treatment of metastatic nonsmall cell lung cancer (NSCLC. Recent evidence reveals that the drug’s efficacy is limited to nonsquamous lung cancer histology. As we further understand the drug’s mechanisms of action, new genomic and proteomic evidence is shedding light on why some patients respond while others do not. The first goal of this review is to briefly review pemetrexed’s mechanism of action, resistance patterns, toxicity profile, and pharmacokinetics. We will also review the clinical trials that led to its use in NSCLC, with special attention to data showing that pemetrexed has greater efficacy in nonsquamous histologies of NSCLC. Furthermore, we will discuss the hypotheses for the genomic and proteomic basis for this variation in efficacy. Finally, we will report the future directions for pemetrexed as a personalized agent for nonsquamous NSCLC.Keywords: nonsmall cell lung cancer, pemetrexed, antifoliate

  18. Strategies for lung regeneration

    Directory of Open Access Journals (Sweden)

    Thomas H. Petersen

    2011-05-01

    Full Text Available Due to the limited ability of the adult lung to regenerate and the frequency of lung disease, the lung is a tissue that can especially benefit from regenerative medicine. Prospects for lung regeneration have made great strides in the past year. In this review, we summarize recent progress and key challenges for approaches in lung regenerative medicine. With a focus on the matrix components critical for the development of regenerative lung tissues, we discuss possible cell sources for lung regeneration, key matrix effects on cell repopulation, and physical stimuli that will aid in the growth of lung tissues in vitro.

  19. Biological Significance and the Related Molecular Mechanism of Ets1 mRNA Expression in Lung Cancer by Tissue Microarray (TMA)

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To investigate the expressions and molecular mechanism of Ets-1 mRNA, and TGFβ1 and c-Met proteins in the pathogenesis, progression of lung cancer by tissue microarray (TMA) method. Methods: The expressions of Ets-1 mRNA, and TGFβ1 and c-Met proteins were detected in 89 primary lung cancers, 12 lung cancer with lymph-node metastasis and 12 precancerous lesions by FISH(fluorescence in situ hybridization) and immunohistochemical method, and 10 normal lung tissues were used as controls. Results: The expressions of Ets-1 mRNA, and TGFβ1 and c-Met proteins were significantly higher in 89 primary lung cancer than in the control group (P<0.05). The expressions of Ets-1 mRNA, and TGFβ1 and c-Met proteins were related to lymph node metastasis and clinical stages. There was a positive correlation between the Ets-1 mRNA expression and TGFβ1 and c-Met proteins (P<0.05). Conclusion: Ets-1 mRNA, TGFβ1 and c-Met proteins may be related to the pathogenesis, progression and malignant behavior of lung cancer. They may play an important role in prognosis assessment of lung cancer.

  20. X-ray diffraction enhanced imaging as a novel method to visualize low-density scaffolds in soft tissue engineering.

    Science.gov (United States)

    Zhu, Ning; Chapman, Dean; Cooper, David; Schreyer, David J; Chen, Xiongbiao

    2011-11-01

    Scaffold visualization is challenging yet essential to the success of various tissue engineering applications. The aim of this study was to explore the potential of X-ray diffraction enhanced imaging (DEI) as a novel method for the visualization of low density engineered scaffolds in soft tissue. Imaging of the scaffolds made from poly(L-lactide) (PLLA) and chitosan was conducted using synchrotron radiation-based radiography, in-line phase-contrast imaging (in-line PCI), and DEI techniques as well as laboratory-based radiography. Scaffolds were visualized in air, water, and rat muscle tissue. Compared with the images from X-ray radiography and in-line PCI techniques, DEI images more clearly show the structure of the low density scaffold in air and have enhanced image contrast. DEI was the only technique able to visualize scaffolds embedded in unstained muscle tissue; this method could also define the microstructure of muscle tissue in the boundary areas. At a photon energy of 20 KeV, DEI had the capacity to image PLLA/chitosan scaffolds in soft tissue with a sample thickness of up to 4 cm. The DEI technique can be applied at high X-ray energies, thus facilitating lower in vivo radiation doses to tissues during imaging as compared to conventional radiography.

  1. Local Tumor Control and Normal Tissue Toxicity of Pulsed Low-Dose Rate Radiotherapy for Recurrent Lung Cancer

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    Peng Zhang

    2015-05-01

    Full Text Available Objectives: This study investigates (1 local tumor control and (2 normal tissue toxicity of pulsed low-dose rate radiotherapy (PLDR for recurrent lung cancer. Methods: For study 1, nude mice were implanted with A549 tumors and divided into the following 3 groups: (1 control (n = 10, (2 conventional radiotherapy (RT; n = 10, and (3 PLDR (n = 10. Tumor-bearing mice received 2 Gy daily dose for 2 consecutive days. Weekly magnetic resonance imaging was used for tumor growth monitoring. For study 2, 20 mice received 8 Gy total body irradiation either continuously (n = 10 or 40 × 0.2 Gy pulses with 3-minute intervals (n = 10. Results: For study 1, both conventional RT and PLDR significantly inhibited the growth of A549 xenografts compared with the control group (>35% difference in the mean tumor volume; P .05. For study 2, the average weight was 20.94 ± 1.68 g and 25.69 ± 1.27 g and the survival time was 8 days and 12 days for mice treated with conventional RT and PLDR (P < .05, respectively. Conclusion: This study showed that PLDR could control A549 tumors as effectively as conventional RT, and PLDR induced much less normal tissue toxicity than conventional RT. Thus, PLDR would be a good modality for recurrent lung cancers. Advances in Knowledge: This article reports our results of an in vivo animal investigation of PLDR for the treatment of recurrent cancers, which may not be eligible for treatment because of the dose limitations on nearby healthy organs that have been irradiated in previous treatments. This was the first in vivo study to quantify the tumor control and normal tissue toxicities of PLDR using mice with implanted tumors, and our findings provided evidence to support the clinical trials that employ PLDR treatment techniques.

  2. Laser resection of lung tissue: heat accumulation from adjacent laser application and how to cool it down.

    Science.gov (United States)

    Kirschbaum, Andreas; Rexin, Peter; Pehl, Anika; Bartsch, Detlef; Quint, Karl

    2014-06-01

    Heat accumulation might induce thermal damage of the surrounding lung tissue, especially when multiple lesions are resected in one session. The present study aimed to investigate whether heat accumulates in the immediate vicinity of the resection surface and leads to thermal damage of the lung parenchyma, and what is the most effective cooling strategy in this situation. In normothermic perfused paracardial swine lobes (n = 6), four punctiform laser lesions forming a square were created. Each lesion was lasered at a power of 100 W for 5 seconds. Two test conditions with square sides of either 1.0 or 0.5 cm were compared. Temperatures were recorded immediately after completing the laser procedure in the square center and in the corners using a thermal camera and continued during the cooling process at 10-second intervals until normothermia (37°C). We examined two cooling methods: rinsing with ice-cold (4°C) Ringer solution during the laser procedure (group B, n = 6) or submerging the lung in ice-cold water for 5 seconds immediately after laser application (group C, n = 6). In the control group A (n = 6), there was no cooling. In the 0.5 cm squares, mean temperature in the center immediately after laser application was 103.17 ± 8.56°C, significantly higher than in the corners (76.39 ± 2.87°C, p Laser application to the lung parenchyma causes considerable heat accumulation in closely related lesions. To prevent such cell damage, a distance of at least 1.0 cm between laser targets should be maintained. If no topical cooling method applied, sufficient time for spontaneous tissue cooling before additional laser application should be provided. The most effective cooling strategy against heat accumulation is submerging in ice-cold water for at least 5 seconds. Georg Thieme Verlag KG Stuttgart · New York.

  3. Mineral density and biomechanical properties of bone tissue from male Arctic foxes (Vulpes lagopus) exposed to organochlorine contaminants and emaciation

    DEFF Research Database (Denmark)

    Sonne, Christian; Wolkers, Hans; Rigét, Frank F;

    2008-01-01

    We investigated the impact from dietary OC (organochlorine) exposure and restricted feeding (emaciation) on bone mineral density (BMD; g hydroxy-apatite cm(-2)) in femoral, vertebrate, skull and baculum osteoid tissue from farmed Arctic blue foxes (Vulpes lagopus). For femur, also biomechanical...

  4. Determination of phagocytic functions of macrophages,vascular density and NPY-nerve within autotransplanted splenic tissue in adult rats

    Institute of Scientific and Technical Information of China (English)

    JIANG Deng-jin; GUO Guang-jin; ZHANG Kun; LAN Yang-jun; WANG Lin; ZHANG Tian-fei; ZUO Yan-fang

    2004-01-01

    Abstract Objective: To estimate directly phagocytic functions of the macrophages because of the importance in innate immunity, determine blood vessel density and re-innervation density which are basis of function. Methods: Eighty adult Wistar rats were randomly divided into experimental and control groups. The formers underwent splenotomy and a half splenic slice was transplanted into greater omentum. The latter only moved. After 6 months, examination was made as follows: ① After injection of 0.4% carbon particles by vein, splenic tissues were taken out at different times for estimating phagocytosis by light microscope. ② When splenic tissues had been intubated into left ventricle under total anesthesia, animals were perfused by formalin and India ink mixture suspension. Splenic tissues were taken out for making sections for measurement of area density of blood vessels. ③ Immunohistochemical procedure was used for detecting neuropeptide Y (NPY). Results: Phagocytic functions had no difference between two groups, but the area density of blood vessels and NPY-positive fibers redued ( P < 0.01 ) in experimental group. Conclusion: Autotransplanted splenic tissues show good innate immunity though regeneration of blood vessels and nerves do not reach normal level.

  5. FIB-SEM imaging of carbon nanotubes in mouse lung tissue

    DEFF Research Database (Denmark)

    Købler, Carsten; Saber, Anne Thoustrup; Jacobsen, Nicklas Raun

    2014-01-01

    Ultrastructural characterisation is important for understanding carbon nanotube (CNT) toxicity and how the CNTs interact with cells and tissues. The standard method for this involves using transmission electron microscopy (TEM). However, in particular, the sample preparation, using a microtome...

  6. 关注结缔组织病相关问质性肺疾病%Focus on connective tissue disease-associated interstitial lung disease

    Institute of Scientific and Technical Information of China (English)

    孙耕耘

    2012-01-01

    @@ 结缔组织病(connective tissues disease,CTD)是风湿性疾病中的一大类,常累及全身多个系统,表现为慢性炎症性自身免疫病,当侵犯呼吸系统时,可出现间质性肺疾病(interstitial lung disease,ILD)、胸膜炎和肺动脉高压等,见表l.CTD与ILD同时存在时,常称为结缔组织病相关间质性肺疾病(connective tissues disease-interstitial lung disease,CTD-ILD).

  7. Tissue sites of degradation of high density lipoprotein apolipoprotein A-IV in rats

    Energy Technology Data Exchange (ETDEWEB)

    Dallinga-Thie, G.M.; Van ' t Hooft, F.M.; Van Tol, A.

    1986-05-01

    The in vivo metabolism of high density lipoprotein (HDL), labeled by incorporation of /sup 125/I-apolipoprotein (apo) A-IV, was studied in the rat and compared with the metabolism of HDL labeled with 131I-apo A-I. The /sup 125/I-apo A-IV labeled HDL was obtained by adding small amounts of radioiodinated apo A-IV to rat serum, followed by separation of the different lipoprotein fractions by chromatography on 6% agarose columns in order to avoid stripping of apolipoproteins by ultracentrifugation. Under both in vitro and in vivo conditions, the /sup 125/I-apo A-IV remained an integral component of HDL and was not exchanged to other lipoproteins, including the free apo A-IV fraction. The serum half-life, measured at between 8 and 28 hours after intravenous injection of labeled HDL, was 8.5 +/- 0.5 hours for HDL apo A-IV and 10.2 +/- 0.7 hours for HDL apo A-I. The tissue sites of catabolism of HDL apo A-IV and HDL apo A-I were analyzed in the leupeptin-model. Only the kidneys and liver showed a significant leupeptin-dependent accumulation of radioactivity. At 4 hours after injection of 125I-apo A-IV/131I-apo A-I labeled HDL, 3.5% +/- 1.0% and 8.4% +/- 2.0% of HDL apo A-IV and 4.6% +/- 1.3% and 2.6% +/- 0.6% of the HDL apo A-I were accumulated in a leupeptin-dependent process in the kidneys and liver, respectively. Immunocytochemical studies revealed that the renal localization of apo A-IV was intracellular and confined to the epithelial cells of the proximal tubuli.

  8. The association between breast tissue optical content and mammographic density in pre- and post-menopausal women.

    Directory of Open Access Journals (Sweden)

    Kristina M Blackmore

    Full Text Available Mammographic density (MD, associated with higher water and lower fat content in the breast, is strongly related to breast cancer risk. Optical attenuation spectroscopy (OS is a non-imaging method of evaluating breast tissue composition by red and near-infrared light transmitted through the breast that, unlike mammography, does not involve radiation. OS provides information on wavelength dependent light scattering of tissue and on absorption by water, lipid, oxy-, deoxy-hemoglobin. We propose that OS could be an alternative marker of breast cancer risk and that OS breast tissue measures will be associated with MD. In the present analysis, we developed an algorithm to estimate breast tissue composition and light scattering parameters using a spectrally constrained global fitting procedure employing a diffuse light transport model. OS measurements were obtained from 202 pre- and post-menopausal women with normal mammograms. Percent density (PD and dense area (DA were measured using Cumulus. The association between OS tissue composition and PD and DA was analyzed using linear regression adjusted for body mass index. Among pre-menopausal women, lipid content was significantly inversely associated with square root transformed PD (β = -0.05, p = 0.0002 and DA (β = -0.05, p = 0.019; water content was significantly positively associated with PD (β = 0.06, p = 0.008. Tissue oxygen saturation was marginally inversely associated with PD (β = -0.03, p = 0.057 but significantly inversely associated with DA (β = -0.10, p = 0.002. Among post-menopausal women lipid and water content were significantly associated (negatively and positively, respectively with PD (β lipid = -0.08, β water = 0.14, both p<0.0001 and DA (β lipid = -0.10, p<0.0001; β water = 0.11, p = 0.001. The association between OS breast content and PD and DA is consistent with more proliferation in dense tissue of younger women, greater lipid content in low density tissue and higher water

  9. Transcriptional alterations of ET-1 axis and DNA damage in lung tissue of a rat obesity model.

    Science.gov (United States)

    Del Ry, Silvia; Cabiati, Manuela; Salvadori, Costanza; Guiducci, Letizia; Caselli, Chiara; Prescimone, Tommaso; Facioni, Maria Sole; Azzarà, Alessia; Chiaramonte, Anna; Mazzoni, Stefano; Bruschi, Fabrizio; Giannessi, Daniela; Scarpato, Roberto

    2015-03-01

    Obesity has been implicated in the development of many cancers. This can lead to genome damage, especially in the form of double-strand break, the presence of which is now easily detected through nuclear phosphorylation of histone H2AX (γ-H2AX) focus assay. Recently, the endothelin (ET) axis has also been shown to have a role in the growth and progression of several tumors, including lung cancer. The aim of this study was to evaluate the ET-1 system transcriptional alterations and γ-H2AX in lung tissue of Zucker rats subdivided into obese (O, n=22) and controls (CO, n=18) rats: under either fasting conditions (CO(fc)-O(fc)) or acute hyperglycemia (CO(AH)-O(AH)). Significantly higher prepro-ET-1 (p=0.05) and ET-converting enzyme (ECE)-2 mRNA expression was observed in O with respect to CO. A significant positive association was observed between prepro-ET-1 and ET-A in the whole rat population (p=0.009) or in the obese group alone (p=0.007). The levels of γ-H2AX in O and in O(AH) rats were significantly higher (p=0.019) than in the corresponding CO and CO(AH) rats (p=0.038). The study shows an inappropriate secretion of ET-1 in O animals with a parallel DNA damage in their lungs, providing novel mechanisms by which ET receptor antagonist may exert organ protection.

  10. Cells determine cell density using a small protein bound to a unique tissue-specific phospholipid

    Directory of Open Access Journals (Sweden)

    Christopher J. Petzold

    2013-10-01

    bone cofactor was identified as a lipid containing a ceramide phosphate, a single chained glycerol lipid and a linker. Tendon uses a different cofactor made up of two fatty acid chains linked directly to the phosphate yielding a molecule about half the size. Moreover, adding the tendon factor/cofactor to osteosarcoma cells causes them to stop growing, which is opposite to its role with tendon cells. Thus, the cofactor is cell type specific both in composition and in the triggered response. Further support of its proposed role came from frozen sections from 5 week old mice where an antibody to the factor stained strongly at the growing ends of the tendon as predicted. In conclusion, the molecule needed for cell density signaling is a small protein bound to a unique, tissue-specific phospholipid yielding a membrane associated but diffusible molecule. Signal transduction is postulated to occur by an increased ordering of the plasma membrane as the concentration of this protein/lipid increases with cell density.

  11. Classification of 27 Tumor-Associated Antigens by Histochemical Analysis of 36 Freshly Resected Lung Cancer Tissues.

    Science.gov (United States)

    Kurosawa, Gene; Sugiura, Mototaka; Hattori, Yoshinobu; Tsuda, Hiroyuki; Kurosawa, Yoshikazu

    2016-11-08

    In previous studies, we identified 29 tumor-associated antigens (TAAs) and isolated 488 human monoclonal antibodies (mAbs) that specifically bind to one of the 29 TAAs. In the present study, we performed histochemical analysis of 36 freshly resected lung cancer tissues by using 60 mAbs against 27 TAAs. Comparison of the staining patterns of tumor cells, bronchial epithelial cells, and normal pulmonary alveolus cells and interalveolar septum allowed us to determine the type and location of cells that express target molecules, as well as the degree of expression. The patterns were classified into 7 categories. While multiple Abs were used against certain TAAs, the differences observed among them should be derived from differences in the binding activity and/or the epitope. Thus, such data indicate the versatility of respective clones as anti-cancer drugs. Although the information obtained was limited to the lung and bronchial tube, bronchial epithelial cells represent normal growing cells, and therefore, the data are informative. The results indicate that 9 of the 27 TAAs are suitable targets for therapeutic Abs. These 9 Ags include EGFR, HER2, TfR, and integrin α6β4. Based on our findings, a pharmaceutical company has started to develop anti-cancer drugs by using Abs to TfR and integrin α6β4. HGFR, PTP-LAR, CD147, CDCP1, and integrin αvβ3 are also appropriate targets for therapeutic purposes.

  12. Classification of 27 Tumor-Associated Antigens by Histochemical Analysis of 36 Freshly Resected Lung Cancer Tissues

    Directory of Open Access Journals (Sweden)

    Gene Kurosawa

    2016-11-01

    Full Text Available In previous studies, we identified 29 tumor-associated antigens (TAAs and isolated 488 human monoclonal antibodies (mAbs that specifically bind to one of the 29 TAAs. In the present study, we performed histochemical analysis of 36 freshly resected lung cancer tissues by using 60 mAbs against 27 TAAs. Comparison of the staining patterns of tumor cells, bronchial epithelial cells, and normal pulmonary alveolus cells and interalveolar septum allowed us to determine the type and location of cells that express target molecules, as well as the degree of expression. The patterns were classified into 7 categories. While multiple Abs were used against certain TAAs, the differences observed among them should be derived from differences in the binding activity and/or the epitope. Thus, such data indicate the versatility of respective clones as anti-cancer drugs. Although the information obtained was limited to the lung and bronchial tube, bronchial epithelial cells represent normal growing cells, and therefore, the data are informative. The results indicate that 9 of the 27 TAAs are suitable targets for therapeutic Abs. These 9 Ags include EGFR, HER2, TfR, and integrin α6β4. Based on our findings, a pharmaceutical company has started to develop anti-cancer drugs by using Abs to TfR and integrin α6β4. HGFR, PTP-LAR, CD147, CDCP1, and integrin αvβ3 are also appropriate targets for therapeutic purposes.

  13. Classification of 27 Tumor-Associated Antigens by Histochemical Analysis of 36 Freshly Resected Lung Cancer Tissues

    Science.gov (United States)

    Kurosawa, Gene; Sugiura, Mototaka; Hattori, Yoshinobu; Tsuda, Hiroyuki; Kurosawa, Yoshikazu

    2016-01-01

    In previous studies, we identified 29 tumor-associated antigens (TAAs) and isolated 488 human monoclonal antibodies (mAbs) that specifically bind to one of the 29 TAAs. In the present study, we performed histochemical analysis of 36 freshly resected lung cancer tissues by using 60 mAbs against 27 TAAs. Comparison of the staining patterns of tumor cells, bronchial epithelial cells, and normal pulmonary alveolus cells and interalveolar septum allowed us to determine the type and location of cells that express target molecules, as well as the degree of expression. The patterns were classified into 7 categories. While multiple Abs were used against certain TAAs, the differences observed among them should be derived from differences in the binding activity and/or the epitope. Thus, such data indicate the versatility of respective clones as anti-cancer drugs. Although the information obtained was limited to the lung and bronchial tube, bronchial epithelial cells represent normal growing cells, and therefore, the data are informative. The results indicate that 9 of the 27 TAAs are suitable targets for therapeutic Abs. These 9 Ags include EGFR, HER2, TfR, and integrin α6β4. Based on our findings, a pharmaceutical company has started to develop anti-cancer drugs by using Abs to TfR and integrin α6β4. HGFR, PTP-LAR, CD147, CDCP1, and integrin αvβ3 are also appropriate targets for therapeutic purposes. PMID:27834817

  14. Inhibition of Radiation-Induced Oxidative Damage in the Lung Tissue: May Acetylsalicylic Acid Have a Positive Role?

    Science.gov (United States)

    Demirel, Can; Kilciksiz, Sevil Cagiran; Gurgul, Serkan; Erdal, Nurten; Yigit, Seyran; Tamer, Lulufer; Ayaz, Lokman

    2016-02-01

    The lung is relatively sensitive to irradiation. It is shown that acetylsalicylic acid (ASA) might reduce oxidative injury and that it has a place in protection from cancer. The aim of this study is to evaluate the potential radioprotective effects of ASA. Whole-body irradiation (6 Gy, single dose) was applied to the rats. Glutathione (GSH), malondialdehyde (MDA), myeloperoxidase (MPO), and nitric oxide (NO) levels in the lung tissue were measured. Control (C), Radiation (R), Radiation + ASA (R + ASA; received irradiation and 25 mg/kg of ASA intraperitoneally (i.p.)), and Radiation + Amifostine (R + WR-2721; received irradiation and 200 mg/kg of WR-2721 i.p.) groups were used. The MPO levels decreased statistically significantly in the group administered ASA. Histopathologically, a radioprotective effect of ASA was more evident in the R + ASA group. ASA is an agent which has not been used as a radioprotector in the clinic yet, and it is worth supporting with more advanced studies.

  15. Rapid OTAN method for localizing unsaturated lipids in lung tissue sections.

    Science.gov (United States)

    Negi, D S; Stephens, R J

    1981-05-01

    The OTAN treatment, which is the only histochemical method available at present for the simultaneous localization of hydrophobic and hydrophilic unsaturated lipids in tissue sections, requires unduly long exposure to OsO4 and use of free-floating sections, which makes handling the sections difficult and often results in their loss or damage. Simple modifications using OsO4 treatment at 37 C and slide-mounted sections eliminate the practical drawbacks of the existing method and provide as good or better localization in less than one-eight of the time. The modified method is applicable to fixed as well as fresh frozen tissues.

  16. Influence of age, sex and rearing systems on Toll-like receptor 7 (TLR7) expression pattern in gut, lung and lymphoid tissues of indigenous ducks.

    Science.gov (United States)

    Kolluri, Gautham; Ramamurthy, N; Churchil, R R; Dhinakar Raj, G; Kannaki, T R

    2014-02-01

    Abstract 1. The objective of the experiment was to determine the influence of age, sex and rearing system on Toll-like receptor 7 (TLR7) gene expression in gut, lung and lymphoid tissues and physiological responses to stress in male and female indigenous ducks of Tamil Nadu, India. 2. A total of 36 ducks (12 males and 24 females) were obtained from local farmers and tissue samples of gut tissues (duodenum, jejunum, ileum and caecum), lymphoid organs (spleen and bursa) and lungs were collected in RNAlater solution followed by RNA extraction. 3. After normalisation to β-actin (endogenous control) qPCR analysis identified a significant effect of age, sex and rearing system on TLR7 expression in the ducks. 4. A significant up-regulation of TLR7 expression was observed in lungs, duodenum, jejunum, ileum and caecum of sexually mature (45 wk) compared with that of immature ducks (16 wk). Among sexes, male ducks had significantly higher TLR7 expression than female ducks. 5. Age and sex interactions were significant in lungs, duodenum, jejunum and caecum. Ducks reared in an extensive housing system showed significantly higher TLR7 expression in bursa, lungs, duodenum, ileum and caecum compared to intensively reared ducks. There were no effects of age, sex and rearing systems on TLR7 expression in the spleen. 6. The heterophil-to-lymphocyte ratio and serum corticosterone were higher in ducks reared on an intensive system compared with ducks from an extensive rearing system.

  17. Macrophomina phaseolina: density and longevity of microsclerotia in soybean root tissues and free on the soil, and competitive saprophytic ability

    Directory of Open Access Journals (Sweden)

    Erlei Melo Reis

    2014-06-01

    Full Text Available In field experiments, the density of Macrophomina phaseolina microsclerotia in root tissues of naturally colonized soybean cultivars was quantified. The density of free sclerotia on the soil was determined for plots of crop rotation (soybean-corn and soybean monoculture soon after soybean harvest. M. phaseolina natural infection was also determined for the roots of weeds grown in the experimental area. To verify the ability of M. phaseolina to colonize dead substrates, senesced stem segments from the main plant species representing the agricultural system of southern Brazil were exposed on naturally infested soil for 30 and 60 days. To quantify the sclerotia, the methodology of Cloud and Rupe (1991 and Mengistu et al. (2007 was employed. Sclerotium density, assessed based on colony forming units (CFU, ranged from 156 to 1,108/g root tissue. Sclerotium longevity, also assessed according to CFU, was 157 days for the rotation and 163 days for the monoculture system. M. phaseolina did not colonize saprophytically any dead stem segment of Avena strigosa,Avena sativa,Hordeum vulgare,Brassica napus,Gossypium hirsutum,Secale cereale,Helianthus annus,Triticosecalerimpaui, and Triticum aestivum. Mp was isolated from infected root tissues of Amaranthus viridis,Bidens pilosa,Cardiospermum halicacabum,Euphorbia heterophylla,Ipomoea sp., and Richardia brasiliensis. The survival mechanisms of M. phaseolina studied in this paper met the microsclerotium longevity in soybean root tissues, free on the soil, as well as asymptomatic colonization of weeds.

  18. Effect of porosity, tissue density, and mechanical properties on radial sound speed in human cortical bone

    Energy Technology Data Exchange (ETDEWEB)

    Eneh, C. T. M., E-mail: chibuzor.eneh@uef.fi, E-mail: markus.malo@uef.fi, E-mail: janne.karjalainen@boneindex.fi, E-mail: jukka.liukkonen@gmail.com, E-mail: juha.toyras@uef.fi; Töyräs, J., E-mail: chibuzor.eneh@uef.fi, E-mail: markus.malo@uef.fi, E-mail: janne.karjalainen@boneindex.fi, E-mail: jukka.liukkonen@gmail.com, E-mail: juha.toyras@uef.fi; Jurvelin, J. S., E-mail: jukka.jurvelin@uef.fi [Department of Applied Physics, University of Eastern Finland, P.O. Box 1627, Kuopio FI-70211, Finland and Diagnostic Imaging Center, Kuopio University Hospital, P.O. Box 100, Kuopio FI-70029 (Finland); Malo, M. K. H., E-mail: chibuzor.eneh@uef.fi, E-mail: markus.malo@uef.fi, E-mail: janne.karjalainen@boneindex.fi, E-mail: jukka.liukkonen@gmail.com, E-mail: juha.toyras@uef.fi; Liukkonen, J., E-mail: chibuzor.eneh@uef.fi, E-mail: markus.malo@uef.fi, E-mail: janne.karjalainen@boneindex.fi, E-mail: jukka.liukkonen@gmail.com, E-mail: juha.toyras@uef.fi [Department of Applied Physics, University of Eastern Finland, P.O. Box 1627, Kuopio FI-70211 (Finland); Karjalainen, J. P., E-mail: chibuzor.eneh@uef.fi, E-mail: markus.malo@uef.fi, E-mail: janne.karjalainen@boneindex.fi, E-mail: jukka.liukkonen@gmail.com, E-mail: juha.toyras@uef.fi [Bone Index Finland Ltd., P.O. Box 1188, Kuopio FI-70211 (Finland)

    2016-05-15

    Purpose: The purpose of this study was to investigate the effect of simultaneous changes in cortical porosity, tissue mineral density, and elastic properties on radial speed of sound (SOS) in cortical bone. The authors applied quantitative pulse-echo (PE) ultrasound techniques that hold much potential especially for screening of osteoporosis at primary healthcare facilities. Currently, most PE measurements of cortical thickness, a well-known indicator of fracture risk, use a predefined estimate for SOS in bone to calculate thickness. Due to variation of cortical bone porosity, the use of a constant SOS value propagates to an unknown error in cortical thickness assessment by PE ultrasound. Methods: The authors conducted 2.25 and 5.00 MHz focused PE ultrasound time of flight measurements on femoral diaphyses of 18 cadavers in vitro. Cortical porosities of the samples were determined using microcomputed tomography and related to SOS in the samples. Additionally, the effect of cortical bone porosity and mechanical properties of the calcified matrix on SOS was investigated using numerical finite difference time domain simulations. Results: Both experimental measurements and simulations demonstrated significant negative correlation between radial SOS and cortical porosity (R{sup 2} ≥ 0.493, p < 0.01 and R{sup 2} ≥ 0.989, p < 0.01, respectively). When a constant SOS was assumed for cortical bone, the error due to variation of cortical bone porosity (4.9%–16.4%) was about 6% in the cortical thickness assessment in vitro. Conclusions: Use of a predefined, constant value for radial SOS in cortical bone, i.e., neglecting the effect of measured variation in cortical porosity, propagated to an error of 6% in cortical thickness. This error can be critical as characteristic cortical thinning of 1.10% ± 1.06% per yr decreases bending strength of the distal radius and results in increased fragility in postmenopausal women. Provided that the cortical porosity can be estimated

  19. X-Ray Methods to Estimate Breast Density Content in Breast Tissue

    Science.gov (United States)

    Maraghechi, Borna

    This work focuses on analyzing x-ray methods to estimate the fat and fibroglandular contents in breast biopsies and in breasts. The knowledge of fat in the biopsies could aid in their wide-angle x-ray scatter analyses. A higher mammographic density (fibrous content) in breasts is an indicator of higher cancer risk. Simulations for 5 mm thick breast biopsies composed of fibrous, cancer, and fat and for 4.2 cm thick breast fat/fibrous phantoms were done. Data from experimental studies using plastic biopsies were analyzed. The 5 mm diameter 5 mm thick plastic samples consisted of layers of polycarbonate (lexan), polymethyl methacrylate (PMMA-lucite) and polyethylene (polyet). In terms of the total linear attenuation coefficients, lexan ≡ fibrous, lucite ≡ cancer and polyet ≡ fat. The detectors were of two types, photon counting (CdTe) and energy integrating (CCD). For biopsies, three photon counting methods were performed to estimate the fat (polyet) using simulation and experimental data, respectively. The two basis function method that assumed the biopsies were composed of two materials, fat and a 50:50 mixture of fibrous (lexan) and cancer (lucite) appears to be the most promising method. Discrepancies were observed between the results obtained via simulation and experiment. Potential causes are the spectrum and the attenuation coefficient values used for simulations. An energy integrating method was compared to the two basis function method using experimental and simulation data. A slight advantage was observed for photon counting whereas both detectors gave similar results for the 4.2 cm thick breast phantom simulations. The percentage of fibrous within a 9 cm diameter circular phantom of fibrous/fat tissue was estimated via a fan beam geometry simulation. Both methods yielded good results. Computed tomography (CT) images of the circular phantom were obtained using both detector types. The radon transforms were estimated via four energy integrating

  20. Predictive Value of Early Tumor Shrinkage and Density Reduction of Lung Metastases in Patients With Metastatic Colorectal Cancer Treated With Regorafenib.

    Science.gov (United States)

    Vanwynsberghe, Hannes; Verbeke, Xander; Coolen, Johan; Van Cutsem, Eric

    2017-03-29

    The benefit of regorafenib in colorectal cancer is not very pronounced. At present, there is lack of predictive biological or radiological markers. We studied if density reduction or small changes in size of lung metastases could be a predictive marker. We retrospectively measured density in size of lung metastases of all patients included in the CORRECT and CONSIGN trials at our center. Contrast-enhanced CT scan at baseline and at week 8 were compared. Data of progressive-free survival and overall survival were collected from the CORRECT and CONSIGN trials. A significant difference in progressive-free survival was seen in 3 groups: response or stable disease in size (5.36 vs. 3.96 months), response in density (6.03 vs. 2.72 months), and response in corrected density (6.14 vs. 3.08 months). No difference was seen for response in size versus stable disease or progressive disease in size. For overall survival, a difference was observed in the same 3 groups: response or stable disease in size (9.89 vs. 6.44 months), response in density (9.59 vs. 7.04 months), and response in corrected density (9.09 vs. 7.16 months). No difference was seen for response in size versus stable disease or progressive disease in size. Density reduction in lung metastases might be a good predictive parameter to predict outcome for regorafenib. Early tumor progression might be a negative predictive factor. If further validated, density reduction and early tumor progression might be useful to ameliorate the cost-benefit of regorafenib. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. The correlation analysis of the expression of VEGF and the DCs’ infiltration density of gastric cancer tissues

    Institute of Scientific and Technical Information of China (English)

    Feng Yang; Ai-Mei Li; De-Huai Jing

    2016-01-01

    Objective:To investigate the correlation of the expression of vascular endothecial growth factor (VEGF) and the dendritic cells (DCs) infiltration density of tumor tissues in patients with gastric cancer and the correlation of the frequency of DCs of VEGF in gastric cancer tissues and the clinic stages; and to analyze the expressions of HLA-DR and CD86 on peripheral blood monocyte-derived DCs.Methods:Immuno fluorescence method was applied to test the expressions of CD11c and VEGF in gastric cancer tissues and para-carcinoma tissues and enzyme-linked immune sorbent assay was used to detect the concentration of serum VEGF. Peripheral blood mononuclear cells of the gastric cancer patients and healthy people were separated and induced DCs by GM-CSF and IL-4in vitro. Then, the expressions of HLA-DR and CD86 on DCs were tested by flow cytometry. Finally, the recombinant VEGF protein was added into DCs cultures to explore how VEGF affected the expression of CD86. Results: There was a negative correlation between the expression intensity of VEGF on gastric cancer cells and the tumor-infiltrating density of DCs; while there was a certain positive correlation between the frequency of DCs of VEGF and the development of the disease. The concentration of serum VEGF had no association with the density of tumor-infiltrating DCs. As for peripheral blood mononuclear cell, it had a certain induced effect on the decrease of DCs, the expressions of HLA-DR and CD86 and the expression of CD86 on DCs’ cell surface by VEGF.Conclusions:The activities of DCs were inhibited by VEGF secretion of gastric cancer tissues so as to mediate immune escape of the cancer cells. In addition, DCs infiltrated in gastric cancer tissues may secrete VEGF to participate the development of the disease.

  2. SU-E-T-92: Achieving Desirable Lung Doses in Total Body Irradiation Based On in Vivo Dosimetry and Custom Tissue Compensation

    Energy Technology Data Exchange (ETDEWEB)

    Cui, G; Shiu, A; Zhou, S; Cui, J; Ballas, L [Univ Southern California, Los Angeles, CA (United States)

    2015-06-15

    Purpose: To achieve desirable lung doses in total body irradiation (TBI) based on in vivo dosimetry and custom tissue compensation. Methods: The 15 MV photon beam of a Varian TrueBeam STx linac was used for TBI. Patients were positioned in the lateral decubitus position for AP/PA treatment delivery. Dose was calculated using the midpoint of the separation distance across the patient’s umbilicus. Patients received 200 cGy twice daily for 3 days. The dose rate at the patient’s midplane was approximately 10 cGy/min. Cerrobend blocks with a 5-HVL thickness were used for the primary lung shielding. A custom styrofoam holder for rice-flour filled bags was created based on the lung block cutouts. This was used to provide further lung shielding based on in vivo dose measurements. Lucite plates and rice-flour bags were placed in the head, neck, chest, and lower extremity regions during the treatment to compensate for the beam off-axis output variations. Two patients were included in the study. Patients 1 and 2 received a craniospinal treatment (1080 cGy) and a mediastinum treatment (2520 cGy), respectively, before the TBI. During the TBI nanoDot dosimeters were placed on the patient skin in the forehead, neck, umbilicus, and lung regions for dose monitoring. The doses were readout immediately after the treatment. Based on the readings, fine tuning of the thickness of the rice-flour filled bags was exploited to achieve the desirable lung doses. Results: For both patients the mean lung doses, which took into consideration all treatments, were controlled within 900 +/−10% cGy, as desired. Doses to the forehead, neck, and umbilicus were achieved within +/−10% of the prescribed dose (1200 cGy). Conclusion: A reliable and robust method was developed to achieve desirable lung doses and uniform body dose in TBI based on in vivo dosimetry and custom tissue compensator.

  3. Bronchus-associated lymphoid tissue (BALT) lymphoma of the lung showing mosaic pattern of inhomogeneous attenuation on thin-section CT: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, In Jae; Kim, Sung Hwan; Koo, Soo Hyun; Kim, Hyun Beom; Hwang, Dae Hyun; Lee, Kwan Seop; Lee, Yul; Jang, Kee Taek; Kim, Duck Hwan [Hallym University Sacred Heart Hospital, Anyang (Korea, Republic of)

    2000-09-01

    The authors present a case of histologically proven bronchus-associated lymphoid tissue (BALT) lymphoma of the lung in a patient with primary Sjogren's syndrome that manifested on thin-section CT scan as a mosaic pattern of inhomogeneous attenuation due to mixed small airway and infiltrative abnormalities.

  4. Breast Tissue Composition and Immunophenotype and Its Relationship with Mammographic Density in Women at High Risk of Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Jia-Min B Pang

    Full Text Available To investigate the cellular and immunophenotypic basis of mammographic density in women at high risk of breast cancer.Mammograms and targeted breast biopsies were accrued from 24 women at high risk of breast cancer. Mammographic density was classified into Wolfe categories and ranked by increasing density. The histological composition and immunophenotypic profile were quantified from digitized haematoxylin and eosin-stained and immunohistochemically-stained (ERα, ERβ, PgR, HER2, Ki-67, and CD31 slides and correlated to mammographic density.Increasing mammographic density was significantly correlated with increased fibrous stroma proportion (rs (22 = 0.5226, p = 0.0088 and significantly inversely associated with adipose tissue proportion (rs (22 = -0.5409, p = 0.0064. Contrary to previous reports, stromal expression of ERα was common (19/20 cases, 95%. There was significantly higher stromal PgR expression in mammographically-dense breasts (p=0.026.The proportion of stroma and fat underlies mammographic density in women at high risk of breast cancer. Increased expression of PgR in the stroma of mammographically dense breasts and frequent and unexpected presence of stromal ERα expression raises the possibility that hormone receptor expression in breast stroma may have a role in mediating the effects of exogenous hormonal therapy on mammographic density.

  5. Breast Tissue Composition and Immunophenotype and Its Relationship with Mammographic Density in Women at High Risk of Breast Cancer.

    Science.gov (United States)

    Pang, Jia-Min B; Byrne, David J; Takano, Elena A; Jene, Nicholas; Petelin, Lara; McKinley, Joanne; Poliness, Catherine; Saunders, Christobel; Taylor, Donna; Mitchell, Gillian; Fox, Stephen B

    2015-01-01

    To investigate the cellular and immunophenotypic basis of mammographic density in women at high risk of breast cancer. Mammograms and targeted breast biopsies were accrued from 24 women at high risk of breast cancer. Mammographic density was classified into Wolfe categories and ranked by increasing density. The histological composition and immunophenotypic profile were quantified from digitized haematoxylin and eosin-stained and immunohistochemically-stained (ERα, ERβ, PgR, HER2, Ki-67, and CD31) slides and correlated to mammographic density. Increasing mammographic density was significantly correlated with increased fibrous stroma proportion (rs (22) = 0.5226, p = 0.0088) and significantly inversely associated with adipose tissue proportion (rs (22) = -0.5409, p = 0.0064). Contrary to previous reports, stromal expression of ERα was common (19/20 cases, 95%). There was significantly higher stromal PgR expression in mammographically-dense breasts (p=0.026). The proportion of stroma and fat underlies mammographic density in women at high risk of breast cancer. Increased expression of PgR in the stroma of mammographically dense breasts and frequent and unexpected presence of stromal ERα expression raises the possibility that hormone receptor expression in breast stroma may have a role in mediating the effects of exogenous hormonal therapy on mammographic density.

  6. Telomere length of tumor tissues and survival in patients with early stage non-small cell lung cancer.

    Science.gov (United States)

    Jeon, Hyo-Sung; Choi, Yi Young; Choi, Jin Eun; Lee, Won Kee; Lee, Eungbae; Yoo, Seung Soo; Lee, Shin Yup; Lee, Jaehee; Cha, Seung Ick; Kim, Chang Ho; Park, Jae Yong

    2014-04-01

    Telomere shortening leads to genomic instability that drives oncogenesis through the activation of telomerase and the generation of other mutations necessary for tumor progression. This study was conducted to determine the impact of telomere shortening on the survival of patients with early stage non-small cell lung cancer (NSCLC). Relative telomere length in tumor tissues was measured by quantitative polymerase chain reaction in 164 patients with surgically resected NSCLC. The association between telomere length and overall survival (OS) and disease-free survival (DFS) was analyzed. When the patients were categorized into quartiles based on telomere length, those patients with the 1st quartile (shortest) of telomere length had a significantly worse OS and DFS compared to patients with the 2nd to the 4th quartiles of telomere length (adjusted hazard ratio for OS = 2.67, 95% confidence interval = 1.50-4.75, P = 0.001; and adjusted hazard ratio for DFS = 1.92, 95% confidence interval = 1.17-3.14, P = 0.01). An association between telomere length and survival outcome was more pronounced in squamous cell carcinomas than adenocarcinomas (P-value of test for homogeneity for OS and DFS = 0.05 and 0.02, respectively). Telomere length of tumor tissues is an independent prognostic factor in patients with surgically resected early stage NSCLC.

  7. Novel muscle and connective tissue design enables high extensibility and controls engulfment volume in lunge-feeding rorqual whales.

    Science.gov (United States)

    Shadwick, Robert E; Goldbogen, Jeremy A; Potvin, Jean; Pyenson, Nicholas D; Vogl, A Wayne

    2013-07-15

    Muscle serves a wide variety of mechanical functions during animal feeding and locomotion, but the performance of this tissue is limited by how far it can be extended. In rorqual whales, feeding and locomotion are integrated in a dynamic process called lunge feeding, where an enormous volume of prey-laden water is engulfed into a capacious ventral oropharyngeal cavity that is bounded superficially by skeletal muscle and ventral groove blubber (VGB). The great expansion of the cavity wall presents a mechanical challenge for the physiological limits of skeletal muscle, yet its role is considered fundamental in controlling the flux of water into the mouth. Our analyses of the functional properties and mechanical behaviour of VGB muscles revealed a crimped microstructure in an unstrained, non-feeding state that is arranged in parallel with dense and straight elastin fibres. This allows the muscles to accommodate large tissue deformations of the VGB yet still operate within the known strain limits of vertebrate skeletal muscle. VGB transverse strains in routine-feeding rorquals were substantially less than those observed in dead ones, where decomposition gas stretched the VGB to its elastic limit, evidence supporting the idea that eccentric muscle contraction modulates the rate of expansion and ultimate size of the ventral cavity during engulfment.

  8. Tissue Microarrays in Non-Small Cell Lung Cancer: Reliability of Immunohistochemically-Determined Biomarkers

    DEFF Research Database (Denmark)

    Pøhl, Mette; Olsen, Karen Ege; Holst, René;

    2014-01-01

    BACKGROUND: The reliability of immunohistochemically-determined biomarkers using tissue microarrays (TMAs) of clinical specimens has long been open to question. Heterogeneity related to tumor biology might compromise determination of accurate biomarker expression in tumors, especially in small core...... samples. However, the optimal number of cores required for biomarkers with functional properties varied from 1 to > 4 cores. The results indicate that the optimal number of biopsies required to compensate for potential biomarker heterogeneity should be determined individually for each biomarker used...

  9. Synchronous changes in coral chromatophore tissue density and skeletal banding as an adaptive response to environmental change

    Science.gov (United States)

    Ardisana, R. N.; Miller, C. A.; Sivaguru, M.; Fouke, B. W.

    2013-12-01

    Corals are a key reservoir of biodiversity in coastal, shallow water tropical marine environments, and density banding in their aragonite skeletons is used as a sensitive record of paleoclimate. Therefore, the cellular response of corals to environmental change and its expression in skeletal structure is of significant importance. Chromatophores, pigment-bearing cells within the ectoderm of hermatypic corals, serve to both enhance the photosynthetic activity of zooxanthellae symbionts, as well as protect the coral animal from harmful UV radiation. Yet connections have not previously been drawn between chromatophore tissue density and the development of skeletal density bands. A histological analysis of the coral Montastrea faveolata has therefore been conducted across a bathymetric gradient of 1-20 m on the southern Caribbean island of Curaçao. A combination of field and laboratory photography, serial block face imaging (SBFI), two-photon laser scanning microscopy (TPLSM), and 3D image analysis has been applied to test whether M. faveolata adapts to increasing water depth and decreasing photosynthetically active radiation by shifting toward a more heterotrophic lifestyle (decreasing zooxanthellae tissue density, increasing mucocyte tissue density, and decreasing chromatophores density). This study is among the first to collect and evaluate histological data in the spatial context of an entire unprocessed coral polyp. TPLSM was used to optically thin section unprocessed tissue biopsies with quantitative image analysis to yield a nanometer-scale three-dimensional map of the quantity and distribution of the symbionts (zooxanthellae) and a host fluorescent pigments (chromatophores), which is thought to have photoprotective properties, within the context of an entire coral polyp. Preliminary results have offered new insight regarding the three-dimensional distribution and abundance of chromatophores and have identified: (1) M. faveolata tissue collected from 8M SWD do

  10. [Effect of dragon's blood on TGF-beta/smads signal transduction molecule mRNA expression in the lung tissue of rats with pulmonary fibrosis].

    Science.gov (United States)

    Nie, Li; Zheng, Bi-xia; Cheng, De-yun; Yang, Li-teng; Mu, Mao; Hu, Xiao-bo; Fang, Xun

    2007-09-01

    To investigate the effect of Dragon's Blood on the expression of TGF-beta signal transduction molecule TGFbetaR II or Smad4 mRNA in the lung tissue of rats with pulmonary fibrosis, and to evaluate the effect and its mechanism of Dragon's Blood on pulmonary fibrosis. 30 SD rats were randomly divided into three groups: fibrosis model, treatment and normal control groups. In model group and treatment group, the pulmonary fibrous tissues were induced to form with the intratracheal injection of bleomycin (5 mg/kg). In normal control group, saline was given intratracheally. Dragon's Blood was administered intragastricly in treatment group with a dose of 180 mg/kg diluted in 2 mL saline while saline was given intragastricly to other two groups with same volume from day 2 till day 28 after modeling. All rats were sacrificed on the 29th day. The rat lung histopathology was examined with HE staining. In situ hybridization was used to detect the expressions of TGFbetaR II and Smad4 mRNAs in lung tissue, and the expression of collagen fibril I was examined by an immunohistochemical staining. The inflammation cell counting in treatment group (12913.78 +/- 5640.12) was significant lower than that in model group (22243.60 +/- 5011.55, P 0.05). The expression of collagen fibril I in the lung tissue of rats in treatment group was significant lower than that in model group (P Dragon's Blood can effectively reduce rats' pulmonary fibrosis, of which the mechanisms may be to inhibit the expression of TGFbetaR II mRNA in the lung tissue and thus to have the preventive effect on the excessive deposit of collagen fibril I.

  11. Effects of aerosolized ketamine on the level of nitric oxide and nitric oxide synthetase in the lung tissue of rat with asthma

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective: To explore the effects of aerosolized ketamine on the level of nitric oxide and nitric oxide synthetase in the lung tissue in rat asthma model. Methods: Forty SD rats were randomly assigned to five groups: control group (group N), asthma model group (group A), two pretreated groups of different concentrations of ketamine (group K1, K2)and dexamethasone group(group D) with eight rats in each group. The rats in group A were sensitized by injection of ovalbumin (OA) together with aluminum hydroxide and bordetella pertussis as adjuvants. Two weeks after the sensitization, aerosolized OA was used to cause asthma. The rats in group K1 and K2 were sensitized with OA as group A , and then exposed to aerosol of ketamine , with the concentration of 25 g/L and 50 g/L respectively. Before using aerosolized OA, the rats in group D were exposed to aerosol of 0.01% dexamethasone . The level of NO2-/NO3- in lung tissues, inducible nitric oxide synthetase(iNOS) and constitute nitric oxide synthetase(cNOS) was measured in all groups. Results: The level of NO2-/NO3- and the activity of iNOS in lung tissues in group A were signiticantly higher than those in the other groups. The iNOS activity and the level of NO2-/NO3- in lung tissues were highly positively correlated. Conclusion: NO can induce airway hyperreactivity that may worsen asthma. Aerosolized ketamine can decrease the iNOS expression and reduce the level of NO in the lung tissue in rat asthma model.

  12. Identification of early-stage usual interstitial pneumonia from low-dose chest CT scans using fractional high-density lung distribution

    Science.gov (United States)

    Xie, Yiting; Salvatore, Mary; Liu, Shuang; Jirapatnakul, Artit; Yankelevitz, David F.; Henschke, Claudia I.; Reeves, Anthony P.

    2017-03-01

    A fully-automated computer algorithm has been developed to identify early-stage Usual Interstitial Pneumonia (UIP) using features computed from low-dose CT scans. In each scan, the pre-segmented lung region is divided into N subsections (N = 1, 8, 27, 64) by separating the lung from anterior/posterior, left/right and superior/inferior in 3D space. Each subsection has approximately the same volume. In each subsection, a classic density measurement (fractional high-density volume h) is evaluated to characterize the disease severity in that subsection, resulting in a feature vector of length N for each lung. Features are then combined in two different ways: concatenation (2*N features) and taking the maximum in each of the two corresponding subsections in the two lungs (N features). The algorithm was evaluated on a dataset consisting of 51 UIP and 56 normal cases, a combined feature vector was computed for each case and an SVM classifier (RBF kernel) was used to classify them into UIP or normal using ten-fold cross validation. A receiver operating characteristic (ROC) area under the curve (AUC) was used for evaluation. The highest AUC of 0.95 was achieved by using concatenated features and an N of 27. Using lung partition (N = 27, 64) with concatenated features had significantly better result over not using partitions (N = 1) (p-value < 0.05). Therefore this equal-volume partition fractional high-density volume method is useful in distinguishing early-stage UIP from normal cases.

  13. Explanatory models for a tactile resonance sensor system-elastic and density-related variations of prostate tissue in vitro.

    Science.gov (United States)

    Jalkanen, Ville; Andersson, Britt M; Bergh, Anders; Ljungberg, Börje; Lindahl, Olof A

    2008-07-01

    Tactile sensors based on piezoelectric resonance have been adopted for medical applications. The sensor consists of an oscillating piezoelectric sensor-circuit system, and a change in resonance frequency is observed when the sensor tip contacts a measured object such as tissue. The frequency change at a constant applied force or mass load is used as a stiffness-sensitive parameter in many applications. Differential relations between force and frequency have also been used for monitoring intraocular pressure and stiffness variations in prostate tissue in vitro. The aim of this study was to relate the frequency change (Deltaf), measured force (F) and the material properties, density and elasticity to an explanatory model for the resonance sensor measurement principle and thereby to give explanatory models for the stiffness parameters used previously. Simulations of theoretical equations were performed to investigate the relation between frequency change and contact impedance. Measurements with a resonance sensor system on prostate tissue in vitro were used for experimental validation of the theory. Tissue content was quantified with a microscopic-based morphometrical method. Simulation results showed that the frequency change was dependent upon density (rho) and contact area (S) according to Deltaf proportional, variant rhoS(3/2). The experiments followed the simulated theory at small impression depths. The measured contact force followed a theoretical model with the dependence of the elastic modulus (E) and contact area, F proportional, variant ES(3/2). Measured density variations related to histological variations were statistically weak or non-significant. Elastic variations were statistically significant with contributions from stroma and cancer relative to normal glandular tissue. The theoretical models of frequency change and force were related through the contact area, and a material-dependent explanatory model was found as Deltaf proportional, variant rhoE(-1

  14. Effective atomic numbers, electron densities, and tissue equivalence of some gases and mixtures for dosimetry of radiation detectors

    Directory of Open Access Journals (Sweden)

    Singh Vishwanath P.

    2012-01-01

    Full Text Available Total mass attenuation coefficients, µm, effective atomic number, Zeff, and effective electron density, Neff, of different gases - carbon dioxide, methane, acetylene, propane, butane, and pentane used in radiation detectors, have been calculated for the photon energy of 1 keV to 100 GeV. Each gas has constant Zeff values between 0.10 to 10 MeV photon energies; however, these values are way far away from ICRU tissue. Carbon dioxide gas shows the closest tissue equivalence in the entire photon energy spectrum. Relative tissue equivalences of the mixtures of gases with respect to ICRU tissue are in the range of 0.998-1.041 for air, argon (4.5% + methane (95.5%, argon (0.5% + carbon dioxide (99.5%, and nitrogen (5% + methane (7% + carbon dioxide (88%. The gas composition of xenon (0.5% + carbon dioxide (99.5% shows 1.605 times higher tissue equivalence compared to the ICRU tissue. The investigated photon interaction parameters are useful for exposure and energy absorption buildup factors calculation and design, and fabrication of gaseous detectors for ambient radiation measurement by the Geiger-Muller detector, ionization chambers and proportional counters.

  15. The prognostic implications of microvascular density and lymphatic vessel density in esophageal squamous cell carcinoma: Comparative analysis between the traditional whole sections and the tissue microarray.

    Science.gov (United States)

    Chen, Bo; Fang, Wang-Kai; Wu, Zhi-Yong; Xu, Xiu-E; Wu, Jian-Yi; Fu, Jun-Hui; Yao, Xiao-Dong; Huang, Jian-Hao; Chen, Jie-Xin; Shen, Jin-Hui; Zheng, Chun-Peng; Wang, Shao-Hong; Li, En-Min; Xu, Li-Yan

    2014-05-01

    Focal distribution of microvascular and lymphatic vessels is a critical issue in cancer, and is measured by tissue microarray (TMA) construction from paraffin-embedded surgically obtained tissues, a process that may not accurately reflect true focal distribution. The aim of this study was to assess the concordance of microvascular density (MVD) and lymphatic vessel density (LVD) in TMAs with corresponding whole sections, and to correlate the MVD or LVD with clinicopathological parameters in 124 cases of esophageal squamous cell carcinoma (ESCC). MVD, determined by CD105 immunohistochemistry of whole sections, was strongly associated with lymph node metastasis (p=0.000) and pTNM stage (p=0.001). Kaplan-Meier survival analysis showed that increasing CD105 microvessel count correlated with decreasing survival (ptissue microarrays. Analysis of continuous data showed a highly significant correlation between whole sections and TMA data (Pearson r=0.522, p<0.001). Increasing LVD, as determined by D2-40 immunohistochemistry of whole sections, correlated with decreasing survival, but this relationship was undetectable using TMAs. In conclusion, we demonstrate that for the selected endothelial markers, TMAs can provide a realistic and reliable estimate of the extent of MVD, but not LVD in ESCC samples. Copyright © 2013 Elsevier GmbH. All rights reserved.

  16. Acceleration of Lung Regeneration by Platelet-Rich Plasma Extract through the Low-Density Lipoprotein Receptor-Related Protein 5-Tie2 Pathway.

    Science.gov (United States)

    Mammoto, Tadanori; Chen, Zhao; Jiang, Amanda; Jiang, Elisabeth; Ingber, Donald E; Mammoto, Akiko

    2016-01-01

    Angiogenesis, the growth of new blood vessels, plays a key role in organ development, homeostasis, and regeneration. The cooperation of multiple angiogenic factors, rather than a single factor, is required for physiological angiogenesis. Recently, we have reported that soluble platelet-rich plasma (PRP) extract, which contains abundant angiopoietin-1 and multiple other angiogenic factors, stimulates angiogenesis and maintains vascular integrity in vitro and in vivo. In this report, we have demonstrated that mouse PRP extract increases phosphorylation levels of the Wnt coreceptor low-density lipoprotein receptor-related protein 5 (LRP5) and thereby activates angiogenic factor receptor Tie2 in endothelial cells (ECs) and accelerates EC sprouting and lung epithelial cell budding in vitro. PRP extract also increases phosphorylation levels of Tie2 in the mouse lungs and accelerates compensatory lung growth and recovery of exercise capacity after unilateral pneumonectomy in mice, whereas soluble Tie2 receptor or Lrp5 knockdown attenuates the effects of PRP extract. Because human PRP extract is generated from autologous peripheral blood and can be stored at -80°C, our findings may lead to the development of novel therapeutic interventions for various angiogenesis-related lung diseases and to the improvement of strategies for lung regeneration.

  17. The use of CT density changes at internal tissue interfaces to correlate internal organ motion with an external surrogate

    Energy Technology Data Exchange (ETDEWEB)

    Gaede, Stewart; Yu, Edward; Van Dyk, Jake; Battista, Jerry [Radiation Oncology Program, London Regional Cancer Program, London, Ontario (Canada); Carnes, Gregory; Lee, Ting-Yim [Department of Medical Biophysics, University of Western Ontario, London, Ontario (Canada)

    2009-01-21

    The purpose of this paper is to describe a non-invasive method to monitor the motion of internal organs affected by respiration without using external markers or spirometry, to test the correlation with external markers, and to calculate any time shift between the datasets. Ten lung cancer patients were CT scanned with a GE LightSpeed Plus 4-Slice CT scanner operating in a cine mode. We retrospectively reconstructed the raw CT data to obtain consecutive 0.5 s reconstructions at 0.1 s intervals to increase image sampling. We defined regions of interest containing tissue interfaces, including tumour/lung interfaces that move due to breathing on multiple axial slices and measured the mean CT number versus respiratory phase. Tumour motion was directly correlated with external marker motion, acquired simultaneously, using the sample coefficient of determination, r{sup 2}. Only three of the ten patients showed correlation higher than r{sup 2} = 0.80 between tumour motion and external marker position. However, after taking into account time shifts (ranging between 0 s and 0.4 s) between the two data sets, all ten patients showed correlation better than r{sup 2} = 0.8. This non-invasive method for monitoring the motion of internal organs is an effective tool that can assess the use of external markers for 4D-CT imaging and respiratory-gated radiotherapy on a patient-specific basis.

  18. Cyclophosphamide in diffuse lung damage.

    Science.gov (United States)

    Musiatowicz, B; Sulkowska, M; Sulik, M; Famulski, W; Dziecioł, J; Sobaniec-Lotowska, M; Baltaziak, M; Arciuch, L; Rółkowski, R; Jabłońska, E

    1997-01-01

    Some cyclophosphamide toxic effects on lung tissue are presented. Cyclophosphamide metabolism, pathogenesis of lung damage and morphological lung tissue changes caused by that agent were characterized. Attention was focused on BAL evaluation as a useful method in the monitoring of lung tissue damage degree.

  19. Metal accumulation in human tissues. Vol. 6. Chromium, nickel, lead, cadmium, and zinc in liver, lungs, spleen, and kidneys. Metallanreicherungen in Humangeweben. Bd. 6. Chrom, Nickel, Blei, Cadmium und Zink in Lunge, Leber, Milz und Niere

    Energy Technology Data Exchange (ETDEWEB)

    Kollmeier, H.; Seemann, J.; Wittig, P.; Witting, C.; Rothe, G.

    1985-01-01

    This paper presents the results of the analytical determination of Cr, Ni, Pb, Cd, and Zn in human lungs, livers, spleens, and kidneys by means of flameless atomic absorption spectrometry, and this on an individual and on a group basis; individually as a combined record which contains the trace metal concentrations of the investigated tissues and the post-mortem findings obtained by autopsy. The retrieval of the findings in case of certain diseases is realized by an index. The tissue concentrations of those metals depend upon many endogenous and exogenous variables, especially as regards time and place. Thus, often interpretations are only possible on an individual basis. For example, we measured an increased tissue concentration of lead in a cadaver which perinatally died of severe vasal malformations. On the other hand, we found a highly positive correlation between age and chromium and nickel content of lungs, which might be interesting in regard to occupational lung cancer. In relation to our results we tried to establish reference levels. However, the interpretation of the measurements remains difficult. Within the scientific literature the results of such studies are very different, and this both in regard to the analytical method used and to the year of publication. This fact is demonstrated by tabular overviews of the investigated metals and tissues. Furthermore, problems of organisation of getting samples, of avoiding sample contamination, of quality assurance etc. are discussed.

  20. BODE-index, modified BODE-index and ADO-score in chronic obstructive pulmonary disease: relationship with COPD phenotypes and CT lung density changes.

    Science.gov (United States)

    Camiciottoli, Gianna; Bigazzi, Francesca; Bartolucci, Maurizio; Cestelli, Lucia; Paoletti, Matteo; Diciotti, Stefano; Cavigli, Edoardo; Magni, Chiara; Buonasera, Luigi; Mascalchi, Mario; Pistolesi, Massimo

    2012-06-01

    COPD is a heterogeneous disorder whose assessment is going to be increasingly multidimensional. Grading systems such as BODE (Body-Mass Index, Obstruction, Dyspnea, Exercise), mBODE (BODE modified in grading of walked distance), ADO (Age, Dyspnea, Obstruction) are proposed to assess COPD severity and outcome. Computed tomography (CT) is deemed to reflect COPD lung pathologic changes. We studied the relationship of multidimensional grading systems (MGS) with clinically determined COPD phenotypes and CT lung density. Seventy-two patients underwent clinical and chest x-ray evaluation, pulmonary function tests (PFT), 6-minute walking test (6MWT) to derive: predominant COPD clinical phenotype, BODE, mBODE, ADO. Inspiratory and expiratory CT was performed to calculate mean lung attenuation (MLA), relative area with density below-950 HU at inspiration (RAI(-950)), and below -910 HU at expiration (RAE(-910)). MGS, PFT, and CT data were compared between bronchial versus emphysematous COPD phenotype. MGS were correlated with CT data. The prediction of CT density by means of MGS was investigated by direct and stepwise multivariate regression. MGS did not differ in clinically determined COPD phenotypes. BODE was more closely related and better predicted CT findings than mBODE and ADO; the better predictive model was obtained for CT expiratory data; stepwise regression models of CT data did not include 6MWT distance; the dyspnea score MRC was included only to predict RA-950 and RA-910 which quantify emphysema extent. BODE reflect COPD severity better than other MGS, but not its clinical heterogeneity. 6MWT does not significantly increase BODE predictivity of CT lung density changes.

  1. Partial liquid ventilation decreases tissue and serum tumor necrosis factor-α concentrations in acute lung injury model of immature piglet induced by oleic acid

    Institute of Scientific and Technical Information of China (English)

    ZHU Yao-bin; FAN Xiang-ming; LI Xiao-feng; LI Zhi-qiang; WANG Qiang; SUN Li-zhong; LIU Ying-long

    2012-01-01

    Background Pediatric patients are susceptible to lung injury.Acute lung injury in children often results in high mortality.Partial liquid ventilation (PLV) has been shown to markedly improve oxygenation and reduce histologic evidence of injury in a number of lung injury models.This study was designed to examine the hypothesis that PLV would attenuate the production of local and systemic tumor necrosis factor (TNF)-α in an immature piglet model of acute lung injury induced by oleic acid (OA).Methods Twelve Chinese immature piglets were induced acute lung injury by OA.The animals were randomly assigned to two groups of six animals,(1) conventional mechanical ventilation (MV) group and (2) PLV with 10 ml/kg FC-77 group.Results Compared with MV group,the PLV group had better cardiopulmonary variables (P <0.05).These variables included heart rate,mean blood pressure,blood pH,partial pressure of arterial oxygen (PaO2),PaO2/inspired O2 fraction (FiO2) and partial pressure of arterial carbon dioxide (PaCO2).PLV reduced TNF-α levels both in plasma and tissue compared with MV group (P <0.05).Conclusion PLV provides protective effects against TNF-a response in OA-induced acute lung injury in immature piglets.

  2. A Comprehensive MicroRNA Expression Profile of Liver and Lung Metastases of Colorectal Cancer with Their Corresponding Host Tissue and Its Prognostic Impact on Survival

    Science.gov (United States)

    Pecqueux, Mathieu; Liebetrau, Isabell; Werft, Wiebke; Dienemann, Hendrik; Muley, Thomas; Pfannschmidt, Joachim; Müssle, Benjamin; Rahbari, Nuh; Schölch, Sebastian; Büchler, Markus W.; Weitz, Jürgen; Reissfelder, Christoph; Kahlert, Christoph

    2016-01-01

    MicroRNAs are small non-coding RNAs with a length of 18–25 nucleotides. They can regulate tumor invasion and metastasis by changing the expression and translation of their target mRNAs. Their expression is substantially altered in colorectal cancer cells as well as in the adjacent tumor-associated stroma. Both of these compartments have a mutual influence on tumor progression. In the development of metastases, cancer cells initially interact with the host tissue. Therefore, compartment-specific expression signatures of these three locations—tumor, associated stroma, and host tissue—can provide new insights into the complex tumor biology of colorectal cancer. Frozen tissue samples of colorectal liver (n = 25) and lung metastases (n = 24) were laser microdissected to separate tumor cells and the adjacent tumor-associated stroma cells. Additionally, normal lung and liver tissue was collected from the same patients. We performed a microarray analysis in four randomly selected liver metastases and four randomly selected lung metastases, analyzing a total of 939 human miRNAs. miRNAs with a significant change >2-fold between the tumor, tumor stroma, and host tissue were analyzed in all samples using RT-qPCR (11 miRNAs) and correlated with the clinical data. We found a differential expression of several miRNAs between the tumor, the tumor-associated stroma, and the host tissue compartment. When comparing liver and lung metastases, miR-194 showed a 1.5-fold; miR-125, miR-127, and miR-192 showed a 2.5-fold; miR-19 and miR-215 a 3-fold; miR-145, miR-199-3, and miR-429 a 5-fold; miR-21 a 7-fold; and, finally, miR-199-5 a 12.5-fold downregulation in liver metastases compared to lung metastases. Furthermore miR-19, miR-125, miR-127, miR-192, miR-194, miR-199-5, and miR-215 showed a significant upregulation in the normal liver tissue compared to the normal lung tissue. Univariate analysis identified an association of poor survival with the expression of miR-125 (p = 0

  3. Features of the physical development, calcium-phosphorus metabolism and mineral density of the bones in children with chronic lung diseases

    Directory of Open Access Journals (Sweden)

    Olya Sharipova

    2011-03-01

    Full Text Available We have studied features of physical development, calcium-phosphorus metabolism and mineral density of the bones in children with chronic lung diseases. Comparison of received results with the standards of physical development in children and adolescents has shown the most significant differences in ages of 10, 11 and 15 years old who had the stature level lower than average. The data obtained suggest that children with this pathology undergoes substantial adverse changes in the main somatomertric indicators and bone mineral density, the degree of which depends on the nature of the primary lesion in the bronchopulmonary system, and duration and severity of disease.

  4. Modulation of the oscillatory mechanics of lung tissue and the oxidative stress response induced by arginase inhibition in a chronic allergic inflammation model.

    Science.gov (United States)

    Aristoteles, Luciana R C R B; Righetti, Renato F; Pinheiro, Nathalia Montouro; Franco, Rosana B; Starling, Claudia M; da Silva, Julie C P; Pigati, Patrícia Angeli; Caperuto, Luciana C; Prado, Carla M; Dolhnikoff, Marisa; Martins, Milton A; Leick, Edna A; Tibério, Iolanda F L C

    2013-08-15

    The importance of the lung parenchyma in the pathophysiology of asthma has previously been demonstrated. Considering that nitric oxide synthases (NOS) and arginases compete for the same substrate, it is worthwhile to elucidate the effects of complex NOS-arginase dysfunction in the pathophysiology of asthma, particularly, related to distal lung tissue. We evaluated the effects of arginase and iNOS inhibition on distal lung mechanics and oxidative stress pathway activation in a model of chronic pulmonary allergic inflammation in guinea pigs. Guinea pigs were exposed to repeated ovalbumin inhalations (twice a week for 4 weeks). The animals received 1400 W (an iNOS-specific inhibitor) for 4 days beginning at the last inhalation. Afterwards, the animals were anesthetized and exsanguinated; then, a slice of the distal lung was evaluated by oscillatory mechanics, and an arginase inhibitor (nor-NOHA) or vehicle was infused in a Krebs solution bath. Tissue resistance (Rt) and elastance (Et) were assessed before and after ovalbumin challenge (0.1%), and lung strips were submitted to histopathological studies. Ovalbumin-exposed animals presented an increase in the maximal Rt and Et responses after antigen challenge (p<0.001), in the number of iNOS positive cells (p<0.001) and in the expression of arginase 2, 8-isoprostane and NF-kB (p<0.001) in distal lung tissue. The 1400 W administration reduced all these responses (p<0.001) in alveolar septa. Ovalbumin-exposed animals that received nor-NOHA had a reduction of Rt, Et after antigen challenge, iNOS positive cells and 8-isoprostane and NF-kB (p<0.001) in lung tissue. The activity of arginase 2 was reduced only in the groups treated with nor-NOHA (p <0.05). There was a reduction of 8-isoprostane expression in OVA-NOR-W compared to OVA-NOR (p<0.001). In this experimental model, increased arginase content and iNOS-positive cells were associated with the constriction of distal lung parenchyma. This functional alteration may be due

  5. [The role of disequilibrium of expression of matrix metalloproteinase-2/9 and their tissue inhibitors in pathogenesis of hyperoxia-induced acute lung injury in mice].

    Science.gov (United States)

    Zhang, Xiang-feng; Zhu, Guang-fa; Liu, Shuang; Foda, Hussein D

    2008-10-01

    To investigate the role of matrix metalloproteinase-2/9 (MMP-2/9) and their tissue inhibitors (TIMP-1/2) in pathogenesis of acute lung injury (ALI) induced by hyperoxia. Seventy-two C57BL/6 mice were randomly divided into normal control group, hyperoxia for 24 hours group, hyperoxia for 48 hours group, and hyperoxia for 72 hours group, with 18 mice in each group. The mice in hyperoxia groups were exposed to >98% oxygen in sealed cages, and the normal control group were placed outside of the cage to breathe room air. At the end of the exposure time the animals were euthanized, the right lung was removed and phosphate buffer solution (PBS) was used to lavage the lung through the endotracheal catheter. The wet/dry weight ratio, broncho-alveolar lavage fluid (BALF) protein content and the volume of pleural fluid were measured, the severity of lung injury was assessed; the expression of MMP-2/9 and TIMP-1/2 mRNA in lung tissue at 24, 48 and 72 hours of hyperoxia were assessed by reverse transcript-polymerase chain reaction (RT-PCR); the amount of MMP-2/9 and TIMP-1/2 protein in lung tissue were measured by enzyme-linked immunosorbent assay (ELISA). Hyperoxia caused ALI as evidenced by the increase in lung wet/dry weight ratio, BALF protein content and the volume of pleural fluid as compared with the normal control group (P<0.05 or P<0.01). RT-PCR study showed increased expression of MMP-2/9 and TIMP-1 mRNA in lung tissues (P<0.05 or P<0.01), and ELISA assay also demonstrated upregulation of MMP-2/9 and an increase in TIMP-1 amount in BALF compared with their normal control group (P<0.05 or P<0.01). The ratios of both MMP-2 mRNA/TIMP-2 mRNA and MMP-2 protein/TIMP-2 protein were all increased in hyperoxia groups as compared with their normal control group (all P<0.01). Hyperoxia causes ALI in mice, and disturbance of MMP-2/TIMP-2 balance plays an important role in the development of hyperoxia-induced ALI in mice.

  6. 非小细胞肺癌肺组织CT灌注成像临床研究%Clinical Study on CT Perfusion Imaging of Lung Tissue in the Non-small Cell Lung Cancer Patients

    Institute of Scientific and Technical Information of China (English)

    胡群超; 顾科; 吴锦昌

    2012-01-01

    目的 研究非小细胞肺癌肺组织的CT灌注成像特点及各参数值,为进一步的放射性肺炎研究提供基础.方法 对18例非小细胞肺癌患者在放疗前行64排螺旋CT灌注成像扫描,得到局部肺组织感兴趣区内各灌注参数值.结果 得到非小细胞肺癌患者肺组织血流量(BF)、血容量(BV)、平均通过时间(MTT)、峰值时间(TTP)数值,但表面通透性 (PS)在75%以上患者中无法测得.非小细胞肺癌肺组织灌注与是否瘤周肺组织无关,不同性别及左右肺对肺组织灌注无影响.结论 CT灌注成像可用于研究非小细胞肺癌肺组织灌注.%Objective To measure perfusion parameters of lung tissue in non-small cell lung cancer(NSCLC) with the technique of CT perfusion imaging(CTPI).Methods 64 slices spiral CTPI were performed in 18 patients with NSCLC before radiotherapy.And varied perfusion parameters of region of interest(ROI) in lung tissue were assessed such as blood flow(BF),blood volume(BV),time to peak(TTP),permeability surface(PS),mean transit time(MTT) and Hounsfield unit(HU). Results BF,BV,TTP,PS and HU were precisely measured in lung tissue,but PS couldn't be detected in more than 75% patients involved.The values of perfusion parameters were similar between para-tumor and non-para tumor lung tissues,male and female patients,left and right lung.Conclusion CTPI was feasible and valuable in studying lung perfusion in NSCLC patients.

  7. Persistent Expression Changes of Fibrosis-Related Genes in the Lung Tissues of Rats Exposed to Lunar Dust Particles

    Science.gov (United States)

    Zhang, Ye; Lam, Chiu-Wing; Scully, Robert R.; Yeshitla, Samrawit A.; Wu, Honglu; Meyers, Valerie; James, John T.

    2014-01-01

    The Moon's surface is covered by a layer of fine, potential reactive dust. Lunar dust contain about 1-2% of very fine respirable dust (less than 3 micrometers). The habitable area of any lunar landing vehicle and outpost would inevitably be contaminated with lunar dust that could pose a health risk. The purpose of the study is to evaluate the toxicity of Apollo moon dust in rodents to assess the health risk of dust exposures to humans. One of the particular interests in the study is to evaluate dust-induced changes of the expression of fibrosis-related genes, and to identify specific signaling pathways involved in lunar dustinduced toxicity. F344 rats were exposed for 4 weeks (6h/d; 5d/wk) in nose-only inhalation chambers to concentrations of 0 (control air), 2.1, 6.8, 21, and 61 milligrams per cubic meters of lunar dust. Five rats per group were euthanized at 1 day, 1 week, 1 month, and 3 months after the last inhalation exposure. The bronchoalveolar lavage fluid (BALF) was collected by lavaging with phosphate-buffered saline (PBS). A zymosan-induced luminolbased chemiluminescence assay was used to assess the activity of BAL cells. The lavaged lung tissue was snap frozen in LN2 and total RNA was isolated using the Qigen RNeasy kit. The expression of 84 fibrosisrelated genes were analyzed using the RT2 Profiler PCR Array technique. The expression of 18 genes of interest were further measured using real-time PCR technique in all the samples. 10 out of 18 genes of interest showed persistently significant expression changes in the local lung tissue exposed to lunar dust, indicating a prolonged proinflammatory response. The expressions of several of these genes were dose- and time-dependent and were significantly correlated with other pathological parameters. The potential signaling pathways and upstream regulators were further analyzed using IPA pathway analysis tool based on the gene expression data. The data presented in this study, for the first time, explore the

  8. Lung iodine mapping by subtraction with image registration allowing for tissue sliding

    Science.gov (United States)

    Mohr, Brian; Brink, Monique; Oostveen, Luuk J.; Schuijf, Joanne D.; Prokop, Mathias

    2016-03-01

    Pulmonary embolism is a fairly common and serious entity, so rapid diagnosis and treatment has a significant impact on morbidity and mortality rates. Iodine maps representing tissue perfusion enhancement are commonly generated by dual-energy CT acquisitions to provide information about the effect of the embolism on pulmonary perfusion. Alternatively, the iodine map can be generated by subtracting pre- from post-contrast CT scans as previously reported. Although accurate image registration is essential, subtraction has the advantage of a higher signal-to-noise ratio and suppression of bone. This paper presents an improvement over the previously reported registration algorithm. Significantly, allowance for sliding motion at tissue boundaries is included in the regularization. Pre- and post-contrast helical CT scans were acquired for thirty subjects using a Toshiba Aquilion ONE scanner. Ten of these subjects were designated for algorithm development, while the remaining twenty were reserved for qualitative clinical evaluation. Quantitative evaluation was performed against the previously reported method and using publicly available data for comparison against other methods. Comparison of 100 landmarks in seven datasets shows no change in the mean Euclidean error of 0.48 mm, compared to the previous method. Evaluation in the publicly available DIR-Lab data with 300 annotations results in a mean Euclidean error of 1.17 mm in the ten 4DCT cases and 3.37 mm in the ten COPDGene cases. Clinical evaluation on a sliding scale from 1 (excellent) to 5 (non-diagnostic) indicates a slight, but non-significant, improvement in registration adequacy from 3.1 to 2.9.

  9. Radiation dose response of normal lung assessed by Cone Beam CT - a potential tool for biologically adaptive radiation therapy

    DEFF Research Database (Denmark)

    Bertelsen, Anders; Schytte, Tine; Bentzen, Søren M;

    2011-01-01

    Density changes of healthy lung tissue during radiotherapy as observed by Cone Beam CT (CBCT) might be an early indicator of patient specific lung toxicity. This study investigates the time course of CBCT density changes and tests for a possible correlation with locally delivered dose....

  10. The protective effect of amiodarone in lung tissue of cecal ligation and puncture-induced septic rats: a perspective from inflammatory cytokine release and oxidative stress.

    Science.gov (United States)

    Polat, Beyzagul; Cadirci, Elif; Halici, Zekai; Bayir, Yasin; Unal, Deniz; Bilgin, Bulent Caglar; Yuksel, Tugba Nurcan; Vancelik, Serhat

    2013-07-01

    Sepsis is a serious medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection. Amiodarone is a class III antiarrhythmic agent, a multichannel blocker (Ca++, Na+, and K+), and a noncompetitive α- and β-adrenergic blocker in cardiac cells. The present study aimed to determine whether amiodarone was protective against experimentally induced cecal ligation and puncture sepsis in rat lung tissue. The relationship between its probable protective effect and antioxidant/anticytokine action biochemically and histopathologically was also examined. Five groups of rats were used, each composed of 20 rats: (1) the sham-operated control group; (2) the CLP group; (3) the 25-mg/kg amiodarone-treated control healthy group; (4) the 50-mg/kg amiodarone-treated CLP group; and (5) the 50-mg/kg amiodarone-treated CLP group. A CLP polymicrobial sepsis model was applied to the rats. All groups were sacrificed 16 h later, and lung and blood samples were analyzed histopathologically and biochemically. Twenty-five and 50 mg/kg amiodarone decreased the level of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in serum and 8-iso-prostaglandin F2α level in lung tissue. They increased the activities of superoxide dismutase and levels of total glutathione in lung tissues of rats. Histopathological scores and examinations were in accordance with the biochemical results. Histopathological analysis revealed significant differences in inflammation scores between the sepsis group and the other groups. The CLP + amiodarone 50 mg/kg group had the lowest inflammation score among CLP groups. Our results indicate that administration of amiodarone prevented oxidative stress and cytokine action and protected lung tissue during sepsis cascade.

  11. A color contrast aided density imaging technique to differentiate between dental hard tissues and its relevance

    Directory of Open Access Journals (Sweden)

    Devi Charan Shetty

    2011-01-01

    Full Text Available Aim: Radiographic interpretation of a disease requires knowledge about normal structures. The calcifying jaw diseases can range from radiolucent areas to varying degrees of calcification. Therefore, it is vital to differentiate radiographically between various hard tissues. Materials and Methods: We have illustrated the use of computed tomography scan to quantify the calcified structures as dentin and enamel in a case of ameloblastic fibro-odontoma. Results: The enamel, dentin and cementum showed different values. Conclusion: The "Dentascan" can be used to distinguish the hard tissues in a variety of calcifying diseases of jaws.

  12. Levels of interleukin-6, superoxide dismutase and malondialdehyde in the lung tissue of a rat model of hypoxia-induced acute pulmonary edema

    Science.gov (United States)

    GAO, HENGBO; TIAN, YINGPING; WANG, WEI; YAO, DONGQI; ZHENG, TUOKANG; MENG, QINGBING

    2016-01-01

    The present study aimed to investigate the levels of malondialdehyde (MDA), superoxide dismutase (SOD) and interleukin (IL)-6 in the lung tissue of a rat model of acute pulmonary edema induced by acute hypoxia, and its pathophysiological significance. A total of 48 adult Wistar rats were randomly divided into group A, a normal group; group B, a model of acute pulmonary edema induced by hypoxia for 24 h; group C, a model of acute pulmonary edema induced by hypoxia for 48 h; and group D, a model of acute pulmonary edema induced by hypoxia for 72 h. The rats in groups B-D were intraperitoneally injected with 6% ammonium chloride to establish the model of acute pulmonary edema, and were subsequently sacrificed following successful modeling for 24, 48 and 72 h. The plasma of rats was isolated and the lungs of the rats were removed. Subsequently, a 10% lung homogenate was prepared and the contents and the activities of MDA, SOD and IL-6 in the lung tissue and IL-6 in the plasma were detected by enzyme-linked immunosorbent assay. MDA and IL-6 expression levels increased and SOD activity decreased in the lung tissue in group B as compared with group A; however the difference did not reach significance (P>0.05). MDA, IL-6 and SOD levels in the lung tissue of rats were significantly altered following the increased duration of pulmonary edema in groups C and D, as compared group A (P<0.05). The plasma IL-6 levels of the rats in groups B-D significantly increased, as compared with those in group A (P<0.05). In conclusion, the results of the present study demonstrated that the incidence of acute pulmonary edema may be associated with oxidative stress. Furthermore, decreased antioxidant capacity and increased free radical levels may be associated with pulmonary edema, as in the present study the levels of IL-6, SOD and MDA in the lung tissue were observed to be associated with the pathological changes of the disease. PMID:26998026

  13. DIFFERENTIAL RESPONSE OF HEAT SHOCK PROTEINS TO UPHILL AND DOWNHILL EXERCISE IN HEART, SKELETAL MUSCLE, LUNG AND KIDNEY TISSUES

    Directory of Open Access Journals (Sweden)

    Pablo C. B. Lollo

    2013-09-01

    Full Text Available Running on a horizontal plane is known to increase the concentration of the stress biomarker heat-shock protein (HSP, but no comparison of the expression of HSP70 has yet been established between the uphill (predominantly concentric and downhill (predominantly eccentric muscle contractions exercise. The objective of the study was to investigate the relationships between eccentric and concentric contractions on the HSP70 response of the lung, kidney, gastrocnemius, soleus and heart. Twenty-four male Wistar weanling rats were divided into four groups: non-exercised and three different grades of treadmill exercise groups: horizontal, uphill (+7% and downhill (-7% of inclination. At the optimal time-point of six hours after the exercise, serum uric acid, creatine kinase (CK and lactate dehydrogenase (LDH were determined by standard methods and HSP70 by the Western blot analysis. HSP70 responds differently to different types of running. For kidney, heart, soleus and gastrocnemius, the HSP70 expression increased, 230, 180, 150 and 120% respectively of the reference (horizontal. When the contraction was concentric (uphill and compared to downhill the increase in response of HSP70 was greater in 80% for kidney, 75% for gastrocnemius, 60% for soleus and 280% for the heart. Uric acid was about 50% higher (0.64 ± 0.03 mg·dL-1 in the uphill group as compared to the horizontal or downhill groups. Similarly, the activities of serum CK and LDH were both 100% greater for both the uphill and downhill groups as compared to the horizontal group (2383 ± 253 and 647.00 ± 73 U/L, respectively. The responsiveness of HSP70 appeared to be quite different depending on the type of tissue, suggesting that the impact of exercise was not restricted to the muscles, but extended to the kidney tissue. The uphill exercise increases HSP70 beyond the eccentric type and the horizontal running was a lower HSP70 responsive stimulus

  14. 煤工尘肺及合并肺癌肺组织Bcl-2基因表达及意义%Expression and Its Significance of Bcl-2 Protein in Lung Tissues of Coal Workers Pneumoconiosis Complicated with Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    范雪云; 马庆坤; 张岩松; 马骏; 张翔

    2011-01-01

    Objective To detect the expression of Bcl-2 protein in lung tissues of coal worker' s pneumoconiosis(CWP) complicated with lung cancer and to explore the relationship between CWP and lung cancer and its molecular mechanism. Methods The dissected lung specimens of CWP were collected. Based on pathologic diagnosis, 54 cases of CWP and 10 cases of CWP complicated with lung cancer were selected as the study subject. Since to obtain healthy persons' lung tissue was very difficult, the lung tissues of normal structure at the side of pathological tissue from of 30 CWP were selected as the control. Bcl-2 gene proteins for all lung tissues were measured by immunohistochemical Elivision plus method. Chi-Square test and t test were used to analyze the data. Results The positive rates of Bcl-2 protein expression in tissues of the control, CWP and CWP complicated with lung cancer group were 16. 7%(5/30), 24. 1 %(13/54), and 90. 0%(9/10), respectively. The average values of optical density were 2. 08 ± 0. 16, 2. 51 ± 0. 19 and 3. 22 ± 0. 41, respectively. The positive rate of Bcl-2 protein expression in CWP complicated with lung cancer was significantly higher than that of CWP and the control tissue (P0. 05). Conclusions The expression of Bcl-2 protein distinctively increases in lung tissues of CWP complicated with lung cancer and CWP. The excessive expression of Bcl-2 might play a role in the development lung cancer in CWP.%目的 检测煤工尘肺及合并肺癌肺组织Bcl-2基因蛋白表达情况,探讨煤工尘肺与肺癌的关系及其分子学机制.方法 收集煤工尘肺及煤工尘肺合并肺癌患者尸解病例为研究对象.依据病理诊断,选择煤工尘肺54例,尘肺合并肺癌10例.选取30例煤工尘肺病变旁正常肺组织(组织结构正常、肺泡间隔无破坏、肺泡腔内未见渗出)作为对照肺组织.利用免疫组化方法检测Bcl-2基因蛋白在肺组织中的表达情况.结果 对照肺组织、煤工尘肺肺组织和煤

  15. Gelatin based on Power-gel.TM. as solders for Cr.sup.4+laser tissue welding and sealing of lung air leak and fistulas in organs

    Science.gov (United States)

    Alfano, Robert R.; Tang, Jing; Evans, Jonathan M.; Ho, Peng Pei

    2006-04-25

    Laser tissue welding can be achieved using tunable Cr.sup.4+ lasers, semiconductor lasers and fiber lasers, where the weld strength follows the absorption spectrum of water. The use of gelatin and esterified gelatin as solders in conjunction with laser inducted tissue welding impart much stronger tensile and torque strengths than albumin solders. Selected NIR wavelength from the above lasers can improve welding and avoid thermal injury to tissue when used alone or with gelatin and esterified gelatin solders. These discoveries can be used to enhance laser tissue welding of tissues such as skin, mucous, bone, blood vessel, nerve, brain, liver, pancreas, spleen, kidney, lung, bronchus, respiratory track, urinary tract, gastrointestinal tract, or gynecologic tract and as a sealant for pulmonary air leaks and fistulas such as intestinal, rectal and urinary fistulas.

  16. ELISA for complexes between urokinase-type plasminogen activator and its receptor in lung cancer tissue extracts

    DEFF Research Database (Denmark)

    de Witte, H; Pappot, H; Brünner, N;

    1997-01-01

    A sandwich-type ELISA has been developed for the assessment of complexes between urokinase-type plasminogen activator (uPA) and its receptor (uPAR) in extracts of squamous cell lung carcinomas. The assay is based on a combination of rabbit polyclonal anti-uPA antibodies and a biotinylated mouse...... extraction of uPAR yields the highest amounts of uPA:uPAR complexes. Absorption of tumor extracts with anti-uPA or anti-uPAR MAbs results in a complete disappearance of the ELISA signal, demonstrating the specificity of the ELISA. The recovery of chemically cross-linked uPA:uPAR complexes added to tumor...... extracts varies between 80% and 105%. The intra- and inter-assay variation coefficients are 5.3% and 9.8%, respectively. Furthermore, a peptide antagonist for uPAR was employed to evaluate de novo uPA:uPAR complex formation during tumor tissue extraction and the immunoassay procedure. Our results strongly...

  17. Tissue non-specific alkaline phosphatase production by human dental pulp stromal cells is enhanced by high density cell culture.

    Science.gov (United States)

    Tomlinson, Matthew J; Dennis, Caitriona; Yang, Xuebin B; Kirkham, Jennifer

    2015-08-01

    The cell surface hydrolase tissue non-specific alkaline phosphatase (TNAP) (also known as MSCA-1) is used to identify a sub-population of bone marrow stromal cells (BMSCs) with high mineralising potential and is found on subsets of cells within the dental pulp. We aim to determine whether TNAP is co-expressed by human dental pulp stromal cells (hDPSCs) alongside a range of BMSC markers, whether this is an active form of the enzyme and the effects of culture duration and cell density on its expression. Cells from primary dental pulp and culture expanded hDPSCs expressed TNAP. Subsequent analyses revealed persistent TNAP expression and co-expression with BMSC markers such as CD73 and CD90. Flow cytometry and biochemical assays showed that increased culture durations and cell densities enhanced TNAP expression by hDPSCs. Arresting the hDPSC cell cycle also increased TNAP expression. These data confirm that TNAP is co-expressed by hDPSCs together with other BMSC markers and show that cell density affects TNAP expression levels. We conclude that TNAP is a potentially useful marker for hDPSC selection especially for uses in mineralised tissue regenerative therapies.

  18. Over, and Underexpression of Endothelin 1 and TGF-Beta Family Ligands and Receptors in Lung Tissue of Broilers with Pulmonary Hypertension

    Science.gov (United States)

    Dominguez-Avila, Norma; Ruiz-Castañeda, Gabriel; González-Ramírez, Javier; Fernandez-Jaramillo, Nora; Escoto, Jorge; Sánchez-Muñoz, Fausto; Marquez-Velasco, Ricardo; Bojalil, Rafael; Espinosa-Cervantes, Román; Sánchez, Fausto

    2013-01-01

    Transforming growth factor beta (TGFβ) is a family of genes that play a key role in mediating tissue remodeling in various forms of acute and chronic lung disease. In order to assess their role on pulmonary hypertension in broilers, we determined mRNA expression of genes of the TGFβ family and endothelin 1 in lung samples from 4-week-old chickens raised either under normal or cold temperature conditions. Both in control and cold-treated groups of broilers, endothelin 1 mRNA expression levels in lungs from ascitic chickens were higher than levels from healthy birds (P 0.05). BAMBI mRNA gene expression was lowest in birds with ascites only in the control group as compared with the values from healthy birds (P < 0.05). PMID:24286074

  19. Airborne particulate matter selectively activates endoplasmic reticulum stress response in the lung and liver tissues.

    Science.gov (United States)

    Laing, Suzette; Wang, Guohui; Briazova, Tamara; Zhang, Chunbin; Wang, Aixia; Zheng, Ze; Gow, Alexander; Chen, Alex F; Rajagopalan, Sanjay; Chen, Lung Chi; Sun, Qinghua; Zhang, Kezhong

    2010-10-01

    Recent studies have suggested a link between inhaled particulate matter (PM) exposure and increased mortality and morbidity associated with pulmonary and cardiovascular diseases. However, a precise understanding of the biological mechanism underlying PM-associated toxicity and pathogenesis remains elusive. Here, we investigated the impact of PM exposure in intracellular stress signaling pathways with animal models and cultured cells. Inhalation exposure of the mice to environmentally relevant fine particulate matter (aerodynamic diameter liver tissues as well as in the mouse macrophage cell line RAW264.7. Ambient PM(2.5) exposure activates double-strand RNA-activated protein kinase-like ER kinase (PERK), leading to phosphorylation of translation initiation factor eIF2α and induction of C/EBP homologous transcription factor CHOP/GADD153. Activation of PERK-mediated UPR pathway relies on the production of reactive oxygen species (ROS) and is critical for PM(2.5)-induced apoptosis. Furthermore, PM(2.5) exposure can activate ER stress sensor IRE1α, but it decreases the activity of IRE1α in splicing the mRNA encoding the UPR trans-activator X-box binding protein 1 (XBP1). Together, our study suggests that PM(2.5) exposure differentially activates the UPR branches, leading to ER stress-induced apoptosis through the PERK-eIF2α-CHOP UPR branch. This work provides novel insights into the cellular and molecular basis by which ambient PM(2.5) exposure elicits its cytotoxic effects that may be related to air pollution-associated pathogenesis.

  20. Dose to level I and II axillary lymph nodes and lung by tangential field radiation in patients undergoing postmastectomy radiation with tissue expander reconstruction

    Directory of Open Access Journals (Sweden)

    Russo James K

    2011-12-01

    Full Text Available Abstract Background To define the dosimetric coverage of level I/II axillary volumes and the lung volume irradiated in postmastectomy radiotherapy (PMRT following tissue expander placement. Methods and Materials Twenty-three patients were identified who had undergone postmastectomy radiotherapy with tangent only fields. All patients had pre-radiation tissue expander placement and expansion. Thirteen patients had bilateral expander reconstruction. The level I/II axillary volumes were contoured using the RTOG contouring atlas. The patient-specific variables of expander volume, superior-to-inferior location of expander, distance between expanders, expander angle and axillary volume were analyzed to determine their relationship to the axillary volume and lung volume dose. Results The mean coverage of the level I/II axillary volume by the 95% isodose line (VD95% was 23.9% (range 0.3 - 65.4%. The mean Ipsilateral Lung VD50% was 8.8% (2.2-20.9. Ipsilateral and contralateral expander volume correlated to Axillary VD95% in patients with bilateral reconstruction (p = 0.01 and 0.006, respectively but not those with ipsilateral only reconstruction (p = 0.60. Ipsilateral Lung VD50% correlated with angle of the expander from midline (p = 0.05. Conclusions In patients undergoing PMRT with tissue expanders, incidental doses delivered by tangents to the axilla, as defined by the RTOG contouring atlas, do not provide adequate coverage. The posterior-superior region of level I and II is the region most commonly underdosed. Axillary volume coverage increased with increasing expander volumes in patients with bilateral reconstruction. Lung dose increased with increasing expander angle from midline. This information should be considered both when placing expanders and when designing PMRT tangent only treatment plans by contouring and targeting the axilla volume when axillary treatment is indicated.

  1. Dose to level I and II axillary lymph nodes and lung by tangential field radiation in patients undergoing postmastectomy radiation with tissue expander reconstruction

    Science.gov (United States)

    2011-01-01

    Background To define the dosimetric coverage of level I/II axillary volumes and the lung volume irradiated in postmastectomy radiotherapy (PMRT) following tissue expander placement. Methods and Materials Twenty-three patients were identified who had undergone postmastectomy radiotherapy with tangent only fields. All patients had pre-radiation tissue expander placement and expansion. Thirteen patients had bilateral expander reconstruction. The level I/II axillary volumes were contoured using the RTOG contouring atlas. The patient-specific variables of expander volume, superior-to-inferior location of expander, distance between expanders, expander angle and axillary volume were analyzed to determine their relationship to the axillary volume and lung volume dose. Results The mean coverage of the level I/II axillary volume by the 95% isodose line (VD95%) was 23.9% (range 0.3 - 65.4%). The mean Ipsilateral Lung VD50% was 8.8% (2.2-20.9). Ipsilateral and contralateral expander volume correlated to Axillary VD95% in patients with bilateral reconstruction (p = 0.01 and 0.006, respectively) but not those with ipsilateral only reconstruction (p = 0.60). Ipsilateral Lung VD50% correlated with angle of the expander from midline (p = 0.05). Conclusions In patients undergoing PMRT with tissue expanders, incidental doses delivered by tangents to the axilla, as defined by the RTOG contouring atlas, do not provide adequate coverage. The posterior-superior region of level I and II is the region most commonly underdosed. Axillary volume coverage increased with increasing expander volumes in patients with bilateral reconstruction. Lung dose increased with increasing expander angle from midline. This information should be considered both when placing expanders and when designing PMRT tangent only treatment plans by contouring and targeting the axilla volume when axillary treatment is indicated. PMID:22204504

  2. Killing effect of EGFR-TKI combined with 125I seed implantation therapy onⅢB-Ⅳ stage lung cancer tissue

    Institute of Scientific and Technical Information of China (English)

    Ai-Sheng Xiang

    2016-01-01

    Objective:To analyze the killing effect of EGFR-TKI combined with 125I seed implantation therapy onⅢB-Ⅳ stage lung cancer tissue.Methods:A total of 78 patients withⅢB-Ⅳ stage lung cancer were randomly divided into observation group and control group (n=39), control group received EGFR-TKI treatment and observation group received EGFR-TKI combined with 125I seed implantation therapy. Differences in apoptosis gene, invasion gene and autophagy gene expression in lung tissue were compared between two groups after 1 month of treatment.Results:Apoptosis genesPDCD5, bax andbcl-xSmRNA expression levels in lung tissue of observation group after 1 month of treatment were higher than those of control group whileBag-1, survivin andbcl-xL mRNA expression levels were lower than those of control group; invasion genesCD147, EGFRandDDX17 mRNA expression levels were lower than those of control group while Bin1, E-cadherin andOvol2mRNA expression levels were higher than those of control group; autophagy genes ARHI, Beclin1, Atg5, LC3B, pULK andPI3KC3 mRNA expression levels were higher than those of control group.Conclusions: EGFR-TKI combined with 125I seed implantation therapy can enhance the tumor killing effect on patients withⅢB-Ⅳ stage lung cancer, and contribute to the optimization of overall condition and the extension of survival time.

  3. High seeding density of human chondrocytes in agarose produces tissue-engineered cartilage approaching native mechanical and biochemical properties.

    Science.gov (United States)

    Cigan, Alexander D; Roach, Brendan L; Nims, Robert J; Tan, Andrea R; Albro, Michael B; Stoker, Aaron M; Cook, James L; Vunjak-Novakovic, Gordana; Hung, Clark T; Ateshian, Gerard A

    2016-06-14

    Animal cells have served as highly controllable model systems for furthering cartilage tissue engineering practices in pursuit of treating osteoarthritis. Although successful strategies for animal cells must ultimately be adapted to human cells to be clinically relevant, human chondrocytes are rarely employed in such studies. In this study, we evaluated the applicability of culture techniques established for juvenile bovine and adult canine chondrocytes to human chondrocytes obtained from fresh or expired osteochondral allografts. Human chondrocytes were expanded and encapsulated in 2% agarose scaffolds measuring ∅3-4mm×2.3mm, with cell seeding densities ranging from 15 to 90×10(6)cells/mL. Subsets of constructs were subjected to transient or sustained TGF-β treatment, or provided channels to enhance nutrient transport. Human cartilaginous constructs physically resembled native human cartilage, and reached compressive Young's moduli of up to ~250kPa (corresponding to the low end of ranges reported for native knee cartilage), dynamic moduli of ~950kPa (0.01Hz), and contained 5.7% wet weight (%/ww) of glycosaminoglycans (≥ native levels) and 1.5%/ww collagen. We found that the initial seeding density had pronounced effects on tissue outcomes, with high cell seeding densities significantly increasing nearly all measured properties. Transient TGF-β treatment was ineffective for adult human cells, and tissue construct properties plateaued or declined beyond 28 days of culture. Finally, nutrient channels improved construct mechanical properties, presumably due to enhanced rates of mass transport. These results demonstrate that our previously established culture system can be successfully translated to human chondrocytes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Adipose tissue deficiency results in severe hyperlipidemia and atherosclerosis in the low-density lipoprotein receptor knockout mice.

    Science.gov (United States)

    Wang, Mengyu; Gao, Mingming; Liao, Jiawei; Qi, Yanfei; Du, Ximing; Wang, Yuhui; Li, Ling; Liu, George; Yang, Hongyuan

    2016-05-01

    Adipose tissue can store over 50% of whole-body cholesterol; however, the physiological role of adipose tissue in cholesterol metabolism and atherogenesis has not been directly assessed. Here, we examined lipoprotein metabolism and atherogenesis in a unique mouse model of severe lipodystrophy: the Seipin(-/-) mice, and also in mice deficient in both low-density lipoprotein receptor (Ldlr) and Seipin: the Ldlr(-/-)Seipin(-/-) mice. Plasma cholesterol was moderately increased in the Seipin(-/-) mice when fed an atherogenic diet. Strikingly, plasma cholesterol reached ~6000 mg/dl in the Seipin(-/-)Ldlr(-/-) mice on an atherogenic diet, as compared to ~1000 mg/dl in the Ldlr(-/-) mice on the same diet. The Seipin(-/-)Ldlr(-/-) mice also developed spontaneous atherosclerosis on chow diet and severe atherosclerosis on an atherogenic diet. Rosiglitazone treatment significantly reduced the hypercholesterolemia of the Seipin(-/-)Ldlr(-/-) mice, and also alleviated the severity of atherosclerosis. Our results provide direct evidence, for the first time, that the adipose tissue plays a critical role in the clearance of plasma cholesterol. Our results also reveal a previously unappreciated strong link between adipose tissue and LDLR in plasma cholesterol metabolism.

  5. Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: provisional core sets of domains and instruments for use in clinical trials.

    Science.gov (United States)

    Saketkoo, Lesley Ann; Mittoo, Shikha; Huscher, Dörte; Khanna, Dinesh; Dellaripa, Paul F; Distler, Oliver; Flaherty, Kevin R; Frankel, Sid; Oddis, Chester V; Denton, Christopher P; Fischer, Aryeh; Kowal-Bielecka, Otylia M; LeSage, Daphne; Merkel, Peter A; Phillips, Kristine; Pittrow, David; Swigris, Jeffrey; Antoniou, Katerina; Baughman, Robert P; Castelino, Flavia V; Christmann, Romy B; Christopher-Stine, Lisa; Collard, Harold R; Cottin, Vincent; Danoff, Sonye; Highland, Kristin B; Hummers, Laura; Shah, Ami A; Kim, Dong Soon; Lynch, David A; Miller, Frederick W; Proudman, Susanna M; Richeldi, Luca; Ryu, Jay H; Sandorfi, Nora; Sarver, Catherine; Wells, Athol U; Strand, Vibeke; Matteson, Eric L; Brown, Kevin K; Seibold, James R

    2014-05-01

    Clinical trial design in interstitial lung diseases (ILDs) has been hampered by lack of consensus on appropriate outcome measures for reliably assessing treatment response. In the setting of connective tissue diseases (CTDs), some measures of ILD disease activity and severity may be confounded by non-pulmonary comorbidities. The Connective Tissue Disease associated Interstitial Lung Disease (CTD-ILD) working group of Outcome Measures in Rheumatology-a non-profit international organisation dedicated to consensus methodology in identification of outcome measures-conducted a series of investigations which included a Delphi process including >248 ILD medical experts as well as patient focus groups culminating in a nominal group panel of ILD experts and patients. The goal was to define and develop a consensus on the status of outcome measure candidates for use in randomised controlled trials in CTD-ILD and idiopathic pulmonary fibrosis (IPF). A core set comprising specific measures in the domains of lung physiology, lung imaging, survival, dyspnoea, cough and health-related quality of life is proposed as appropriate for consideration for use in a hypothetical 1-year multicentre clinical trial for either CTD-ILD or IPF. As many widely used instruments were found to lack full validation, an agenda for future research is proposed. Identification of consensus preliminary domains and instruments to measure them was attained and is a major advance anticipated to facilitate multicentre RCTs in the field.

  6. Cryopreserved Human Precision-Cut Lung Slices as a Bioassay for Live Tissue Banking. A Viability Study of Bronchodilation with Bitter-Taste Receptor Agonists.

    Science.gov (United States)

    Bai, Yan; Krishnamoorthy, Nandini; Patel, Kruti R; Rosas, Ivan; Sanderson, Michael J; Ai, Xingbin

    2016-05-01

    Human precision-cut lung slices (hPCLSs) provide a unique ex vivo model for translational research. However, the limited and unpredictable availability of human lung tissue greatly impedes their use. Here, we demonstrate that cryopreservation of hPCLSs facilitates banking of live human lung tissue for routine use. Our results show that cryopreservation had little effect on overall cell viability and vital functions of immune cells, including phagocytes and T lymphocytes. In addition, airway contraction and relaxation in response to specific agonists and antagonists, respectively, were unchanged after cryopreservation. At the subcellular level, cryopreserved hPCLSs maintained Ca(2+)-dependent regulatory mechanisms for the control of airway smooth muscle cell contractility. To exemplify the use of cryopreserved hPCLSs in smooth muscle research, we provide evidence that bitter-taste receptor (TAS2R) agonists relax airways by blocking Ca(2+) oscillations in airway smooth muscle cells. In conclusion, the banking of cryopreserved hPCLSs provides a robust bioassay for translational research of lung physiology and disease.

  7. Histological changes in lung tissues related with sub-chronic exposure to ambient urban levels of PM2.5 in Córdoba, Argentina

    Science.gov (United States)

    Tavera Busso, Iván; Vera, Anahí; Mateos, Ana Carolina; Amarillo, Ana Carolina; Carreras, Hebe

    2017-10-01

    Concentration of fine particulate matter (PM2.5) is one of the most important environmental parameters to estimate health impacts attributable to air pollution. Despite the fact there are many studies regarding PM2.5 effects on human health, most of them were performed under conditions that do not simulate the natural particles interaction with the organism. In the present paper, we studied the effects of mammals' sub-chronic exposure to PM2.5 on the lower respiratory tract, addressing realistic exposure conditions to normal urban air. Thus, we exposed Wistar rats under controlled settings to the same normal urban air, with and without particles. Next, we analyzed chemical composition of PM2.5 and lungs samples, performed a histologic examination and run the comet assay to assess genotoxic effects. We found a strong agreement between lung tissues and PM2.5 elemental composition suggesting that metals found in lungs came from the particles inhaled. Histological analysis showed a mild to moderate infiltration, with a reduction of alveoli lumen and increment of alveolar macrophages and periodic acid-Schiff (PAS) (+) cells in treated animals. We also observed an increase in the number of nuclei with comets, mostly comets type 3, with a high DNA fragmentation as well. These results provide strong evidence that sub-chronic exposure to low particle levels, even below the 24 h WHO standard, can cause injuries in lungs tissues and DNA damage, as well.

  8. LOW DOSE PIRFENIDONE SUPPRESSES TRANSFORMING GROWTH FACTOR BETA-1 AND TISSUE INHIBITOR OF METALLOPROTEINASE-1,AND PROTECTS RATS FROM LUNG FIBROSIS INDUCED BY BLEOMYCIN

    Institute of Scientific and Technical Information of China (English)

    Xin-lun Tian; Wei Yao; Zi-jian Guo; Li Gu; Yuan-jue Zhu

    2006-01-01

    Objective To investigate the optimal dosage of pirfenidone for the treatment of pulmonary fibrosis induced by bleomycin in Wistar rats, and the alteration of expressions of transforming growth factor beta-1 (TGF-β1), tissue inhibitor of metalloproteinase-1 (TIMP-1), and matrix metalloproteinase-13 (MMP-13) in lung tissue.Methods Male Wistar rats were endotracheally instilled with bleomycin or normal saline. Pirfenidone (25-800 mg·kg-1·d-1), dexamethasone (3 mg/kg), or 1% carboxymethylcellulose sodium were given daily by feed 2 days before instillation of bleomycin. Groups T7 and T14 were fed pirfenidone 50 mg·kg -1·d-1 at 7 days or 14 days after bleomycin instillation. Lungs were harvested at 28 days after bleomycin instillation. Patholological changes in lung tissues were evaluated with HE staining. Lung collagen was stained by sirius red and measured by content of hydroxyproline. Expression of proteins of TGF-β, TIMP-1, and MMP-13 were detected by Western blotting.Results At doses of 25, 50, and 100 mg·kg-1·d-1, pirfenidone had significant anti-fibrofic effects for bleomycin-induced rat pulmonary fibrosis, and these effects were most significantly attenuated at the dosage of 50mg·kg-1 1d-1 (HE: P<0.01, P<0.01, and P =0.064; sirius red: P<0.05, P<0.01, and P<0. 05; hydroxyproline: P=0.595, P<0.01, and P=0.976). Pirfenidone at a dosage of 50 mg·kg -1·d-1 inhibited protein expression of TGF-β1 and TIMP-1 in lung tissue in the early phase (0.79 and 0.75 times of control group), but had no effect on expression of MMP-13.Conclusion Low dose pirfenidone, especially at dosage of 50 mg·kg-1·d-1, has significant anti-fibrotic effects on bleomycin-induced rat pulmonary fibrosis. Pirfenidone partially inhibits the enhancement of the expression of TGF-β1 and TIMP-1 in lung tissue.

  9. Tissue distribution of 2-methoxyestradiol nanosuspension in rats and its antitumor activity in C57BL/6 mice bearing lewis lung carcinoma.

    Science.gov (United States)

    Shen, Guopeng; Wang, Qingyu; Zhang, Qingqing; Sun, Huibin; Zhao, Ya; Zhang, Zhenzhong; Du, Bin

    2012-01-01

    The purpose of the present study was to evaluate the tissue distribution and antitumor activity of 2-methoxyestradiol (2-ME) nanosuspension compared with 2-ME solution both in vitro and in vivo. 2-ME nanosuspension was made by nanoprecipitation-high-frequency ultrasonication method with the particle size of 168.4 ± 3.2 nm and the zeta potential of -29.79 ± 1.89 mV. The overall targeting efficiency (TE(Q)) of 2-ME nanosuspension was improved from 28.71 to 51.95% in the lung of rats. MTT assay showed that 2-ME nanosuspension could significantly enhance the in vitro cytotoxicity against lewis lung carcinoma (LLC) cells compared with the 2-ME solution, the IC(50) at 72 h was reduced from 6.35 µM for 2-ME solution to 3.56 µM for 2-ME nanosuspension. The antitumor activity in vivo was investigated in C57BL/6 mice bearing LLC, and the results indicated that 2-ME nanosuspension not only exhibited significant suppression of the tumor growth when compared with that of positive group or cyclophosphamide group at the same dose, but also enhanced the spleen indices. Overall, 2-ME nanosuspension could mainly deliver the drug to lungs and made the drug accumulate in the lungs, so 2-ME nanosuspension has a possible lung cancer therapeutic potential.

  10. The immediate effect of soft tissue manual therapy intervention on lung function in severe chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Cruz-Montecinos C

    2017-02-01

    Full Text Available Carlos Cruz-Montecinos,1–3 Diego Godoy-Olave,4 Felipe A Contreras-Briceño,5 Paulina Gutiérrez,4 Rodrigo Torres-Castro,2 Leandro Miret-Venegas,3 Roger M Engel6 1Laboratory of Biomechanics and Kinesiology, San José Hospital, Santiago, Chile; 2Department of Physical Therapy, Faculty of Medicine, University of Chile, Santiago, Chile; 3Unit of Kinesiology and Physical Therapy, San José Hospital, Santiago, Chile; 4Departamento de Kinesiología, Universidad Metropolitana de Ciencias de la Educación, Santiago, Chile; 5Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile; 6Department of Chiropractic, Macquarie University, Sydney, Australia Background and objective: In chronic obstructive pulmonary disease (COPD, accessory respiratory muscles are recruited as a compensatory adaptation to changes in respiratory mechanics. This results in shortening and overactivation of these and other muscles. Manual therapy is increasingly being investigated as a way to alleviate these changes. The aim of this study was to measure the immediate effect on lung function of a soft tissue manual therapy protocol (STMTP designed to address changes in the accessory respiratory muscles and their associated structures in patients with severe COPD.Methods: Twelve medically stable patients (n=12 with an existing diagnosis of severe COPD (ten: GOLD Stage III and two: GOLD Stage IV were included. Residual volume, inspiratory capacity and oxygen saturation (SpO2 were recorded immediately before and after administration of the STMTP. A Student’s t-test was used to determine the effect of the manual therapy intervention (P<0.05.Results: The mean age of the patients was 62.4 years (range 46–77. Nine were male. Residual volume decreased from 4.5 to 3.9 L (P=0.002, inspiratory capacity increased from 2.0 to 2.1 L (P=0.039 and SpO2 increased from 93% to 96% (P=0.001.Conclusion: A single application of an STMTP appears to have the potential to produce

  11. Morphological appearance, content of extracellular matrix and vascular density of lung metastases predicts permissiveness to infiltration by adoptively transferred natural killer and T cells

    DEFF Research Database (Denmark)

    Yang, Q.; Goding, S.; Hagenaars, M.

    2006-01-01

    We have recently shown that adoptively transferred, IL-2-activated natural killer (A-NK) cells are able to eliminate well-established B16-F10.P1 melanoma lung metastases. However, some B16-F10.P1 lung metastases were resistant to infiltration by the A-NK cells and also resistant to the A-NK cell...... (3LL), MCA-102 sarcoma, and MC38 colon carcinoma as well as rat MADB106 mammary carcinoma origin. Furthermore, the infiltration resistance of the compact tumors is not restricted to A-NK cells, since PHA and IL-2 stimulated CD8+ T-cells (T-LAK cells) also infiltrated the compact tumors poorly...... infiltration by activated NK and T cells correlates with the presence of ECM components and PECAM-1(+) vasculature in the malignant tissue. Thus, analysis of the distribution of ECM and vasculature in tumor biopsies may help select patients most likely to benefit from cellular adoptive immunotherapy....

  12. Effect of antisense TIMP-1 cDNA on the expression of TIMP-1 and MMP-2 in lung tissue with pulmonary fibrosis induced by bleomycin.

    Science.gov (United States)

    Tang, Haiying; Mao, Jingwei; Gao, Lili; Liu, Jia; Wu, Taihua

    2013-01-01

    The aim of this study was to observe the effect of antisense tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) cDNA on the concentration of hydroxyproline (HYP) and the expression of TIMP-1 and matrix metalloproteinase-2 (MMP-2) in the lung tissue of rats with bleomycin (BLM)‑induced pulmonary fibrosis. Sprague-Dawley rats were randomly divided into 5 groups: the control, pulmonary fibrosis model, sense TIMP-1 transfection, antisense TIMP-1 transfection and empty vector transfection groups. For the transfection groups, following the intratracheal injection of BLM on days 1, 3, 7, 14, 28 and 60, the rats were treated with retroviral vectors and sacrificed on day 28. The control and pulmonary fibrosis groups were treated with normal saline at the same time‑points. The concentration of HYP and the expression levels of TIMP-1 and MMP-2 in the lung tissue were detected. The HYP concentration and lung tissue TIMP-1 expression levels of the antisense TIMP-1 group decreased significantly on days 1 and 3 compared with those of the empty vector and pulmonary fibrosis groups at the same time-points (Ppulmonary fibrosis groups on days 7, 14, 28 and 60. The lung expression levels of MMP-2 in all groups, with the exception of the control group, had no significant differences at all time-points (P>0.05). Antisense TIMP-1 cDNA retroviral vectors are able to suppress the development of pulmonary fibrosis in the early stages.

  13. Tumor-Derived Tissue Factor Aberrantly Activates Complement and Facilitates Lung Tumor Progression via Recruitment of Myeloid-Derived Suppressor Cells

    OpenAIRE

    Xiao Han; Haoran Zha; Fei Yang; Bo Guo; Bo Zhu

    2017-01-01

    The initiator of extrinsic coagulation, tissue factor (TF), and its non-coagulant isoform alternatively spliced TF (asTF) are closely associated with tumor development. In the tumor microenvironment, the role of TF-induced coagulation in tumor progression remains to be fully elucidated. Using TF-knockdown lung tumor cells, we showed that TF is the dominant component of procoagulant activity but is dispensable in the cellular biology of tumor cells. In a xenograft model, using immunohistochemi...

  14. Prognostic significance of Ki67 proliferation index, HIF1 alpha index and microvascular density in patients with non-small cell lung cancer brain metastases

    Energy Technology Data Exchange (ETDEWEB)

    Berghoff, A.S. [Medical University of Vienna, Institute of Neurology, Vienna (Austria); Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Medical University of Vienna, Department of Medicine I, Vienna (Austria); Ilhan-Mutlu, A.; Preusser, M. [Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Medical University of Vienna, Department of Medicine I, Vienna (Austria); Woehrer, A.; Hainfellner, J.A. [Medical University of Vienna, Institute of Neurology, Vienna (Austria); Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Hackl, M. [Austrian National Cancer Registry, Statistics Austria, Vienna (Austria); Widhalm, G. [Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Medical University of Vienna, Department of Neurosurgery, Vienna (Austria); Dieckmann, K. [Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Medical University of Vienna, Department of Radiotherapy, Vienna (Austria); Melchardt, T. [Paracelsus Medical University Hospital Salzburg, Third Medical Department, Salzburg (Austria); Dome, B. [Medical University of Vienna, Department of Surgery, Vienna (Austria); Heinzl, H. [Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Medical University of Vienna, Center for Medical Statistics, Informatics, and Intelligent Systems, Vienna (Austria); Birner, P. [Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Medical University of Vienna, Institute of Clinical Pathology, Vienna (Austria)

    2014-07-15

    Survival upon diagnosis of brain metastases (BM) in patients with non-small cell lung cancer (NSCLC) is highly variable and established prognostic scores do not include tissue-based parameters. Patients who underwent neurosurgical resection as first-line therapy for newly diagnosed NSCLC BM were included. Microvascular density (MVD), Ki67 tumor cell proliferation index and hypoxia-inducible factor 1 alpha (HIF-1 alpha) index were determined by immunohistochemistry. NSCLC BM specimens from 230 patients (151 male, 79 female; median age 56 years; 199 nonsquamous histology) and 53/230 (23.0 %) matched primary tumor samples were available. Adjuvant whole-brain radiation therapy (WBRT) was given to 153/230 (66.5 %) patients after neurosurgical resection. MVD and HIF-1 alpha indices were significantly higher in BM than in matched primary tumors. In patients treated with adjuvant WBRT, low BM HIF-1 alpha expression was associated with favorable overall survival (OS), while among patients not treated with adjuvant WBRT, BM HIF-1 alpha expression did not correlate with OS. Low diagnosis-specific graded prognostic assessment score (DS-GPA), low Ki67 index, high MVD, low HIF-1 alpha index and administration of adjuvant WBRT were independently associated with favorable OS. Incorporation of tissue-based parameters into the commonly used DS-GPA allowed refined discrimination of prognostic subgroups. Ki67 index, MVD and HIF-1 alpha index have promising prognostic value in BM and should be validated in further studies. (orig.) [German] Die Ueberlebensprognose von Patienten mit zerebralen Metastasen eines nicht-kleinzelligen Lungenkarzinoms (NSCLC) ist sehr variabel. Bisher werden gewebsbasierte Parameter nicht in die prognostische Beurteilung inkludiert. Neurochirurgische Resektate zerebraler NSCLC-Metastasen wurden in dieser Studie untersucht. Die Gefaessdichte (''microvascular density'', MVD), der Ki67-Proliferationsindex sowie der HIF-1α-Index wurden mittels

  15. High-density polytetrafluoroethylene membranes in guided bone and tissue regeneration procedures: a literature review.

    Science.gov (United States)

    Carbonell, J M; Martín, I Sanz; Santos, A; Pujol, A; Sanz-Moliner, J D; Nart, J

    2014-01-01

    Expanded polytetrafluoroethylene (e-PTFE) has been used successfully as a membrane barrier for regeneration procedures. However, when exposed to the oral cavity, its high porosity increases the risk of early infection, which can affect surgical outcomes. An alternative to e-PTFE is non-expanded and dense polytetrafluoroethylene (n-PFTE), which results in lower levels of early infection following surgical procedures. The aim of this literature review was to analyze and describe the available literature on n-PFTE, report the indications for use, advantages, disadvantages, surgical protocols, and complications. The medical databases Medline-PubMed and Cochrane Library were searched and supplemented with a hand search for reports published between 1980 and May 2012 on n-PTFE membranes. The search strategy was limited to animal, human, and in vitro studies in dental journals published in English. Twenty-four articles that analyzed the use of n-PTFE as a barrier membrane for guided tissue regeneration and guided bone regeneration around teeth and implants were identified: two in vitro studies, seven experimental studies, and 15 clinical studies. There is limited clinical and histological evidence for the use of n-PTFE membranes at present, with some indications in guided tissue regeneration and guided bone regeneration in immediate implants and fresh extraction sockets.

  16. Initial implementation of the conversion from the energy-subtracted CT number to electron density in tissue inhomogeneity corrections: An anthropomorphic phantom study of radiotherapy treatment planning

    Energy Technology Data Exchange (ETDEWEB)

    Tsukihara, Masayoshi [Division of Radiological Technology, Graduate School of Health Sciences, Niigata University, Niigata 951-8518 (Japan); Noto, Yoshiyuki [Department of Radiology, Niigata University Medical and Dental Hospital, Niigata 951-8520 (Japan); Sasamoto, Ryuta; Hayakawa, Takahide; Saito, Masatoshi, E-mail: masaito@clg.niigata-u.ac.jp [Department of Radiological Technology, School of Health Sciences, Faculty of Medicine, Niigata University, Niigata 951-8518 (Japan)

    2015-03-15

    Purpose: To achieve accurate tissue inhomogeneity corrections in radiotherapy treatment planning, the authors had previously proposed a novel conversion of the energy-subtracted computed tomography (CT) number to an electron density (ΔHU–ρ{sub e} conversion), which provides a single linear relationship between ΔHU and ρ{sub e} over a wide range of ρ{sub e}. The purpose of this study is to present an initial implementation of the ΔHU–ρ{sub e} conversion method for a treatment planning system (TPS). In this paper, two example radiotherapy plans are used to evaluate the reliability of dose calculations in the ΔHU–ρ{sub e} conversion method. Methods: CT images were acquired using a clinical dual-source CT (DSCT) scanner operated in the dual-energy mode with two tube potential pairs and an additional tin (Sn) filter for the high-kV tube (80–140 kV/Sn and 100–140 kV/Sn). Single-energy CT using the same DSCT scanner was also performed at 120 kV to compare the ΔHU–ρ{sub e} conversion method with a conventional conversion from a CT number to ρ{sub e} (Hounsfield units, HU–ρ{sub e} conversion). Lookup tables for ρ{sub e} calibration were obtained from the CT image acquisitions for tissue substitutes in an electron density phantom (EDP). To investigate the beam-hardening effect on dosimetric uncertainties, two EDPs with different sizes (a body EDP and a head EDP) were used for the ρ{sub e} calibration. Each acquired lookup table was applied to two radiotherapy plans designed using the XiO TPS with the superposition algorithm for an anthropomorphic phantom. The first radiotherapy plan was for an oral cavity tumor and the second was for a lung tumor. Results: In both treatment plans, the performance of the ΔHU–ρ{sub e} conversion was superior to that of the conventional HU–ρ{sub e} conversion in terms of the reliability of dose calculations. Especially, for the oral tumor plan, which dealt with dentition and bony structures, treatment

  17. A guide for calculation of spot size to determine power density for free fiber irradiation of tissue

    Science.gov (United States)

    Tate, Lloyd P., Jr.; Blikslager, Anthony T.

    2005-04-01

    Transendoscopic laser treatment for upper airway disorders has been performed in the horse for over twenty years. Endoscopic laser transmission utilizing flexible fiber optics is limited to certain discreet wavelengths. Initially, the laser of choice was the Nd: YAG laser (1064nm), but in the early 1990's, diode lasers (810nm, 980nm) were introduced to veterinary medicine and are currently used in private practice and universities. Precise application of laser irradiation is dependent on the user knowing the laser's output as well as the amount of energy that is delivered to tissue. Knowledge of dosimetry is important to the veterinarian for keeping accurate medical records by being able to describe very specific treatment regimes. The applied energy is best described as power density or energy density. Calculation of this energy is dependent upon the users ability to determine the laser's spot size when irradiating tissue in a non-contact mode. The charts derived from this study provide the veterinarian the ability to estimate spot size for a number of commonly used lasers with the fiber positioned at various distances from the target.

  18. Density gradient multilayered polymerization (DGMP): a novel technique for creating multi-compartment, customizable scaffolds for tissue engineering.

    Science.gov (United States)

    Joshi-Barr, Shivanjali; Karpiak, Jerome V; Ner, Yogesh; Wen, Jessica H; Engler, Adam J; Almutairi, Adah

    2013-02-12

    Complex tissue culture matrices, in which types and concentrations of biological stimuli (e.g. growth factors, inhibitors, or small molecules) or matrix structure (e.g. composition, concentration, or stiffness of the matrix) vary over space, would enable a wide range of investigations concerning how these variables affect cell differentiation, migration, and other phenomena. The major challenge in creating layered matrices is maintaining the structural integrity of layer interfaces without diffusion of individual components from each layer. Current methodologies to achieve this include photopatterning, lithography, sequential functionalization5, freeze drying, microfluidics, or centrifugation, many of which require sophisticated instrumentation and technical skills. Others rely on sequential attachment of individual layers, which may lead to delamination of layers. DGMP overcomes these issues by using an inert density modifier such as iodixanol to create layers of varying densities. Since the density modifier can be mixed with any prepolymer or bioactive molecule, DGMP allows each scaffold layer to be customized. Simply varying the concentration of the density modifier prevents mixing of adjacent layers while they remain aqueous. Subsequent single step polymerization gives rise to a structurally continuous multilayered scaffold, in which each layer has distinct chemical and mechanical properties. The density modifier can be easily removed with sufficient rinsing without perturbation of the individual layers or their components. This technique is therefore well suited for creating hydrogels of various sizes, shapes, and materials. A protocol for fabricating a 2D-polyethylene glycol (PEG) gel, in which alternating layers incorporate RGDS-350, is outlined below. We use PEG because it is biocompatible and inert. RGDS, a cell adhesion peptide, is used to demonstrate spatial restriction of a biological cue, and the conjugation of a fluorophore (Alexa Fluor 350) enables

  19. A single intratracheal instillation of single-walled carbon nanotubes induced early lung fibrosis and subchronic tissue damage in mice.

    Science.gov (United States)

    Park, Eun-Jung; Roh, Jinkyu; Kim, Soo-Nam; Kang, Min-Sung; Han, Young-Ah; Kim, Younghun; Hong, Jin Tae; Choi, Kyunghee

    2011-09-01

    Large amounts of nanomaterials may reach both the natural and occupational environments. This represents a potential health hazard. People have forecasted that CNTs may lead to the toxicity such as mesothelioma and fibrosis like asbestos. To identify dominant immune responses induced by SWCNTs, we investigated the composition of bronchioalveolar lavage (BAL) cells, the secretion of cytokine and collagen, histopathology, protein expression, and cell phenotypes over time after a single administration of single-walled carbon nanotubes (SWCNT). In our results, the number of total cells and macrophages remained at the up-regulated level until Day 28, neutrophils rapidly increased at Day 1, and lymphocytes increased from Day 7. In the BAL fluid, pro-inflammatory cytokines rapidly increased at Day 1 and remained at an up-regulated level throughout the experimental period. IL-12 and IL-10 rapidly increased at Day 1 after administration and remained at a similar level until Day 28. IFN-γ and IL-4 reached the maximum at Day 1, and IL-5, TGF-β, and collagen reached the maximum at Day 7. IL-13 and IL-17 increased in a time-dependent manner. The distribution of B cells and cytotoxic T cells markedly increased at Days 7 and 14, and fibrotic lesions were histopathologically observed at Days 7 and 14. The expressions of caspase-3, p53, COL1A1, COX-2, iNOS, MMP-9, and MMP-2 were also markedly increased at Days 7 and 14. In addition, the expression of mesothelin, iNOS, MMP-9, and p53 was up-regulated until Day 28. Based on these findings, we suggest that a single intratracheal instillation of SWCNTs may induce early lung fibrosis and subchronic tissue damage.

  20. 宣威地区肺癌患者血清和肺组织硒水平研究%Serum and Lung Tissue Selenium Measurements in Subjects with Lung Cancer from Xuanwei, China

    Institute of Scientific and Technical Information of China (English)

    周岚; 黄云超; 王竹; 叶联华; 候文俊; 杨凯云

    2011-01-01

    背景与目的 宣威是我国肺癌高发区,有研究发现肿瘤的死亡率与硒的地理分布及摄入量呈负相关,肺癌死亡率与血硒水平呈负相关.本研究通过检测宣威肺癌患者的血清硒含量和肺组织硒水平.以初步探讨宣威地区肺癌高发与硒的关系.方法 取120例宣威女性的血清,其中试验组为60例肺癌患者,对照组为60例非肿瘤非呼吸道疾病人群,测定其血清硒水平.术中取60例肺癌患者的肺癌组织、癌旁肺组织和正常肺组织,其中31例来自于宣威地区,29例来自于非宣威地区,分析癌组织、癌旁组织及正常组织的硒含量.血清和组织硒均采用荧光法进行测定.结果 宣威地区女性肺癌患者血清硒含量为(55.22±13.34)μg/L,低于对照组(60.33±13.82)μg/L(P<0.05).宣威地区肺癌组织硒含量为(0.105±0.034)μg/g,低于正常肺组织(0.140±0.048)μg/g(P<0.05).宣威地区和非宣威地区肺癌组织、癌旁肺组织和正常肺组织间硒水平无统计学差异.腺癌和鳞癌、不同分期的肺癌组织、癌旁肺组织和正常肺组织之间的硒水平均无统计学差异.结论 宣威地区肺癌的发生与低血硒状态有关,肺组织细胞低硒可能足导致癌变的潜在危险凶素.%Background and objective Xuanwei is an area of the highest incidence and mortality with lung cancer in China. The aim of this study is to determine serum selenium concentrations in lung cancer patients from Xuanwei as well as selenium levels of cancerous tissues, cancer-adjacent pulmonary tissues, and normal pulmonary lung tissues from lung cancer patients, and the relationship between selenium and the high incidence of lung cancer in Xuanwei. Methods One hundred and twenty female adults from Xuanwei were enrolled in the study (60 lung cancer patients and 60 with non-tumor and non-respiratory diseases, respectively) and blood samples were collected. Sixty fresh cancerous tissues and their adjacent as well as

  1. The Affection of High-fat Diet on CTGF of Rat Lung Tissue%高脂饮食对大鼠肺组织CTGF的影响

    Institute of Scientific and Technical Information of China (English)

    于洪志

    2013-01-01

    Objective To explore the relation between high-fat diet and interstitial lung damage by detecting the content of SOD, MDA, HYP and CTGF in lung tissue with the set-up rat model of high-fat diet. Methods 20 SD rats were randomly divided into 2 groups:high-fat diet and control group, 10 in each, and high-fat diet and Lieber-Decarli liquid were provided respectively every day;all rats were single-caged with no water feeding;rats in both groups were killed after feeding for 12 weeks;HE staining was applied to ob-serve the structure of lung tissues while Masson staining to observe the collagen deposition of interstitial lung, colorimetry to detect the content of SOD, MDA and HYP in lung tissues and enzyme linked immunoassay to detect the content of CTGF in lung tissues. Results Pathological study suggested that, in high-fat diet group, there was an inflammatory cell infiltration in alveolar and alveolar septum, some alveolar walls were damaged or collapsed, collagen deposition among alveolar septum increased and the septum became wider;the content of MDA, HYP and CTGF in lung homogenate in high-fat diet group was higher than that in control group while its content of SOD was lower than that in control group. Conclusions High-fat diet leads to the increase of the expression of CTGF in lung tissues of rats, the damage of alveolar structure and the increase of interstitial collagen, it may be one of the factors in causing interstitial lung damage.%目的建立高脂饮食大鼠模型,测定肺组织中超氧化物歧化酶(SOD)、丙二醛(MDA)、羟脯氨酸(HYP)和结缔组织生长因子(CTGF)含量,探讨高脂饮食与肺间质损伤的关系。方法 SD大鼠20只,随机分为高脂饮食组与对照组各10只,每日分别给予高脂(脂肪占71%总热量)和对照(脂肪占35%总热量)Lieber-De-Carli液体饲料单笼喂养,不再提供饮水。各组动物均于12周后处死,HE染色观察肺组织结构;Masson染色观察

  2. Effects of diterpene phenol extract of Rosmarinus Officinalis on TGFβ1 and mRNA expressions of its signaling pathway molecules in the lung tissue of pulmonary fibrosis rats

    Institute of Scientific and Technical Information of China (English)

    杨礼腾

    2013-01-01

    Objective To investigate the regulative mechanism of the diterpene phenol extract of Rosmarinus Officinalis (DERO) on the imbalance of collagen metabolism of the lung tissue in pulmonary fibrosis rats.Methods Fifty healthy Sprague-Dawley rats were randomly divided into normal saline group (NS) ,bleomycin-induced lung

  3. Effects of density of anisotropic microstamped silica thin films on guided bone tissue regeneration--in vitro study.

    Science.gov (United States)

    Pelaez-Vargas, Alejandro; Gallego-Perez, Daniel; Carvalho, Angela; Fernandes, Maria H; Hansford, Derek J; Monteiro, Fernando J

    2013-07-01

    The growing demand for better implant aesthetics has led to increased research on the development of all-ceramic dental implants. The use of microtextured coatings with enhanced properties has been presented as a viable way to improve tissue integrability of all-ceramic implants. The aim of this study was to evaluate the effects of different densities of anisotropic microtextured silica thin films, which served as a model coating, on the behavior of human osteoblast-like cells. The differential responses of human osteoblast-like cells to anisotropic silica microtextures with varying densities, produced via a combination of sol-gel and soft lithography processing, were evaluated in terms of alignment, elongation (using fluorescence microscopy), overall cellular activity, and the expression/activity levels of alkaline phosphatase (ALP). Statistical analysis was conducted using one-way ANOVA/Tukey HSD post hoc test. The thin films were thoroughly characterized via scanning electron microscopy/energy dispersive spectroscopy, Fourier transform infrared, and contact angle measurements. Thin film characterization revealed increased nanoscale roughness and reduced wettability on the micropatterned surfaces. Cell culture experiments indicated that the microtextures induced cell alignment, elongation, and guided colonization on the surface. Cells cultured on denser micropatterns exhibited increased metabolic activity (t = 14-21 days). The early expression/activity levels of ALP released into the medium were found to be significantly higher only on the least dense micropattern. These results suggest the possibility that microstructured silica thin films could be used to guide and enhance peri-implant cell/tissue responses, potentially improving tissue integration for metallic and all-ceramic dental implants.

  4. Synchrotron soft X-ray imaging and fluorescence microscopy reveal novel features of asbestos body morphology and composition in human lung tissues

    Directory of Open Access Journals (Sweden)

    Polentarutti Maurizio

    2011-02-01

    Full Text Available Abstract Background Occupational or environmental exposure to asbestos fibres is associated with pleural and parenchymal lung diseases. A histopathologic hallmark of exposure to asbestos is the presence in lung parenchyma of the so-called asbestos bodies. They are the final product of biomineralization processes resulting in deposition of endogenous iron and organic matter (mainly proteins around the inhaled asbestos fibres. For shedding light on the formation mechanisms of asbestos bodies it is of fundamental importance to characterize at the same length scales not only their structural morphology and chemical composition but also to correlate them to the possible alterations in the local composition of the surrounding tissues. Here we report the first correlative morphological and chemical characterization of untreated paraffinated histological lung tissue samples with asbestos bodies by means of soft X-ray imaging and X-Ray Fluorescence (XRF microscopy, which reveals new features in the elemental lateral distribution. Results The X-ray absorption and phase contrast images and the simultaneously monitored XRF maps of tissue samples have revealed the location, distribution and elemental composition of asbestos bodies and associated nanometric structures. The observed specific morphology and differences in the local Si, Fe, O and Mg content provide distinct fingerprints characteristic for the core asbestos fibre and the ferruginous body. The highest Si content is found in the asbestos fibre, while the shell and ferruginous bodies are characterized by strongly increased content of Mg, Fe and O compared to the adjacent tissue. The XRF and SEM-EDX analyses of the extracted asbestos bodies confirmed an enhanced Mg deposition in the organic asbestos coating. Conclusions The present report demonstrates the potential of the advanced synchrotron-based X-ray imaging and microspectroscopy techniques for studying the response of the lung tissue to the

  5. The post-synaptic density of human postmortem brain tissues: an experimental study paradigm for neuropsychiatric illnesses.

    Directory of Open Access Journals (Sweden)

    Chang-Gyu Hahn

    Full Text Available Recent molecular genetics studies have suggested various trans-synaptic processes for pathophysiologic mechanisms of neuropsychiatric illnesses. Examination of pre- and post-synaptic scaffolds in the brains of patients would greatly aid further investigation, yet such an approach in human postmortem tissue has yet to be tested. We have examined three methods using density gradient based purification of synaptosomes followed by detergent extraction (Method 1 and the pH based differential extraction of synaptic membranes (Methods 2 and 3. All three methods separated fractions from human postmortem brains that were highly enriched in typical PSD proteins, almost to the exclusion of pre-synaptic proteins. We examined these fractions using electron microscopy (EM and verified the integrity of the synaptic membrane and PSD fractions derived from human postmortem brain tissues. We analyzed protein composition of the PSD fractions using two dimensional liquid chromatography tandem mass spectrometry (2D LC-MS/MS and observed known PSD proteins by mass spectrometry. Immunoprecipitation and immunoblot studies revealed that expected protein-protein interactions and certain posttranscriptional modulations were maintained in PSD fractions. Our results demonstrate that PSD fractions can be isolated from human postmortem brain tissues with a reasonable degree of integrity. This approach may foster novel postmortem brain research paradigms in which the stoichiometry and protein composition of specific microdomains are examined.

  6. Near real-time automated dose restoration in IMPT to compensate for daily tissue density variations in prostate cancer

    Science.gov (United States)

    Jagt, Thyrza; Breedveld, Sebastiaan; van de Water, Steven; Heijmen, Ben; Hoogeman, Mischa

    2017-06-01

    Proton therapy is very sensitive to daily density changes along the pencil beam paths. The purpose of this study is to develop and evaluate an automated method for adaptation of IMPT plans to compensate for these daily tissue density variations. A two-step restoration method for ‘densities-of-the-day’ was created: (1) restoration of spot positions (Bragg peaks) by adapting the energy of each pencil beam to the new water equivalent path length; and (2) re-optimization of pencil beam weights by minimizing the dosimetric difference with the planned dose distribution, using a fast and exact quadratic solver. The method was developed and evaluated using 8-10 repeat CT scans of 10 prostate cancer patients. Experiments demonstrated that giving a high weight to the PTV in the re-optimization resulted in clinically acceptable restorations. For all scans we obtained V 95%  ⩾  98% and V 107%  ⩽  2%. For the bladder, the differences between the restored and the intended treatment plan were below  +2 Gy and  +2%-point. The rectum differences were below  +2 Gy and  +2%-point for 90% of the scans. In the remaining scans the rectum was filled with air, which partly overlapped with the PTV. The air cavity distorted the Bragg peak resulting in less favorable rectum doses.

  7. Density and SUV Ratios from PET/CT in the Detection of Mediastinal Lymph Node Metastasis in Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Tingting SHAO

    2015-03-01

    Full Text Available Background and objective Mediastinal involvement in lung cancer is a highly significant prognostic factor for survival, and accurate staging of the mediastinum will correctly identify patients who will benefit the most from surgery. Positron emission tomography/computed tomography (PET/CT has become the standard imaging modality for the staging of patients with lung cancer. The aim of this study is to investigate 18-fluoro-2-deoxy-glucose (18F-FDG PET/CT imaging in the detection of mediastinal disease in lung cancer. Methods A total of 72 patients newly diagnosed with non-small cell lung cancer (NSCLC who underwent preoperative whole-body 18F-FDG PET/CT were retrospectively included. All patients underwent radical surgery and mediastinal lymph node dissection. Mediastinal disease was histologically confirmed in 45 of 413 lymph nodes. PET/CT doctors analyzed patients’ visual images and evaluated lymph node’s short axis, lymph node’s maximum standardized uptake value (SUVmax, node/aorta density ratio, node/aorta SUV ratio, and other parameters using the histopathological results as the reference standard. The optimal cutoff value for each ratio was determined by receiver operator characteristic curve analysis. Results Using a threshold of 0.9 for density ratio and 1.2 for SUV ratio yielded high accuracy for the detection of mediastinal disease. The lymph node’s short axis, lymph node’s SUVmax, density ratio, and SUV ratio of integrated PET/CT for the accuracy of diagnosing mediastinal lymph node was 95.2%. The diagnostic accuracy of mediastinal lymph node with conventional PET/CT was 89.8%, whereas that of PET/CT comprehensive analysis was 90.8%. Conclusion Node/aorta density ratio and SUV ratio may be complimentary to conventional visual interpretation and SUVmax measurement. The use of lymph node’s short axis, lymph node’s SUVmax, and both ratios in combination is better than either conventional PET/CT analysis or PET

  8. Association of Inorganics Accumulation with the Activation of NF-κB Signaling Pathway and the iNOS Expression of Lung Tissue in Xuanwei Lung Cancer Patients

    OpenAIRE

    Jiapeng YANG; Li, Guangjian; Huang, Yunchao; YE, LIANHUA; Yongchun ZHOU; Guangqiang ZHAO; Yujie LEI; Xiaobo CHEN; Wang, Kun; Chen, Ying; Dai, Chun; Zhang, Yanjun

    2016-01-01

    Background and objective Indoor air pollution induces asthma, leads to chronic obstructive pulmonary disease, and may promote lung cancer. Our previous studies found that the accumulation of inorganic particulate matter that is due to indoor air pollution can lead to damage to alveolar cells and activation of signaling pathway, and ultimately provoke tumorigenesis. The aim of this study is to explore the accumulation of inorganics and activation of nuclear factor κB (NF-κB)-inducible nitric o...

  9. Improved PCR amplification for molecular analysis using DNA from long-term preserved formalin-fixed, paraffin-embedded lung cancer tissue specimens.

    Science.gov (United States)

    Taga, Masataka; Eguchi, Hidetaka; Shinohara, Tomoko; Takahashi, Keiko; Ito, Reiko; Yasui, Wataru; Nakachi, Kei; Kusunoki, Yoichiro; Hamatani, Kiyohiro

    2013-01-01

    Archival tissue specimens are valuable resources of materials for molecular biological analyses in retrospective studies, especially for rare diseases or those associated with exposure to uncommon environmental events. Although successful amplification with PCR is essential for analysis of DNA extracted from archival formalin-fixed, paraffin-embedded (FFPE) tissue specimens, we have often encountered problems with poor PCR amplification of target fragments. To overcome this, we examined whether heat treatment in alkaline solution could efficiently restore the PCR template activity of DNA that had already been extracted from FFPE lung cancer tissue specimens. The effect of the heat treatment was assessed by PCR for the TP53 gene and other lung cancer-related gene loci. The heat treatment of DNA samples in borate buffer resulted in successful PCR amplification of DNA fragments ranging from 91 to 152 bp. This technique for restoration of template activity of DNA for PCR amplification is very simple and economical, and requires no special apparatus, so it may be applicable for molecular analysis of DNA samples from FFPE tissue specimens at various laboratories.

  10. Over, and Underexpression of Endothelin 1 and TGF-Beta Family Ligands and Receptors in Lung Tissue of Broilers with Pulmonary Hypertension

    Directory of Open Access Journals (Sweden)

    Norma Dominguez-Avila

    2013-01-01

    Full Text Available Transforming growth factor beta (TGFβ is a family of genes that play a key role in mediating tissue remodeling in various forms of acute and chronic lung disease. In order to assess their role on pulmonary hypertension in broilers, we determined mRNA expression of genes of the TGFβ family and endothelin 1 in lung samples from 4-week-old chickens raised either under normal or cold temperature conditions. Both in control and cold-treated groups of broilers, endothelin 1 mRNA expression levels in lungs from ascitic chickens were higher than levels from healthy birds (, whereas levels in animals with cardiac failure were intermediate. Conversely, TGFβ2 and TGFβ3 gene expression in lungs were higher in healthy animals than in ascitic animals in both groups (. TGFβ1, TβRI, and TβRII mRNA gene expression among healthy, ascitic, and chickens with cardiac failure showed no differences (. BAMBI mRNA gene expression was lowest in birds with ascites only in the control group as compared with the values from healthy birds (.

  11. Characterization CSMD1 in a large set of primary lung, head and neck, breast and skin cancer tissues

    National Research Council Canada - National Science Library

    Ma, Changqing; Quesnelle, Kelly M; Sparano, Anthony; Rao, Shilpa; Park, Min S; Cohen, Marc A; Wang, Yan; Samanta, Minu; Kumar, Madhu S; Aziz, M. Usman; Naylor, Tara L; Weber, Barbara; Fakharzadeh, Steven S; Weinstein, Gregory S; Vachani, Anil; D. Feldman, Michael; Brose, Marcia S

    2009-01-01

    ...). To understand the extent of CSMD1 aberrations in vivo, we characterized 184 primary tumors from the head and neck, lung, breast, and skin for gene copy number and analyzed expression in our HNSCCs...

  12. The role of endogenous H2S formation in reversible remodeling of lung tissue during hibernation in the Syrian hamster

    NARCIS (Netherlands)

    Talaei, Fatemeh; Bouma, Hjalmar R.; Hylkema, Machteld N.; Strijkstra, Arjen M.; Boerema, Ate S.; Schmidt, Martina; Henning, Rob H.

    During hibernation, small mammals alternate between periods of metabolic suppression and low body temperature ('torpor') and periods of full metabolic recovery with euthermic temperatures ('arousal'). Previously, we demonstrated marked structural remodeling of the lung during torpor, which is

  13. PPARγexpression in rat lung tissue after ventilator-induced lung injury%机械通气致大鼠肺损伤时肺组织PPARγ表达的变化

    Institute of Scientific and Technical Information of China (English)

    王秀芹; 王凯国; 罗红敏; 李浩; 王宝胜; 王培民

    2014-01-01

    Objective To observe the changes of PPARγ expression in ventilator-induced lung injury rats and explore the role of PPARγ in the pathogenesis of ventilator-induced lung injury. Methods Sixty male Sprague-Dawley rats were randomly divided into 3 groups ( n=21 each ):group N received large tidal volume with mechanical ventilation ( Vt=12 mL/kg);group C received lower tidal volume with mechanical ventilation ( Vt=6 mL/kg);group R received room air without mechanical ventilation. Rats in every group were randomly divided into 3 subgroups respectively by 1,4 and 8 h. The samples of lung were collected at 1,4 and 8 h after ventilation. Lung pathological examina-tion, total protein and white blood cells in bronchoalveolar fluid and wet-to-dry weight were detected. The exoressions of PPARγmRNA were detected by RTPCR;PPARγ protein in lung tissues was detected by western bolt. Result After 4 and 8 h ventilation in group N,total pro-tein and WBC in bronchoalvelor fluid,W/D were markedly higher than those of group C and R (P 0. 05). Conclusion PPARγmRNA and protein expressions in the rats lung tissue of ventilator-induced lung injury were decreased and as-sociated with inflammation and damage of lung tissue.%目的:观察PPARγ在通气相关性肺损伤大鼠肺组织中的表达,探讨PPARγ在通气相关性肺损伤中的作用。方法清洁雄性SD大鼠,随机分为大潮气量( Tidal volume,VT)组,Vt=12 mL;小潮气量组,Vt=6 mL;自主呼吸组。每组又分为3个亚组:即通气1h、4h、8h组。于各时间段末放血处死动物,收集肺组织和肺灌洗液标本,测定肺灌洗液中蛋白总量、白细胞计数;测定肺组织湿/干重比( W/D);逆转录聚合酶链反应检测PPARγmRNA的表达;western blot检测PPARγ蛋白的变化。结果大潮气量组机械通气4 h、8 h后,与小潮气量组及自主呼吸组相比,肺灌洗液中白细胞计数、蛋白总量明显增加(P 0.05)。结论通气相关性肺损伤大鼠肺组织

  14. Metals in lung tissue from autopsy cases in Mexico City residents: comparison of cases from the 1950s and the 1980s.

    Science.gov (United States)

    Fortoul, T I; Osorio, L S; Tovar, A T; Salazar, D; Castilla, M E; Olaiz-Fernández, G

    1996-06-01

    In autopsies performed on residents of Mexico City during the 1950s and 1980s (45 males and 24 females and 42 males and 42 females, respectively), concentrations of cadmium, copper, cobalt, nickel, and lead in the lungs were studied by atomic absorption spectrometry. Sharp increases were noted in samples taken in the 1980s compared to those from the 1950s. In samples from both time periods, the concentrations were influenced by gender. Smoking was not associated with higher levels of the metals. Only lead seemed to have a relation with age. The enormous differences by gender in the 1950s could be due to different patterns of exposure. The differences among samples from both periods appear to be associated with the increase of air pollutants in the metropolitan areas of Mexico City during the years under study. These results reinforce the importance of studying lung tissue to monitor air pollution by metals.

  15. Association of proton density fat fraction in adipose tissue with imaging-based and anthropometric obesity markers in adults.

    Science.gov (United States)

    Franz, D; Weidlich, D; Freitag, F; Holzapfel, C; Drabsch, T; Baum, T; Eggers, H; Witte, A; Rummeny, E J; Hauner, H; Karampinos, D C

    2017-08-14

    The purpose of this study was to examine the relationship of the proton density fat fraction (PDFF), measured by magnetic resonance imaging (MRI), of supraclavicular and gluteal adipose tissue with subcutaneous and visceral adipose tissue (SAT and VAT) volumes, liver fat fraction and anthropometric obesity markers. The supraclavicular fossa was selected as a typical location where brown adipocytes may be present in humans and the gluteal region was selected as a typical location enclosing primarily white adipocytes. In this cross-sectional study, 61 adults (44 women, median age 29.3 years, range 21-68 years) underwent an MRI examination of the neck and the abdomen/pelvis (3T, Ingenia, Philips Healthcare). PDFF maps of the supraclavicular and gluteal adipose tissue and the liver were generated. Volumes of SAT and VAT were calculated and supraclavicular and subcutaneous fat were segmented using custom-built post-processing algorithms. Body mass index (BMI), waist circumference and waist-to-height ratio were recorded. Statistical analysis was conducted using the Student's t-test and Pearson correlation analysis. Mean supraclavicular PDFF was 75.3±4.7% (range 65.4-83.8%) and mean gluteal PDFF was 89.7±2.9% (range 82.2-94%), resulting in a significant difference (P<0.0001). Supraclavicular PDFF was positively correlated with VAT (r=0.76, P<0.0001), SAT (r=0.73, P<0.0001), liver PDFF (r=0.42, P=0.0008) and all measured anthropometric obesity markers. Gluteal subcutaneous PDFF also correlated with VAT (r=0.59, P<0.0001), SAT (r=0.63, P<0.0001), liver PDFF (r=0.3, P=0.02) and anthropometric obesity markers. The positive correlations between adipose tissue PDFF and imaging, as well as anthropometric obesity markers suggest that adipose tissue PDFF may be useful as a biomarker for improving the characterization of the obese phenotype, for risk stratification and for selection of appropriate treatment strategies.International Journal of Obesity advance online publication

  16. Chrysotile effects on the expression of anti-oncogene P53 and P16 and oncogene C-jun and C-fos in Wistar rats' lung tissues.

    Science.gov (United States)

    Cui, Yan; Wang, Yuchan; Deng, Jianjun; Hu, Gongli; Dong, Faqin; Zhang, Qingbi

    2017-09-13

    Chrysotile is the most widely used form of asbestos worldwide. China is the world's largest consumer and second largest producer of chrysotile. The carcinogenicity of chrysotile has been extensively documented, and accumulative evidence has shown that chrysotile is capable of causing lung cancer and other forms of cancer. However, molecular mechanisms underlying the tumorigenic effects of chrysotile remained poorly understood. To explore the carcinogenicity of chrysotile, Wistar rats were administered by intratracheal instillation (by an artificial route of administration) for 0, 0.5, 2, or 8 mg/ml of natural chrysotile (from Mangnai, Qinghai, China) dissolved in saline, repeated once a month for 6 months (a repeated high-dose exposure which may have little bearing on the effects following human exposure). The lung tissues were analyzed for viscera coefficients and histopathological alterations. Expression of P53, P16, C-JUN, and C-FOS was measured by western blotting and qRT-PCR. Our results found that chrysotile exposure leads the body weight to grow slowly and lung viscera coefficients to increase in a dose-dependent manner. General sample showed white nodules, punctiform asbestos spots, and irregular atrophy; moreover, HE staining revealed inflammatory infiltration, damage of alveolar structures, agglomerations, and pulmonary fibrosis. In addition, chrysotile can induce inactivation of the anti-oncogene P53 and P16 and activation of the proto-oncogenes C-JUN and C-FOS both in the messenger RNA and protein level. In conclusion, chrysotile induced an imbalanced expression of cancer-related genes in rats' lung tissue. These results contribute to our understanding of the carcinogenic mechanism of chrysotile.

  17. Assessment of CCL2 and CXCL8 chemokines in serum, bronchoalveolar lavage fluid and lung tissue samples from dogs affected with canine idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Roels, Elodie; Krafft, Emilie; Farnir, Frederic; Holopainen, Saila; Laurila, Henna P; Rajamäki, Minna M; Day, Michael J; Antoine, Nadine; Pirottin, Dimitri; Clercx, Cecile

    2015-10-01

    Canine idiopathic pulmonary fibrosis (CIPF) is a progressive disease of the lung parenchyma that is more prevalent in dogs of the West Highland white terrier (WHWT) breed. Since the chemokines (C-C motif) ligand 2 (CCL2) and (C-X-C motif) ligand 8 (CXCL8) have been implicated in pulmonary fibrosis in humans, the aim of the present study was to investigate whether these same chemokines are involved in the pathogenesis of CIPF. CCL2 and CXCL8 concentrations were measured by ELISA in serum and bronchoalveolar lavage fluid (BALF) from healthy dogs and WHWTs affected with CIPF. Expression of the genes encoding CCL2 and CXCL8 and their respective receptors, namely (C-C motif) receptor 2 (CCR2) and (C-X-C motif) receptor 2 (CXCR2), was compared in unaffected lung tissue and biopsies from dogs affected with CIPF by quantitative PCR and localisation of CCL2 and CXCL8 proteins were determined by immunohistochemistry. Significantly greater CCL2 and CXCL8 concentrations were found in the BALF from WHWTs affected with CIPF, compared with healthy dogs. Significantly greater serum concentrations of CCL2, but not CXCL8, were found in CIPF-affected dogs compared with healthy WHWTs. No differences in relative gene expression for CCL2, CXCL8, CCR2 or CXCR2 were observed when comparing lung biopsies from control dogs and those affected with CIPF. In affected lung tissues, immunolabelling for CCL2 and CXCL8 was observed in bronchial airway epithelial cells in dogs affected with CIPF. The study findings suggest that both CCL2 and CXCL8 are involved in the pathogenesis of CIPF. Further studies are required to determine whether these chemokines might have a clinical use as biomarkers of fibrosis or as targets for therapeutic intervention.

  18. Photobiomodulation Therapy Decreases Oxidative Stress in the Lung Tissue after Formaldehyde Exposure: Role of Oxidant/Antioxidant Enzymes

    Directory of Open Access Journals (Sweden)

    Rodrigo Silva Macedo

    2016-01-01

    Full Text Available Formaldehyde is ubiquitous pollutant that induces oxidative stress in the lung. Several lung diseases have been associated with oxidative stress and their control is necessary. Photobiomodulation therapy (PBMT has been highlighted as a promissory treatment, but its mechanisms need to be better investigated. Our objective was to evaluate the effects of PBMT on the oxidative stress generated by FA exposure. Male Wistar rats were submitted to FA exposure of 1% or vehicle (3 days and treated or not with PBMT (1 and 5 h after each FA exposure. Rats treated only with laser were used as control. Twenty-four hours after the last FA exposure, we analyzed the effects of PBMT on the generation of nitrites and hydrogen peroxide, oxidative burst, glutathione reductase, peroxidase, S-transferase enzyme activities, the gene expression of nitric oxide, cyclooxygenase, superoxide dismutase, the catalase enzyme, and heme oxygenase-1. PBMT reduced the generation of nitrites and hydrogen peroxide and increased oxidative burst in the lung cells. A decreased level of oxidant enzymes was observed which were concomitantly related to an increased level of antioxidants. This study provides new information about the antioxidant mechanisms of PBMT in the lung and might constitute an important tool for lung disease treatment.

  19. Photobiomodulation Therapy Decreases Oxidative Stress in the Lung Tissue after Formaldehyde Exposure: Role of Oxidant/Antioxidant Enzymes

    Science.gov (United States)

    Braga, Tarcio Teodoro; Barioni, Éric Diego; de Oliveira Duro, Stephanie; Ratto Tempestini Horliana, Anna Carolina; Câmara, Niels Olsen Saraiva; Marcourakis, Tânia; Farsky, Sandra Helena Poliselli; Lino-dos-Santos-Franco, Adriana

    2016-01-01

    Formaldehyde is ubiquitous pollutant that induces oxidative stress in the lung. Several lung diseases have been associated with oxidative stress and their control is necessary. Photobiomodulation therapy (PBMT) has been highlighted as a promissory treatment, but its mechanisms need to be better investigated. Our objective was to evaluate the effects of PBMT on the oxidative stress generated by FA exposure. Male Wistar rats were submitted to FA exposure of 1% or vehicle (3 days) and treated or not with PBMT (1 and 5 h after each FA exposure). Rats treated only with laser were used as control. Twenty-four hours after the last FA exposure, we analyzed the effects of PBMT on the generation of nitrites and hydrogen peroxide, oxidative burst, glutathione reductase, peroxidase, S-transferase enzyme activities, the gene expression of nitric oxide, cyclooxygenase, superoxide dismutase, the catalase enzyme, and heme oxygenase-1. PBMT reduced the generation of nitrites and hydrogen peroxide and increased oxidative burst in the lung cells. A decreased level of oxidant enzymes was observed which were concomitantly related to an increased level of antioxidants. This study provides new information about the antioxidant mechanisms of PBMT in the lung and might constitute an important tool for lung disease treatment. PMID:27293324

  20. Cigarette Smoke Activates the Proto-Oncogene c-Src to Promote Airway Inflammation and Lung Tissue Destruction

    Science.gov (United States)

    Geraghty, Patrick; Hardigan, Andrew

    2014-01-01

    The diagnosis of chronic obstructive pulmonary disease (COPD) confers a 2-fold increased lung cancer risk even after adjusting for cigarette smoking, suggesting that common pathways are operative in both diseases. Although the role of the tyrosine kinase c-Src is established in lung cancer, less is known about its impact in other lung diseases, such as COPD. This study examined whether c-Src activation by cigarette smoke contributes to the pathogenesis of COPD. Cigarette smoke increased c-Src activity in human small airway epithelial (SAE) cells from healthy donors and in the lungs of exposed mice. Similarly, higher c-Src activation was measured in SAE cells from patients with COPD compared with healthy control subjects. In SAE cells, c-Src silencing or chemical inhibition prevented epidermal growth factor (EGF) receptor signaling in response to cigarette smoke but not EGF stimulation. Further studies showed that cigarette smoke acted through protein kinase C α to trigger c-Src to phosphorylate EGF receptor and thereby to induce mitogen-activated protein kinase responses in these cells. To further investigate the role of c-Src, A/J mice were orally administered the specific Src inhibitor AZD-0530 while they were exposed to cigarette smoke for 2 months. AZD-0530 treatment blocked c-Src activation, decreased macrophage influx, and prevented airspace enlargement in the lungs of cigarette smoke–exposed mice. Moreover, inhibiting Src deterred the cigarette smoke–mediated induction of matrix metalloproteinase-9 and -12 in alveolar macrophages and lung expression of cathepsin K, IL-17, TNF-α, MCP-1, and KC, all key factors in the pathogenesis of COPD. These results indicate that activation of the proto-oncogene c-Src by cigarette smoke promotes processes linked to the development of COPD. PMID:24111605

  1. RKIP在肺鳞癌组织中的表达及其意义%The Expression and Significance of RKIP in Lung Squamous Cell Carcinoma Tissues

    Institute of Scientific and Technical Information of China (English)

    徐海源; 王馨; 沈文香; 王李强; 沈刚; 陈敏斌; 周丽娜

    2011-01-01

    Background and objective Raf kinase inhibitory protein (RKIP) belongs to the phosphatidylethanolamine binding protein (PEBP) family.RKIP is an endogenous inhibitor of the Raf-1-MEK1/2-ERKl/2 signaling pathway, NFkappaB signaling pathway and G protein coupled receptors signaling pathway.The aim of this study is to explore the expression of RKIP in lung squamous cell carcinoma, and the relationship between RKIP expression and clinical pathology of lung squamous cell carcinoma.Methods The expression of RKIP mRNA was detected in 56 lung squamous cell carcinoma tissues and adjacent cancer tissues by RT-PCR.The expression level of RKIP protein was detected by Western blot.The positive rates of RKIP expression in cancer tissues and adjacent cancer tissues were analyzed.Results RKIP mRNA positive expression rate in cancer tissues was significantly lower than that in adjacent cancer tissues (P<0.05).The positive rate of RKIP mRNA expression in the cancer tissues with lymph node metastasis was significantly lower than that without lymph node metastasis (P<0.05).RKIP mRNA expression has no remarkable correlation with age, sex, tumor differentiation and size (P>0.05).RKIP protein expression in the cancer tissues was significantly Iower than that in adjacent cancer tissues (P<0.05).Conclusion The deficiency of RKIP expression is positively correlated with carcinogenesis and invasion metastasis of lung squamous cell carcinoma.%背景与目的 Raft(酶抑制蛋白(Raf kinase inhibitor protein,RKIP)属于磷脂酞乙醇胺结合蛋白家族的成员,可干扰Raf-1-MEKl/2-ERK1/2信号通路,抑制NF-kB和G蛋白偶联受体激酶等信号传导过程,且RKIP的表达减弱或丢失与多种肿瘤的发生发展以及侵润转移相关.本研究旨在探讨RKIP在肺鳞癌组织中的表达及其与肺鳞癌临床病理的相关性.方法 应用RT-PCR方法检测56例肺鳞癌组织及其癌旁正常组织中RKIP基因的表达,计算其阳性率;并用Western blot方法

  2. Clinical analysis of connective tissue diseases with interstitial lung disease%结缔组织病肺间质病变临床分析

    Institute of Scientific and Technical Information of China (English)

    张佳林; 叶宝国; 陈宏浦

    2013-01-01

    目的 提高对结缔组织病肺间质病变的认识及诊断.方法 回顾性分析124例结缔组织病肺间质病变患者呼吸系统的临床表现、肺功能检查、肺部影像学特点、有无肺动脉高压、肺功能与肺部影像学关系.结果 124例结缔组织病肺间质病变患者呼吸系统临床表现为咳嗽、咳痰、气短、胸闷憋气,严重时表现为活动耐量下降、呼吸闲难.64例行肺功能检查均有弥散功能减低,其中26例为单纯弥散功能减低,32例为限制性通气功能障碍伴弥散功能减低,4例为混合性通气功能障碍伴弥散功能减低,2例为阻塞性通气功能障碍伴弥散功能减低.22例合并有肺动脉高压.肺间质病变在影像学上可有结节影、索条影、斑片影、网格影、磨玻璃影、肺大泡等多种改变.32例限制性通气功能障碍伴弥散功能减低患者中有15例表现为网格样、纤维化样改变,26例单纯弥散功能减低患者中有8例表现为网格样、纤维化样改变.结论 结缔组织病肺间质病变患者呼吸系统表现多种多样,肺功能检查主要表现为限制性通气功能障碍伴弥散功能减低.混合性结缔组织病、重叠综合征、系统性红斑狼疮、系统性硬化症是较易出现肺间质病变合并肺动脉高压的结缔组织病.结缔组织病肺间质病变在影像学上可有多种多样改变,影像学上表现为网格样、纤维化样改变的患者肺功能易出现限制性通气伴弥散功能障碍.%Objective To observe the diagnosis of connective tissue diseases with interstitial lung disease.Methods The clinical manifestations of respiratory,pulmonary function tests,lung imaging characteristics,the presence or absence of pulmonary hypertension,pulmonary function in 124 patients with interstitial lung disease associated with connective tissue disease were retrospective analyzed.Results Cough,expectoration,shortness of breath,chest stuffiness and choking were

  3. Relative Tissue Factor Deficiency Attenuates Ventilator-Induced Coagulopathy but Does Not Protect against Ventilator-Induced Lung Injury in Mice

    Directory of Open Access Journals (Sweden)

    Esther K. Wolthuis

    2012-01-01

    Full Text Available Preventing tissue-factor-(TF- mediated systemic coagulopathy improves outcome in models of sepsis. Preventing TF-mediated pulmonary coagulopathy could attenuate ventilator-induced lung injury (VILI. We investigated the effect of relative TF deficiency on pulmonary coagulopathy and inflammation in a murine model of VILI. Heterozygous TF knockout (TF+/− mice and their wild-type (TF+/+ littermates were sedated (controls or sedated, tracheotomized, and mechanically ventilated with either low or high tidal volumes for 5 hours. Mechanical ventilation resulted in pulmonary coagulopathy and inflammation, with more injury after mechanical ventilation with higher tidal volumes. Compared with TF+/+ mice, TF+/− mice demonstrated significantly lower pulmonary thrombin-antithrombin complex levels in both ventilation groups. There were, however, no differences in lung wet-to-dry ratio, BALF total protein levels, neutrophil influx, and lung histopathology scores between TF+/− and TF+/+ mice. Notably, pulmonary levels of cytokines were significantly higher in TF+/− as compared to TF+/+ mice. Systemic levels of cytokines were not altered by the relative absence of TF. TF deficiency is associated with decreased pulmonary coagulation independent of the ventilation strategy. However, relative TF deficiency does not reduce VILI and actually results in higher pulmonary levels of inflammatory mediators.

  4. Study the level of sputum matrix metalloproteinase-9 and tissue inhibitor metaloprotienase-1 in patients with interstitial lung diseases

    Directory of Open Access Journals (Sweden)

    Sherif A. Esa

    2016-01-01

    Results: In this study, we have demonstrated that levels of sputum MMP-9 and TIMP-1 were significantly increased in patients with interstitial lung diseases than normal persons with highly significant statistical differences (p = 0.001. MMP-9 was positively correlated with number of neutrophils in the airway with highly significant statistical difference (p = 0.001.

  5. Study of effective atomic numbers and electron densities, kerma of alcohols, phantom and human organs, and tissues substitutes

    Directory of Open Access Journals (Sweden)

    Singh Vishwanath P.

    2013-01-01

    Full Text Available Effective atomic numbers (ZPIeff and electron densities of eighteen alcohols such as wood alcohol, CH3OH; grain alcohol, C2H5OH; rubbing alcohol, C3H7OH; butanol, C4H9OH; amyl alcohol, C5H11OH; cetyl alcohol, C16H33OH; ethylene glycol, C2H4(OH2; glycerin, C3H5(OH3; PVA, C2H4O; erythritol, C4H6(OH4; xylitol, C5H7(OH5; sorbitol, C6H8(OH6; volemitol, C7H9(OH7; allyl alcohol, C3H5OH; geraniol, C10H17OH; propargyl alcohol, C3H3OH; inositol, C6H6(OH6, and menthol, C10H19OH have been calculated in the photon energy region of 1 keV-100 GeV. The estimated values have been compared with experimental values wherever possible. The comparison of ZPIeff of the alcohols with water phantom and PMMA phantom indicate that the ethylene glycol, glycerin, and PVA are substitute for PMMA phantom and PVA is substitute of water phantom. ZPIeff of alcohols have also been compared with human organs and tissues. Ethylene glycol, glycerin and PVA, allyl alcohol, and wood alcohols are found tissue substitutes for most of human organs. Kerma which is the product of the energy fluence and mass energy-absorption coefficient, have been calculated in the energy region from 1 keV to 20 MeV for the alcohols. The results show the kerma is more or less independent of energy above 100 keV.

  6. Combination of body mass index and oxidized low density lipoprotein receptor 1 in prognosis prediction of patients with squamous non-small cell lung cancer.

    Science.gov (United States)

    Jiang, Long; Jiang, Shanshan; Lin, Yongbin; Yang, Han; Zhao, Zerui; Xie, Zehua; Lin, Yaobin; Long, Hao

    2015-09-08

    Lung cancer, especially non-small cell lung cancer (NSCLC), represents enormous challenges in continuously achieving treatment improvements. Besides cancer, obesity is becoming ever more prevalent. Obesity is increasingly acknowledged as a major risk factor for several types of common cancers. Significant mechanisms overlap in the pathobiology of obesity and tumorigenesis. One of these mechanisms involves oxidized low density lipoprotein receptor 1 (OLR1), as a link between obesity and cancer. Additionally, body mass index (BMI) has been widely used in exploiting the role of obesity on a series of diseases, including cancer. Significantly, squamous NSCLC revealed to be divergent clinical and molecular phenotypes compared with non-squamous NSCLC. Consequently, OLR1 immunostaining score and BMI were assessed by Fisher's linear discriminant analysis to discriminate if progression-free survival (PFS) would exceed 2 years. In addition, the final model was utilized to calculate the discriminant score in each study participant. Finally, 131 patients with squamous NCSLC were eligible for analysis. And a prediction model was established for PFS based on these 2 markers and validated in a second set of squamous NCSLC patients. The model offers a novel tool for survival prediction and could establish a framework for future individualized therapy for patients with squamous NCSLC.

  7. Comparison of contrast-to-noise ratios of transmission and dark-field signal in grating-based X-ray imaging for healthy murine lung tissue

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    Schwab, Felix [Ludwig Maximilians-Univ. Hospital Munich (Germany). Inst. for Clinical Radiology; Schleede, Simone; Hahn, Dieter [Technische Univ. Muenchen, Garching (Germany). Dept. of Physics and Inst. of Medical Engineering] [and others

    2013-10-01

    Purpose: An experimental comparison of the contrast-to-noise ratio (CNR) between transmission and dark-field signals in grating-based X-ray imaging for ex-vivo murine lung tissue. Materials and Methods: Lungs from three healthy mice were imaged ex vivo using a laser-driven compact synchrotron X-ray source. Background noise of transmission and dark-field signal was quantified by measuring the standard deviation in a region of interest (ROI) placed in a homogeneous area outside the specimen. Image contrast was quantified by measuring the signal range in rectangular ROIs placed in central and peripheral lung parenchyma. The relative contrast gain (RCG) of dark-field over transmission images was calculated as CNRDF / CNRT. Results: In all images, there was a trend for contrast-to-noise ratios of dark-field images (CNRDF) to be higher than for transmission images (CNRT) for all ROIs (median 61 vs. 38, p = 0.10), but the difference was statistically significant only for peripheral ROIs (61 vs. 32, p = 0.03). Median RCG was >1 for all ROIs (1.84). RCG values were significantly smaller for central ROIs than for peripheral ROIs (1.34 vs. 2.43, p = 0.03). Conclusion: The contrast-to-noise ratio of dark-field images compares more favorably to the contrast-to-noise ratio of transmission images for peripheral lung regions as compared to central regions. For any specific specimen, a calculation of the RCG allows comparing which X-ray modality (dark-field or transmission imaging) produces better contrast-to-noise characteristics in a well-defined ROI. (orig.)

  8. Prognostic value of tissue inhibitor of metalloproteinase-2 expression in patients with non-small cell lung cancer: a systematic review and meta-analysis.

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    Lin Zhu

    Full Text Available Tissue inhibitor of metalloproteinase-2 (TIMP-2 is a small