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Sample records for surrounding lung tissue

  1. Unilateral lung agenesis--detrimental roles of surrounding vessels.

    Science.gov (United States)

    Chou, An-Kou; Huang, Shu-Chien; Chen, Shyh-Jye; Huang, Pei-Ming; Wang, Jou-Kou; Wu, Mei-Hwan; Chen, Yih-Sharng; Chang, Chung-I; Chiu, Ing-Sh; Wu, En-Ting

    2007-03-01

    Unilateral lung agenesis is a rare congenital defect and could be associated with multiple abnormalities. The patients usually have poor long-term outcomes especially in those with right lung agenesis. We reviewed the 10-year experience in our hospital to describe special clinical features and try to delineate the causes of poor outcomes. From 1995 to 2005, 14 patients less than 18 years of age with unilateral lung agenesis (4 with left agenesis, 10 with right agenesis) were enrolled. Medical records reviewed included diagnosis, presentation, chromosome anomalies, cardiovascular anomalies and interventions, outcomes. We found that the mechanisms of severe airway disease in right lung agenesis included (1) trachea compression by the aortic arch, (2) the presence of "pseudo-ring-sling complex," (3) distended pulmonary artery due to left to right shunt which impinged the only bronchus, and finally (4) the persistent LSVC that restricts the growth of trachea. The etiologies of airway complication in left lung agenesis included anomalous aortic arch compression on trachea and the coexisting heart disease with significant left to right shunt, which impinged on the bronchus. In conclusion, unilateral lung agenesis has frequently associated airway problems due to its surrounding vessels. Satisfactory airway intervention remains challenging. This disease still requires great effort to improve patient outcomes.

  2. Tissue reaction surrounding miniscrews for orthodontic anchorage: An animal experiment

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    Stephanie Shih-Hsuan Chen

    2012-03-01

    Results and conclusions: (1 Tissue surrounding roots damaged by a miniscrew showed a significant inflammatory response. (2 Root resorption was occasionally observed after 3 weeks following insertion of a miniscrew even if the miniscrew was not in direct contact with the root. (3 Root repair was noted with a cementoblast lining along the resorption surface at as early as 3 weeks after miniscrew insertion. Alveolar bone filled in the lesion when the root damage was large so that the contour of the alveolar bone followed that of the damaged root, with the width of the periodontal ligament space being maintained. (4 Stable miniscrews were mainly those which did not contact adjacent roots, and for which the surrounding tissue showed only a small inflammatory response with some extent of direct bone contact around the miniscrew. On the contrary, most of the failed miniscrews were those which had direct contact with adjacent roots, and which exhibited severe tissue inflammation and were covered by thick layers of soft tissue. Failure was detected 3 weeks after insertion. Surprisingly, the epithelial lining surrounding the miniscrews might not have spontaneously resolved 6 weeks after screw removal. Persistent infection in the sinus tract was noted, and this would require attention.

  3. The importance of surrounding tissues and window settings for contouring of moving targets

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    Borm, Kai Joachim [Technische Universitaet Muenchen, Medical School, Munich (Germany); Klinikum rechts der Isar, Technische Universitaet Muenchen, Department of Radiation Oncology, Munich (Germany); Oechsner, Markus; Berndt, Johannes; Combs, Stephanie Elisabeth; Molls, Michael; Duma, Marciana Nona [Klinikum rechts der Isar, Technische Universitaet Muenchen, Department of Radiation Oncology, Munich (Germany)

    2015-09-15

    The aim of the study was to assess the importance of surrounding tissues for the delineation of moving targets in tissue-specific phantoms and to find optimal settings for lung, soft tissue, and liver tumors. Tumor movement was simulated by a water-filled table tennis ball (target volume, TV). Three phantoms were created: corkboards to simulate lung tissue (lung phantom, LunPh), animal fat as fatty soft tissue (fatty tissue phantom, FatPh), and water enhanced with contrast medium as the liver tissue (liver phantom, LivPh). Slow planning three-dimensional compute tomography images (3D-CTs) were acquired with and without phantom movements. One-dimensional tumor movement (1D), three-dimensional tumor movement (3D), as well as a real patient's tumor trajectories were simulated. The TV was contoured using two lung window settings, two soft-tissue window settings, and one liver window setting. The volumes were compared to mathematical calculated values. TVs were underestimated in all phantoms due to movement. The use of soft-tissue windows in the LivPh led to a significantunderestimation of the TV (70.8 % of calculated TV). When common window settings [LunPh + 200 HU/-1,000 HU (upper window/lower window threshold); FatPh: + 240 HU/-120 HU; LivPh: + 175 HU/+ 50 HU] were used, the contoured TVs were: LivPh, 84.0 %; LunPh, 93.2 %, and FatPh, 92.8 %. The lower window threshold had a significant impact on the size of the delineated TV, whereas changes of the upper threshold led only to small differences. The decisive factor for window settings is the lower window threshold (for adequate TV delineation in the lung and fatty-soft tissue it should be lower than density values of surrounding tissue). The use of a liver window should be considered. (orig.) [German] Das Ziel dieser Arbeit war es, den Einfluss des umgebenden Gewebes auf die Konturierung bewegter Objekte zu untersuchen. Um die optimalen CT-Fensterungen fuer Lungen-, Weichteil- und Lebertumoren zu bestimmen

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

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    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.

  5. Lung tissue classification using wavelet frames.

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    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.

  6. VEGF in hepatocellular carcinoma and surrounding cirrhotic liver tissues

    Institute of Scientific and Technical Information of China (English)

    Muriel Mathonnet; Bernard Descottes; Denis Valleix; Francois Labrousse; Yves Denizot

    2006-01-01

    @@ TO THE EDITOR We read with a great interest the recent work of Deli and colleagues.[1] in the World Journal of Gastroenterology reporting vascular endothelial growth factor (VEGF) expression in hepatocellular carcinoma (HCC) and cirrhotic liver tissues.

  7. Ethical issues surrounding the transplantation of human fetal tissues.

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    Hurd, R E

    1992-12-01

    Organ transplants have been one of the greatest advances in medicine. However, organs from living relatives or cadavers are in short supply, and many people die awaiting a donor organ. Increasing the donor pool by using organs from aborted fetuses has been proposed to increase the supply. In addition, there are benefits of using fetal tissue including its particular usefulness in children, the fact that it is not readily rejected, and its potential for growth. Guidelines for fetal research were issued in 1975, but a research moratorium was imposed in 1988 to allow study of ethical and legal issues. While the federal government delays in lifting the ban, several states have written laws governing experimentation with fetuses. Ethical arguments against using fetal tissue for organ transplant include a concern that this would create a branch of biomedicine which depends on the continuation of induced abortions. This could lead to neglect of research for other therapies. The timing and type of abortion should continue to benefit the mother, rather than the organ recipient. Ethicists debate whether or not use of aborted tissue implies complicity in the abortion process beyond that which exists for all members of a society which permits abortion. They also wonder whether knowing that some good could come of an abortion would influence a woman's decision to have one. Proposals to keep the use of fetal tissue ethical include banning the commercial use of sale of tissues, forbidding designation of the tissue recipient (to prevent harvesting fetal tissue for a relative), separating abortion counseling and management from harvesting of the tissue, and obtaining informed consent (perhaps from a proxy surrogate rather than from the mother) for the use of fetal tissue. When the medical and ethical communities have reached some consensus on these issues, crafted safeguards, and precluded conflicts of interest, then restrictions on government funding should be lifted. Whereas it

  8. Impact of surrounding tissue on conductance measurement of coronary and peripheral lumen area.

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    Won Choi, Hyo; Jansen, Benjamin; Zhang, Zhen-Du; Kassab, Ghassan S

    2012-11-07

    Parallel conductance (electric current flow through surrounding tissue) is an important determinant of accurate measurements of arterial lumen diameter, using the conductance method. The present study is focused on the role of non-uniform geometrical/electrical configurations of surrounding tissue, which are a primary source of electric current leakage. Computational models were constructed to simulate the conductance catheter measurement with two different excitation electrodes spacings (i.e. 12 and 20 mm for coronary and peripheral sizing, respectively) for different vessel-tissue configurations: (i) blood vessel fully embedded in muscle tissue, (ii) blood vessel superficially embedded in muscle tissue, and (iii) blood vessel superficially embedded in muscle tissue with fat covering half of the arterial vessel (anterior portion). The simulations suggest that the parallel conductance and accuracy of measurement is dependent on the inhomogeneous/anisotropic configuration of surrounding tissue, including the asymmetric dimension and anisotropy in electrical conductivity of surrounding tissue. Specifically, the measurement was shown to be accurate as long as the vessel was superficial, regardless of the considerable total surrounding tissue dimension for coronary or peripheral arteries. Moreover, it was shown that the unfavourable impact of parallel conductance on the accuracy of conductance catheter measurement is decreased by the combination of a lower transverse electrical conductivity of surrounding muscle tissue, a smaller electrode spacing and a larger lumen diameter. The present findings confirm that the conductance catheter technique provides an accurate platform for sizing of clinically relevant (i.e. superficial and diseased) arteries.

  9. The surrounding tissue modifies the placental stem villous vascular responses

    DEFF Research Database (Denmark)

    Brøgger, Torbjørn; Forman, Axel; Aalkjær, Christian;

    2014-01-01

    Background: The placenta is the base for the exchange of nutrients, oxygen and waste products for the fetus. The placental vessels hold a crucial role in regulation of blood flow, and compromised function may lead to complications like growth retardation and preeclampsia where no specific treatment...... is available. In-depth understanding of the mechanisms involved in control of placental vascular tone are needed to develop new tissue targets for therapeutic intervention. Method: From fresh born placentas segments of stem villous arteries were carefully dissected. The artery branches were divided...

  10. Alveolar rhabdomyosarcoma involving the mandibular ramus and its surrounding tissues

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    Yoon, Suk Ja; Kang, Byung Cheol [Chonnam National University College of Medicine, Gwangju (Korea, Republic of)

    2004-06-15

    Rhabdomyosarcoma, when it occurs in the head and neck, is primarily found in children. Alveolar rhabdomyosarcoma is rarely seen in the oral lesion, comparing to the embryonal and the pleomorphic variants. This is a report of a case of alveolar rhabdomyosarcoma in the mandible in a ten-year old girl who complained of a non-painful swelling on the right cheek. The right lower 1st molar was mobile. Her radiographs revealed an extensive radiolucency with somewhat irregular border on the right mandibular ramus. The right mandibular 1st and 2nd molars lost their lamina dura and were floating. CT images revealed smooth-outlined soft tissue mass occupying the pterygomandibular space, the infratemporal space, and the masseteric muscle with thinning and perforation of the right mandibular angle and ramus. Histopathological and immunohistochemical findings established the final diagnosis of alveolar rhabdomyosarcoma.

  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

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    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. 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.

  14. TELOMERASE ACTIVITY IN HUMAN GASTRIC AND COLORECTAL CANCER AND SURROUNDING TISSUES

    Institute of Scientific and Technical Information of China (English)

    CHEN Wen; ZHANG Qiao; WAN De-sen; CUN Ling-yun; WU Cheng-qiu; PAN Zhi-zhong

    1999-01-01

    Objective: To study the telomerase activities in human gastric and colorectal tumors. Methods: The telomerase activity was assayed by the telomeric repeat amplification protocol (TRAP) technique. Forty human tumor samples including 9 colonic, 20 rectal and 11gastric carcinomas and their surrounding tissues were used for the detection. Results: Thirty-six out of 40human tumor samples exhibited telomerase activity regardless of the stages or the differentiation of the tumors. However, only 1 out of 39 tumor surrounding tissues showed telomerase activity. Conclusion: Telomerase may be a good diagnosis biomarker for tumor detection.

  15. 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.

  16. 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.

  17. The Tissue Implant Response Surrounding Subcutaneous TCP, HA, And ALCAP Bioceramics.

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    Butler, K R; Benghuzzi, Hamed; Tucci, Michelle; Puckett, A D

    2015-01-01

    The objective of this investigation was to quantify and further elucidate the tissue-implant response in the fibrous tissue surrounding tricalcium phosphate (TCP), hydroxyapatite (HA), and aluminum calcium phosphate (ALCAP) implants when implanted subcutaneously. Sixteen animals in four experimental groups (n = 4/group) were implanted with one implant each: Group I (control, TCP), Group II (HA), and Group III (ALCAP). At 90 days post-implantation, the fibrous tissue surrounding the implants was harvested. Sections of stained fibrous tissue were evaluated for the presence of macrophages, fibrocytes, neutrophils, vascularity and thickness for all three groups using semi-automated quantitative methods. The analysis indicated Group III demonstrated a significantly higher number of neutrophils but fewer macrophages and blood vessels per high power field and had a substantially thinner fibrous tissue capsule thickness compared to Groups I and II (alpha=0.05). Group II elicited a greater response of fibroblasts compared to Groups I and III suggesting HA may provide a slightly higher degree of stability to the implant. In total, these findings suggest both TCP and HA behave similarly in vivo when compared to ALCAP and may be better choices for subcutaneous soft-tissue application compared to ALCAP.

  18. 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.

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

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    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.

  20. Optical detection of carotenoid antioxidants in human bone and surrounding tissue.

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    Ermakov, Igor V; Ermakova, Maia R; Rosenberg, Thomas D; Gellermann, Werner

    2013-11-01

    Carotenoids are known to play an important role in health and disease state of living human tissue based on their antioxidant and optical filtering functions. In this study, we show that carotenoids exist in human bone and surrounding fatty tissue both in significant and individually variable concentrations. Measurements of biopsied tissue samples with molecule-specific Raman spectroscopy and high-performance liquid chromatography reveal that all carotenoids that are known to exist in human skin are also present in human bone. This includes all carotenes, lycopene, β-cryptoxanthin, lutein, and zeaxanthin. We propose quantitative reflection imaging as a noncontact optical method suitable for the measurement of composite carotenoid levels in bone and surrounding tissue exposed during open surgeries such as total knee arthroplasty, and as a proof of concept, demonstrate carotenoid measurements in biopsied bone samples. This will allow one to establish potential correlations between internal tissue carotenoid levels and levels in skin and to potentially use already existing optical skin carotenoid tests as surrogate marker for bone carotenoid status.

  1. Electromagnetic effects on the biological tissue surrounding a transcutaneous transformer for an artificial anal sphincter system*

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    Zan, Peng; Yang, Bang-hua; Shao, Yong; Yan, Guo-zheng; Liu, Hua

    2010-01-01

    This paper reports on the electromagnetic effects on the biological tissue surrounding a transcutaneous transformer for an artificial anal sphincter. The coupling coils and human tissues, including the skin, fat, muscle, liver, and blood, were considered. Specific absorption rate (SAR) and current density were analyzed by a finite-length solenoid model. First, SAR and current density as a function of frequency (10–107 Hz) for an emission current of 1.5 A were calculated under different tissue thickness. Then relations between SAR, current density, and five types of tissues under each frequency were deduced. As a result, both the SAR and current density were below the basic restrictions of the International Commission on Non-Ionizing Radiation Protection (ICNIRP). The results show that the analysis of these data is very important for developing the artificial anal sphincter system. PMID:21121071

  2. The dorsal skinfold chamber: window into the dynamic interaction of biomaterials with their surrounding host tissue

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    MW Laschke

    2011-09-01

    Full Text Available The implantation of biomaterials into the human body has become an indispensable part of almost all fields of modern medicine. Accordingly, there is an increasing need for appropriate approaches, which can be used to evaluate the suitability of different biomaterials for distinct clinical indications. The dorsal skinfold chamber is a sophisticated experimental model, which has been proven to be extremely valuable for the systematic in vivo analysis of the dynamic interaction of small biomaterial implants with the surrounding host tissue in rats, hamsters and mice. By means of intravital fluorescence microscopy, this chronic model allows for repeated analyses of various cellular, molecular and microvascular mechanisms, which are involved in the early inflammatory and angiogenic host tissue response to biomaterials during the initial 2-3 weeks after implantation. Therefore, the dorsal skinfold chamber has been broadly used during the last two decades to assess the in vivo performance of prosthetic vascular grafts, metallic implants, surgical meshes, bone substitutes, scaffolds for tissue engineering, as well as for locally or systemically applied drug delivery systems. These studies have contributed to identify basic material properties determining the biocompatibility of the implants and vascular ingrowth into their surface or internal structures. Thus, the dorsal skinfold chamber model does not only provide deep insights into the complex interactions of biomaterials with the surrounding soft tissues of the host but also represents an important tool for the future development of novel biomaterials aiming at an optimisation of their biofunctionality in clinical practice.

  3. Dynamic myosin activation promotes collective morphology and migration by locally balancing oppositional forces from surrounding tissue.

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    Aranjuez, George; Burtscher, Ashley; Sawant, Ketki; Majumder, Pralay; McDonald, Jocelyn A

    2016-06-15

    Migrating cells need to overcome physical constraints from the local microenvironment to navigate their way through tissues. Cells that move collectively have the additional challenge of negotiating complex environments in vivo while maintaining cohesion of the group as a whole. The mechanisms by which collectives maintain a migratory morphology while resisting physical constraints from the surrounding tissue are poorly understood. Drosophila border cells represent a genetic model of collective migration within a cell-dense tissue. Border cells move as a cohesive group of 6-10 cells, traversing a network of large germ line-derived nurse cells within the ovary. Here we show that the border cell cluster is compact and round throughout their entire migration, a shape that is maintained despite the mechanical pressure imposed by the surrounding nurse cells. Nonmuscle myosin II (Myo-II) activity at the cluster periphery becomes elevated in response to increased constriction by nurse cells. Furthermore, the distinctive border cell collective morphology requires highly dynamic and localized enrichment of Myo-II. Thus, activated Myo-II promotes cortical tension at the outer edge of the migrating border cell cluster to resist compressive forces from nurse cells. We propose that dynamic actomyosin tension at the periphery of collectives facilitates their movement through restrictive tissues.

  4. Surface position, not signaling from surrounding maternal tissues, specifies aleurone epidermal cell fate in maize.

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    Gruis, Darren Fred; Guo, Hena; Selinger, David; Tian, Qing; Olsen, Odd-Arne

    2006-07-01

    Maize (Zea mays) endosperm consists of an epidermal-like surface layer of aleurone cells, an underlying body of starchy endosperm cells, and a basal layer of transfer cells. To determine whether surrounding maternal tissues perform a role in specifying endosperm cell fates, a maize endosperm organ culture technique was established whereby the developing endosperm is completely removed from surrounding maternal tissues. Using cell type-specific fluorescence markers, we show that aleurone cell fate specification occurs exclusively in response to surface position and does not require specific, continued maternal signal input. The starchy endosperm and aleurone cell fates are freely interchangeable throughout the lifespan of the endosperm, with internalized aleurone cells converting to starchy endosperm cells and with starchy endosperm cells that become positioned at the surface converting to aleurone cells. In contrast to aleurone and starchy endosperm cells, transfer cells fail to develop in in vitro-grown endosperm, supporting earlier indications that maternal tissue interaction is required to fully differentiate this cell type. Several parameters confirm that the maize endosperm organ cultures described herein retain the main developmental features of in planta endosperm, including fidelity of aleurone mutant phenotypes, temporal and spatial control of cell type-specific fluorescent markers, specificity of cell type transcripts, and control of mitotic cell divisions.

  5. CD163/Hemoglobin Oxygenase-1 Pathway Regulates Inflammation in Hematoma Surrounding Tissues after Intracerebral Hemorrhage.

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    Liu, BaoHua; Hu, BeiLei; Shao, ShengMin; Wu, Wei; Fan, LiuBo; Bai, GuangHui; Shang, Ping; Wang, XiaoTong

    2015-12-01

    The aim of the present study was to investigate changes in the expression of CD163 and hemoglobin oxygenase-1 (HO-1) in brain tissue surrounding hematomas after intracerebral hemorrhage (ICH), and correlations with other factors. Brain tissues in the close surrounding of ICH hematomas (n = 27, ICH group) were collected at 6 hours or less, 6-24 hours, 24-72 hours, and more than 72 hours after bleeding onset, and more distant tissues (n = 12, control group) were histologically analyzed with hematoxylin and eosin staining and transmission electron microscopy. Interleukin (IL)-1, IL-10, and tumor necrosis factor-alpha, as well as the expression of CD163 and HO-1, were assessed using immunochemistry, Western blotting, and reverse transcription-polymerase chain reaction. Apoptosis rates were determined with terminal deoxynucleotidyl transferase dUTP nick end labeling assays. The expressions of the inflammatory cytokines IL-1 and tumor necrosis factor-alpha were increased at 6-24 hours (P CD163 and HO-1 expressions gradually increased from 6 to 24 hours to peaks at more than 72 hours after ICH onset (P CD163 and HO-1 expressions reached peaks and inflammatory cytokine expressions dropped. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  6. Impact of mechanical stretch on the cell behaviors of bone and surrounding tissues

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    Hye-Sun Yu

    2016-02-01

    Full Text Available Mechanical loading is recognized to play an important role in regulating the behaviors of cells in bone and surrounding tissues in vivo. Many in vitro studies have been conducted to determine the effects of mechanical loading on individual cell types of the tissues. In this review, we focus specifically on the use of the Flexercell system as a tool for studying cellular responses to mechanical stretch. We assess the literature describing the impact of mechanical stretch on different cell types from bone, muscle, tendon, ligament, and cartilage, describing individual cell phenotype responses. In addition, we review evidence regarding the mechanotransduction pathways that are activated to potentiate these phenotype responses in different cell populations.

  7. 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

  8. Mandibular advancement decreases pressures in the tissues surrounding the upper airway in rabbits.

    Science.gov (United States)

    Kairaitis, Kristina; Stavrinou, Rosie; Parikh, Radha; Wheatley, John R; Amis, Terence C

    2006-01-01

    The pharyngeal airway can be considered as an airway luminal shape formed by surrounding tissues, contained within a bony enclosure formed by the mandible, skull base, and cervical vertebrae. Mandibular advancement (MA), a therapy for obstructive sleep apnea, is thought to increase the size of this bony enclosure and to decrease the pressure in the upper airway extraluminal tissue space (ETP). We examined the effect of MA on upper airway airflow resistance (Rua) and ETP in a rabbit model. We studied 11 male, supine, anesthetized, spontaneously breathing New Zealand White rabbits in which ETP was measured via pressure transducer-tipped catheters inserted into the tissues surrounding the lateral (ETPlat) and anterior (ETPant) pharyngeal wall. Airflow, measured via surgically inserted pneumotachograph in series with the trachea, and tracheal pressure were recorded while graded MA at 75 degrees and 100 degrees to the horizontal was performed using an external traction device. Data were analyzed using a linear mixed-effects statistical model. We found that MA at 100 degrees increased mouth opening from 4.7 +/- 0.4 to 6.6 +/- 0.4 (SE) mm (n = 7; P < 0.004), whereas mouth opening did not change from baseline (4.0 +/- 0.2 mm) with MA at 75 degrees . MA at both 75 degrees and 100 degrees decreased mean ETPlat and ETPant by approximately 0.1 cmH2O/mm MA (n = 7-11; all P < 0.0005). However, the fall in Rua (measured at 20 ml/s) with MA was greater for MA at 75 degrees (approximately 0.03 mmH2O.ml(-1).s.mm(-1)) than at 100 degrees (approximately 0.01 mmH2O.ml(-1).s.mm(-1); P < 0.02). From these findings, we conclude that MA decreases ETP and is more effective in reducing Rua without mouth opening.

  9. Distribution of natural killer cells and T-lymphocyte subsets in peripheral blood, gallbladder cancer and surrounding tissue

    Institute of Scientific and Technical Information of China (English)

    Gang Liu; Hong Ren; Xue-Jun Sun; Jing-Sen Shi

    2007-01-01

    BACKGROUND:The patient with malignant tumor always show immunologic function drawback and ingravescent with tumor development, especially in the aspect of cell-mediated immunity. This study was undertaken to deifne the relationship between the immune function of local cells and cancer development by investigating the distribution of natural killer (NK) cells and T-lymphocyte subsets in peripheral blood, the cancer tissue and the tissue surrounding gallbladder carcinoma. METHODS:The numbers of CD4+and CD8+T-lymphocytes and NK cells were measured by lfow cytometry in samples taken from gallbladder cancer tissue, the surrounding tissues and peripheral blood of 38 patients, and compared with the numbers in the peripheral blood and gallbladder tissue of 30 patients with cholecystitis as controls. RESULTS:The numbers of CD4+and CD8+T-cells and NK cells in gallbladder cancer tissues were signiifcantly higher than those in the surrounding tissue and gallbladder with gallstone. However, the ratio of CD4+/CD8+was lower in the cancer tissue than that in the surrounding tissue and tissue from gallbladders with gallstones. The distribution of CD4+ and CD8+ T-cells and NK cells in mucous membrane of cholecystitis gallbladder and that in the tissue surrounding gallbladder cancer were signiifcantly different. CONCLUSIONS:Disproportionate and imbalanced distri-bution of NK cells and subsets of T-lymphocytes occurs in the mucous membrane proper of gallbladder cancer and surrounding tissue. Although gallbladder cancer tissue has higher expressions of CD4+, CD8+and NK cells, the immune function is low or in an inhibited state. In gallbladder cancer immunization therapy, local cellular immunological function should be enhanced and the protective barrier improved.

  10. 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.

  11. Characterisation by PIXE RBS of metallic contamination of tissues surrounding a metallic prosthesis on a knee

    Science.gov (United States)

    Guibert, G.; Irigaray, J. L.; Moretto, Ph.; Sauvage, T.; Kemeny, J. L.; Cazenave, A.; Jallot, E.

    2006-09-01

    Implants used as biomaterials have to fulfill conditions of functionality, compatibility and sometimes bioactivity. There are four main families of biomaterials: metals and metal alloys, polymers, bioceramics and natural materials. Because of corrosion and friction in the human body, implants generate debris. This debris may develop toxicity, inflammation and prosthetic unsealing by osseous dissolution. Nature, size, morphology and amount of debris are the parameters influencing the tissue responses. In this paper, we characterised metallic contamination produced by knee prosthesis, composed with TiAl 6V 4 or Co-Cr-Mo alloys, into surrounding capsular tissue by depth migration, in vivo behaviour, content, size and nature of debris by PIXE (Particle Induced X-ray Emission) method associated with RBS (Rutherford Backscattering Spectroscopy). Debris distribution in the whole articulation is very heterogeneous. Debris migrates several thousand micrometers in tissues, with a characteristic decrease. Solid metallic particles of about micrometer size are found in the most polluted samples, in both alloys TiAl 6V 4 and Cr-Co-Mo. In the mean volume analysed by PIXE, the concentration mass ratios [Ti]/[V] and [Co]/[Cr] confirm the chemical stability of TiAl 6V 4 debris and show the chemical evolution of Cr-Co-Mo debris. Development of a protocol to prepare thin targets permits us to correlate PIXE and histological analysis in the same zone. The fibrous tissue (collagen fibres, fibroblasts) and macrophage cells are observed with optical microscope in polluted areas. This protocol could locate other pathologies in ppm contamination range, thanks to the great sensitivity of the PIXE method.

  12. 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.

  13. 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...

  14. In vivo corrosion behaviour of magnesium alloy in association with surrounding tissue response in rats.

    Science.gov (United States)

    Miura, Chieko; Shimizu, Yoshinaka; Imai, Yoshimichi; Mukai, Toshiji; Yamamoto, Akiko; Sano, Yuya; Ikeo, Naoko; Isozaki, Shuji; Takahashi, Toru; Oikawa, Miho; Kumamoto, Hiroyuki; Tachi, Masahiro

    2016-03-07

    Biodegradable magnesium (Mg) alloys are the most promising candidates for osteosynthesis devices. However, their in vivo corrosion behaviour has not been fully elucidated. The aim of this study was to clarify the influence of the physiological environment surrounding Mg alloys on their corrosion behaviour. A Mg-1.0Al alloy with a fine-grained structure was formed into plates using titanium (Ti) as a control. These plates were implanted into the subperiosteum in the head, subcutaneous tissue of the back, and in the muscle of the femur of rats for 1, 2 and 4 weeks. The volumes of the remaining Mg alloy and of the insoluble salt deposition and gas cavities around the Mg alloy were determined by microtomography, and the volume losses were calculated. Then, the tissue response around the plates in each implantation site was examined histopathologically, and its relation to the respective volume loss was analyzed. These analyses determined that the Mg alloy was corroded fastest in the head, at an intermediate level in the back, and slowest in the femur. The insoluble salt deposition at the Mg alloy surface had no influence on the volume loss. Gas cavities formed around the Mg alloy at all implantation sites and decreased after 4 weeks. Histopathological examination revealed that the Mg alloy exhibited good biocompatibility, as was seen with Ti. In addition, vascularized fibrous capsules formed around the plates and became mature with time. Notably, the volume loss in the different anatomical locations correlated with capsule thickness. Together, our results suggest that, to facilitate the successful clinical application of Mg alloys, it will be necessary to further comprehend their interactions with specific in vivo environments.

  15. 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

  16. Evaluation of alginate as a substitute for root-surrounding tissues in electronic root canal measurements.

    Science.gov (United States)

    Lipski, Mariusz; Trąbska-Świstelnicka, Marlena; Woźniak, Krzysztof; Dembowska, Elżbieta; Droździk, Agnieszka

    2013-12-01

    Alginate as a substitute for root-surrounding tissue was investigated. The electronic working lengths of root canals under clinical conditions were compared with an in vitro simulation of the same teeth extracted and embedded in alginate. The working lengths in 26 teeth were determined on two occasions using an electronic apex locator, before extraction and after extraction with the same teeth embedded in an alginate mass. The apical 4 mm of the root canals were exposed following the measurements, and the distances between the apical constrictions and the tips of files repositioned in the canals were measured and recorded. The mean distance between the file tip and the constriction was +0.33 mm (±0.38) in vivo and +0.32 mm (±0.30) in vitro. The Wilcoxon signed-rank test indicated that these means were not significantly different. The apical constriction was assessed to be within the limits of 0.5 mm in 80.7% of in vivo cases and in 76.9% of extracted teeth. Statistical analysis demonstrated that there was no significant difference between the results recorded in vivo and in vitro regarding apical constriction localisation. Based on the results of this study, the alginate mass is a useful tool in evaluating the performance of electronic apex locators.

  17. 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).

  18. 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

  19. 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

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. [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.

  6. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    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)

  8. [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.

  9. 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.

  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. Nodular osteochondrogenic activity in soft tissue surrounding osteoma in neurogenic para osteo-arthropathy: morphological and immunohistochemical study

    Directory of Open Access Journals (Sweden)

    Denys P

    2004-11-01

    Full Text Available Abstract Background Neurogenic Para-Osteo-Arthropathy (NPOA occurs as a consequence of central nervous system injuries or some systemic conditions. They are characterized by bone formation around the main joints. Methods In order to define some biological features of NPOAs, histological and immunohistological studies of the soft tissue surrounding osteoma and Ultrasound examination (US of NPOA before the appearance of abnormal ossification on plain radiographs were performed. Results We have observed a great number of ossifying areas scattered in soft tissues. US examination have also shown scattered ossifying areas at the early stage of ossification. A high osteogenic activity was detected in these tissues and all the stages of the endochondral process were observed. Mesenchymal cells undergo chondrocytic differentiation to further terminal maturation with hypertrophy, which sustains mineralization followed by endochondral ossification process. Conclusion We suggest that periosteoma soft tissue reflect early stage of osteoma formation and could be a model to study the mechanism of osteoma formation and we propose a mechanism of the NPOA formation in which sympathetic dystony and altered mechanical loading induce changes which could be responsible for the cascade of cellular events leading to cartilage and bone formation.

  14. The importance of tissue environment surrounding the tumor on the development of cancer cachexia.

    Science.gov (United States)

    Chiba, Fumihiro; Soda, Kuniyasu; Yamada, Shigeki; Tokutake, Yuka; Chohnan, Shigeru; Konishi, Fumio; Rikiyama, Toshiki

    2014-01-01

    The relationship between host factors and cancer cachexia was investigated. A single cell clone (clone 5 tumor) established from colon 26 adenocarcinoma by limiting dilution cell cloning methods was employed to eliminate the inoculation site-dependent differences in the composition of cell clones. Clone 5 tumor did not provoke manifestations of cancer cachexia when inoculated in subcutaneous tissue. However, when inoculated in the gastrocnemius muscle, the peritoneal cavity or the thoracic cavity of CD2F1 male mice, typical manifestations of cancer cachexia were observed in all groups of mice with intergroup variations. The blood levels of various cytokines, chemokines and hormones were increased but with wide intergroup variations. Analyses by stepwise multiple regression models revealed that serum interleukin-10 was the most significant factor associated with manifestations of cancer cachexia, suggesting the possible involvement of mechanisms similar to cancer patients suffering cancer cachexia. White blood cells, especially neutrophils, seemed to have some roles on the induction of cancer cachexia, because massive infiltrations and an increase in peripheral blood were observed in cachectic mice bearing clone 5 tumors. The amount of malonyl-CoA in liver correlated with manifestations of cancer cachexia, however the mRNA levels of spermidine/spermine N-1 acetyl transferase (SSAT) (of which overexpression has been shown to provoke manifestations similar to cancer cachexia) were not necessarily associated with cancer cachexia. These data suggest that the induction of cancer cachexia depends on the environment in which the tumor grows and that the infiltration of host immune cells into the tumor and the resultant increase in inflammation result in the production of cachectic factors, such as cytokines, leading to SSAT activation. Further, multiple factors likely mediate the mechanisms of cancer cachexia. Finally, this animal model was suitable for the investigation

  15. 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.

  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. Lipidomic differentiation between human kidney tumors and surrounding normal tissues using HILIC-HPLC/ESI-MS and multivariate data analysis.

    Science.gov (United States)

    Cífková, Eva; Holčapek, Michal; Lísa, Miroslav; Vrána, David; Melichar, Bohuslav; Študent, Vladimír

    2015-09-01

    The characterization of differences among polar lipid classes in tumors and surrounding normal tissues of 20 kidney cancer patients is performed by hydrophilic interaction liquid chromatography (HILIC) coupled to electrospray ionization mass spectrometry (ESI-MS). The detailed analysis of identified lipid classes using relative abundances of characteristic ions in negative- and positive-ion modes is used for the determination of more than 120 individual lipid species containing attached fatty acyls of different chain length and double bond number. Lipid species are described using relative abundances, providing a better visualization of lipidomic differences between tumor and normal tissues. The multivariate data analysis methods using unsupervised principal component analysis (PCA) and supervised orthogonal partial least square (OPLS) are used for the characterization of statistically significant differences in identified lipid species. Ten most significant up- and down-regulated lipids in OPLS score plots are also displayed by box plots. A notable increase of relative abundances of lipids containing four and more double bonds is detected in tumor compared to normal tissues. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. A Three-Dimensional Finite Element Study on the Biomechanical Simulation of Various Structured Dental Implants and Their Surrounding Bone Tissues

    OpenAIRE

    Zhang, Gong; Yuan, Hai; Chen, Xianshuai; Wang, Weijun; Chen, Jianyu; Liang, Jimin; Zhang, Peng

    2016-01-01

    Background/Purpose. This three-dimensional finite element study observed the stress distribution characteristics of 12 types of dental implants and their surrounding bone tissues with various structured abutments, implant threads, and healing methods under different amounts of concentrated loading. Materials and Methods. A three-dimensional geometrical model of a dental implant and its surrounding bone tissue was created; the model simulated a screw applied with a preload of 200 N or a torque...

  19. Photodynamic Inactivation of Root Canal Bacteria by Light Activation through Human Dental Hard and Simulated Surrounding Tissue

    Science.gov (United States)

    Cieplik, Fabian; Pummer, Andreas; Leibl, Christoph; Regensburger, Johannes; Schmalz, Gottfried; Buchalla, Wolfgang; Hiller, Karl-Anton; Maisch, Tim

    2016-01-01

    Introduction: Photodynamic inactivation of bacteria (PIB) may be a supportive antimicrobial approach for use in endodontics, but sufficient activation of photosensitizers (PS) in root canals is a critical point. Therefore, aim of this study was to evaluate the ability of PS absorbing blue (TMPyP) or red light (Methylene Blue; MB) for light activation through human dental hard and simulated surrounding tissue to inactivate root canal bacteria. Methods: A tooth model was fabricated with a human premolar and two molars in an acrylic resin bloc simulating the optical properties of a porcine jaw. The distal root canal of the first molar was enlarged to insert a glass tube (external diameter 2 mm) containing PS and stationary-phase Enterococcus faecalis. Both PS (10 μM) were irradiated for 120 s with BlueV (20 mW/cm2; λem = 400–460 nm) or PDT 1200L (37.8 mW/cm2; λem = 570–680 nm; both: Waldmann Medizintechnik), respectively. Irradiation parameters ensured identical numbers of photons absorbed by each PS. Three setups were chosen: irradiating the glass pipette only (G), the glass pipette inside the single tooth without (GT) and with (GTM) simulated surrounding tissues. Colony forming units (CFU) were evaluated. Transmission measurements of the buccal halves of hemisected mandibular first molars were performed by means of a photospectrometer. Results: PIB with both PS led to reduction by ≥ 5 log10 of E. faecalis CFU for each setup. From transmission measurements, a threshold wavelength λth for allowing an amount of light transmission for sufficient activation of PS was determined to be 430 nm. Conclusion: This study can be seen as proof of principle that light activation of given intra-canal PS from outside a tooth may be possible at wavelengths ≥ 430 nm, facilitating clinical application of PIB in endodontics. PMID:27379059

  20. 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

  1. 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...

  2. 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

  3. Characterisation by PIXE-RBS of metallic contamination of tissues surrounding a metallic prosthesis on a knee

    Energy Technology Data Exchange (ETDEWEB)

    Guibert, G. [Laboratoire de Physique Corpusculaire de Clermont-Ferrand, IN2P3/CNRS UMR 6533, Universite Blaise Pascal, 63177 Aubiere Cedex (France)]. E-mail: geoffroy.guibert@he-arc.ch; Irigaray, J.L. [Laboratoire de Physique Corpusculaire de Clermont-Ferrand, IN2P3/CNRS UMR 6533, Universite Blaise Pascal, 63177 Aubiere Cedex (France); Moretto, Ph. [Centre d' Etudes Nucleaires de Bordeaux-Gradignan, IN2P3/CNRS UMR 5797, Le Haut Vigneau, BP 120, 33175 Gradignan Cedex (France); Sauvage, T. [Centre d' Etudes et de Recherches par Irradiation, CNRS Orleans France, 3A rue de la ferollerie, 45071 Orleans Cedex 2 (France); Kemeny, J.L. [CHU, Service d' Anatomie et de Cytologie Pathologiques, Universite d' Auvergne, 63100 Clermont-Ferrand (France); Cazenave, A. [Institut Calot, 62608 Berck sur Mer Cedex (France); Jallot, E. [Laboratoire de Physique Corpusculaire de Clermont-Ferrand, IN2P3/CNRS UMR 6533, Universite Blaise Pascal, 63177 Aubiere Cedex (France)

    2006-09-15

    Implants used as biomaterials have to fulfill conditions of functionality, compatibility and sometimes bioactivity. There are four main families of biomaterials: metals and metal alloys, polymers, bioceramics and natural materials. Because of corrosion and friction in the human body, implants generate debris. This debris may develop toxicity, inflammation and prosthetic unsealing by osseous dissolution. Nature, size, morphology and amount of debris are the parameters influencing the tissue responses. In this paper, we characterised metallic contamination produced by knee prosthesis, composed with TiAl{sub 6}V{sub 4} or Co-Cr-Mo alloys, into surrounding capsular tissue by depth migration, in vivo behaviour, content, size and nature of debris by PIXE (Particle Induced X-ray Emission) method associated with RBS (Rutherford Backscattering Spectroscopy). Debris distribution in the whole articulation is very heterogeneous. Debris migrates several thousand micrometers in tissues, with a characteristic decrease. Solid metallic particles of about micrometer size are found in the most polluted samples, in both alloys TiAl{sub 6}V{sub 4} and Cr-Co-Mo. In the mean volume analysed by PIXE, the concentration mass ratios [Ti]/[V] and [Co]/[Cr] confirm the chemical stability of TiAl{sub 6}V{sub 4} debris and show the chemical evolution of Cr-Co-Mo debris. Development of a protocol to prepare thin targets permits us to correlate PIXE and histological analysis in the same zone. The fibrous tissue (collagen fibres, fibroblasts) and macrophage cells are observed with optical microscope in polluted areas. This protocol could locate other pathologies in ppm contamination range, thanks to the great sensitivity of the PIXE method.

  4. 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.

  5. 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.

  6. 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).

  7. 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.

  8. 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.

  9. 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.

  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. 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.

  12. Large-scale automated image analysis for computational profiling of brain tissue surrounding implanted neuroprosthetic devices using Python

    Directory of Open Access Journals (Sweden)

    Nicolas eRey-Villamizar

    2014-04-01

    Full Text Available In this article, we describe use of Python for large-scale automated server-based bio-image analysis in FARSIGHT, a free and open-source toolkit of image analysis methods for quantitative studies of complex and dynamic tissue microenvironments imaged by modern optical microscopes including confocal, multi-spectral, multi-photon, and time-lapse systems. The core FARSIGHT modules for image segmentation, feature extraction, tracking, and machine learning are written in C++, leveraging widely used libraries including ITK, VTK, Boost, and Qt. For solving complex image analysis task, these modules must be combined into scripts using Python. As a concrete example, we consider the problem of analyzing 3-D multi-spectral brain tissue images surrounding implanted neuroprosthetic devices, acquired using high-throughput multi-spectral spinning disk step-and-repeat confocal microscopy. The resulting images typically contain 5 fluorescent channels, 6,000$times$10,000$times$500 voxels with 16 bits/voxel, implying image sizes exceeding 250GB. These images must be mosaicked, pre-processed to overcome imaging artifacts, and segmented to enable cellular-scale feature extraction. The features are used to identify cell types, and perform large-scale analytics for identifying spatial distributions of specific cell types relative to the device. Python was used to build a server-based script (Dell 910 PowerEdge servers with 4 sockets/server with 10 cores each, 2 threads per core and 1TB of RAM running on Red Hat Enterprise Linux linked to a RAID 5 SAN capable of routinely handling image datasets at this scale and performing all these processing steps in a collaborative multi-user multi-platform environment consisting. Our Python script enables efficient data storage and movement between compute and storage servers, logging all processing steps, and performs full multi-threaded execution of all codes, including open and closed-source third party libraries.

  13. Large-scale automated image analysis for computational profiling of brain tissue surrounding implanted neuroprosthetic devices using Python.

    Science.gov (United States)

    Rey-Villamizar, Nicolas; Somasundar, Vinay; Megjhani, Murad; Xu, Yan; Lu, Yanbin; Padmanabhan, Raghav; Trett, Kristen; Shain, William; Roysam, Badri

    2014-01-01

    In this article, we describe the use of Python for large-scale automated server-based bio-image analysis in FARSIGHT, a free and open-source toolkit of image analysis methods for quantitative studies of complex and dynamic tissue microenvironments imaged by modern optical microscopes, including confocal, multi-spectral, multi-photon, and time-lapse systems. The core FARSIGHT modules for image segmentation, feature extraction, tracking, and machine learning are written in C++, leveraging widely used libraries including ITK, VTK, Boost, and Qt. For solving complex image analysis tasks, these modules must be combined into scripts using Python. As a concrete example, we consider the problem of analyzing 3-D multi-spectral images of brain tissue surrounding implanted neuroprosthetic devices, acquired using high-throughput multi-spectral spinning disk step-and-repeat confocal microscopy. The resulting images typically contain 5 fluorescent channels. Each channel consists of 6000 × 10,000 × 500 voxels with 16 bits/voxel, implying image sizes exceeding 250 GB. These images must be mosaicked, pre-processed to overcome imaging artifacts, and segmented to enable cellular-scale feature extraction. The features are used to identify cell types, and perform large-scale analysis for identifying spatial distributions of specific cell types relative to the device. Python was used to build a server-based script (Dell 910 PowerEdge servers with 4 sockets/server with 10 cores each, 2 threads per core and 1TB of RAM running on Red Hat Enterprise Linux linked to a RAID 5 SAN) capable of routinely handling image datasets at this scale and performing all these processing steps in a collaborative multi-user multi-platform environment. Our Python script enables efficient data storage and movement between computers and storage servers, logs all the processing steps, and performs full multi-threaded execution of all codes, including open and closed-source third party libraries.

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

    Science.gov (United States)

    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)

  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. 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

  17. 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.

  18. 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.

  19. 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

  20. 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....

  1. 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.

  2. 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...

  3. 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...

  4. 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.

  5. 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.

  6. 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.

  7. 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...

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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...

  19. The chemical form of metallic debris in tissues surrounding metal-on-metal hips with unexplained failure.

    Science.gov (United States)

    Hart, Alister J; Quinn, Paul D; Sampson, Barry; Sandison, Ann; Atkinson, Kirk D; Skinner, John A; Powell, Jonathan J; Mosselmans, J Fred W

    2010-11-01

    Implant-derived material from metal-on-metal (MOM) hip arthroplasties may be responsible for an unexplained tissue inflammatory response. The chemical form of the metal species in the tissues is predominantly chromium (Cr), but the currently used techniques have not been able to determine whether this is Cr(III) phosphate or Cr(III) oxide. The analytical challenge must overcome the fact that the metal in the tissues is at a relatively low concentration and tissue preparation or the microscopy beam used can affect the results. Microfocus X-ray spectroscopy using a synchrotron beam is useful in addressing both these issues. Using this technique we compared tissue from failed MOM hips with: (1) tissue from metal-on-polyethylene (MOP) hips; (2) chemical standards; (3) metal discs cut from MOM hips. The most abundant implant-related species in all MOM hip tissues contained Cr. Comparison with standards revealed the chemical form was Cr(III) phosphate, which did not vary with manufacturer type (four types analysed) or level of blood metal ions. Cobalt (Co) and molybdenum (Mo) were occasionally present in areas of high Cr. Co was normally found in a metallic state in the tissue, while Mo was found in an oxidized state. The variety of metallic species may have arisen from corrosion, wear or a combination of both. No evidence of Cr(VI) was seen in the tissues examined.

  20. 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...

  1. 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.)

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Safety Study of Photodynamic Therapy Using Talaporfin Sodium in the Pancreas and Surrounding Tissues in the Syrian Golden Hamster

    Directory of Open Access Journals (Sweden)

    Johannes Wittmann

    2014-01-01

    Full Text Available Aim. To assess the safety of photodynamic therapy (PDT using talaporfin sodium on the pancreas and surrounding organs in normal hamsters. Methods. Fluorescence microscopy documented talaporfin levels in liver, duodenum, and pancreas up to 24 hours after photosensitisation. Lesion size in liver 3 days after PDT (50 J, 5 mg/kg, variable drug-light interval (DLI was documented to optimise the DLI. Using optimum DLI, pancreas and surrounding organs were treated with laser fibre touching the surface and animals were killed at 3 or 21 days. Results. Peak fluorescence was seen in duodenum and pancreas at 15 mins (second lower peak at 2 hours. Liver fluorescence was consistently high (peak 1 hour until after 4 hours. Optimum DLI was seen at 15 minutes. The pancreas was relatively resistant to direct PDT injury (small lesions at high doses but surrounding stomach, duodenum, and liver were more susceptible with evidence of adhesions and full thickness damage (localised peritonitis and duodenal perforation at highest doses. Conclusion. The safety profile is similar to PDT with longer acting photosensitisers. The pancreas appears safe to treat, but care is required to avoid high light doses to the intestinal tract, particularly the duodenum.

  7. A Three-Dimensional Finite Element Study on the Biomechanical Simulation of Various Structured Dental Implants and Their Surrounding Bone Tissues.

    Science.gov (United States)

    Zhang, Gong; Yuan, Hai; Chen, Xianshuai; Wang, Weijun; Chen, Jianyu; Liang, Jimin; Zhang, Peng

    2016-01-01

    Background/Purpose. This three-dimensional finite element study observed the stress distribution characteristics of 12 types of dental implants and their surrounding bone tissues with various structured abutments, implant threads, and healing methods under different amounts of concentrated loading. Materials and Methods. A three-dimensional geometrical model of a dental implant and its surrounding bone tissue was created; the model simulated a screw applied with a preload of 200 N or a torque of 0.2 N·m and a prosthetic crown applied with a vertical or an inclined force of 100 N. The Von Mises stress was evaluated on the 12 types of dental implants and their surrounding bone tissues. Results. Under the same loading force, the stress influence on the implant threads was not significant; however, the stress influence on the cancellous bone was obvious. The stress applied to the abutment, cortical bone, and cancellous bone by the inclined force applied to the crown was larger than the stress applied by the vertical force to the crown, and the abutment stress of the nonsubmerged healing implant system was higher than that of the submerged healing implant system. Conclusion. A dental implant system characterised by a straight abutment, rectangle tooth, and nonsubmerged healing may provide minimum value for the implant-bone interface.

  8. A Three-Dimensional Finite Element Study on the Biomechanical Simulation of Various Structured Dental Implants and Their Surrounding Bone Tissues

    Directory of Open Access Journals (Sweden)

    Gong Zhang

    2016-01-01

    Full Text Available Background/Purpose. This three-dimensional finite element study observed the stress distribution characteristics of 12 types of dental implants and their surrounding bone tissues with various structured abutments, implant threads, and healing methods under different amounts of concentrated loading. Materials and Methods. A three-dimensional geometrical model of a dental implant and its surrounding bone tissue was created; the model simulated a screw applied with a preload of 200 N or a torque of 0.2 N·m and a prosthetic crown applied with a vertical or an inclined force of 100 N. The Von Mises stress was evaluated on the 12 types of dental implants and their surrounding bone tissues. Results. Under the same loading force, the stress influence on the implant threads was not significant; however, the stress influence on the cancellous bone was obvious. The stress applied to the abutment, cortical bone, and cancellous bone by the inclined force applied to the crown was larger than the stress applied by the vertical force to the crown, and the abutment stress of the nonsubmerged healing implant system was higher than that of the submerged healing implant system. Conclusion. A dental implant system characterised by a straight abutment, rectangle tooth, and nonsubmerged healing may provide minimum value for the implant-bone interface.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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; ...

  2. Molecular identification of foreign inclusions in inflammatory tissue surrounding metal implants by Fourier transform laser microprobe mass spectrometry.

    Science.gov (United States)

    De Nollin, S; Poels, K; Van Vaeck, L; De Clerck, N; Bakker, A; Duwel, V; Vandevelde, D; Van Marck, E

    1997-01-01

    Fourier transform laser microprobe mass spectrometry (FT LMMS) is a novel technique for micro-analysis of solids with a lateral resolution in the 5 microns range. One of the major advantages of the technique is the capability to perform characterisation of the molecular composition of both organic and inorganic compounds. The information is directly deduced from the signals without the aid of reference spectra. FT LMMS was applied to the characterisation of black tissue fragments in a biopsy from a patient, in which a constrained condylar nodular knee system was implanted ten years ago. The tissue contained numerous foreign giant cells with a black non-birefringent pigment in their cytoplasm. FT LMMS analysis allowed us to detect directly by means of molecular signals, that the debris consisted primarily of titanium oxide and not metallic titanium, while the implant itself only contained titanium.

  3. 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.

  4. [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.

  5. Phenotypic changes of p53, HER2, and FAS system in multiple normal tissues surrounding breast cancer.

    Science.gov (United States)

    Mottolese, Marcella; Nádasi, Edit A; Botti, Claudio; Cianciulli, Anna M; Merola, Roberta; Buglioni, Simonetta; Benevolo, Maria; Giannarelli, Diana; Marandino, Ferdinando; Donnorso, Raffaele Perrone; Venturo, Irene; Natali, Pier Giorgio

    2005-07-01

    To determine whether phenotypic field changes occur in tissues adjacent to carcinoma, we assayed, by immunohistochemistry, the expression of HER-2, p53, Fas, and FasL in 72 breast cancers (BC) and multiple autologous peritumoral tissues (PTTs) sampled up to 5 cm distance and in 44 benign breast tumors (BBTs). About 5% and 3% of the PTTs and 4.5% and 6.8% of BBTs showed alterations in HER2 and p53 expression, respectively. Of interest, gene amplification was observed in 50% of HER2 positive PTTs, but not in any HER2 positive BBTs. Fas, highly expressed in BBTs and downregulated in BC, maintained its expression in PTTs, whereas FasL, usually negative in BBTs, was upregulated in BC as well as in the PTTs closest (1 cm) to the invasive lesion. Our data suggest that FasL could be a potential novel biomarker of transformation, which may identify, along with HER2 and p53, precursor lesions in a genetically altered breast tissue.

  6. [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.

  7. 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

  8. 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.

  9. 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.

  10. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  12. 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...

  13. Large-scale proteomics differentiates cholesteatoma from surrounding tissues and identifies novel proteins related to the pathogenesis.

    Directory of Open Access Journals (Sweden)

    Anders Britze

    Full Text Available Cholesteatoma is the growth of keratinizing squamous epithelium in the middle ear. It is associated with severe complications and has a poorly understood etiopathogenesis. Here, we present the results from extensive bioinformatics analyses of the first large-scale proteomic investigation of cholesteatoma. The purpose of this study was to take an unbiased approach to identifying alterations in protein expression and in biological processes, in order to explain the characteristic phenotype of this skin-derived tumor. Five different human tissue types (cholesteatoma, neck of cholesteatoma, tympanic membrane, external auditory canal skin, and middle ear mucosa were analyzed. More than 2,400 unique proteins were identified using nanoLC-MS/MS based proteomics (data deposited to the ProteomeXchange, and 295 proteins were found to be differentially regulated in cholesteatoma. Validation analyses were performed by SRM mass spectrometry. Proteins found to be up- or down-regulated in cholesteatoma were analyzed using Ingenuity Pathway Analysis and clustered into functional groups, for which activation state and associations to disease processes were predicted. Cholesteatoma contained high levels of pro-inflammatory S100 proteins, such as S100A7A and S100A7. Several proteases, such as ELANE, were up-regulated, whereas extracellular matrix proteins, such as COL18A1 and NID2, were under-represented. This may lead to alterations in integrity and differentiation of the tissue (as suggested by the up-regulation of KRT4 in the cholesteatoma. The presented data on the differential protein composition in cholesteatoma corroborate previous studies, highlight novel protein functionalities involved in the pathogenesis, and identify new areas for targeted research that hold therapeutic potential for the disease.

  14. Differences between perivascular adipose tissue surrounding the heart and the internal mammary artery: possible role for the leptin-inflammation-fibrosis-hypoxia axis.

    Science.gov (United States)

    Drosos, Ioannis; Chalikias, Georgios; Pavlaki, Maria; Kareli, Dimitra; Epitropou, Grigorios; Bougioukas, Georgios; Mikroulis, Dimitrios; Konstantinou, Fotios; Giatromanolaki, Alexandra; Ritis, Konstantinos; Münzel, Thomas; Tziakas, Dimitrios; Konstantinides, Stavros; Schäfer, Katrin

    2016-11-01

    The factors mediating the paracrine effects of perivascular adipose tissue (PVAT) in atherosclerosis are largely unknown. The adipokine leptin has been implicated in the increased cardiovascular risk in obesity and may locally promote neointima formation independently of circulating leptin levels. In patients with established coronary artery disease, we examined the expression of leptin as well as of its possible inducers in 'cardiac' PVAT surrounding the aortic root and coronary arteries (C-PVAT), and compared it to the PVAT surrounding the internal mammary artery (IMA-PVAT), a vessel resistant to atherosclerosis. Tissue specimens collected from male patients undergoing coronary artery bypass surgery were processed for real-time PCR, ELISA, in situ hybridization, and immunohistochemistry analysis. Leptin protein expression was elevated in C-PVAT compared to IMA-PVAT, independent of serum leptin levels. Compared to IMA-PVAT, C-PVAT exhibited more pronounced angiogenesis and inflammation, as indicated by significantly higher numbers of PECAM1-positive vessels and CD68-positive macrophages, and was characterized by a greater extent of fibrosis and hypoxia. Increased expression of hypoxia-inducible factor-1α and Fos-like antigen (FOSL)2, factors known to enhance leptin gene transcription, was observed in C-PVAT. As a proof of concept, exposure of human adipocytes to chemical hypoxia resulted in significantly increased FOSL2 and leptin mRNA levels. A higher degree of local tissue hypoxia and up-regulation of leptin expression in the perivascular adipose tissue, along with increased vascularization, inflammation, and fibrosis, may contribute to the increased atherosclerotic plaque burden in the coronary arteries compared to the IMA.

  15. 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.

  16. 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

  17. 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...

  18. Innervation and functional characteristics of connective tissues, especially elastic fibers, in human fetal thoracic intervertebral articular capsule and its surroundings.

    Science.gov (United States)

    Shiraishi, Yosuke; Kobayashi, Miya; Yasui, Masaya; Ozaki, Noriyuki; Sugiura, Yasuo

    2003-05-01

    The articular capsules between the thoracic vertebrae, which have physiologically different functions from those of other levels of the vertebrae, have yet to be subjected to neuro-anatomical and fine structural analysis. In the present study, we analyzed serial frozen sections of decalcified thoracic vertebrae in human fetuses, and identified the articular capsule tissue with its unique distribution of elastic fibers. The fine structure of the elastic fibers was studied by transmission electron microscopy. In the early-stage fetus, the fibrous membrane forming the lateral intervertebral articular capsule contained abundant thin elastic fibers consisting of microfibrils. In the late-stage fetus, the lateral capsule of fibrous membrane was occupied by thick elastic fibers. A medial articular capsule, namely the ligamenta flava, contained numerous thick elastic fibers in both early and late-stage fetuses. The distributional differences in nerve fibers between early and late-stage fetuses were determined by immunostaining, using antibodies raised against protein gene product 9.5 (PGP 9.5; ubiquitin carboxyl-terminal hydrolase). Innervation by PGP 9.5 immunoreactive fibers was limited to the areas of the articular capsules near the blood vessels, which may indicate their functional relation with blood flow. No PGP 9.5 immunoreactive fibers were found in the ligamenta flava of the late-stage fetus. Innervation might be directly involved in the development of the intervertebral articular capsules in normal human fetuses.

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

    Directory of Open Access Journals (Sweden)

    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

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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...

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. Bevacizumab Inhibits Breast Cancer-Induced Osteolysis, Surrounding Soft Tissue Metastasis, and Angiogenesis in Rats as Visualized by VCT and MRI

    Directory of Open Access Journals (Sweden)

    Tobias Bäuerle

    2008-05-01

    Full Text Available The aim of this study was to evaluate the effect of an antiangiogenic treatment with the vascular endothelial growth factor antibody bevacizumab in an experimental model of breast cancer bone metastasis and to monitor osteolysis, soft tissue tumor, and angiogenesis in bone metastasis noninvasively by volumetric computed tomography (VCT and magnetic resonance imaging (MRI. After inoculation of MDA-MB-231 human breast cancer cells into nude rats, bone metastasis was monitored with contrast-enhanced VCT and MRI from day 30 to day 70 after tumor cell inoculation, respectively. Thereby, animals of the treatment group (10 mg/kg bevacizumab IV weekly, n = 15 were compared with sham-treated animals (n = 17. Treatment with bevacizumab resulted in a significant difference versus control in osteolytic as well as soft tissue lesion sizes (days 50 to 70 and 40 to 70 after tumor cell inoculation, respectively; P < .05. This observation was paralleled with significantly reduced vascularization in the treatment group as shown by reduced increase in relative signal intensity in dynamic contrast-enhanced MRI from days 40 to 70 (P < .05. Contrast-enhanced VCT and histology confirmed decreased angiogenesis as well as new bone formation after application of bevacizumab. In conclusion, bevacizumab significantly inhibited osteolysis, surrounding soft tissue tumor growth, and angiogenesis in an experimental model of breast cancer bone metastasis as visualized by VCT and MRI.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. The enzyme profiles in the connective tissue attaching pin bones to the surrounding tissue is specific in farmed salmon (Salmo salar) and cod (Gadus morhua L.).

    Science.gov (United States)

    Vuong, Tram T; Rønning, Sissel B; Kolset, Svein O; Pedersen, Mona E

    2017-02-01

    Post mortem storage is a necessary process for removal of pin bones without destruction of fillets, thereby avoiding volume and economic loss. However, the enzymes involved in loosening pin bones during storage have not been studied to a great extent. In this study, the activities and localization of MMPs in the connective tissue (CT) of pin bones dissected from fillet of salmon and cod were investigated. Interestingly, the enzyme activity profile in these two species was different during post mortem storage of fish fillets. Adding MMP inhibitor (GM6001) and serine protease inhibitor (Pefabloc) revealed different effects in the two species, suggesting different regulations in salmon and cod. In situ zymography with the same inhibitors verified MMP and serine protease activity in CT close to pin bone at early post mortem (6 h) in salmon. However, MMP inhibition was not evident in cod in this area at that time point. Immunohistochemistry further revealed MMP9 and MMP13 were located more to the outer rim of CT, facing the pin bone and adipose tissue, while MMP7 was more randomly distributed within CT in salmon. In contrast, all these three MMPs were randomly distributed in CT in cod. In summary, our study reveals different MMP enzyme profiles in salmon and cod in the pin bone area, influenced by serine proteases, and suggests that MMPs and serine proteases must be taken in consideration when studying the conditions for early pin bone removal.

  3. 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.

  4. 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

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

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    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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. Analysis of specific absorption rate and internal electric field in human biological tissues surrounding an air-core coil-type transcutaneous energy transmission transformer.

    Science.gov (United States)

    Shiba, Kenji; Zulkifli, Nur Elina Binti; Ishioka, Yuji

    2017-06-01

    In this study, we analyzed the internal electric field E and specific absorption rate (SAR) of human biological tissues surrounding an air-core coil transcutaneous energy transmission transformer. Using an electromagnetic simulator, we created a model of human biological tissues consisting of a dry skin, wet skin, fat, muscle, and cortical bone. A primary coil was placed on the surface of the skin, and a secondary coil was located subcutaneously inside the body. The E and SAR values for the model representing a 34-year-old male subject were analyzed using electrical frequencies of 0.3-1.5 MHz. The transmitting power was 15 W, and the load resistance was 38.4 Ω. The results showed that the E values were below the International Commission on Non-ionizing Radiation Protection (ICNIRP) limit for the general public exposure between the frequencies of 0.9 and 1.5 MHz, and SAR values were well below the limit prescribed by the ICNIRP for the general public exposure between the frequencies of 0.3 and 1.2 MHz.

  13. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

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

    Science.gov (United States)

    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

  2. Differential expression of tissue repair genes in the pathogenesis of chronic obstructive pulmonary disease

    National Research Council Canada - National Science Library

    Gosselink, John V; Hayashi, Shizu; Elliott, W Mark; Xing, Li; Chan, Becky; Yang, Luojia; Wright, Claire; Sin, Don; Paré, Peter D; Pierce, John A; Pierce, Richard A; Patterson, Alex; Cooper, Joel; Hogg, James C

    2010-01-01

    .... The expression of 54 genes associated with repair of repetitively damaged tissue was measured in 136 paired samples of small bronchioles and surrounding lung tissue separated by laser capture microdissection...

  3. 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.

  4. 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

  5. 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

  6. 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.

  7. 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

  8. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  10. 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 ...

  11. 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.

  12. 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.

  13. 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.

  14. Modeling Airflow Using Subject-Specific 4DCT-Based Deformable Volumetric Lung Models

    OpenAIRE

    Olusegun J. Ilegbusi; Zhiliang Li; Behnaz Seyfi; Yugang Min; Sanford Meeks; Patrick Kupelian; Santhanam, Anand P.

    2012-01-01

    Lung radiotherapy is greatly benefitted when the tumor motion caused by breathing can be modeled. The aim of this paper is to present the importance of using anisotropic and subject-specific tissue elasticity for simulating the airflow inside the lungs. A computational-fluid-dynamics (CFD) based approach is presented to simulate airflow inside a subject-specific deformable lung for modeling lung tumor motion and the motion of the surrounding tissues during radiotherapy. A flow-structure inter...

  15. 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....

  16. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  18. 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.

  19. 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.

  20. 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.

  1. Automatic lung segmentation from thoracic computed tomography scans using a hybrid approach with error detection.

    NARCIS (Netherlands)

    Rikxoort, E.M. van; Hoop, B. de; Viergever, M.A.; Prokop, M.; Ginneken, B. van

    2009-01-01

    Lung segmentation is a prerequisite for automated analysis of chest CT scans. Conventional lung segmentation methods rely on large attenuation differences between lung parenchyma and surrounding tissue. These methods fail in scans where dense abnormalities are present, which often occurs in clinical

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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...

  7. 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

  8. 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

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. [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.

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

    Science.gov (United States)

    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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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,

  4. The dosimetric impact of daily setup error on target volumes and surrounding normal tissue in the treatment of prostate cancer with intensity-modulated radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Algan, Ozer, E-mail: oalgan@ouhsc.edu [Department of Radiation Oncology, Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Jamgade, Ambarish; Ali, Imad; Christie, Alana; Thompson, J. Spencer; Thompson, David; Ahmad, Salahuddin; Herman, Terence [Department of Radiation Oncology, Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States)

    2012-01-01

    parameter for the surrounding normal tissue except for the dose received by the penile bulb and the right hip. Our dosimetric evaluation suggests significant underdosing with inaccurate target localization and emphasizes the importance of accurate patient setup and target localization. Further studies are needed to evaluate the impact of intrafraction organ motion, rotation, and deformation on doses delivered to target volumes.

  5. 阴茎及其毗邻组织三维虚拟模型的建立%3-Dimensional model reconstruction of penis and surrounding tissue

    Institute of Scientific and Technical Information of China (English)

    王睿恒; 曹川; 梅文铭; 王文献; 谭立文; 李世荣

    2012-01-01

    目的 探讨基于磁共振图像建立阴茎及其毗邻结构三维虚拟模型的可行性,为个性化阴茎整复手术仿真系统的开发提供建模方法.方法 采用适宜的参数获得磁共振图像,在Amira软件中运用面绘制方法对正常成人阴茎及其毗邻组织进行三维重建和立体显示.结果 3.0 mm层厚的快速自旋回波T2加权磁共振图像,可清晰显示阴茎及周围解剖结构且轮廓分明,以此建立的模型可清晰显示阴茎海绵体、阴茎悬韧带等结构的形态和相互位置关系,可见阴茎悬韧带呈纵行附着于耻骨联合与阴茎海绵体背侧之间,阴茎海绵体脚附着于耻骨下支.结论 基于磁共振图像建立阴茎及其毗邻组织三维模型是一种可行的方法,建立的模型可用于开发个性化阴茎整复手术仿真系统.%Objective To evaluate the feasibility of 3-Dimensional(3-D) model reconstruction of penis and surrounding structures based on magnetic resonance images,which may provide the model building method for modeling surgery of individual penoplasty.Methods Magnetic resonance (MR)images of penis with different imaging parameters were evaluated.With the surface rendering construction,the 3D virtual model was established by Amira software.Results The anatomical details imaging is better in T2-weighted fast spin-echo images with 3.0 mm slice thickness.The established model based on the MR images can show the soft-tissue,suspensory ligament of the penis.The suspensory ligament stretches between the pubic symphysis and the corpora cavernosa.The penile roots attach to inferior ramus of pubis.Conclusions MR imaging provides enough anatomical information for modeling.It can be used for the development of model surgery system of individual penoplasty.

  6. The dosimetric impact of daily setup error on target volumes and surrounding normal tissue in the treatment of prostate cancer with intensity-modulated radiation therapy.

    Science.gov (United States)

    Algan, Ozer; Jamgade, Ambarish; Ali, Imad; Christie, Alana; Thompson, J Spencer; Thompson, David; Ahmad, Salahuddin; Herman, Terence

    2012-01-01

    The purpose of this study was to evaluate the impact of daily setup error and interfraction organ motion on the overall dosimetric radiation treatment plans. Twelve patients undergoing definitive intensity-modulated radiation therapy (IMRT) treatments for prostate cancer were evaluated in this institutional review board-approved study. Each patient had fiducial markers placed into the prostate gland before treatment planning computed tomography scan. IMRT plans were generated using the Eclipse treatment planning system. Each patient was treated to a dose of 8100 cGy given in 45 fractions. In this study, we retrospectively created a plan for each treatment day that had a shift available. To calculate the dose, the patient would have received under this plan, we mathematically "negated" the shift by moving the isocenter in the exact opposite direction of the shift. The individualized daily plans were combined to generate an overall plan sum. The dose distributions from these plans were compared with the treatment plans that were used to treat the patients. Three-hundred ninety daily shifts were negated and their corresponding plans evaluated. The mean isocenter shift based on the location of the fiducial markers was 3.3 ± 6.5 mm to the right, 1.6 ± 5.1 mm posteriorly, and 1.0 ± 5.0 mm along the caudal direction. The mean D95 doses for the prostate gland when setup error was corrected and uncorrected were 8228 and 7844 cGy (p 1200 cGy and for the PTV8100 could approach almost 2000 cGy when comparing corrected against uncorrected plans. There was no statistically significant difference in the D35 parameter for the surrounding normal tissue except for the dose received by the penile bulb and the right hip. Our dosimetric evaluation suggests significant underdosing with inaccurate target localization and emphasizes the importance of accurate patient setup and target localization. Further studies are needed to evaluate the impact of intrafraction organ motion, rotation

  7. 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.

  8. 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

  9. 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...

  10. 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.

  11. Treatment of Superior Lobe Central Lung Cancer with Lung Replantation

    Directory of Open Access Journals (Sweden)

    Yulun YANG

    2010-11-01

    Full Text Available Background and objective Patients suffering from lung cancer often have poor quality of life after pneumonectomy. It has clinical significances to preserve maximum lobes of the “healthy” lung. The aim of this study is to report the applications of lung replantation in treatment of superior lobe central lung cancer. Methods Three lung cancer cases were included and analysed. The bronchus and margin of lower lung lobe were encroached by cancer. Pulmonary artery was invaded and surrounded by metastatic lymph node. Complete pneumonectomy, antegrade perfusion and retroperfusion with low-potassium dextran (LPD solution in vitro were performed. The retainable lower pulmonary lobe was selected from the isolated lung and superior pulmonary vein was replaced with inferior pulmonary veins. The bronchus and pulmonary artery were inosculated by turns. Results The operative cumulative time ranged from 220 min to 250 min. The isolated time of lobus inferior pulmonary ranged from 120 min to 150 min. The chest tube was pulled out after chest X-ray confirmed the reimplant lung full re-expansion. The patients were followed up for 4 months to 8 months and accomplished adjuvant chemotherapy for 3 or 4 periodicities. The patients had a sound quality of life. Conclusion Lung replantation removing the extensive tumor tissue and retaining the maximum pulmonary normal tissue is an useful method for treatment of lung cancer.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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)

  20. 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.

  1. 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.

  2. 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.

  3. 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.

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

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    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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. Automated lung segmentation of low resolution CT scans of rats

    Science.gov (United States)

    Rizzo, Benjamin M.; Haworth, Steven T.; Clough, Anne V.

    2014-03-01

    Dual modality micro-CT and SPECT imaging can play an important role in preclinical studies designed to investigate mechanisms, progression, and therapies for acute lung injury in rats. SPECT imaging involves examining the uptake of radiopharmaceuticals within the lung, with the hypothesis that uptake is sensitive to the health or disease status of the lung tissue. Methods of quantifying lung uptake and comparison of right and left lung uptake generally begin with identifying and segmenting the lung region within the 3D reconstructed SPECT volume. However, identification of the lung boundaries and the fissure between the left and right lung is not always possible from the SPECT images directly since the radiopharmaceutical may be taken up by other surrounding tissues. Thus, our SPECT protocol begins with a fast CT scan, the lung boundaries are identified from the CT volume, and the CT region is coregistered with the SPECT volume to obtain the SPECT lung region. Segmenting rat lungs within the CT volume is particularly challenging due to the relatively low resolution of the images and the rat's unique anatomy. Thus, we have developed an automated segmentation algorithm for low resolution micro-CT scans that utilizes depth maps to detect fissures on the surface of the lung volume. The fissure's surface location is in turn used to interpolate the fissure throughout the lung volume. Results indicate that the segmentation method results in left and right lung regions consistent with rat lung anatomy.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Transcriptomic Microenvironment of Lung Adenocarcinoma.

    Science.gov (United States)

    Bossé, Yohan; Sazonova, Olga; Gaudreault, Nathalie; Bastien, Nathalie; Conti, Massimo; Pagé, Sylvain; Trahan, Sylvain; Couture, Christian; Joubert, Philippe

    2017-03-01

    Background: Tissues surrounding tumors are increasingly studied to understand the biology of cancer development and identify biomarkers.Methods: A unique geographic tissue sampling collection was obtained from patients that underwent curative lobectomy for stage I pulmonary adenocarcinoma. Tumor and nontumor lung samples located at 0, 2, 4, and 6 cm away from the tumor were collected. Whole-genome gene expression profiling was performed on all samples (n = 5 specimens × 12 patients = 60). Analyses were carried out to identify genes differentially expressed in the tumor compared with adjacent nontumor lung tissues at different distances from the tumor as well as to identify stable and transient genes in nontumor tissues with respect to tumor proximity.Results: The magnitude of gene expression changes between tumor and nontumor sites was similar with increasing distance from the tumor. A total of 482 up- and 843 downregulated genes were found in tumors, including 312 and 566 that were consistently differentially expressed across nontumor sites. Twenty-nine genes induced and 34 knocked-down in tumors were also identified. Tumor proximity analyses revealed 15,700 stable genes in nontumor lung tissues. Gene expression changes across nontumor sites were subtle and not statistically significant.Conclusions: This study describes the transcriptomic microenvironment of lung adenocarcinoma and adjacent nontumor lung tissues collected at standardized distances relative to the tumor.Impact: This study provides further insights about the molecular transitions that occur from normal tissue to lung adenocarcinoma and is an important step to develop biomarkers in nonmalignant lung tissues. Cancer Epidemiol Biomarkers Prev; 26(3); 389-96. ©2016 AACR.

  20. 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.

  1. 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...

  2. 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...

  3. 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.

  4. Dosimetric Evaluation of Three Partial Breast Irradiation Devices and the Dosimetric Effect of Tissue Thickness Surrounding a Multi-Lumen Partial Breast Applicator

    Science.gov (United States)

    Detwiler, Jordyn Ashle

    Many High Dose Rate treatment planning systems that are in use fail to correct for heterogeneities. If the treatment planning system does not correct for heterogeneities, it would assume that the patient is receiving full scatter when in reality, the patient will possibly be underdosed. A 1cm diameter planning target volume for a lumpectomy cavity could extend beyond the skin or chest wall for the patient and could be a great problem when it comes to treatment with the MammoSiteRTM single lumen breast applicator. A previous Monte Carlo study tested 3 MammoSiteRTM balloon sizes at various depths beyond the planning target volume to see how much tissue would be needed to achieve full scatter. The results showed that on average, if there was no tissue beyond the prescription line of 1cm there would be a 10% dose reduction for the breast -- skin interface. The purpose of this study is to use the Strut Adjusted Volume Implant (SAVI) multi-lumen breast applicator to re-create the measurements done with the MammoSiteRTM balloon and expand these measurements to include tissue thicknesses less than the PTV. Previous simulations with the MammoSiteRTM were done using Monte Carlo, with tissue thicknesses beyond the planning target volume of 0 -- 10cm. This study will re-create these measurements using Metal Oxide Semiconductor Field Effect Transistors (MOSFETs) and also take measurements below the prescription line of 1cm due to the ability of the SAVI applicator to adjust dose to the skin.

  5. Can Breast Tumors Affect the Oxidative Status of the Surrounding Environment? A Comparative Analysis among Cancerous Breast, Mammary Adjacent Tissue, and Plasma.

    Science.gov (United States)

    Panis, C; Victorino, V J; Herrera, A C S A; Cecchini, A L; Simão, A N C; Tomita, L Y; Cecchini, R

    2015-01-01

    In this paper, we investigated the oxidative profile of breast tumors in comparison with their normal adjacent breast tissue. Our study indicates that breast tumors present enhanced oxidative/nitrosative stress, with concomitant augmented antioxidant capacity when compared to the adjacent normal breast. These data indicate that breast cancers may be responsible for the induction of a prooxidant environment in the mammary gland, in association with enhanced TNF-α and nitric oxide.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. Marking 100 years since Rudolf Höber’s discovery of the insulating envelope surrounding cells and of the beta-dispersion exhibited by tissue

    Directory of Open Access Journals (Sweden)

    Ronald Pethig

    2012-11-01

    Full Text Available Between 1910 and 1913 Rudolf Höber presented proof that the interiors of red blood cells and muscle cells contain conducting electrolytes, and that each conducting core is contained within an insulating membrane.  He did this by demonstrating, in a series of remarkable electrical experiments, that the conductivity of compacted cell samples at low frequencies (~150 Hz was about ten-times less than the value obtained at ~5 MHz.  On perforation of the membrane, the low-frequency conductivity increased to a value approaching that exhibited at MHz frequencies. Apart from representing a major milestone in the development of cell biology and electrophysiology, Höber’s work was the first description of what we now call the dielectric b-dispersion exhibited by cell suspensions and fresh tissue.

  14. 利用残根行种植牙周围组织重建的牙龈美学效果分析%Dental implants gums surrounding tissue reconstruction of the aeshetic effect analysis

    Institute of Scientific and Technical Information of China (English)

    孙勇; 邹廷前; 罗铁柱; 丁少华

    2014-01-01

    目的:总结美学区域种植牙周围组织重建的临床效果。方法:通过残根引导牙龈再生,即刻种植+引导骨再生(guided bone regeneration GBR),临时冠修复获得种植牙牙龈美学效果。结果:所有种植体都发生了骨结合,龈乳头在邻间隙充盈效果满意。结论:种植牙周围组织重建使种植牙更容易获得良好的牙龈美学效果。%Objective:To summarize the clinical effect of dental implant surrounding tissue reconstruction. Method:through the residual root guide the gingival regeneration, immediate implant placement plus guided bone regeneration, temporary crown to obtain dental implant gingival aesthetic effectiveness. Result:all implants remained osseointegrated, gingival papilla in the adjacent gap filling effect is satisfactory. Conclusion:Dental implant surrounding tissue reconstruc-tion make it easier to obtain good effect of gingival aesthetics.

  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. Usefulness of Color Coding Resected Samples from a Pancreaticoduodenectomy with Tissue Marking Dyes for a Detailed Examination of Surgical Margin Surrounding the Uncinate Process of the Pancreas.

    Science.gov (United States)

    Mizutani, Satoshi; Suzuki, Hideyuki; Aimoto, Takayuki; Yamagishi, Seiji; Mishima, Keisuke; Watanabe, Masanori; Kitayama, Yasuhiko; Motoda, Norio; Isshiki, Saiko; Uchida, Eiji

    2017-01-01

    Characteristics of a cancer-positive margin around a resected uncinate process of the pancreas (MUP) due to a pancreticoduodenectomy are difficult to understand by standardized evaluation because of its complex anatomy. The purposes of this study were to subclassify the MUP with tissue marking dyes of different colors and to identify the characteristics of sites that showed positivity for cancer cells in patients with pancreatic head carcinoma who underwent circumferential superior mesenteric arterial nerve plexus-preserving pancreaticoduodenectomy. Results of this evaluation were used to review operation procedures and perioperative methods. We divided the MUP into 4 sections and stained each section with a different color. These sections were the pancreatic head nerve plexus margin (Area A), portal vein groove margin (Area B), superior mesenteric artery margin (Area C), and left of the superior mesenteric artery margin (Area D). The subjects evaluated were 45 patients who had carcinoma of the pancreatic head and were treated with circumferential superior mesenteric arterial nerve plexus-preserving pancreaticoduodenectomy. Of the 45 patients, nine cases (90%) of incomplete resection showed cancer-positivity in the MUP. Among the 4 sections of the MUP, the most cases of positive results [MUP (+) ] were found in Area B, with Area A (+), 0 case; Area B (+), 6 cases; Area C (+), 2 cases; and Area D (+), 3 cases (total, 11 sites in 9 patients). Relapse occurred in 7 of the 9 patients with MUP (+). Local recurrence was observed as initial relapse in all 3 patients with Area D (+). In contrast, the most common site of recurrence other than that in patients with Area D (+) was the liver. By subclassifying the MUP with tissue marking dyes of different colors, we could confirm regional characteristics of MUP (+). As a result, circumferential superior mesenteric arterial nerve plexus-preserving pancreticoduodenectomy was able to be performed in R0 operations in selected

  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. 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.

  7. 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.

  8. 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.

  9. Sonographic evaluation of surrounding soft tissue lesions complicated with femur fracture%髋部股骨骨折合并周围软组织损伤的超声诊断

    Institute of Scientific and Technical Information of China (English)

    陈静; 农恒荣; 袁勇卫; 杜二珠; 王豫平

    2011-01-01

    目的 探讨超声检查髋部股骨骨折合并周围软组织损伤的多种声像图表现类型及其临床意义.方法 对154例X线检查证实髋部股骨骨折患者的X线图像及超声图像进行对比观察,重点观察骨折及其周围软组织损伤、髋关节囊积液及血肿等的影像显示(X线和超声),包括超声检查治疗前后的比较.结果 在X线检查证实髋部股骨骨折154例患者中,143例超声提示骨折的部位与X线片一致,11例超声不能明确提示X线片所示的骨折部位;超声检出髋部股骨骨折时合并周围软组织损伤148例(96.1%,148/154);总结其声像图表现有以下几种类型:(1)髋关节腔积液(12例).(2)髋关节腔内血块(35例).(3)骨折碎片嵌入肌肉(24例).(4)肌肉血肿(46例).(5)肌肉转子囊内积血(31例).X线通常难以提示髋部骨折合并软组织损伤的具体病变细节,154例中仅有9例臀大肌转子囊内积血合并肌肉内血肿时提示软组织肿胀.结论 超声能够充分显示髋部股骨骨折合并肌肉、韧带、关节囊等软组织损伤,其检测率远高于X线检查,其声像图存在多种类型,从而为临床治疗骨折后关节及肌肉损伤提供重要诊断信息;但超声存在着显示骨折损伤全貌的局限性.%Objective The surrounding soft tissue lesions complicated with femur fracture are extremely common. The detection rate of ultrasound and sonographic features were evaluated in this study. Methods A total of 154 cases with the femur fracture of hip confirmed by X-ray, were compared with those by ultrasonography, especially for the surrounding soft tissue lesions with femur fracture near the hip. Results In the 154 femur fracture cases confirmed by X-ray, the ultrasound finding in 143 cases were in accordance with those by X-ray, the 11 cases of femur fracture could not be found by ultrasound. There are 148 cases with soft tissue lesions surrounding the femur fracture near the hip had been diagnosed by

  10. 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

  11. 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.

  12. 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.

  13. Local Tumor Control and Normal Tissue Toxicity of Pulsed Low-Dose Rate Radiotherapy for Recurrent Lung Cancer

    Directory of Open Access Journals (Sweden)

    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.

  14. Towards a biomechanical model of the human lung

    OpenAIRE

    Núñez Marquez, Gloria

    2011-01-01

    Radiotherapy of the lung is challenging due to the motion induced by respiration. Plans of radiotherapy treatments are developed based on static computed tomography (CT) images, while treatment is performed in moving organs. This leads to a lack of precise knowledge of the actual position of the tumor and internal organs during treatment makes the calculation of actual dose absorbed by the lungs and surrounding tissues unknown. In the Center for Advanced Radiotherapy Technologies (CART), the ...

  15. Towards a biomechanical model of the human lung

    OpenAIRE

    Núñez Marquez, Gloria

    2011-01-01

    Radiotherapy of the lung is challenging due to the motion induced by respiration. Plans of radiotherapy treatments are developed based on static computed tomography (CT) images, while treatment is performed in moving organs. This leads to a lack of precise knowledge of the actual position of the tumor and internal organs during treatment makes the calculation of actual dose absorbed by the lungs and surrounding tissues unknown. In the Center for Advanced Radiotherapy Technologies (CART), the ...

  16. 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...

  17. 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).

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  11. Practices Surrounding Event Photos

    NARCIS (Netherlands)

    Vyas, Dhaval; Nijholt, Antinus; van der Veer, Gerrit C.; Kotzé, P.; Marsden, G.; Lindgaard, G.; Wesson, J.; Winckler, M.

    Sharing photos through mobile devices has a great potential for creating shared experiences of social events between co-located as well as remote participants. In order to design novel event sharing tools, we need to develop indepth understanding of current practices surrounding these so called

  12. [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.

  13. 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.

  14. A GPU-based framework for modeling real-time 3D lung tumor conformal dosimetry with subject-specific lung tumor motion

    Energy Technology Data Exchange (ETDEWEB)

    Min Yugang; Santhanam, Anand; Ruddy, Bari H [University of Central Florida, FL (United States); Neelakkantan, Harini; Meeks, Sanford L [M D Anderson Cancer Center Orlando, FL (United States); Kupelian, Patrick A, E-mail: anand.santhanam@orlandohealth.co [Department of Radiation Oncology, University of California, Los Angeles, CA (United States)

    2010-09-07

    In this paper, we present a graphics processing unit (GPU)-based simulation framework to calculate the delivered dose to a 3D moving lung tumor and its surrounding normal tissues, which are undergoing subject-specific lung deformations. The GPU-based simulation framework models the motion of the 3D volumetric lung tumor and its surrounding tissues, simulates the dose delivery using the dose extracted from a treatment plan using Pinnacle Treatment Planning System, Phillips, for one of the 3DCTs of the 4DCT and predicts the amount and location of radiation doses deposited inside the lung. The 4DCT lung datasets were registered with each other using a modified optical flow algorithm. The motion of the tumor and the motion of the surrounding tissues were simulated by measuring the changes in lung volume during the radiotherapy treatment using spirometry. The real-time dose delivered to the tumor for each beam is generated by summing the dose delivered to the target volume at each increase in lung volume during the beam delivery time period. The simulation results showed the real-time capability of the framework at 20 discrete tumor motion steps per breath, which is higher than the number of 4DCT steps (approximately 12) reconstructed during multiple breathing cycles.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. [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.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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.

  8. 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...

  9. 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

  10. Preclinical studies on the use of interstitial laser photocoagulation in the lung parenchyma

    Science.gov (United States)

    Fielding, D. I.; Buonaccorsi, Giovanni A.; Hanby, A.; Hetzel, M. R.; Bown, Stephen G.

    1996-12-01

    A preliminary assessment was made of the effect of interstitial laser photocoagulation on normal lung parenchyma. Using rats lesions were created by passing the laser fiber percutaneously into the normal lung under general anaesthetic. The lungs were removed post mortem at 3 days. The lesions were ellipsoid in shape and well circumscribed. Histology showed central charring surrounded by zones of coagulative and hemorrhagic necrosis. there was a clear margin between the treated and normal tissue. These results indicate that further examination is warranted of the use of ILP for treatment of small primary lung tumors in patients unsuitable for surgery.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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...

  3. 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.

  4. 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

  5. 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

  6. 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

  7. Enhanced expression of G-protein coupled estrogen receptor (GPER/GPR30 in lung cancer

    Directory of Open Access Journals (Sweden)

    Jala Venkatakrishna Rao

    2012-12-01

    Full Text Available Abstract Background G-protein-coupled estrogen receptor (GPER/GPR30 was reported to bind 17β-estradiol (E2, tamoxifen, and ICI 182,780 (fulvestrant and promotes activation of epidermal growth factor receptor (EGFR-mediated signaling in breast, endometrial and thyroid cancer cells. Although lung adenocarcinomas express estrogen receptors α and β (ERα and ERβ, the expression of GPER in lung cancer has not been investigated. The purpose of this study was to examine the expression of GPER in lung cancer. Methods The expression patterns of GPER in various lung cancer lines and lung tumors were investigated using standard quantitative real time PCR (at mRNA levels, Western blot and immunohistochemistry (IHC methods (at protein levels. The expression of GPER was scored and the pairwise comparisons (cancer vs adjacent tissues as well as cancer vs normal lung tissues were performed. Results Analysis by real-time PCR and Western blotting revealed a significantly higher expression of GPER at both mRNA and protein levels in human non small cell lung cancer cell (NSCLC lines relative to immortalized normal lung bronchial epithelial cells (HBECs. The virally immortalized human small airway epithelial cell line HPL1D showed higher expression than HBECs and similar expression to NSCLC cells. Immunohistochemical analysis of tissue sections of murine lung adenomas as well as human lung adenocarcinomas, squamous cell carcinomas and non-small cell lung carcinomas showed consistently higher expression of GPER in the tumor relative to the surrounding non-tumor tissue. Conclusion The results from this study demonstrate increased GPER expression in lung cancer cells and tumors compared to normal lung. Further evaluation of the function and regulation of GPER will be necessary to determine if GPER is a marker of lung cancer progression.

  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. Effect of anodized oxidation on the surrounding tissue of orthodontic microscrew implants%正畸微种植体表面阳极氧化处理对周围骨组织的影响

    Institute of Scientific and Technical Information of China (English)

    陈岩; 赵文婷; 咏梅; 牛一山

    2012-01-01

    Objective To evaluate the effect of anodized oxidation of Ti-alloy microscrew implants on the osseointegration.Methods Twenty-four Ti-alloy microscrew implants were inserted in the femurs in two rabbits for six weeks.Half of the implants were pretreated in anodized solution as experimental group and others not treated as controls.Undecalcified and decalcified sections of the implants and surrounding tissue were examined with light microscope and the osseointegration rate was calculated.Results Osseointegration was seen in all samples in both groups and no fibrous tissue was seen between bone and implant.The osseointegration rate was slightly higher in the experimental group than in the controls.Conclusions Anodized oxidation could improve the osseointegration rate of Ti-alloy microscrew implants.%目的 通过组织形态学及组织形态测量学评价正畸微螺旋种植体表面阳极氧化处理对周围骨组织愈合情况的影响.方法 24枚钛合金正畸用微螺旋种植体种植于两只新西兰大白兔的后腿,在闭合环境下生长6周.12枚微种植体经过表面阳极氧化处理作为研究组;另外12枚表面没有经过任何处理作为对照组.兔处死后,部分微种植体及周围骨组织进行组织学苏木精-伊红染色(hematoxylin-eosin staining,HE)处理,每组有4枚微种植体及周围骨组织块采用维拉努埃瓦(Villanueva)染色.光学显微镜评价种植体的组织学变化并计算种植体的骨结合率.结果 两组种植体均与周围骨组织有一定的结合,其间无结缔组织可见.螺旋区骨纤维走向紊乱,表面阳极氧化组微种植体周围有较多的骨组织可见.阳极氧化组微种植体的骨结合率略高于对照组.结论 阳极氧化处理可能促进钛合金微种植体与周围骨组织的结合.

  10. 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.

  11. 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 (.

  12. Adaptive Radiation for Lung Cancer

    Science.gov (United States)

    Gomez, Daniel R.; Chang, Joe Y.

    2011-01-01

    The challenges of lung cancer radiotherapy are intra/inter-fraction tumor/organ anatomy/motion changes and the need to spare surrounding critical structures. Evolving radiotherapy technologies, such as four-dimensional (4D) image-based motion management, daily on-board imaging and adaptive radiotherapy based on volumetric images over the course of radiotherapy, have enabled us to deliver higher dose to target while minimizing normal tissue toxicities. The image-guided radiotherapy adapted to changes of motion and anatomy has made the radiotherapy more precise and allowed ablative dose delivered to the target using novel treatment approaches such as intensity-modulated radiation therapy, stereotactic body radiation therapy, and proton therapy in lung cancer, techniques used to be considered very sensitive to motion change. Future clinical trials using real time tracking and biological adaptive radiotherapy based on functional images are proposed. PMID:20814539

  13. 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...

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. Tissue holding device for use during surgical procedure, has contact body with suction foot and suction mouth that is surrounded by rim, and suction pipe connected to suction chamber

    NARCIS (Netherlands)

    Vonck, D.; Goossens, R.H.M.; Flipsen, S.F.J.; Jakimowicz, J.J.; Van der Putten, E.P.W.

    2009-01-01

    The device has a locking ring (5), a connector (6), and a contact body (1) with a suction foot and a suction mouth (8), where the mouth is surrounded by a rim (10), which is substantially located in a plane of the suction foot. A suction chamber (9) has a sieve-shaped inner wall (2) and a

  20. 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.

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. Clinical Application of Surrounding Puncture

    Institute of Scientific and Technical Information of China (English)

    GUO Yao-jie; HAN Chou-ping

    2003-01-01

    Surrounding puncture can stop pathogenic qi from spreading, consolidate the connection between local meridians and enrich local qi and blood, which can eventually supplement anti-pathogenic qi and remove pathogenic qi, and consequently remedy diseases. The author of this article summrized and analyzed the clinical application of surrounding puncture for the purpose of studying this technique and improving the therapeutic effect.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Comparison of contrast-to-noise ratios of transmission and dark-field signal in grating-based X-ray imaging for healthy murine lung tissue

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  10. Prognostic value of tissue inhibitor of metalloproteinase-2 expression in patients with non-small cell lung cancer: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Lin Zhu

    Full Text Available Tissue inhibitor of metalloproteinase-2 (TIMP-2 is a small secretory glycoprotein with anti-matrix metalloproteinase activity. Data on the value of TIMP-2 as a prognostic factor in non-small cell lung cancer (NSCLC are discordant and remain controversial. A systematic review and meta-analysis was performed to explore this issue.We identified the relevant literature by searching the PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure, SinoMed, and Wanfang Data databases (search terms: "non-small cell lung cancer" or "NSCLC" or "Lung Carcinoma, Non-Small-Cell", "Tissue Inhibitor of Metalloproteinase-2" or "TIMP-2", and "prognosis" or "prognostic" or "survive" for updates prior to March 1, 2014. The pooled hazard ratio (HR of overall survival with a 95% confidence interval (95% CI was used to evaluate the strength of the association between positive TIMP-2 expression and survival in patients with NSCLC.We included 12 studies in our systematic review; five studies involving 399 patients with NSCLC were meta-analyzed. The pooled HR of all included patients was 0.57 (95% CI: 0.43-0.77, and the HRs of subgroup analysis according to stage (I-IV, testing method (immunohistochemistry and high TIMP-2 expression percentage (<50% were 0.63 (95% CI: 0.43-0.92, 0.55 (95% CI: 0.41-0.74, and 0.50 (95% CI: 0.28-0.88, respectively. These data suggested that high TIMP-2 expression is associated with favorable prognosis in NSCLC. The meta-analysis did not reveal heterogeneity or publication bias.TIMP-2 expression indicates favorable prognosis in patients with NSCLC; as a protective factor, it could help predict outcome and may guide clinical therapy in the future.

  11. Expression of Formyl-peptide Receptors in Human Lung Carcinoma.

    Science.gov (United States)

    Cattaneo, Fabio; Guerra, Germano; Parisi, Melania; Lucariello, Angela; De Luca, Antonio; De Rosa, Nicolina; Mazzarella, Gennaro; Bianco, Andrea; Ammendola, Rosario

    2015-05-01

    Formyl-peptide receptors (FPRs) are expressed in several tissues and cell types. The identification of markers involved in cell growth may further allow for molecular profiling of lung cancer. We investigated the possible role of FPRs as molecular markers in several types of lung carcinomas which is the main cause of cancer death worldwide. Tumor tissue samples were collected from six patients affected by lung cancer. Biopsies were analyzed for expression of FPR isoforms both in tumoral and peritumoral tissue by real-time polymerase chain reaction (PCR), western blot and immunofluorescence. Real-time PCR, western blot and immunofluorescence analyses showed that FPR expression is lower in types of human lung cancer tissues when compared to the surrounding peritumoral tissues. The study of the mechanistic basis for the control of FPR expression in normal peritumoral versus tumoral tissues could provide the basis for new diagnostic and therapeutic interventions. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  12. Nested-PCR for the detection of Mycoplasma hyopneumoniae in bronchial alveolar swabs, frozen tissues and formalin-fixed paraffin-embedded swine lung samples: comparative evaluation with immunohistochemical findings and histological features

    Directory of Open Access Journals (Sweden)

    Paula R. Almeida

    2012-08-01

    Full Text Available The diagnosis of Mycoplasma hyopneumoniae infection is often performed through histopathology, immunohistochemistry (IHC and polymerase chain reaction (PCR or a combination of these techniques. PCR can be performed on samples using several conservation methods, including swabs, frozen tissue or formalin-fixed and paraffin-embedded (FFPE tissue. However, the formalin fixation process often inhibits DNA amplification. To evaluate whether M. hyopneumoniae DNA could be recovered from FFPE tissues, 15 lungs with cranioventral consolidation lesions were collected in a slaughterhouse from swine bred in herds with respiratory disease. Bronchial swabs and fresh lung tissue were collected, and a fragment of the corresponding lung section was placed in neutral buffered formalin for 48 hours. A PCR assay was performed to compare FFPE tissue samples with samples that were only refrigerated (bronchial swabs or frozen (tissue pieces. M. hyopneumoniae was detected by PCR in all 15 samples of the swab and frozen tissue, while it was detected in only 11 of the 15 FFPE samples. Histological features of M. hyopneumoniae infection were presented in 11 cases and 7 of these samples stained positive in IHC. Concordance between the histological features and detection results was observed in 13 of the FFPE tissue samples. PCR was the most sensitive technique. Comparison of different sample conservation methods indicated that it is possible to detect M. hyopneumoniae from FFPE tissue. It is important to conduct further research using archived material because the efficiency of PCR could be compromised under these conditions.

  13. Immunohistochemical algorithm for differentiation of lung adenocarcinoma and squamous cell carcinoma based on large series of whole-tissue sections with validation in small specimens.

    Science.gov (United States)

    Rekhtman, Natasha; Ang, Daphne C; Sima, Camelia S; Travis, William D; Moreira, Andre L

    2011-10-01

    Immunohistochemistry is increasingly utilized to differentiate lung adenocarcinoma and squamous cell carcinoma. However, detailed analysis of coexpression profiles of commonly used markers in large series of whole-tissue sections is lacking. Furthermore, the optimal diagnostic algorithm, particularly the minimal-marker combination, is not firmly established. We therefore studied whole-tissue sections of resected adenocarcinoma and squamous cell carcinoma (n=315) with markers commonly used to identify adenocarcinoma (TTF-1) and squamous cell carcinoma (p63, CK5/6, 34βE12), and prospectively validated the devised algorithm in morphologically unclassifiable small biopsy/cytology specimens (n=38). Analysis of whole-tissue sections showed that squamous cell carcinoma had a highly consistent immunoprofile (TTF-1-negative and p63/CK5/6/34βE12-diffuse) with only rare variation. In contrast, adenocarcinoma showed significant immunoheterogenetity for all 'squamous markers' (p63 (32%), CK5/6 (18%), 34βE12 (82%)) and TTF-1 (89%). As a single marker, only diffuse TTF-1 was specific for adenocarcinoma whereas none of the 'squamous markers,' even if diffuse, were entirely specific for squamous cell carcinoma. In contrast, coexpression profiles of TTF-1/p63 had only minimal overlap between adenocarcinoma and squamous cell carcinoma, and there was no overlap if CK5/6 was added as a third marker. An algorithm was devised in which TTF-1/p63 were used as the first-line panel, and CK5/6 was added for rare indeterminate cases. Prospective validation of this algorithm in small specimens showed 100% accuracy of adenocarcinoma vs squamous cell carcinoma prediction as determined by subsequent resection. In conclusion, although reactivity for 'squamous markers' is common in lung adenocarcinoma, a two-marker panel of TTF-1/p63 is sufficient for subtyping of the majority of tumors as adenocarcinomas vs squamous cell carcinoma, and addition of CK5/6 is needed in only a small subset of cases

  14. Herniation of malignant lung cavity

    Institute of Scientific and Technical Information of China (English)

    Saurabh Kumar Singh; Rakesh Bhargava; Zuber Ahmad; Deepak K.Pandey; Shirin Naaz; Vibhanshu Gupta

    2008-01-01

    @@ Hernia of the lung is defined as a protrusion of lung tissue,covered by parietal and visceral pleurae,through an abnormal opening in the chest wall,diaphragm or mediastinum.1 It is a relatively uncommon condition.We report a case of lung hernia following cavitation in malignant lung mass.

  15. Targeting lung cancer through inhibition of checkpoint kinases

    Directory of Open Access Journals (Sweden)

    Randi Gussgard Syljuåsen

    2015-02-01

    Full Text Available Inhibitors of checkpoint kinases ATR, Chk1 and Wee1 are currently being tested in preclinical and clinical trials. Here, we review the basic principles behind the use of such inhibitors as anticancer agents, and particularly discuss their potential for treatment of lung cancer. As lung cancer is one of the most deadly cancers, new treatment strategies are highly needed. We discuss how checkpoint kinase inhibition in principle can lead to selective killing of lung cancer cells while sparing the surrounding normal tissues. Several features of lung cancer may potentially be exploited for targeting through inhibition of checkpoint kinases, including mutated p53, low ERCC1 levels, amplified Myc, tumor hypoxia and presence of lung cancer stem cells. Synergistic effects have also been reported between inhibitors of ATR/Chk1/Wee1 and conventional lung cancer treatments, such as gemcitabine, cisplatin or radiation. Altogether, inhibitors of ATR, Chk1 and Wee1 are emerging as new cancer treatment agents, likely to be useful in lung cancer treatment. However, as lung tumors are very diverse, the inhibitors are unlikely to be effective in all patients, and more work is needed to determine how such inhibitors can be utilized in the most optimal ways.

  16. Expression of Syk in non-small cell lung cancer and its relationship with clinicopathological parameters

    Institute of Scientific and Technical Information of China (English)

    Fen LAN; Shengdao XIONG; Weining XIONG; Guopeng XU; Xiaoxia LU

    2009-01-01

    This study aims to research the expression of spleen tyrosine kinase (Syk) in non-small cell lung cancer (NSCLC) and the relationship between Syk and clinico-pathologic factors and p53. Immunohistochemistry was applied to detect the expression of Syk and p53 protein in 39 cases of NSCLC (23 cases of lung squamous cell can-cer, 16 cases of lung adenocarcinoma) and tumor-sur-rounding normal lung tissues. The positive rate of Syk was 46.15% (18/39) and 100% (39/39) in NSCLC and tumor-surrounding normal lung tissues, respectively. The expres-sion level of Syk in NSCLC was significantly lower than that in tumor-surrounding normal lung tissues (P = 0.000). The Syk expression was positively correlated with the p53 expression in NSCLC specimens (P = 0.025). There was no significant association between Syk expression and lymph node metastasis, differentiation degree, tumor size and tumor node metastasis (TNM). The present study demonstrated that Syk was aberrantly expressed in the NSCLC and might have a significant impact on tumor growth and progression.

  17. Anti-Inflammatory Effects of Ginsenoside Rg3 via NF-κB Pathway in A549 Cells and Human Asthmatic Lung Tissue

    Directory of Open Access Journals (Sweden)

    In-Seung Lee

    2016-01-01

    Full Text Available Objective. There is limited information of the anti-inflammatory effects of Rg3 on inflamed lung cells and tissues. Therefore, we confirmed the anti-inflammatory mechanism of ginsenoside Rg3 in inflamed human airway epithelial cells (A549 and tissues whether Rg3 regulates nuclear factor kappa B (NF-κB activity. Methods. To induce the inflammation, IL-1β (10 ng/ml was treated to A549 cells for 4 h. The effects of Rg3 on NF-κB activity and COX-2 expression were evaluated by western blotting analysis in both IL-1β-induced inflamed A549 cell and human asthmatic airway epithelial tissues. Using multiplex cytokines assay, the secretion levels of NF-κB-mediated cytokines/chemokines were measured. Result. Rg3 showed the significant inhibition of NF-κB activity thereby reduced COX-2 expression was determined in both IL-1β-induced inflamed A549 cell and human asthmatic airway epithelial tissues. In addition, among NF-κB-mediated cytokines, the secretion levels of IL-4, TNF-α, and eotaxin were significantly decreased by Rg3 in asthma tissues. Even though there was no significant difference, IL-6, IL-9, and IL-13 secretion showed a lower tendency compared to saline-treated human asthmatic airway epithelial tissues. Conclusion. The results from this study demonstrate the potential of Rg3 as an anti-inflammatory agent through regulating NF-κB activity and reducing the secretion of NF-κB-mediated cytokines/chemokines.

  18. Decrease of reactive oxygen species-related biomarkers in the tissue-mimic 3D spheroid culture of human lung cells exposed to zinc oxide nanoparticles.

    Science.gov (United States)

    Kim, Eunjoo; Jeon, Won Bae; Kim, Soonhyun; Lee, Soo-Keun

    2014-05-01

    Common 2-dimensional (2D) cell cultures do not adequately represent cell-cell and cell-matrix signaling and substantially different diffusion/transport pathways. To obtain tissue-mimic information on nanoparticle toxicity from in vitro cell tests, we used a 3-dimensional (3D) culture of human lung cells (A549) prepared with elastin-like peptides modified with an arginine-glycine-aspartate motif. The 3D cells showed different cellular phenotypes, gene expression profiles, and functionalities compared to the 2D cultured cells. In gene array analysis, 3D cells displayed the induced extracellular matrix (ECM)-related biological functions such as cell-to-cell signaling and interaction, cellular function and maintenance, connective tissue development and function, molecular transport, and tissue morphology. Additionally, the expression of ECM-related molecules, such as laminin, fibronectin, and insulin-like growth factor binding protein 3 (IGFBP3), was simultaneously induced at both mRNA and protein levels. When 0.08-50 microg/ml zinc oxide nanoparticles (ZnO-NPs) were administered to 2D and 3D cells, the cell proliferation was not significantly changed. The level of molecular markers for oxidative stress, such as superoxide dismutase (SOD), Bcl-2, ATP synthase, and Complex IV (cytochrome C oxidase), was significantly reduced in 2D culture when exposed to 10 microg/ml ZnO-NPs, but no significant decrease was detected in 3D culture when exposed to the same concentration of ZnO-NPs. In conclusion, the tissue-mimic phenotype and functionality of 3D cells could be achieved through the elevated expression of ECM components. The 3D cells were expected to help to better predict the nanotoxicity of ZnO-NPs at tissue-level by increased cell-cell and cell-ECM adhesion and signaling. The tissue-mimic morphology would also be useful to simulate the diffusion/transport of the nanoparticles in vitro.

  19. Association of serum KL-6 levels with interstitial lung disease in patients with connective tissue disease: a cross-sectional study.

    Science.gov (United States)

    Oguz, Ekin Oktay; Kucuksahin, Orhan; Turgay, Murat; Yildizgoren, Mustafa Turgut; Ates, Askin; Demir, Nalan; Kumbasar, Ozlem Ozdemir; Kinikli, Gulay; Duzgun, Nursen

    2016-03-01

    It was aimed to evaluate KL-6 glycoprotein levels to determine if it may be a diagnostic marker for the connective tissue diseases (CTDs) predicting CTD-related interstitial lung diseases (ILDs) (CTD-ILD) development and to examine if there was a difference between patients and healthy controls. The study included 113 patients with CTD (45 CTD without lung involvement, 68 CTD-ILD) and 45 healthy control subjects. KL-6 glycoprotein levels were analyzed with ELISA in patients and the control group. The relationship between KL-6 glycoprotein levels and CTD-ILD was assessed. In the comparison of all the groups in the study, significantly higher levels of KL-6 were determined in the CTD-ILD group than in either the CTD without pulmonary involvement group or the healthy control group (p connective tissue diseases in the diagnostic groups (systemic lupus erythematosus, Sjögren's syndrome, rheumatoid arthritis, mixed connective tissue disease, scleroderma, polymyositis/ dermatomyositis). In the healthy control group, there was a statistically significant difference between KL-6 levels in smokers and non-smokers. Smokers had significantly higher serum KL-6 levels compared with non-smokers (p < 0.05). There was no statistically significant difference between smoking status (pack-year) and serum KL-6 levels. There was no statistically significant correlation between serum KL-6 levels and time since diagnosis of CTD and CTD-ILD. The level of KL-6 as a predictive factor could be used to identify the clinical development of ILD before it is detected on imaging modality. Further prospective clinical studies are needed to define whether levels of KL-6 might have prognostic value or might predict progressive ILD.

  20. Visual surround suppression in schizophrenia

    Directory of Open Access Journals (Sweden)

    Marc Samuel Tibber

    2013-02-01

    Full Text Available Compared to unaffected observers patients with schizophrenia show characteristic differences in visual perception, including a reduced susceptibility to the influence of context on judgements of contrast - a manifestation of weaker surround suppression. To examine the generality of this phenomenon we measured the ability of 24 individuals with schizophrenia to judge the luminance, contrast, orientation and size of targets embedded in contextual surrounds that would typically influence the target’s appearance. Individuals with schizophrenia demonstrated weaker surround suppression compared to matched controls for stimuli defined by contrast or size, but not for those defined by luminance or orientation. As perceived luminance is thought to be regulated at the earliest stages of visual processing our findings are consistent with a suppression deficit that is predominantly cortical in origin. In addition, we propose that preserved orientation surround suppression in schizophrenia may reflect the sparing of broadly tuned mechanisms of suppression. We attempt to reconcile these data with findings from previous studies.

  1. Educational Success and Surrounding Culture

    Science.gov (United States)

    Walters, Garrison

    2016-01-01

    The curriculum, instruction, and services we provide in schools, colleges, and universities matter a lot, but if we continue to ignore our students' "surrounding culture," progress toward a more educated nation will continue to be disappointing.

  2. Educational Success and Surrounding Culture

    Science.gov (United States)

    Walters, Garrison

    2016-01-01

    The curriculum, instruction, and services we provide in schools, colleges, and universities matter a lot, but if we continue to ignore our students' "surrounding culture," progress toward a more educated nation will continue to be disappointing.

  3. A novel method for sample preparation of fresh lung cancer tissue for proteomics analysis by tumor cell enrichment and removal of blood contaminants

    Directory of Open Access Journals (Sweden)

    Orre Lotta

    2010-02-01

    was an effective removal of contaminants from red blood cells and plasma proteins resulting in larger proteome coverage compared to the direct lysis of frozen samples. This sample preparation method may be successfully implemented for the discovery of lung cancer biomarkers on tissue samples using mass spectrometry-based proteomics.

  4. Multichannel spatial surround sound system

    Institute of Scientific and Technical Information of China (English)

    RAO Dan; XIE Bosun

    2004-01-01

    Based on the consideration of being compatible with 5.1 channel horizontal surround sound system, a spatial surround sound system is proposed. Theoretical and experimental results show that the system has a wide listening area. It can not only recreate stable image in the front and rear direction, but also eliminate the defect of poor lateral image of 5.1 channel system. The system can be used to reproduce special 3D sound effect and the spaciousness of hall.

  5. Distribution and coassociations of trace elements in soft tissue and byssus of Mytilus galloprovincialis relative to the surrounding seawater and suspended matter of the southern part of the Korean Peninsula.

    Science.gov (United States)

    Szefer, P; Kim, B-S; Kim, C-K; Kim, E-H; Lee, C-B

    2004-05-01

    The concentrations of Cd, Co, Cu, Cr, Fe, Hg, Mn, Ni, Pb, Sn, Ti and Zn were analyzed by AAS, ICP MS and AFS in soft tissues and byssal threads of Mytilus galloprovincialis from Masan Bay and Ulsan Bay, Korea. Spatial variations in metal concentrations were found. The levels of Cd, Pb, Hg, Cu, Zn, Co and Mn were very high in the mussels from Ulsan Bay (Sts. U1, U2) and comparable with elevated concentrations of these elements in Mytilus sp. reported to date for other geographical areas. Seasonal differences in some metal concentrations were also observed. These variations may be caused by factors such as: a large difference in seawater temperature, food supply for the mussel population and/or freshwater runoff of particulate metal to the coastal water and weight changes brought about by gonadal development and the release of sexual products. Pb, Cu, Zn, Co, Ni, Fe and Mn were more enriched in byssal threads than in the soft tissues, hence the byssus seems to be more sensitive in reflecting the availabilities of trace metals in the ambient waters. Concentrations of trace metals varied with respect to the size of mussels and season, depending on many factors like sexual development, and seawater temperature, etc. The levels of some trace metals in seawater, especially in suspended matter were correlated significantly with those in soft tissues and byssal threads. There were spatial variations in metal concentrations in the soft tissue and byssus attributed to different sources of trace elements located near the sampling sites. There were significant relationships between concentrations of some metals (Cd, Cu, Pb, and Zn) in mussel soft tissues and byssal threads and suspended matter. This suggests that M. galloprovincialis can be used as a sensitive biomonitor for the availabilities of trace elements in the coastal waters off Korea.

  6. Distribution and coassociations of trace elements in soft tissue and byssus of Mytilus galloprovincialis relative to the surrounding seawater and suspended matter of the southern part of the Korean Peninsula

    Energy Technology Data Exchange (ETDEWEB)

    Szefer, P.; Kim, B.-S.; Kim, C.-K.; Kim, E.-H.; Lee, C.-B

    2004-05-01

    The concentrations of Cd, Co, Cu, Cr, Fe, Hg, Mn, Ni, Pb, Sn, Ti and Zn were analyzed by AAS, ICP MS and AFS in soft tissues and byssal threads of Mytilus galloprovincialis from Masan Bay and Ulsan Bay, Korea. Spatial variations in metal concentrations were found. The levels of Cd, Pb, Hg, Cu, Zn, Co and Mn were very high in the mussels from Ulsan Bay (Sts. U1, U2) and comparable with elevated concentrations of these elements in Mytilus sp. reported to date for other geographical areas. Seasonal differences in some metal concentrations were also observed. These variations may be caused by factors such as: a large difference in seawater temperature, food supply for the mussel population and/or freshwater runoff of particulate metal to the coastal water and weight changes brought about by gonadal development and the release of sexual products. Pb, Cu, Zn, Co, Ni, Fe and Mn were more enriched in byssal threads than in the soft tissues, hence the byssus seems to be more sensitive in reflecting the availabilities of trace metals in the ambient waters. Concentrations of trace metals varied with respect to the size of mussels and season, depending on many factors like sexual development, and seawater temperature, etc. The levels of some trace metals in seawater, especially in suspended matter were correlated significantly with those in soft tissues and byssal threads. There were spatial variations in metal concentrations in the soft tissue and byssus attributed to different sources of trace elements located near the sampling sites. There were significant relationships between concentrations of some metals (Cd, Cu, Pb, and Zn) in mussel soft tissues and byssal threads and suspended matter. This suggests that M. galloprovincialis can be used as a sensitive biomonitor for the availabilities of trace elements in the coastal waters off Korea. - Mytilus galloprovincialis can be used as a biomonitor for trace elements in coastal waters off Korea.

  7. Distribution and mRNA Expression of BAMBI in Non-small-cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Shen MIAO

    2009-03-01

    Full Text Available Background and objective BAMBI structure is similar with that of the receptor Ⅰof TGF-β, it broadly participates in the control of TGF-β signaling. The aim of this study is to investigate the expression and its significance of BAMBI in non-small cell lung cancer (NSCLC and explore the relation between BAMBI and clinical and pathological factors of NSCLC. Methods Sixty-three cases with NSCLC and adjacent normal tissue specimens were used for immunohistochemical assay. Thirty-one fresh lung cancer tissue specimens and surrounding normal lung tissue specimens was preserved for RT-PCR in -70 ℃ after quick-frozen in liquid nitrogen immediately. Results The level of BAMBI mRNA in cancer tissues was higher than that in the corresponding adjacent tissues (0.358±0.135 vs 0.249±0.129, with the difference being statistically significant (P =0.003. BAMBI protein expressed mainly in the membrane and the cytoplasm close to the membrane, its expression in the cancer tissue was higher than that in the adjacent tissues, the difference was significant (P <0.01. Expression of BAMBI in the cancer tissue was higher than that in the adjacent tissues, and the expression of BAMBI in adenocarcinoma of lung is higher than that in squamous carcinoma. Conclusion The expressions of BAMBI significantly increase in NSCLC. It might be a common affair in carcinogenesis of NSCLC.

  8. Study of deposited energy in lung tissue from radon's progeny calculated by Monte Carlo

    Energy Technology Data Exchange (ETDEWEB)

    Angeles, A. [ININ, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico); Espinosa, G. [UNAM, Instituto de Fisica, Apdo. Postal 20-364, 01000 Mexico D. F. (Mexico)

    2011-02-15

    Because the deposited {sup 222}Rn progeny distribution in lung airways, these sources can contribute hardly to critical cells absorbed dose in neighbourhood of a alpha track by the alpha particles from {sup 218}Po and {sup 214}Po. According to epidemiological data, lung cancers are primarily bronchogenic and mainly originate in the first five airway generations of the bronchial tree. Generally for deposited energy calculations, uniform deposit in source layers and the whole layers as sources has been considerate d too. Discretion al point deposits in the different and most important bronqui (B B) and bronchial (b b) layers for main generations is a more realistic case. Because that facts we have calculated the average deposited energy by Monte Carlo in the most important different target cell layers for the main B B and b b branch generations considering the radioactive {sup 222}Rn progeny punctual deposit in the source epithelium walls, from this location. It irradiate the neighbor cells in all directions. (Author)

  9. Tissue Factor Pathway Inhibitor-1 Is a Valuable Marker for the Prediction of Deep Venous Thrombosis and Tumor Metastasis in Patients with Lung Cancer

    Science.gov (United States)

    Yuan, Wufeng

    2017-01-01

    Activation of blood coagulation contributes to cancer progression. Tissue factor pathway inhibitor-1 (TFPI-1) is the main inhibitor of extrinsic coagulation pathway. The aim of this study is to assess the predicting significance of TFPI-1 for thrombotic complication and metastasis in lung cancer patients. Total of 188 non-small cell lung cancer (NSCLC) patients were included in this study. Plasma TFPI-1, D-dimer (D-D), antithrombin (AT), Fibrinogen (Fbg), and coagulating factor VIII activity (FVIII:C) were measured. In NSCLC patients, significantly decreased TFPI-1 and AT and increased D-D, Fbg, and FVIII:C levels were observed, and there was a significant correlation between TFPI-1 and other hemostatic parameters (P metastasis had significantly lower TFPI-1 levels than those without DVT or metastasis (P metastasis in NSCLC patients [OR: 4.15 or 3.28, P metastasis (P metastasis, respectively. Combination of TFPI-1 and D-D measurements can improve the predicting power for DVT or metastasis in NSCLC patients. Our findings suggested that TFPI-1 was a valuable predictor of DVT and tumor metastasis in NSCLC patients.

  10. 肺癌组织中神经元特异性烯醇化酶和总RNA的表达与改变%EXPRESSION AND ALTERATION OF NEURON-SPECIFIC ENOLASE (NSE) AND TOTAL RNA IN LUNG CANCER TISSUES

    Institute of Scientific and Technical Information of China (English)

    曹飞; 吴玮; 姚登福; 邱历伟; 陆建新

    2001-01-01

    目的:探讨神经元特异性烯醇化酶(NSE)在肺癌中的表达及其诊断价值。 方法:收集人肺癌,癌周及远癌组织各30份,制备和定量总RNA水平,并在 肺癌组织匀浆后,分析组织中NSE的浓度变化。结果:肺癌组织NSE表达显 著高于癌周及远癌组织(P<0.01 ),并与总RNA浓度成正相关(r[ WTBZ]=0.04,P<0.01),各种肺癌组织中NSE及RNA浓度无显著性差异。结论:提示肺癌组织核酸代谢旺盛,分析过度表达的NSE有助于肺癌的早期诊断 。%Objective: To explore the expression and diagnostic value of neuron- specific enolase (NSE) in patients with lung cancer. Methods: Human lung cancerous, paracancerous and distant tissues were collected, homogenates we re prepared, total RNAs were purified. The concerntrations of NSE and total RNA in tissues of 30 patients with lung cancer were investigated in this study. Results: The levels of NSE and total RNA in lung cancerous tissues were significantly higher (P<0.001) than those in paracancerous and in di stant tissues. The levels of NSE expression was positively correlated with lung to tal RNA concerntration (P<0.01). Conclusions: The data s uggest that nucleic acid metabolism is active in lung cancer tissues. Analysis o f excessive expression of NSE is useful for diagnosing and distinguishing lun g cancer.

  11. UPLC-MS method for quantification of pterostilbene and its application to comparative study of bioavailability and tissue distribution in normal and Lewis lung carcinoma bearing mice.

    Science.gov (United States)

    Deng, Li; Li, Yongzhi; Zhang, Xinshi; Chen, Bo; Deng, Yulin; Li, Yujuan

    2015-10-10

    A UPLC-MS method was developed for determination of pterostilbene (PTS) in plasma and tissues of mice. PTS was separated on Agilent Zorbax XDB-C18 column (50 × 2.1 mm, 1.8 μm) with gradient mobile phase at the flow rate of 0.2 ml/min. The detection was performed by negative ion electrospray ionization in multiple reaction monitoring mode. The linear calibration curve of PTS in mouse plasma and tissues ranged from 1.0 to 5000 and 0.50 to 500 ng/ml (r(2)>0.9979), respectively, with lowest limits of quantification (LLOQ) were between 0.5 and 2.0 ng/ml, respectively. The accuracy and precision of the assay were satisfactory. The validated method was applied to the study of bioavailability and tissue distribution of PTS in normal and Lewis lung carcinoma (LLC) bearing mice. The bioavailability of PTS (dose 14, 28 and 56 mg/kg) in normal mice were 11.9%, 13.9% and 26.4%, respectively; and the maximum level (82.1 ± 14.2 μg/g) was found in stomach (dose 28 mg/kg). The bioavailability, peak concentration (Cmax), time to peak concentration (Tmax) of PTS in LLC mice was increased compared with normal mice. The results indicated the UPLC-MS method is reliable and bioavailability and tissue distribution of PTS in normal and LLC mice were dramatically different. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Lung metastases

    Science.gov (United States)

    Metastases to the lung; Metastatic cancer to the lung; Lung cancer - metastases ... Metastatic tumors in the lungs are cancers that developed at other places in the body (or other parts of the lungs). They then spread through ...

  13. A Combined 3D Tissue Engineered In Vitro/In Silico Lung Tumor Model for Predicting Drug Effectiveness in Specific Mutational Backgrounds.

    Science.gov (United States)

    Göttlich, Claudia; Müller, Lena C; Kunz, Meik; Schmitt, Franziska; Walles, Heike; Walles, Thorsten; Dandekar, Thomas; Dandekar, Gudrun; Nietzer, Sarah L

    2016-01-01

    In the present study, we combined an in vitro 3D lung tumor model with an in silico model to optimize predictions of drug response based on a specific mutational background. The model is generated on a decellularized porcine scaffold that reproduces tissue-specific characteristics regarding extracellular matrix composition and architecture including the basement membrane. We standardized a protocol that allows artificial tumor tissue generation within 14 days including three days of drug treatment. Our article provides several detailed descriptions of 3D read-out screening techniques like the determination of the proliferation index Ki67 staining's, apoptosis from supernatants by M30-ELISA and assessment of epithelial to mesenchymal transition (EMT), which are helpful tools for evaluating the effectiveness of therapeutic compounds. We could show compared to 2D culture a reduction of proliferation in our 3D tumor model that is related to the clinical situation. Despite of this lower proliferation, the model predicted EGFR-targeted drug responses correctly according to the biomarker status as shown by comparison of the lung carcinoma cell lines HCC827 (EGFR -mutated, KRAS wild-type) and A549 (EGFR wild-type, KRAS-mutated) treated with the tyrosine-kinase inhibitor (TKI) gefitinib. To investigate drug responses of more advanced tumor cells, we induced EMT by long-term treatment with TGF-beta-1 as assessed by vimentin/pan-cytokeratin immunofluorescence staining. A flow-bioreactor was employed to adjust culture to physiological conditions, which improved tissue generation. Furthermore, we show the integration of drug responses upon gefitinib treatment or TGF-beta-1 stimulation - apoptosis, proliferation index and EMT - into a Boolean in silico model. Additionally, we explain how drug responses of tumor cells with a specific mutational background and counterstrategies against resistance can be predicted. We are confident that our 3D in vitro approach especially with its

  14. EGFR Mutations Detection in Non-small Cell Lung Cancer Tissues by Real-time PCR and DNA Sequencing

    Directory of Open Access Journals (Sweden)

    Qinghua ZHOU

    2009-12-01

    Full Text Available Background and objective Small molecule tyrosine kinase inhibitors (TKIs, such as gefitinib and erlotinib that target the kinase domain of epidermal growth factor receptor (EGFR are making successful progression for advanced non-small cell lung cancer patients treatment. The growing evidences revealed that EGFR exon 19 and 21 mutation status in NSCLC patients was correlated with the outcome for EGFR-TKI treatment. In this study, two methods of Real-time PCR and DNA sequencing were compared to detected EGFR exon 19 and 21 mutations. Methods EGFR exon19 mutation del-E746-A750 and exon 21mutation L858R were detected by Real-time PCR and DNA sequencing in 103 NSCLC patients. Chi-square test was used to analyze the consistance. Results There was no significant difference between the two methods. However, Real-time PCR was more convenient and sensitive compared to DNA sequencing. Conclusion Real-time PCR was more suitable for clinical testing than DNA sequencing.

  15. Tissue-engineered lung seed cells and extracellular matrix%组织工程肺种子细胞及其细胞外基质的研究与进展

    Institute of Scientific and Technical Information of China (English)

    冯一; 刘升明

    2011-01-01

    背景:至今为止,构建组织工程肺并运用于临床尚并未取得较大进展,原因在于种子细胞来源及鉴定,移植时限选择,支撑架安全性,细胞分化程序的标准化,细胞外基质分泌的控制等多个方面都存在难点.目的:总结组织工程肺的种子细胞来源及鉴定、细胞外基质替代物的研究与进展.方法:检索中国期刊全文数据库(CNKI:1989/2011)和PubMed(1989/2011)数据库,检索词分别为"组织工程肺,细胞源,支架,细胞外基质,体内植入"和"Tissue-engineered Lung,Cell Source,Support Scaffolding,lung matrices,Vivo Implantation",语言分别设定为中文和英文.阅读文题和摘要进行筛选,选择具有原创性,论点论据可靠且分析全面、密切相关的文章,排除重复性研究以及质量较差文章.共检索到72篇文章,按纳入及排除标准筛选后,共纳入36篇文章.结果与结论:利用合适的细胞源与支撑架进行组织工程肺研究可培育出功能健全的可用来替换的肺组织,但目前组织工程肺的研究尚无重大进展.最近研究成功运用于临床的脱细胞气管为组织工程肺治疗肺部疾病带来新的希望.%BACKGROUND: There is slow progress in the reconstruction and clinical application of tissue-engineered lung because of the difficulty in the identification and utilization of cell sources, development of standardized procedures for cell differentiation, control of extracellular matrix production to meet the needs of the lung and so on. OBJECTIVE: To review the identification and utilization of cell sources and the replacement of extracellular matrix in the tissue-engineered lung research. METHODS: A computer-based online search of China Journal Full-text Database and PubMed was performed for articles and reviews in Chinese and English from 1989 to 2011. The key words were “tissue-engineered lung, cell source, support scaffolding, lung matrices, vivo implantation”. Screened following reading

  16. The Influence of Tissue Ischemia Time on RNA Integrity and Patient-Derived Xenografts (PDX Engraftment Rate in a Non-Small Cell Lung Cancer (NSCLC Biobank.

    Directory of Open Access Journals (Sweden)

    Francesco Guerrera

    Full Text Available Bio-repositories are invaluable resources to implement translational cancer research and clinical programs. They represent one of the most powerful tools for biomolecular studies of clinically annotated cohorts, but high quality samples are required to generate reliable molecular readouts and functional studies. The objective of our study was to define the impact of cancer tissue ischemia time on RNA and DNA quality, and for the generation of Patient-Derived Xenografts (PDXs.One-hundred thirty-five lung cancer specimens were selected among our Institutional BioBank samples. Associations between different warm (surgical and cold (ex-vivo ischemia time ranges and RNA quality or PDXs engraftment rates were assessed. RNA quality was determined by RNA integrity number (RINs values. Fresh viable tissue fragments were implanted subcutaneously in NSG mice and serially transplanted.RNAs with a RIN>7 were detected in 51% of the sample (70/135, with values of RIN significantly lower (OR 0.08, P = 0.01 in samples preserved for more than 3 hours before cryopreservation. Higher quality DNA samples had a concomitant high RIN. Sixty-three primary tumors (41 adenocarcinoma were implanted with an overall engraftment rate of 33%. Both prolonged warm (>2 hours and ex-vivo ischemia time (>10 hours were associated to a lower engraftment rate (OR 0.09 P = 0.01 and OR 0.04 P = 0.008, respectively.RNA quality and PDXs engraftment rate were adversely affected by prolonged ischemia times. Proper tissue collection and processing reduce failure rate. Overall, NSCLC BioBanking represents an innovative modality, which can be successfully executed in routine clinical settings, when stringent Standard Operating Procedures are adopted.

  17. The Influence of Tissue Ischemia Time on RNA Integrity and Patient-Derived Xenografts (PDX) Engraftment Rate in a Non-Small Cell Lung Cancer (NSCLC) Biobank

    Science.gov (United States)

    Maletta, Francesca; Gaudiano, Marcello; Ercole, Elisabetta; Annaratone, Laura; Todaro, Maria; Boita, Monica; Filosso, Pier Luigi; Solidoro, Paolo; Delsedime, Luisa; Oliaro, Alberto; Sapino, Anna; Ruffini, Enrico; Inghirami, Giorgio

    2016-01-01

    Introduction Bio-repositories are invaluable resources to implement translational cancer research and clinical programs. They represent one of the most powerful tools for biomolecular studies of clinically annotated cohorts, but high quality samples are required to generate reliable molecular readouts and functional studies. The objective of our study was to define the impact of cancer tissue ischemia time on RNA and DNA quality, and for the generation of Patient-Derived Xenografts (PDXs). Methods One-hundred thirty-five lung cancer specimens were selected among our Institutional BioBank samples. Associations between different warm (surgical) and cold (ex-vivo) ischemia time ranges and RNA quality or PDXs engraftment rates were assessed. RNA quality was determined by RNA integrity number (RINs) values. Fresh viable tissue fragments were implanted subcutaneously in NSG mice and serially transplanted. Results RNAs with a RIN>7 were detected in 51% of the sample (70/135), with values of RIN significantly lower (OR 0.08, P = 0.01) in samples preserved for more than 3 hours before cryopreservation. Higher quality DNA samples had a concomitant high RIN. Sixty-three primary tumors (41 adenocarcinoma) were implanted with an overall engraftment rate of 33%. Both prolonged warm (>2 hours) and ex-vivo ischemia time (>10 hours) were associated to a lower engraftment rate (OR 0.09 P = 0.01 and OR 0.04 P = 0.008, respectively). Conclusion RNA quality and PDXs engraftment rate were adversely affected by prolonged ischemia times. Proper tissue collection and processing reduce failure rate. Overall, NSCLC BioBanking represents an innovative modality, which can be successfully executed in routine clinical settings, when stringent Standard Operating Procedures are adopted. PMID:26731692

  18. Effects of mechanical ventilation on cell apoptosis in lung tissue of rat with acute lung injury%机械通气对急性肺损伤大鼠细胞凋亡的影响

    Institute of Scientific and Technical Information of China (English)

    陈宁; 赵鹤龄; 程彤; 申丽旻; 张耀宗

    2011-01-01

    Objective To investigate the effects of different tidal volumes and positive end expiratory pressures on cell apoptosis in lung tissue of rats with acute lung injury.Methods Forty healthy male Sprague-Dawley rats were randomly(random number)divided into five groups,namely low tidal volume group(LV,VT 8 mL/kg),high tidal volume group(HV,VT 30 mL/kg),low tidal volume group with PEEP 2cmH2O(LV2P,VT 8 mL/kg,PEEP 2 cmH2O),low tidal volume group and PEEP 5cmH2O (LV5P,VT 8 mL/kg,PEEP 5 cmH2O)and low tidal volume group and PEEP 8 cmH2O(LV8P,VT 8 mL/kg,PEEP 8 cmH2O).After intravenous administration of oleic acid(OA,0.1 mL/kg),the rat model of acute lung injury was made.Mechanical ventilation was employed in rats of the experiment groups.Rats were sacrificed and their whole lungs were taken after mechanical ventilation for 2 hours.The transferase d-UTP end labeling assay(TUNEL)was used to define the extent and distribution of apoptotic cells in bronchus and lung tissues.The level of caspase-3 protein was determined by immunohistochemistry.Results The apoptotic cells on both alveolar septum and bronchial epithelium obviously increased with high level of caaspase-3 protein in HV group.The number of apoptotic cells obviously decreased with decrease in caspase-3 protein after PEEP ventilation.These changes were more significant in LV5P than those in other groups(P < 0.01).Conclusions The mechanical ventilation with low tidal volume and PEEP produces protective effects on lung from injury.The cell apoptosis plays an important role in the course of VILI.%目的 研究不同潮气量及不同呼气末正压(PEEP)水平对急性肺损伤(AU)大鼠支气管和肺组织细胞凋亡的影响,并初步探讨细胞凋亡在呼吸机相关性肺损伤(VILI)中的作用机制.方法 选用40只SD大鼠,制作ALI模型,随机(随机数字法)分为:(1)小潮气量组(LV组),潮气量8 mL/kg,不加PEEP;(2)大潮气量组,潮气量30 mL./kg,不加PEEP;(3)小潮气量+ 2PEEP组(LV2P

  19. Visual Surround Suppression in Schizophrenia

    Science.gov (United States)

    Tibber, Marc S.; Anderson, Elaine J.; Bobin, Tracy; Antonova, Elena; Seabright, Alice; Wright, Bernice; Carlin, Patricia; Shergill, Sukhwinder S.; Dakin, Steven C.

    2013-01-01

    Compared to unaffected observers patients with schizophrenia (SZ) show characteristic differences in visual perception, including a reduced susceptibility to the influence of context on judgments of contrast – a manifestation of weaker surround suppression (SS). To examine the generality of this phenomenon we measured the ability of 24 individuals with SZ to judge the luminance, contrast, orientation, and size of targets embedded in contextual surrounds that would typically influence the target’s appearance. Individuals with SZ demonstrated weaker SS compared to matched controls for stimuli defined by contrast or size, but not for those defined by luminance or orientation. As perceived luminance is thought to be regulated at the earliest stages of visual processing our findings are consistent with a suppression deficit that is predominantly cortical in origin. In addition, we propose that preserved orientation SS in SZ may reflect the sparing of broadly tuned mechanisms of suppression. We attempt to reconcile these data with findings from previous studies. PMID:23450069

  20. Tissue Factor Pathway Inhibitor-1 Is a Valuable Marker for the Prediction of Deep Venous Thrombosis and Tumor Metastasis in Patients with Lung Cancer

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    Xianming Fei

    2017-01-01

    Full Text Available Activation of blood coagulation contributes to cancer progression. Tissue factor pathway inhibitor-1 (TFPI-1 is the main inhibitor of extrinsic coagulation pathway. The aim of this study is to assess the predicting significance of TFPI-1 for thrombotic complication and metastasis in lung cancer patients. Total of 188 non-small cell lung cancer (NSCLC patients were included in this study. Plasma TFPI-1, D-dimer (D-D, antithrombin (AT, Fibrinogen (Fbg, and coagulating factor VIII activity (FVIII:C were measured. In NSCLC patients, significantly decreased TFPI-1 and AT and increased D-D, Fbg, and FVIII:C levels were observed, and there was a significant correlation between TFPI-1 and other hemostatic parameters (P<0.001, resp.. NSCLC patients with deep venous thrombosis (DVT or metastasis had significantly lower TFPI-1 levels than those without DVT or metastasis (P<0.01, resp.. Multivariate regression revealed that TFPI-1 acted as a predictor for DVT or tumor metastasis in NSCLC patients [OR: 4.15 or 3.28, P<0.05, resp.]. The area under ROC curve of TFPI-1 was 0.905 (95% CI, 0.842~0.967 or 0.828 (95% CI, 0.742~0.915 for predicting DVT or metastasis (P<0.001, resp.. The optimal point of TFPI-1 was 57.7 or 54.3 ng/mL for predicting DVT or metastasis, respectively. Combination of TFPI-1 and D-D measurements can improve the predicting power for DVT or metastasis in NSCLC patients. Our findings suggested that TFPI-1 was a valuable predictor of DVT and tumor metastasis in NSCLC patients.

  1. Chemical compositions responsible for inflammation and tissue damage in the mouse lung by coarse and fine particulate samples from contrasting air pollution in Europe

    Energy Technology Data Exchange (ETDEWEB)

    Happo, M.S.; Hirvonen, M.R.; Halinen, A.I.; Jalava, P.I.; Pennanen, A.S.; Sillanpaa, M.; Hillamo, R.; Salonen, R.O. [National Public Health Institute, Kuopio (Finland). Dept. of Environmental Health

    2008-07-01

    Inflammation is regarded as an important mechanism in mortality and morbidity associated with exposures of cardiorespiratory patients to urban air particulate matter. We investigated the association of the chemical composition and sources of urban air fine (PM2.5-0.2) and coarse (PM10-2.5) particulate samples with the inflammatory activity in the mouse lung. The particulate samples were collected during selected seasons in six European cities using a high-volume cascade impactor. Healthy C57BL/6J mice were intratracheally instilled with a single dose (10 mg/kg) of the particulate samples. At 4, 12, and 24 h after the exposure, the lungs were lavaged and the bronchoalveolar lavage fluid (BALF) was assayed for indicators of inflammation and tissue damage: cell number, total protein, and cytokines (tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and KC). Dicarboxylic acids and transition metals, especially Ni and V, in PM2.5-0.2 correlated positively and some secondary inorganic ions (NO{sub 3}{sup -}, NH{sub 4}{sup +}) negatively with the inflammatory activity. Total organic matter and SO{sub 4}{sup 2-} had no consistent correlations. In addition, the soil-derived constituents (Ca{sup 2+}, Al, Fe, Si) showed positive correlations with the PM2.5-0.2-induced inflammatory activity, but their role in PM10 (2.5) remained obscure, possibly due to largely undefined biogenic material. Markers of poor biomass and coal combustion, i.e., monosaccharide anhydrides and As, were associated with elevated PAH contents in PM2.5 (0.2) and a consistent immunosuppressive effect. Overall, our results support epidemiological findings that the local sources of incomplete combustion and resuspended road dust are important in urban air particulate pollution-related health effects.

  2. Andes Hantavirus-Infection of a 3D Human Lung Tissue Model Reveals a Late Peak in Progeny Virus Production Followed by Increased Levels of Proinflammatory Cytokines and VEGF-A.

    Science.gov (United States)

    Sundström, Karin B; Nguyen Hoang, Anh Thu; Gupta, Shawon; Ahlm, Clas; Svensson, Mattias; Klingström, Jonas

    2016-01-01

    Andes virus (ANDV) causes hantavirus pulmonary syndrome (HPS), a severe acute disease with a 40% case fatality rate. Humans are infected via inhalation, and the lungs are severely affected during HPS, but little is known regarding the effects of ANDV-infection of the lung. Using a 3-dimensional air-exposed organotypic human lung tissue model, we analyzed progeny virus production and cytokine-responses after ANDV-infection. After a 7-10 day period of low progeny virus production, a sudden peak in progeny virus levels was observed during approximately one week. This peak in ANDV-production coincided in time with activation of innate immune responses, as shown by induction of type I and III interferons and ISG56. After the peak in ANDV production a low, but stable, level of ANDV progeny was observed until 39 days after infection. Compared to uninfected models, ANDV caused long-term elevated levels of eotaxin-1, IL-6, IL-8, IP-10, and VEGF-A that peaked 20-25 days after infection, i.e., after the observed peak in progeny virus production. Notably, eotaxin-1 was only detected in supernatants from infected models. In conclusion, these findings suggest that ANDV replication in lung tissue elicits a late proinflammatory immune response with possible long-term effects on the local lung cytokine milieu. The change from an innate to a proinflammatory response might be important for the transition from initial asymptomatic infection to severe clinical disease, HPS.

  3. 甲状腺转录因子-1在肺癌组织中的表达及临床意义%Expression and Clinical Significance of Thyroid Transcription Factor 1 in Lung Cancer Tissues

    Institute of Scientific and Technical Information of China (English)

    黄克锋; 冼磊

    2014-01-01

    Objective To investigate the expression and diagnostic significance of thyroid transcription factor 1( TTF-1) in lung cancer tissues .Methods The expression of TTF-1 was detected by immunohistochemical staining in 50 cases of primary lung cancer ( including 23 cases of adenocarcinoma ,14 cases of squamous carcinoma ,9 cases of small-cell lung cancer ,and 4 cases of large-cell lung cancer ) and para-carcinoma tissues as well as 21 cases of metastatic lung adenocarcinomas from digestive tract and ovaries .The diagnostic and differential diagnostic values of TTF-1 in lung cancer were assessed .Results The positive expression rates of TTF-1 were 73 .9%( 17/23 ) in adenocarcinoma ,0 in squamouse cell carcinoma,77.8%(7/9)in small-cell lung cancer tissues and 50.0%(2/4)in large-cell lung cancer tissues,0 in metastatic lung adenocarcinomas ,respectively.The positive expression rates of TTF-1 in adenocarcinoma and small-cell lung cancer tissues were higher than that in squamouse cell carcinoma tissues (P0.05).Conclusion TTF-1 can be used as a specific indicator for the differential diagnosis of primary or secondary lung adenocarcinomas ,and it provides some references for the judgement of histological type of primary lung cancer .%目的:探讨甲状腺转录因子-1(TTF-1)在肺癌组织中表达情况其临床诊断意义。方法采用免疫组织化学法分别检测50例原发性肺癌(腺癌23例、鳞癌14例、肺小细胞癌9例、肺大细胞癌4例)组织、癌旁组织及21例来源于胃肠道或卵巢转移性肺腺癌组织标本中TTF-1的表达情况,并分析TTF-1在肺癌诊断与鉴别诊断中的意义。结果腺癌、鳞癌、肺小细胞癌、肺大细胞癌、转移性肺腺癌组织TTF-1表达阳性率分别为73.9%(17/23)、0、77.8%(7/9)、50.0%(2/4)、0,腺癌、肺小细胞癌组织 TTF-1表达阳性率较鳞癌高( P<0.05)。原发肺癌的癌旁组织中,正常或增生肺泡上皮大部

  4. Quantitative differentiation of dendritic cells in lung tissues of smokers with and without chronic obstructive pulmonary disease

    Institute of Scientific and Technical Information of China (English)

    SU Yan-wei; XU Yong-jian; LIU Xian-sheng

    2010-01-01

    Background Chronic obstructive pulmonary disease (COPD) is thought to be an inflammatory immune response disease. In most cases, the disease is caused by cigarette smoke, but it has been demonstrated that only 10% to 20% of smokers will definitely suffer from COPD. Dendritic cells (DCs) are considered to be the promoter of immune responses.However, the underlying mechanisms involved are still unrevealed. In this study, we aimed to investigate the quantitative differentiation of pulmonary DC in smokers with or without COPD to explore the possible role of DCs in smokers suffering COPD.Methods Peripheral lung specimens from non-smokers without airflow obstruction (control group, n=7), smokers without airflow obstruction (smoker group, n=7) and patients with COPD (COPD group, n=7) were investigated to detect the quantity of S-100 and CD1a positive cells by immunohistochemical or immunofluorescent assay.Results In smokers with COPD, the number of S-100+ DCs was higher than in the controls and smokers without COPD (P 0.05). An inverse correlation was found between the number of DCs and forced expiratory volume in the first second (FEV1)% pred (r=-0.75, P <0.05), which was also found between the number of DCs and FEV1/forced vital capacity (FVC) (r=-0.72, P <0.05). The mean number of CD1a+ DCs, increased from non-smokers to non-COPD smokers to COPD patients, with significant differences between each group (P <0.01).Conclusions The quantity of DCs significantly increased in smokers with COPD compared with non-smokers or smokers without COPD. The results suggest that DCs may play an important role in the pathogenesis of smoking-induced COPD, and the upregulation of DCs may be a potential maker to identify the smokers who have more liability to suffer from COPD.

  5. A radiomics model from joint FDG-PET and MRI texture features for the prediction of lung metastases in soft-tissue sarcomas of the extremities.

    Science.gov (United States)

    Vallières, M; Freeman, C R; Skamene, S R; El Naqa, I

    2015-07-21

    This study aims at developing a joint FDG-PET and MRI texture-based model for the early evaluation of lung metastasis risk in soft-tissue sarcomas (STSs). We investigate if the creation of new composite textures from the combination of FDG-PET and MR imaging information could better identify aggressive tumours. Towards this goal, a cohort of 51 patients with histologically proven STSs of the extremities was retrospectively evaluated. All patients had pre-treatment FDG-PET and MRI scans comprised of T1-weighted and T2-weighted fat-suppression sequences (T2FS). Nine non-texture features (SUV metrics and shape features) and forty-one texture features were extracted from the tumour region of separate (FDG-PET, T1 and T2FS) and fused (FDG-PET/T1 and FDG-PET/T2FS) scans. Volume fusion of the FDG-PET and MRI scans was implemented using the wavelet transform. The influence of six different extraction parameters on the predictive value of textures was investigated. The incorporation of features into multivariable models was performed using logistic regression. The multivariable modeling strategy involved imbalance-adjusted bootstrap resampling in the following four steps leading to final prediction model construction: (1) feature set reduction; (2) feature selection; (3) prediction performance estimation; and (4) computation of model coefficients. Univariate analysis showed that the isotropic voxel size at which texture features were extracted had the most impact on predictive value. In multivariable analysis, texture features extracted from fused scans significantly outperformed those from separate scans in terms of lung metastases prediction estimates. The best performance was obtained using a combination of four texture features extracted from FDG-PET/T1 and FDG-PET/T2FS scans. This model reached an area under the receiver-operating characteristic curve of 0.984 ± 0.002, a sensitivity of 0.955 ± 0.006, and a specificity of 0.926 ± 0.004 in bootstrapping

  6. Evaluation of splanchnic perfusion and oxygenation during positive end-expiratory pressure ventilation in relation to subcutaneous tissue gases and pH. An experimental study in pigs with oleic acid-induced lung injury.

    Science.gov (United States)

    Jedlińska, B; Mellström, A; Månsson, P; Hartmann, M; Jönsson, K

    2001-01-01

    Evaluation of splanchnic perfusion and oxygenation was performed by measurements of serosal tissue oxygen tension (PserO2) and intramucosal pH (pHi) in relation to subcutaneous oxygen tension (PscO2), subcutaneous carbon dioxide tension (PscCO2) and subcutaneous pH (pHsc) in pigs subjected to oleic acid-induced lung injury during ventilation with increasing levels of positive end-expiratory pressure (PEEP). Lung injury resulted in a general hypoxia and redistribution of perfusion away from the subcutaneous and splanchnic tissues, illustrated by a decrease in PaO2 from 93 to 37 mm Hg (p portal vein oxygen tension (PportaO2) from 21 to 34 mm Hg (p oxygenation was better reflected by serosal oxygen tension than pHi in the colon. Changes in serosal oxygenation of the colon paralleled changes in subcutaneous tissue oxygenation. Copyright 2001 S. Karger AG, Basel

  7. Lung tumor production and tissue metal distribution after exposure to manual metal ARC-stainless steel welding fume in A/J and C57BL/6J mice.

    Science.gov (United States)

    Zeidler-Erdely, Patti C; Battelli, Lori A; Salmen-Muniz, Rebecca; Li, Zheng; Erdely, Aaron; Kashon, Michael L; Simeonova, Petia P; Antonini, James M

    2011-01-01

    Stainless steel welding produces fumes that contain carcinogenic metals. Therefore, welders may be at risk for the development of lung cancer, but animal data are inadequate in this regard. Our main objective was to examine lung tumor production and histopathological alterations in lung-tumor-susceptible (A/J) and -resistant C57BL/6J (B6) mice exposed to manual metal arc-stainless steel (MMA-SS) welding fume. Male mice were exposed to vehicle or MMA-SS welding fume (20 mg/kg) by pharyngeal aspiration once per month for 4 mo. At 78 wk postexposure, gross tumor counts and histopathological changes were assessed and metal analysis was done on extrapulmonary tissue (aorta, heart, kidney, and liver). At 78 wk postexposure, gross lung tumor multiplicity and incidence were unremarkable in mice exposed to MMA-SS welding fume. Histopathology revealed that only the exposed A/J mice contained minimal amounts of MMA-SS welding fume in the lung and statistically increased lymphoid infiltrates and alveolar macrophages. A significant increase in tumor multiplicity in the A/J strain was observed at 78 wk. Metal analysis of extrapulmonary tissue showed that only the MMA-SS-exposed A/J mice had elevated levels of Cr, Cu, Mn, and Zn in kidney and Cr in liver. In conclusion, this study further supports that MMA-SS welding fume does not produce a significant tumorigenic response in an animal model, but may induce a chronic lung immune response. In addition, long-term extrapulmonary tissue alterations in metals in the susceptible A/J mouse suggest that the adverse effects of this fume might be cumulative.

  8. Expression and significance of Notch1 and Bmi-1 protein in lung cancer tissue%Notch1和Bmi-1蛋白在肺癌组织中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    蔡华荣; 江跃全

    2016-01-01

    BACKGROUND:Studies have found that Notch pathway and Bmi-1 gene both have the ability to regulate stem cel self-renew. Functional dysfunction of the both may have a great relationship with tumorigenesis. OBJECTIVE:To investigate the expression and clinical significance of Notch1 and Bmi-1 protein in lung tissue. METHODS:Eighty-seven lung cancer tissue samples (lung cancer group) and forty pathologicaly confirmed normal lung tissue samples (normal group) were obtained from related surgeries and included as research objects. The protein expression of Notch1 and Bmi-1 in specimens of these two groups was measured by immunohistochemistry SP method. The relationship between Notch1 and Bmi-1 protein expression and clinicopathological features of lung cancer patients was analyzed. RESULTS AND CONCLUSION: The positive rate of Notch1, Bmi-1 protein expression was respectively 61% and 47%, which was significantly higher in the lung cancer group than that in the normal group (P 0.05);低分化肺癌、发生淋巴结转移、TNM分期Ⅲ-Ⅳ级患者的Notch1、Bmi-1蛋白阳性表达率显著高于高中分化肺癌、无淋巴结转移、TNM分期Ⅰ、Ⅱ级患者(P <0.05)。结果表明Notch1基因和Bmi-1基因可能与肺癌的发生、发展有一定的关系。

  9. Lung needle biopsy

    Science.gov (United States)

    ... biopsy Lung tissue biopsy References Ettinger DS. Lung cancer and other pulmonary neoplasms. In: Goldman L, Schafer AI, eds. Goldman's ... 2010:chap 47. Read More Aspiration ... by: Denis Hadjiliadis, MD, Associate Professor of Medicine, Pulmonary, Allergy, and Critical Care, Perelman School of Medicine, ...

  10. Genome-wide gene expression profiles in lung tissues of pig breeds differing in resistance to porcine reproductive and respiratory syndrome virus.

    Directory of Open Access Journals (Sweden)

    Jinyi Xing

    Full Text Available Porcine reproductive and respiratory syndrome (PRRS caused by PRRS virus (PRRSV is an infectious disease characterized by severe reproductive deficiency in pregnant sows, typical respiratory symptoms in piglets, and high mortality rate of piglets. In this study, we employed an Affymetrix microarray chip to compare the gene expression profiles of lung tissue samples from Dapulian (DPL pigs (a Chinese indigenous pig breed and Duroc×Landrace×Yorkshire (DLY pigs after infection with PRRSV. During infection with PRRSV, the DLY pigs exhibited a range of clinical features that typify the disease, whereas the DPL pigs showed only mild signs of the disease. Overall, the DPL group had a lower percentage of CD4(+ cells and lower CD4(+/CD8(+ratios than the DLY group (p<0.05. For both IL-10 and TNF-α, the DLY pigs had significantly higher levels than the DPL pigs (p<0.01. The DLY pigs have lower serum IFN-γ levels than the DPL pigs (p<0.01. The serum IgG levels increased slightly from 0 dpi to 7 dpi, and peaked at 14 dpi (p<0.0001. Microarray data analysis revealed 16 differentially expressed (DE genes in the lung tissue samples from the DLY and DPL pigs (q≤5%, of which LOC100516029 and LOC100523005 were up-regulated in the PRRSV-infected DPL pigs, while the other 14 genes were down-regulated in the PRRSV-infected DPL pigs compared with the PRRSV-infected DLY pigs. The mRNA expression levels of 10 out of the 16 DE genes were validated by real-time quantitative RT-PCR and their fold change was consistent with the result of microarray data analysis. We further analyzed the mRNA expression level of 8 differentially expressed genes between the DPL and DLY pigs for both uninfected and infected groups, and found that TF and USP18 genes were important in underlying porcine resistance or susceptibility to PRRSV.

  11. Impact of sample acquisition and linear amplification on gene expression profiling of lung adenocarcinoma: laser capture micro-dissection cell-sampling versus bulk tissue-sampling

    Directory of Open Access Journals (Sweden)

    Wigle Dennis A

    2009-03-01

    Full Text Available Abstract Background The methods used for sample selection and processing can have a strong influence on the expression values obtained through microarray profiling. Laser capture microdissection (LCM provides higher specificity in the selection of target cells compared to traditional bulk tissue selection methods, but at an increased processing cost. The benefit gained from the higher tissue specificity realized through LCM sampling is evaluated in this study through a comparison of microarray expression profiles obtained from same-samples using bulk and LCM processing. Methods Expression data from ten lung adenocarcinoma samples and six adjacent normal samples were acquired using LCM and bulk sampling methods. Expression values were evaluated for correlation between sample processing methods, as well as for bias introduced by the additional linear amplification required for LCM sample profiling. Results The direct comparison of expression values obtained from the bulk and LCM sampled datasets reveals a large number of probesets with significantly varied expression. Many of these variations were shown to be related to bias arising from the process of linear amplification, which is required for LCM sample preparation. A comparison of differentially expressed genes (cancer vs. normal selected in the bulk and LCM datasets also showed substantial differences. There were more than twice as many down-regulated probesets identified in the LCM data than identified in the bulk data. Controlling for the previously identified amplification bias did not have a substantial impact on the differences identified in the differentially expressed probesets found in the bulk and LCM samples. Conclusion LCM-coupled microarray expression profiling was shown to uniquely identify a large number of differentially expressed probesets not otherwise found using bulk tissue sampling. The information gain realized from the LCM sampling was limited to differential analysis

  12. Matrikines and the lungs

    NARCIS (Netherlands)

    Burgess, Janette K; Weckmann, Markus

    2012-01-01

    The extracellular matrix is a complex network of fibrous and nonfibrous molecules that not only provide structure to the lung but also interact with and regulate the behaviour of the cells which it surrounds. Recently it has been recognised that components of the extracellular matrix proteins are re

  13. Nuclear survivin and its relationship to DNA damage repair genes in non-small cell lung cancer investigated using tissue array.

    Directory of Open Access Journals (Sweden)

    Songliu Hu

    Full Text Available PURPOSE: To investigate the predictive role and association of nuclear survivin and the DNA double-strand breaks repair genes in non-small cell lung cancer (NSCLC: DNA-dependent protein kinase catalytic subunit (DNA-PKcs, Ku heterodimeric regulatory complex 70-KD subunit (Ku70 and ataxia-telangiectasia mutated (ATM. METHODS: The protein expression of nuclear survivin, DNA-PKcs, Ku70 and ATM were investigated using immunohistochemistry in tumors from 256 patients with surgically resected NSCLC. Furthermore, we analyzed the correlation between the expression of nuclear survivin, DNA-PKcs, Ku70 and ATM. Univariate and multivariate analyses were performed to determine the prognostic factors that inuenced the overall survival and disease-free survival of NSCLC. RESULTS: The expression of nuclear survivin, DNA-PKcs, Ku70 and ATM was significantly higher in tumor tissues than in normal tissues. By dichotomizing the specimens as expressing low or high levels of nuclear survivin, nuclear survivin correlated significantly with the pathologic stage (P = 0.009 and lymph node status (P = 0.004. The nuclear survivin levels were an independent prognostic factor for both the overall survival and the disease-free survival in univariate and multivariate analyses. Patients with low Ku70 and DNA-PKcs expression had a greater benefit from radiotherapy than patients with high expression of Ku70 (P = 0.012 and DNA-PKcs (P = 0.02. Nuclear survivin expression positively correlated with DNA-PKcs (P<0.001 and Ku70 expression (P<0.001. CONCLUSIONS: Nuclear survivin may be a prognostic factor for overall survival in patients with resected stage I-IIIA NSCLC. DNA-PKcs and Ku70 could predict the effect of radiotherapy in patients with NSCLC. Nuclear survivin may also stimulates DNA double-strand breaks repair by its interaction with DNA-PKcs and Ku70.

  14. Lung Emergencies

    Science.gov (United States)

    ... Emergencies Cardiac Emergencies Eye Emergencies Lung Emergencies Surgeries Lung Emergencies People with Marfan syndrome can be at ... should be considered an emergency. Symptoms of sudden lung collapse (pneumothorax) Symptoms of a sudden lung collapse ...

  15. Expression of innate immune genes, proteins and microRNAs in lung tissue and leukocytes of pigs infected with influenza virus

    DEFF Research Database (Denmark)

    Skovgaard, Kerstin; Cirera, Susanna; Vasby, Ditte

    This study aimed at providing a better understanding of the involvement of innate immune factors including microRNA (miRNA) in the local and systemic host response to influenza virus infection. Twenty pigs were challenged by influenza A virus subtype H1N2. Expression of miRNA, mRNA and proteins...... acute phase proteins. Likewise, the following miRNAs were differentially expressed in one or more time groups compared to the control pigs: miR-15a, miR-21, miR-146, miR-206, miR-223 and miR-451. At day one pi lung tissue protein levels of IL-6, IL-12 and IFN-α were significantly increased compared...... to the control group, and haptoglobin and C-reactive protein were at significantly increased at day three pi. MiRNA are small non coding RNA molecules, that regulate gene expression in a wide range of organisms. Cellular miRNAs might be involved in influenza infection, both by targeting immune related host...

  16. Functional EpoR pathway utilization is not detected in primary tumor cells isolated from human breast, non-small cell lung, colorectal, and ovarian tumor tissues.

    Directory of Open Access Journals (Sweden)

    Scott D Patterson

    Full Text Available Several clinical trials in oncology have reported increased mortality or disease progression associated with erythropoiesis-stimulating agents. One hypothesis proposes that erythropoiesis-stimulating agents directly stimulate tumor proliferation and/or survival through cell-surface receptors. To test this hypothesis and examine if human tumors utilize the erythropoietin receptor pathway, the response of tumor cells to human recombinant erythropoietin was investigated in disaggregated tumor cells obtained from 186 patients with colorectal, breast, lung, ovarian, head and neck, and other tumors. A cocktail of well characterized tumor growth factors (EGF, HGF, and IGF-1 were analyzed in parallel as a positive control to determine whether freshly-isolated tumor cells were able to respond to growth factor activation ex vivo. Exposing tumor cells to the growth factor cocktail resulted in stimulation of survival and proliferation pathways as measured by an increase in phosphorylation of the downstream signaling proteins AKT and ERK. In contrast, no activation by human recombinant erythropoietin was observed in isolated tumor cells. Though tumor samples exhibited a broad range of cell-surface expression of EGFR, c-Met, and IGF-1R, no cell-surface erythropoietin receptor was detected in tumor cells from the 186 tumors examined (by flow cytometry or Western blot. Erythropoiesis-stimulating agents did not act directly upon isolated tumor cells to stimulate pathways known to promote proliferation or survival of human tumor cells isolated from primary and metastatic tumor tissues.

  17. Reconciling healthcare professional and patient perspectives in the development of disease activity and response criteria in connective tissue disease-related interstitial lung diseases.

    Science.gov (United States)

    Saketkoo, Lesley Ann; Mittoo, Shikha; Frankel, Sid; LeSage, Daphne; Sarver, Catherine; Phillips, Kristine; Strand, Vibeke; Matteson, Eric L

    2014-04-01

    Interstitial lung diseases (ILD), including those related to connective tissue disease (CTD), and idiopathic pulmonary fibrosis (IPF) carry high morbidity and mortality. Great efforts are under way to develop and investigate meaningful treatments in the context of clinical trials. However, efforts have been challenged by a lack of validated outcome measures and by inconsistent use of measures in clinical trials. Lack of consensus has fragmented effective use of strategies in CTD-ILD and IPF, with a history of resultant difficulties in obtaining agency approval of treatment interventions. Until recently, the patient perspective to determine domains and outcome measures in CTD-ILD and IPF had never been applied. Efforts described here demonstrate unequivocally the value and influence of patient involvement on core set development. Regarding CTD-ILD, this is the first OMERACT working group to directly address a manifestation/comorbidity of a rheumatic disease (ILD) as well as a disease not considered rheumatic (IPF). The OMERACT 11 proceedings of the CTD-ILD Working Group describe the forward and lateral process to include both the medical and patient perspectives in the urgently needed identification of a core set of preliminary domains and outcome measures in CTD-ILD and IPF.

  18. 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

  19. 耐药相关蛋白P-gp、MRP、LRP在非小细胞肺癌组织中的表达及意义%The expression and significance of the multidrug resistance-related proteins P-gp, MRP and LRP in human non-small cell lung cancer tissues

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To explore the expression and significance of the multidrug resistance-related proteins P-glycoprotein (P-gp), multidrug resistance-related protein (MRP), lung resistance protein (LRP) in human non-small cell lung cancer (NSCLC) tissues and paratumor tissues. Methods: Immunohistochemistry (IHC) was used to examine the expression level of proteins P-gp, MRP and LRP in 43 samples of NSCLC and 15 samples of paratumor tissues. Results: The expression rates of P-gp, MRP and LRP in 43 tumor tissues were 74.42% (32/43), 67.44% (29/43) and 88.37% (38/43), respectively, while in 15 paratumor tissues were 13.33% (2/15), 20.00% (3/15) and 6.67% (1/15), respectively. There was significant difference in the expression of proteins (P-gp, MRP and LRP) between lung cancer tissues and paratumor tissues (P < 0.05). The expression of proteins P-gp, LRP in lung adenocarcinoma were higher than that in other pathological carcinomas (P < 0.05). The expression of protein MRP was not related to pathological type, clinical stage and classification of histodifferentiation (P >0.05). Conclusion: Multidrug resistance is more common in NSCLC. The proteins of P-gp, MRP and LRP participated in the formation of multidrug resistance in lung cancer. Detection of multidrug resistance-related proteins in lung cancer tissues may be useful to choice drugs.

  20. Placental vascular responses are dependent on surrounding tissue

    DEFF Research Database (Denmark)

    Brøgger, Torbjørn Halle

    Background: The placenta is the base for the exchange of nutrients, oxygen and waste products for the fetus. The placental vessels hold a crucial role in regulation the blood flow, and a compromised placental function leads to serious complications such as fetal death or growth retardation. An in...

  1. Placental vascular responses are dependent on surrounding tissue

    DEFF Research Database (Denmark)

    Brøgger, Torbjørn Halle

    Background. The placenta is the base for the exchange of nutrients, oxygen and waste products for the fetus.The placental vessels hold a crucial role in regulation the blood flow, and a compromised placental function leads to serious complications such as fetal death or growth retardation...

  2. Induction of CYP1A1, CYP1A2, CYP1B1, increased oxidative stress and inflammation in the lung and liver tissues of rats exposed to incense smoke.

    Science.gov (United States)

    Hussain, Tajamul; Al-Attas, Omar S; Al-Daghri, Nasser M; Mohammed, Arif A; De Rosas, Edgard; Ibrahim, Shebl; Vinodson, Benjamin; Ansari, Mohammed G; El-Din, Khaled I Alam

    2014-06-01

    Incense smoke is increasingly being recognized as a potential environmental contaminant and is linked to malignant and non-malignant respiratory diseases. The detoxification of environmental contaminants including polycyclic aromatic hydrocarbons (PAHs) involves the induction of cytochrome P-450 family enzymes (CYPs) by PAHs. However, the detoxification of PAHs also results in the generation of reactive and unstable intermediary metabolites which are implicated in the oxidative stress, DNA damage, and inflammation. It is unclear whether CYPs are similarly induced by incense smoke, which incidentally contains substantial amounts of PAHs. Here, we examined the impact of long-term incense smoke exposure on the induction of CYPs in male Wister Albino rats. Incense smoke exposure significantly induced the expression of CYP1A1, CYP1A2, and CYP1B1 mRNAs in both lung and liver tissues. The extent of CYP1A1 and CYP1B1 induction was significantly higher in the liver compared to that in the lung, while that of CYP1A2 was greater in the lung than in liver. Incense smoke exposure also increased malondialdehyde and reduced glutathione levels in lung and liver tissues, and the catalase activity in the liver tissues to significant levels. Furthermore incense smoke exposure led to a marked increase in TNF-α and IL-4 levels. The data demonstrate for the first time the capacity of incense smoke to induce CYP1 family enzymes in the target and non-target tissues. Induction of CYPs increased oxidative stress and inflammation appear to be intimately linked to promote the carcinogenesis and health complications in people chronically exposed to incense smoke.

  3. Elemental analysis of occupational and environmental lung diseases by electron probe microanalyzer with wavelength dispersive spectrometer.

    Science.gov (United States)

    Takada, Toshinori; Moriyama, Hiroshi; Suzuki, Eiichi

    2014-01-01

    Occupational and environmental lung diseases are a group of pulmonary disorders caused by inhalation of harmful particles, mists, vapors or gases. Mineralogical analysis is not generally required in the diagnosis of most cases of these diseases. Apart from minerals that are encountered rarely or only in specific occupations, small quantities of mineral dusts are present in the healthy lung. As such when mineralogical analysis is required, quantitative or semi-quantitative methods must be employed. An electron probe microanalyzer with wavelength dispersive spectrometer (EPMA-WDS) enables analysis of human lung tissue for deposits of elements by both qualitative and semi-quantitative methods. Since 1993, we have analyzed 162 cases of suspected occupational and environmental lung diseases using an EPMA-WDS. Our institute has been accepting online requests for elemental analysis of lung tissue samples by EPMA-WDS since January 2011. Hard metal lung disease is an occupational interstitial lung disease that primarily affects workers exposed to the dust of tungsten carbide. The characteristic pathological findings of the disease are giant cell interstitial pneumonia (GIP) with centrilobular fibrosis, surrounded by mild alveolitis with giant cells within the alveolar space. EPMA-WDS analysis of biopsied lung tissue from patients with GIP has demonstrated that tungsten and/or cobalt is distributed in the giant cells and centrilobular fibrosing lesion in GIP. Pneumoconiosis, caused by amorphous silica, and acute interstitial pneumonia, associated with the giant tsunami, were also elementally analyzed by EPMA-WDS. The results suggest that commonly found elements, such as silicon, aluminum, and iron, may cause occupational and environmental lung diseases.

  4. Preparation of monoclonal antibodies to nuclear matrix proteins of tissues surrounding esophagus cancer and its preliminary identification%食管癌旁组织核基质蛋白单克隆抗体的制备及初步鉴定

    Institute of Scientific and Technical Information of China (English)

    张新梅; 林汉良; 刘乐和; 张昌卿; 钟叔平; 曾金云; 郑克立

    2000-01-01

    目的 制备抗食管癌旁组织核基质蛋白的特异性单抗。方法 SDS-PAGE分析正常食管组织、食管癌旁组织及 食管癌组织核基质蛋白间的差异。用食管癌旁组织核基质蛋白做免疫原免疫Balb/c小鼠,利用杂交瘤技术制备了5株能稳定 分泌单克隆抗体的杂交瘤细胞株,并对9-1-2/D、9-1-7/D 2株细胞作了初步鉴定。结果 免疫组化分析发现9-1-2/D单抗与食管 癌及正常食管组织均有反应,而9-1-7/D单抗只与食管癌组织反应,与正常食管组织无反应。Western Blotting分析显示: 9-1-2/D单抗与电泳图谱上正常食管组织核基质和食管癌旁组织核基质52 kD的蛋白反应,而与食管癌组织核基质55 kD的蛋 白反应。9-1-7/D单抗只与电泳图谱上食管癌旁组织及癌组织核基质46 kD的蛋白反应,与正常食管组织核基质无反应。结论 本实验为食管癌的早期诊断作了初步有意义的探讨。%Objective To prepare anti-nuclear matrix proteins of tissues surrounding esophagus cancer monoclonal anti- bodies. Methods Differences among nuclear matrix proteins (NMPS) of normal esophagus tissues, esophagus cancer tissues and tissues adjacent to cancer were identified by SDS-PAGE. Balb/c mouse were hyperimmunized with NMPS of tissues adja- cent to esophagus cancer. Five mouse lymphocyte hybridoma cell lines were established and preliminary identification of cell lines 9-1-2/D, 9-1-7/D were made. Results Immunohistochemical analysis showed monoclonal antibody 9-1-2/D reacted both with esophagus cancer and normal esophageal tissues; monoclonal antibody 9-1-7/D reacted only with nucleoli of esophagus cancer cells. Western Blotting analysis showed monoclonal antibody 9-1-2/D reacted with 52 kD NMPS of normal esophagus tissues and tissues adjacent to esophagus cancer and reacted with 55 kD NMP of esophagus cancer tissue. Monoclonal anti- body 9-1-7/D reacted only with 46 kD protein of esophagus cancer

  5. Responses of Giving n-Hexane Jaloh Extract on Broiler Chicken which Heat Stress Condition to Expression of iNOS Enzyme in Lung Tissue, Serum level of Glucose and Calcium

    Directory of Open Access Journals (Sweden)

    Sugito Sugito

    2008-10-01

    Full Text Available Giving of extract n-hexane of jaloh bark (EHJ can lessen impact heat stress on broiler chicken. The studies of activity of EHJ in lessening heat stress impact at broiler chicken have not been conducted yet. An experiment was conducted to study the effect of extract n-hexane of jaloh bark (EHJ administration on body temperature, level of calcium and glucose in serum, inducible nitric oxide synthase (iNOS in lung tissue, and behaviors of broilers exposed to heat stress at temperature 33 ± 1oC. This study used 18 broilers aged 20 days which were divided into 3 groups. The first group was broilers given heat stress without EHJ (CP. The second group was treated heat stress and EHJ at dose 10 mg/kg BW (CP+EHJ. The EHJ was given 1 hour before cage temperature was raised. Broilers in group CP and CP+EHJ were divided into 3 periods of slaughtering i.e. 2 and 4 hours after given heat stress and 2 hours after heat stress termination. Each of slaughtering period consisted of 3 broilers as replication. Result of this research indicated that CP+EHJ lessen stress in the form of restlessness and increased expression of iNOS in the lung tissue. It was assumed that one of mechanism of EHJ in lessening stress on broiler related to forming of iNOS enzyme in the lung tissue.

  6. Binaural Rendering in MPEG Surround

    Directory of Open Access Journals (Sweden)

    Kristofer Kjörling

    2008-04-01

    Full Text Available This paper describes novel methods for evoking a multichannel audio experience over stereo headphones. In contrast to the conventional convolution-based approach where, for example, five input channels are filtered using ten head-related transfer functions, the current approach is based on a parametric representation of the multichannel signal, along with either a parametric representation of the head-related transfer functions or a reduced set of head-related transfer functions. An audio scene with multiple virtual sound sources is represented by a mono or a stereo downmix signal of all sound source signals, accompanied by certain statistical (spatial properties. These statistical properties of the sound sources are either combined with statistical properties of head-related transfer functions to estimate “binaural parameters” that represent the perceptually relevant aspects of the auditory scene or used to create a limited set of combined head-related transfer functions that can be applied directly on the downmix signal. Subsequently, a binaural rendering stage reinstates the statistical properties of the sound sources by applying the estimated binaural parameters or the reduced set of combined head-related transfer functions directly on the downmix. If combined with parametric multichannel audio coders such as MPEG Surround, the proposed methods are advantageous over conventional methods in terms of perceived quality and computational complexity.

  7. Reduced surround inhibition in musicians.

    Science.gov (United States)

    Shin, Hae-Won; Kang, Suk Y; Hallett, Mark; Sohn, Young H

    2012-06-01

    To investigate whether surround inhibition (SI) in the motor system is altered in professional musicians, we performed a transcranial magnetic stimulation (TMS) study in 10 professional musicians and 15 age-matched healthy non-musicians. TMS was set to be triggered by self-initiated flexion of the index finger at different intervals ranging from 3 to 1,000 ms. Average motor evoked potential (MEP) amplitudes obtained from self-triggered TMS were normalized to average MEPs of the control TMS at rest and expressed as a percentage. Normalized MEP amplitudes of the abductor digiti minimi (ADM) muscles were compared between the musicians and non-musicians with the primary analysis being the intervals between 3 and 80 ms (during the movement). A mixed-design ANOVA revealed a significant difference in normalized ADM MEPs during the index finger flexion between groups, with less SI in the musicians. This study demonstrated that the functional operation of SI is less strong in musicians than non-musicians, perhaps due to practice of movement synergies involving both muscles. Reduced SI, however, could lead susceptible musicians to be prone to develop task-specific dystonia.

  8. Binaural Rendering in MPEG Surround

    Science.gov (United States)

    Breebaart, Jeroen; Villemoes, Lars; Kjörling, Kristofer

    2008-12-01

    This paper describes novel methods for evoking a multichannel audio experience over stereo headphones. In contrast to the conventional convolution-based approach where, for example, five input channels are filtered using ten head-related transfer functions, the current approach is based on a parametric representation of the multichannel signal, along with either a parametric representation of the head-related transfer functions or a reduced set of head-related transfer functions. An audio scene with multiple virtual sound sources is represented by a mono or a stereo downmix signal of all sound source signals, accompanied by certain statistical (spatial) properties. These statistical properties of the sound sources are either combined with statistical properties of head-related transfer functions to estimate "binaural parameters" that represent the perceptually relevant aspects of the auditory scene or used to create a limited set of combined head-related transfer functions that can be applied directly on the downmix signal. Subsequently, a binaural rendering stage reinstates the statistical properties of the sound sources by applying the estimated binaural parameters or the reduced set of combined head-related transfer functions directly on the downmix. If combined with parametric multichannel audio coders such as MPEG Surround, the proposed methods are advantageous over conventional methods in terms of perceived quality and computational complexity.

  9. The expression profiles of circRNAs in lung tissues from rats with lipopolysaccharide-induced acute respiratory distress syndrome: A microarray study.

    Science.gov (United States)

    Wan, Qi-Quan; Wu, Di; Ye, Qi-Fa

    2017-08-31

    The development of circular RNA (circRNA) microarray has facilitated the study of the role of circRNAs in regulating gene expression through a circRNA-miRNA-mRNA network. In our study, microarray was performed to detect the expression profiles of circRNAs during lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS). Twenty rats were randomly divided into 2 groups, the control group and the LPS group, 10 rats in each group. Three rats each from both groups were randomly selected. Using circRNA microarray data, we compared the circRNA expression profiles in lung tissues between these 6 rats. The most differentially expressed circRNA species from these profiles were validated and optimized as ARDS biomarkers and potential therapeutic targets. Overall, 395 and 562 circRNAs were significantly up- and down-regulated in LPS group vs. control group, respectively. Six up-regulated and 4 down-regulated circRNAs from the top 10 candidates were eventually selected to be validated. Among them, only 4 up-regulated circRNAs (mmu_circRNA_19423, rno_circRNA_010489, rno_circRNA_011426, mmu_circRNA_30664) and 1 down-regulated circRNA (rno_circRNA_005564) exhibited significant validation. The 5 highest ranking target miRNAs of these 5 validated circRNAs were predicted according to the miRNA support vector regression method. This is the first study to investigate circRNA expression profile and a large number of aberrantly expressed circRNAs were revealed during ARDS. The significantly over- or under-expressed circRNA may represent a novel biomarker and be developed as a novel therapeutic target for the clinical management of ARDS. The results are preliminary and need to be confirmed in further well-designed studies with larger sample size. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. A role for mesenchyme dynamics in mouse lung branching morphogenesis.

    Directory of Open Access Journals (Sweden)

    Pierre Blanc

    Full Text Available Mammalian airways are highly ramified tree-like structures that develop by the repetitive branching of the lung epithelium into the surrounding mesenchyme through reciprocal interactions. Based on a morphometric analysis of the epithelial tree, it has been recently proposed that the complete branching scheme is specified early in each lineage by a programme using elementary patterning routines at specific sites and times in the developing lung. However, the coupled dynamics of both the epithelium and mesenchyme have been overlooked in this process. Using a qualitative and quantitative in vivo morphometric analysis of the E11.25 to E13.5 mouse whole right cranial lobe structure, we show that beyond the first generations, the branching stereotypy relaxes and both spatial and temporal variations are common. The branching pattern and branching rate are sensitive to the dynamic changes of the mesoderm shape that is in turn mainly dependent upon the volume and shape of the surrounding intrathoracic organs. Spatial and temporal variations of the tree architecture are related to local and subtle modifications of the mesoderm growth. Remarkably, buds never meet after suffering branching variations and continue to homogenously fill the opening spaces in the mesenchyme. Moreover despite inter-specimen variations, the growth of the epithelial tree and the mesenchyme remains highly correlated over time at the whole lobe level, implying a long-range regulation of the lung lobe morphogenesis. Together, these findings indicate that the lung epithelial tree is likely to adapt in real time to fill the available space in the mesenchyme, rather than being rigidly specified and predefined by a global programme. Our results strongly support the idea that a comprehensive understanding of lung branching mechanisms cannot be inferred from the branching pattern or behavior alone. Rather it needs to be elaborated upon with the reconsideration of mesenchyme

  11. Influence of Three Methods on Morphological Alternation in Lung Tissue of Mouse Infected by Influenza Virus%3种治法对流感病毒感染小鼠肺形态学改变的影响

    Institute of Scientific and Technical Information of China (English)

    周坤福; 刘琳琳; 王均琴; 陆平成

    2012-01-01

    目的 通过观察清热解毒、宣肺化痰、养阴清肺3种治法对流感病毒感染小鼠肺组织形态学改变的影响,进一步验证3种治法治疗流感病毒性肺炎作用的有效性.方法 选择3种治法的中药复方代表,并设利巴韦林为阳性对照,观察其对流感病毒感染小鼠肺组织形态学变化.结果 3种治法均能减轻流感病毒所致小鼠肺损伤的形态学变化.结论 3种治法均能有效减轻流感病毒所致小鼠肺病理损伤.%OBJECTIVE To further confirm the effectiveness of three therapeutic methods(clearing away heat and relieving toxin,proclaims lung and removing phlegm,nourishing yin and tonifying lung)on the treatment of flu viral pneumonia,through observing the influence of these three methods on morphological alternation in lung tissue of mouse infected by influenza virus. METHODS Select Traditional Chinese Medicine compound representative of these three methods,set ribavirin as positive contrast,and observe its influence on morphological alternation in lung tissue of mouse infected by influenza virus. RESULTS These three methods all can reduce the morphological alternation caused by influenza virus. CONCLUSION Three methods all can effectively reduce the pathological damage on lung caused by influenza virus.

  12. Estimation of Lung Ventilation

    Science.gov (United States)

    Ding, Kai; Cao, Kunlin; Du, Kaifang; Amelon, Ryan; Christensen, Gary E.; Raghavan, Madhavan; Reinhardt, Joseph M.

    Since the primary function of the lung is gas exchange, ventilation can be interpreted as an index of lung function in addition to perfusion. Injury and disease processes can alter lung function on a global and/or a local level. MDCT can be used to acquire multiple static breath-hold CT images of the lung taken at different lung volumes, or with proper respiratory control, 4DCT images of the lung reconstructed at different respiratory phases. Image registration can be applied to this data to estimate a deformation field that transforms the lung from one volume configuration to the other. This deformation field can be analyzed to estimate local lung tissue expansion, calculate voxel-by-voxel intensity change, and make biomechanical measurements. The physiologic significance of the registration-based measures of respiratory function can be established by comparing to more conventional measurements, such as nuclear medicine or contrast wash-in/wash-out studies with CT or MR. An important emerging application of these methods is the detection of pulmonary function change in subjects undergoing radiation therapy (RT) for lung cancer. During RT, treatment is commonly limited to sub-therapeutic doses due to unintended toxicity to normal lung tissue. Measurement of pulmonary function may be useful as a planning tool during RT planning, may be useful for tracking the progression of toxicity to nearby normal tissue during RT, and can be used to evaluate the effectiveness of a treatment post-therapy. This chapter reviews the basic measures to estimate regional ventilation from image registration of CT images, the comparison of them to the existing golden standard and the application in radiation therapy.

  13. 基于文献挖掘的高氧损伤肺组织相关基因的生物信息学分析%Literature and bioinformatic analysis of dysregulated genes in lung tissues of hyperoxic lung injury

    Institute of Scientific and Technical Information of China (English)

    黄宇戈; 张山丹; 韩浩; 陈星; 殷海平; 郑学辉

    2013-01-01

    Objective To explore the pathogenesis mechanism of hyperoxic lung injury and the effective means for its clinical treatment,the difference of the gene expressions between lung tissues of hyperoxic lung injury and normal lung was compared.Methods The differentially expressed genes between lung tissues of hyperoxic lung injury and normal lung were obtained from PubMed.The dysregulated genes in lung tissues of hyperoxic lung injury were analyzed by a series of bioinformatics methods,including pathways,gene ontology and functional annotation clustering analysis.Results 467 lines of differentially expressed genes were found and genes more than 2-fold regulated were 189.We sought the mapping of genes in the KEGG databases through functional annotation tools,and we discovered there were 5 lines of pathways with difference having outstangding statistical significance through metabolic pathways enrichment degree analysis.It reflected the pathways were closely related to hyperoxic lung injury (the 2-fold upregulated genes were 14,the 2-fold down-regulated genes were 6).GO analysis revealed that these genes were involved in hematopietic cell lineage,axon guidance,adherens junction,T cell receptor signaling pathway and focal adhesion.Conclusions Therefore,it is believed that the above-mentioned 20 lines of gnes are the major ones for the hyperoxic lung injury and the research on them will provide effective means for revealing the molecular mechanism of hyperoxic lung injury and identifying the targeted therapy.%目的 比较小鼠高氧肺损伤肺组织与正常肺组织的差异表达基因,从分子水平揭示高氧肺损伤的发病机制.方法 利用PubMed数据库获取小鼠高氧肺损伤肺组织与正常肺组织的差异表达基因,并进行生物学通路、基因本体和功能注释聚类等生物信息分析.结果 两组间差异表达基因共467条,以2倍标准筛选出189条差异表达基因,再用功能注释工具将超过2倍差异表达的基因

  14. General Information about Small Cell Lung Cancer

    Science.gov (United States)

    ... lung cancer is a disease in which malignant (cancer) cells form in the tissues of the lung. The ... diagnosed, tests are done to find out if cancer cells have spread within the chest or to other ...

  15. Treatment Option Overview (Small Cell Lung Cancer)

    Science.gov (United States)

    ... lung cancer is a disease in which malignant (cancer) cells form in the tissues of the lung. The ... diagnosed, tests are done to find out if cancer cells have spread within the chest or to other ...

  16. Stages of Small Cell Lung Cancer

    Science.gov (United States)

    ... lung cancer is a disease in which malignant (cancer) cells form in the tissues of the lung. The ... diagnosed, tests are done to find out if cancer cells have spread within the chest or to other ...

  17. 生物全降解聚左旋乳酸/无定形磷酸钙支架植入大鼠体内后周围组织的钙化%Effect of poly-L-lactic acid/amorphous calcium phosphate scaffold on the surrounding tissue calcification after implantation into the rats