Oxidative damage induced by cigarette smoke exposure in mice: impact on lung tissue and diaphragm muscle,

Directory of Open Access Journals (Sweden)

Samanta Portão de Carlos

2014-08-01

Full Text Available OBJECTIVE: To evaluate oxidative damage (lipid oxidation, protein oxidation, thiobarbituric acid-reactive substances [TBARS], and carbonylation and inflammation (expression of phosphorylated AMP-activated protein kinase and mammalian target of rapamycin [p-AMPK and p-mTOR, respectively] in the lung parenchyma and diaphragm muscles of male C57BL-6 mice exposed to cigarette smoke (CS for 7, 15, 30, 45, or 60 days. METHODS: Thirty-six male C57BL-6 mice were divided into six groups (n = 6/group: a control group; and five groups exposed to CS for 7, 15, 30, 45, and 60 days, respectively. RESULTS: Compared with control mice, CS-exposed mice presented lower body weights at 30 days. In CS-exposed mice (compared with control mice, the greatest differences (increases in TBARS levels were observed on day 7 in diaphragm-muscle, compared with day 45 in lung tissue; the greatest differences (increases in carbonyl levels were observed on day 7 in both tissue types; and sulfhydryl levels were lower, in both tissue types, at all time points. In lung tissue and diaphragm muscle, p-AMPK expression exhibited behavior similar to that of TBARS. Expression of p-mTOR was higher than the control value on days 7 and 15 in lung tissue, as it was on day 45 in diaphragm muscle. CONCLUSION: Our data demonstrate that CS exposure produces oxidative damage, not only in lung tissue but also (primarily in muscle tissue, having an additional effect on respiratory muscle, as is frequently observed in smokers with COPD.

Telomere elongation protects heart and lung tissue cells from fatal damage in rats exposed to severe hypoxia.

Science.gov (United States)

Wang, Yaping; Zhao, Zhen; Zhu, Zhiyong; Li, Pingying; Li, Xiaolin; Xue, Xiaohong; Duo, Jie; Ma, Yingcai

2018-02-17

The effects of acute hypoxia at high altitude on the telomere length of the cells in the heart and lung tissues remain unclear. This study aimed to investigate the change in telomere length of rat heart and lung tissue cells in response to acute exposure to severe hypoxia and its role in hypoxia-induced damage to heart and lung tissues. Forty male Wistar rats (6-week old) were randomized into control group (n = 10) and hypoxia group (n = 30). Rats in control group were kept at an altitude of 1500 m, while rats in hypoxia group were exposed to simulated hypoxia with an altitude of 5000 m in a low-pressure oxygen chamber for 1, 3, and 7 days (n = 10). The left ventricular and right middle lobe tissues of each rat were collected for measurement of telomere length and reactive oxygen species (ROS) content, and the mRNA and protein levels of telomerase reverse transcriptase (TERT), hypoxia-inducible factor1α (HIF-1α), and hypoxia-inducible factor1α (HIF-2α). Increased exposure to hypoxia damaged rat heart and lung tissue cells and increased ROS production and telomere length. The mRNA and protein levels of TERT and HIF-1α were significantly higher in rats exposed to hypoxia and increased with prolonged exposure; mRNA and protein levels of HIF-2α increased only in rats exposed to hypoxia for 7 days. TERT was positively correlated with telomere length and the levels of HIF-1α but not HIF-2α. Acute exposure to severe hypoxia causes damage to heart and lung tissues due to the production of ROS but promotes telomere length and adaptive response by upregulating TERT and HIF-1α, which protect heart and lung tissue cells from fatal damage.

Reduced generation of lung tissue-resident memory T cells during infancy.

Science.gov (United States)

Zens, Kyra D; Chen, Jun Kui; Guyer, Rebecca S; Wu, Felix L; Cvetkovski, Filip; Miron, Michelle; Farber, Donna L

2017-10-02

Infants suffer disproportionately from respiratory infections and generate reduced vaccine responses compared with adults, although the underlying mechanisms remain unclear. In adult mice, lung-localized, tissue-resident memory T cells (TRMs) mediate optimal protection to respiratory pathogens, and we hypothesized that reduced protection in infancy could be due to impaired establishment of lung TRM. Using an infant mouse model, we demonstrate generation of lung-homing, virus-specific T effectors after influenza infection or live-attenuated vaccination, similar to adults. However, infection during infancy generated markedly fewer lung TRMs, and heterosubtypic protection was reduced compared with adults. Impaired TRM establishment was infant-T cell intrinsic, and infant effectors displayed distinct transcriptional profiles enriched for T-bet-regulated genes. Notably, mouse and human infant T cells exhibited increased T-bet expression after activation, and reduction of T-bet levels in infant mice enhanced lung TRM establishment. Our findings reveal that infant T cells are intrinsically programmed for short-term responses, and targeting key regulators could promote long-term, tissue-targeted protection at this critical life stage. © 2017 Zens et al.

Trace element load in cancer and normal lung tissue

International Nuclear Information System (INIS)

Kubala-Kukus, A.; Braziewicz, J.; Banas, D.; Majewska, U.; Gozdz, S.; Urbaniak, A.

1999-01-01

Samples of malignant and benign human lung tissues were analysed by two complementary methods, i.e., particle induced X-ray emission (PIXE) and total reflection X-ray fluorescence (TRXRF). The concentration of trace elements of P, S, K, Ca, Ti, Cr, Mn, Fe, Cu, Zn, Se, Sr, Hg and Pb was determined in squamous cancer of lung tissue from 65 people and in the benign lung tumour tissue from 5 people. Several elements shows enhancement in cancerous lung tissue of women in comparison to men, i.e., titanium show maximum enhancement by 48% followed by Cr (20%) and Mn (36%). At the same time trace element concentration of Sr and Pb are declaimed by 30% and 20% in women population. Physical basis of used analytical methods, experimental set-up and the procedure of sample preparation are described

Metabolomic profiling of lung and prostate tumor tissues by capillary electrophoresis time-of-flight mass spectrometry.

Science.gov (United States)

Kami, Kenjiro; Fujimori, Tamaki; Sato, Hajime; Sato, Mutsuko; Yamamoto, Hiroyuki; Ohashi, Yoshiaki; Sugiyama, Naoyuki; Ishihama, Yasushi; Onozuka, Hiroko; Ochiai, Atsushi; Esumi, Hiroyasu; Soga, Tomoyoshi; Tomita, Masaru

2013-04-01

Metabolic microenvironment of tumor cells is influenced by oncogenic signaling and tissue-specific metabolic demands, blood supply, and enzyme expression. To elucidate tumor-specific metabolism, we compared the metabolomics of normal and tumor tissues surgically resected pairwise from nine lung and seven prostate cancer patients, using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). Phosphorylation levels of enzymes involved in central carbon metabolism were also quantified. Metabolomic profiles of lung and prostate tissues comprised 114 and 86 metabolites, respectively, and the profiles not only well distinguished tumor from normal tissues, but also squamous cell carcinoma from the other tumor types in lung cancer and poorly differentiated tumors from moderately differentiated tumors in prostate cancer. Concentrations of most amino acids, especially branched-chain amino acids, were significantly higher in tumor tissues, independent of organ type, but of essential amino acids were particularly higher in poorly differentiated than moderately differentiated prostate cancers. Organ-dependent differences were prominent at the levels of glycolytic and tricarboxylic acid cycle intermediates and associated energy status. Significantly high lactate concentrations and elevated activating phosphorylation levels of phosphofructokinase and pyruvate kinase in lung tumors confirmed hyperactive glycolysis. We highlighted the potential of CE-TOFMS-based metabolomics combined with phosphorylated enzyme analysis for understanding tissue-specific tumor microenvironments, which may lead to the development of more effective and specific anticancer therapeutics.

The lung tissue microbiota of mild and moderate chronic obstructive pulmonary disease.

Science.gov (United States)

Pragman, Alexa A; Lyu, Tianmeng; Baller, Joshua A; Gould, Trevor J; Kelly, Rosemary F; Reilly, Cavan S; Isaacson, Richard E; Wendt, Chris H

2018-01-09

Oral taxa are often found in the chronic obstructive pulmonary disease (COPD) lung microbiota, but it is not clear if this is due to a physiologic process such as aspiration or experimental contamination at the time of specimen collection. Microbiota samples were obtained from nine subjects with mild or moderate COPD by swabbing lung tissue and upper airway sites during lung lobectomy. Lung specimens were not contaminated with upper airway taxa since they were obtained surgically. The microbiota were analyzed with 16S rRNA gene qPCR and 16S rRNA gene hypervariable region 3 (V3) sequencing. Data analyses were performed using QIIME, SourceTracker, and R. Streptococcus was the most common genus in the oral, bronchial, and lung tissue samples, and multiple other taxa were present in both the upper and lower airways. Each subject's own bronchial and lung tissue microbiota were more similar to each other than were the bronchial and lung tissue microbiota of two different subjects (permutation test, p = 0.0139), indicating more within-subject similarity than between-subject similarity at these two lung sites. Principal coordinate analysis of all subject samples revealed clustering by anatomic sampling site (PERMANOVA, p = 0.001), but not by subject. SourceTracker analysis found that the sources of the lung tissue microbiota were 21.1% (mean) oral microbiota, 8.7% nasal microbiota, and 70.1% unknown. An analysis using the neutral theory of community ecology revealed that the lung tissue microbiota closely reflects the bronchial, oral, and nasal microbiota (immigration parameter estimates 0.69, 0.62, and 0.74, respectively), with some evidence of ecologic drift occurring in the lung tissue. This is the first study to evaluate the mild-moderate COPD lung tissue microbiota without potential for upper airway contamination of the lung samples. In our small study of subjects with COPD, we found oral and nasal bacteria in the lung tissue microbiota, confirming that

Histopathology of lung disease in the connective tissue diseases.

Science.gov (United States)

Vivero, Marina; Padera, Robert F

2015-05-01

The pathologic correlates of interstitial lung disease (ILD) secondary to connective tissue disease (CTD) comprise a diverse group of histologic patterns. Lung biopsies in patients with CTD-associated ILD tend to demonstrate simultaneous involvement of multiple anatomic compartments of the lung. Certain histologic patterns tend to predominate in each defined CTD, and it is possible in many cases to confirm connective tissue-associated lung disease and guide patient management using surgical lung biopsy. This article will cover the pulmonary pathologies seen in rheumatoid arthritis, systemic sclerosis, myositis, systemic lupus erythematosus, Sjögren syndrome, and mixed CTD. Copyright © 2015 Elsevier Inc. All rights reserved.

Connective tissue diseases, multimorbidity and the ageing lung.

Science.gov (United States)

Spagnolo, Paolo; Cordier, Jean-François; Cottin, Vincent

2016-05-01

Connective tissue diseases encompass a wide range of heterogeneous disorders characterised by immune-mediated chronic inflammation often leading to tissue damage, collagen deposition and possible loss of function of the target organ. Lung involvement is a common complication of connective tissue diseases. Depending on the underlying disease, various thoracic compartments can be involved but interstitial lung disease is a major contributor to morbidity and mortality. Interstitial lung disease, pulmonary hypertension or both are found most commonly in systemic sclerosis. In the elderly, the prevalence of connective tissue diseases continues to rise due to both longer life expectancy and more effective and better-tolerated treatments. In the geriatric population, connective tissue diseases are almost invariably accompanied by age-related comorbidities, and disease- and treatment-related complications, which contribute to the significant morbidity and mortality associated with these conditions, and complicate treatment decision-making. Connective tissue diseases in the elderly represent a growing concern for healthcare providers and an increasing burden of global health resources worldwide. A better understanding of the mechanisms involved in the regulation of the immune functions in the elderly and evidence-based guidelines specifically designed for this patient population are instrumental to improving the management of connective tissue diseases in elderly patients. Copyright ©ERS 2016.

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.

Production of decellularized porcine lung scaffolds for use in tissue engineering.

Science.gov (United States)

Balestrini, Jenna L; Gard, Ashley L; Liu, Angela; Leiby, Katherine L; Schwan, Jonas; Kunkemoeller, Britta; Calle, Elizabeth A; Sivarapatna, Amogh; Lin, Tylee; Dimitrievska, Sashka; Cambpell, Stuart G; Niklason, Laura E

2015-12-01

There is a growing body of work dedicated to producing acellular lung scaffolds for use in regenerative medicine by decellularizing donor lungs of various species. These scaffolds typically undergo substantial matrix damage due to the harsh conditions required to remove cellular material (e.g., high pH, strong detergents), lengthy processing times, or pre-existing tissue contamination from microbial colonization. In this work, a new decellularization technique is described that maintains the global tissue architecture, key matrix components, mechanical composition and cell-seeding potential of lung tissue while effectively removing resident cellular material. Acellular lung scaffolds were produced from native porcine lungs using a combination of Triton X-100 and sodium deoxycholate (SDC) at low concentrations in 24 hours. We assessed the effect of matrix decellularization by measuring residual DNA, biochemical composition, mechanical characteristics, tissue architecture, and recellularization capacity.

Measurement of asbestos bodies in lung tissue of autopsy cases diagnosed with primary lung cancer

International Nuclear Information System (INIS)

Idei, Yuka; Kamada, Satoe; Matsumoto, Shoji; Ohnishi, Kazuo; Kitazawa, Riko; Kitazawa, Sohei

2007-01-01

To investigate the relation between asbestos-related lung cancer and the concentration of asbestos bodies in lung tissue, we analyzed the concentration in 24 autopsy cases diagnosed with primary lung cancer, with regard to the gender, age, histological type of lung cancer and occupation of each case. The asbestos bodies were measured according to Kohyama's method. Positive cases (more than 5,000 bodies per 1 g of dry lung tissue) were further analyzed for asbestosis and pleural plaques by chest X-ray and chest CT. Two cases exhibited more than 5,000 bodies, five cases between 1,000 and 5,000, and seventeen cases less than 1,000. The occupation of the two positive cases was not informative: one demonstrated neither asbestosis nor pleural plaques, and the other showed only pleural plaques. Although the number of cases of asbestos-related lung cancer is minimal among all lung cancer cases, the number of the former may exceed that of mesothelioma patients. Not only physicians but also radiologists, surgeons and pathologists need to collaborate in the diagnosis of asbestos-related lung cancer. (author)

Production of decellularized porcine lung scaffolds for use in tissue engineering†

Science.gov (United States)

Balestrini, Jenna L.; Gard, Ashley L.; Liu, Angela; Leiby, Katherine L.; Schwan, Jonas; Kunkemoeller, Britta; Calle, Elizabeth A.; Sivarapatna, Amogh; Lin, Tylee; Dimitrievska, Sashka; Cambpella, Stuart G.; Niklason, Laura E.

2015-01-01

There is a growing body of work dedicated to producing acellular lung scaffolds for use in regenerative medicine by decellularizing donor lungs of various species. These scaffolds typically undergo substantial matrix damage due to the harsh conditions required to remove cellular material (e.g., high pH, strong detergents), lengthy processing times, or pre-existing tissue contamination from microbial colonization. In this work, a new decellularization technique is described that maintains the global tissue architecture, key matrix components, mechanical composition and cell-seeding potential of lung tissue while effectively removing resident cellular material. Acellular lung scaffolds were produced from native porcine lungs using a combination of Triton X-100 and sodium deoxycholate (SDC) at low concentrations in 24 hours. We assessed the effect of matrix decellularization by measuring residual PMID:26426090

Transgenic Mice Overexpressing Vitamin D Receptor (VDR) Show Anti-Inflammatory Effects in Lung Tissues.

Science.gov (United States)

Ishii, Masaki; Yamaguchi, Yasuhiro; Isumi, Kyoko; Ogawa, Sumito; Akishita, Masahiro

2017-12-01

Vitamin D insufficiency is increasingly recognized as a prevalent problem worldwide, especially in patients with a chronic lung disease. Chronic obstructive pulmonary disease (COPD) is a type of chronic inflammatory lung disease. Previous clinical studies have shown that COPD leads to low vitamin D levels, which further increase the severity of COPD. Vitamin D homeostasis represents one of the most important factors that potentially determine the severity of COPD. Nonetheless, the mechanisms underlying the anti-inflammatory effects of vitamin D receptor (VDR) in lung tissues are still unclear. To investigate the anti-inflammatory effects of VDR, we generated transgenic mice that show lung-specific VDR overexpression under the control of the surfactant protein C promoter (TG mice). The TG mice were used to study the expression patterns of proinflammatory cytokines using real-time polymerase chain reaction and immunohistochemistry. The TG mice had lower levels of T helper 1 (Th1)-related cytokines than wild-type (WT) mice did. No significant differences in the expression of Th2 cytokines were observed between TG and WT mice. This study is the first to achieve lung-specific overexpression of VDR in TG mice: an interesting animal model useful for studying the relation between airway cell inflammation and vitamin D signaling. VDR expression is an important factor that influences anti-inflammatory responses in lung tissues. Our results show the crucial role of VDR in anti-inflammatory effects in lungs; these data are potentially useful for the treatment or prevention of COPD.

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. © 2015 Wiley Periodicals, Inc.

Calculation of microplanar beam dose profiles in a tissue/lung/tissue phantom

International Nuclear Information System (INIS)

Company, F.Z.; Allen, B.J.

1998-01-01

Recent advances in synchrotron generated x-ray beams with a high fluence rate permit investigation of the application of an array of closely spaced, parallel or converging microplanar beams in radiotherapy. The proposed technique takes advantage of the hypothesized repair mechanism of capillary cells between alternate microbeam zones, which regenerates the lethally irradiated endothelial cells. The lateral and depth doses of 100 keV microplanar beams are investigated for different beam dimensions and spacings in a tissue, lung and tissue/lung/tissue phantom. The EGS4 Monte Carlo code is used to calculate dose profiles at different depths and bundles of beams (up to 20x20cm square cross section). The maximum dose on the beam axis (peak) and the minimum interbeam dose (valley) are compared at different depths, bundles, heights, widths and beam spacings. (author)

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.

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).

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...... 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....... CONCLUSIONS: The microdialysis technique allowed measurements of histamine release from mast cells in intact lung ex vivo. The method may prove useful since a number of experiments can be performed in a few hours in intact lung tissue without any dispersion or enzymatic treatment....

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.

Radiation induced COX-2 expression and mutagenesis at non-targeted lung tissues of gpt delta transgenic mice

Science.gov (United States)

Chai, Y; Calaf, G M; Zhou, H; Ghandhi, S A; Elliston, C D; Wen, G; Nohmi, T; Amundson, S A; Hei, T K

2013-01-01

Background: Although radiation-induced bystander effects have been confirmed using a variety of endpoints, the mechanism(s) underlying these effects are not well understood, especially for in vivo study. Methods: A 1-cm2 area (1 cm × 1 cm) in the lower abdominal region of gpt delta transgenic mice was irradiated with 5 Gy of 300 keV X-rays, and changes in out-of-field lung and liver were observed. Results: Compared with sham-treated controls, the Spi− mutation frequency increased 2.4-fold in non-targeted lung tissues at 24 h after partial body irradiation (PBIR). Consistent with dramatic Cyclooxygenase 2 (COX-2) induction in the non-targeted bronchial epithelial cells, increasing levels of prostaglandin, together with 8-hydroxydeoxyguanosine, in the out-of-field lung tissues were observed after PBIR. In addition, DNA double-strand breaks and apoptosis were induced in bystander lung tissues after PBIR. Conclusion: The PBIR induces DNA damage and mutagenesis in non-targeted lung tissues, especially in bronchial epithelial cells, and COX-2 has an essential role in bystander mutagenesis. PMID:23321513

Analysis of lung tissue using ion beams

International Nuclear Information System (INIS)

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

2002-01-01

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

Radiation-induced changes in production of prostaglandins Fsub(2α), E, and thromboxane B2 in guinea pig parenchymal lung tissues

International Nuclear Information System (INIS)

Steel, L.K.; Catravas, G.N.

1982-01-01

At 1 hour to 4 days after unilateral exposure of guinea pigs to a single dose (0.5, 1.5, or 3.0 Gy) of gamma-radiation, changes were detected in prostaglandin and thromboxane concentrations in parenchymal lung tissues. At 1-3 hours after exposure, tissue levels of PGFsub(2α), PGE, and thromboxane B 2 were significantly elevated in animals receiving 3.0 Gy, with the magnitude of alteration revealing a radiation dose effect. By 24 hours, tissue prostaglandin and thromboxane levels returned to near control values. Lung tissue synthesis of prostaglandins in response to H-1 receptor stimulation by the exogenous addition of histamine revealed similar radiation dose effects. The carboxylic acid ionophore A23187, exogenously applied to lung tissues, revealed a transient peak of increased sensitivity to ionophore stimulation for TxB 2 synthesis at 24 hours and for PGFsub(2α) at 72 hours post-irradiation. The data suggest that significant alterations in prostaglandin and thromboxane concentrations in parenchymal lung tissues occur following irradiation, in a dose-dependent manner, and that altered responsiveness to H-1 receptor stimulation and divalent cation transport also occur

Expression and Significance of gp96 and Immune-related Gene CTLA-4, CD8 in Lung Cancer Tissues

Directory of Open Access Journals (Sweden)

Haiyan ZHENG

2010-08-01

Full Text Available Background and objective It has been proven that gp96 plays an important role in specific cytotoxic immune response which is involved in anti-tumor effect in the body. The aim of this study is to investigate the biological significance of heat shock protein gp96 and immune-related gene CTLA-4, CD8 expressions in lung cancer tissues of different progressive stages. Methods We used Envision immunohistochemistry method to detect the levels of expression of gp96, CTLA-4, CD8 in tissue microarray, which contained 89 primary lung cancer tissues, 12 lymph node metastasis lung cancer tissues, 12 precancerous lesions and 10 normal lung tissues, and analyzed the relationship between their expressions and clinicopathological parameters. Results (1 The positive rate of gp96 in primary lung cancer was remarkably higher than that in precancerous lesion and normal lung tissue (P < 0.05. The positive rate of CTLA-4 in primary lung cancer tissue and precancerous lesion was significantly higher than that in normal lung tissue (P < 0.05. The positive rate of CD8 in primary lung cancer tissue was significantly higher than that in normal lung tissue (P < 0.05. The positive rate of gp96 in CD8-positive lymphocytes in the high expression group was less than that in the low group (P < 0.05. (2 The positive rate of gp96 was closely related to sex, differentiation and clinical stage (P < 0.05, but not to age, gross type, histological type and lymph node metastasis (P > 0.05. The positive rate of CTLA-4 was closely related to age and differentiation (P < 0.05, but not to sex, gross type, histological type, clinical stage and lymph node metastasis (P > 0.05. CD8 expression was related to clinical stage (P < 0.05, but not to sex, age, gross type, histological type, differentiation and lymph node metastasis (P > 0.05. The positive rates of gp96, CTLA-4 were higher than that of CD8 in squamous cell carcinoma and SCLC, respectively. (3 There was positive correlation between gp

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

Esophageal involvement and interstitial lung disease in mixed connective tissue disease.

Science.gov (United States)

Fagundes, M N; Caleiro, M T C; Navarro-Rodriguez, T; Baldi, B G; Kavakama, J; Salge, J M; Kairalla, R; Carvalho, C R R

2009-06-01

Mixed connective tissue disease is a systemic inflammatory disorder that results in both pulmonary and esophageal manifestations. We sought to evaluate the relationship between esophageal dysfunction and interstitial lung disease in patients with mixed connective tissue disease. We correlated the pulmonary function data and the high-resolution computed tomography findings of interstitial lung disease with the results of esophageal evaluation in manometry, 24-hour intraesophageal pH measurements, and the presence of esophageal dilatation on computed tomography scan. Fifty consecutive patients with mixed connective tissue disease, according to Kasukawa's classification criteria, were included in this prospective study. High-resolution computed tomography parenchymal abnormalities were present in 39 of 50 patients. Esophageal dilatation, gastroesophageal reflux, and esophageal motor impairment were also very prevalent (28 of 50, 18 of 36, and 30 of 36, respectively). The presence of interstitial lung disease on computed tomography was significantly higher among patients with esophageal dilatation (92% vs. 45%; pmotor dysfunction (90% vs. 35%; pesophageal and pulmonary involvement, our series revealed a strong association between esophageal motor dysfunction and interstitial lung disease in patients with mixed connective tissue disease.

Mannose binding lectin (MBL levels predict lung function decline in severe asthma

Directory of Open Access Journals (Sweden)

Ilonka. H. van Veen

2006-12-01

Full Text Available There is increasing evidence that activation of the complement system in asthma contributes to ongoing inflammation, tissue damage and airway remodeling. Mannose binding lectin (MBL is a pattern recognition molecule that serves as the key mediator of the lectin pathway of complement activation. MBL levels are genetically determined and vary widely amongst individuals. In the present study we hypothesized that high MBL levels in asthma are associated with increased loss of lung function over time, as a consequence of inflammatory tissue damage. We measured serum MBL levels by ELISA in 68 patients with severe asthma and prospectively determined the change in post-bronchodilator (pb FEV1 over a mean period of 5.7 years. The relationship between MBL and change in pbFEV1 (FEV1 was analysed using (multiple regression analysis and corrected for possible confounders (age, sex, age of onset, asthma duration, and pbFEV1. The median (range MBL level was 332 (10.8-3587 ng·ml–1. MBL was significantly associated with FEV1 (p<0.04. Patients with a high MBL level (332 ng·ml–1 had an increased risk of lung function decline compared to those with low MBL levels (OR (CI: 3.16 (1.14-8.79, p = 0.027; the excess decline being 42 ml·yr–1 (p = 0.01. We conclude that a high MBL level is associated with an increased decline in lung function in patients with severe asthma. MBL might provide a clue towards better understanding of the pathophysiology of ongoing inflammation and subsequent decline in lung function of patients with severe asthma.

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...

Protective effect of gel form of gastric gavage applicated aloe vera on ischemia reperfusion injury in renal and lung tissue.

Science.gov (United States)

Sahin, Hasan; Yener, Ali Umit; Karaboga, Ihsan; Sehitoglu, Muserref Hilal; Dogu, Tugba; Altinisik, Hatice Betul; Altinisik, Ugur; Simsek, Tuncer

2017-12-30

The aloe vera plant has become increasingly popular in recent years. This study aimed to research the effect of aloe vera to prevent renal and lung tissue damage in an experimental ischemia-reperfusion (I/R) injury model. The study included 21 male Wistar Albino rats, which were categorized into control group, n = 7 (no procedures), Sham group n = 7 (I/R); and aloe vera therapy group, n = 7 (aloe vera and I/R). Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA) were evaluated from lung and kidney tissues for biochemical investigations. As histopathological, hematoxylin and eosin and anti-iNOS were also examined. In biochemical investigations, SOD, CAT, and GPx levels of the Sham group were found to be lower compared with the other groups (P < 0.05). The aloe vera therapy group was not statistically different from control groups but significantly different compared with the Sham group. In the same way, the MDA levels of kidney and lung tissues were statistically significant in the aloe vera therapy group, compared to the Sham group. In the Sham group, the peribronchial and perialveolar edema were observed in lung parenchyma. Also, excess interstitial hemorrhage, leukocyte infiltration, and alveolar wall thickening were identified in ischemic groups. The histopathological changes were much lighter than in the aloe vera therapy group. In renal tissues, excess epithelial cell deterioration, tubular desqumination, and glomerular atrophy were observed in the Sham group. The histopathological changes were markedly reduced in the aloe vera therapy  group. In the kidney and lung tissue, the level of iNOS activity in the Sham group was significantly higher than in the control and aloe vera therapy group. This study indicated that aloe vera is protective against oxidative damage formed by I/R in distant organs like the lungs and kidneys.

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

Toward in vivo lung's tissue incompressibility characterization for tumor motion modeling in radiation therapy

International Nuclear Information System (INIS)

Shirzadi, Zahra; Sadeghi-Naini, Ali; Samani, Abbas

2013-01-01

Purpose: A novel technique is proposed to characterize lung tissue incompressibility variation during respiration. Estimating lung tissue incompressibility parameter variations resulting from air content variation throughout respiration is critical for computer assisted tumor motion tracking. Continuous tumor motion is a major challenge in lung cancer radiotherapy, especially with external beam radiotherapy. If not accounted for, this motion may lead to areas of radiation overdosage for normal tissue. Given the unavailability of imaging modality that can be used effectively for real-time lung tumor tracking, computer assisted approach based on tissue deformation estimation can be a good alternative. This approach involves lung biomechanical model where its fidelity depends on input tissue properties. This investigation shows that considering variable tissue incompressibility parameter is very important for predicting tumor motion accurately, hence improving the lung radiotherapy outcome. Methods: First, an in silico lung phantom study was conducted to demonstrate the importance of employing variable Poisson's ratio for tumor motion predication. After it was established that modeling this variability is critical for accurate tumor motion prediction, an optimization based technique was developed to estimate lung tissue Poisson's ratio as a function of respiration cycle time. In this technique, the Poisson's ratio and lung pressure value were varied systematically until optimal values were obtained, leading to maximum similarity between acquired and simulated 4D CT lung images. This technique was applied in an ex vivo porcine lung study where simulated images were constructed using the end exhale CT image and deformation fields obtained from the lung's FE modeling of each respiration time increment. To model the tissue, linear elastic and Marlow hyperelastic material models in conjunction with variable Poisson's ratio were used. Results: The phantom study showed that

Lung Tissue Concentrations of Pyrazinamide among Patients with Drug-Resistant Pulmonary Tuberculosis

Science.gov (United States)

Heinrichs, M. Tobias; Nikolaishvili, Ketino; Sabulua, Irina; Bablishvili, Nino; Gogishvili, Shota; Avaliani, Zaza; Tukvadze, Nestani; Little, Brent; Bernheim, Adam; Read, Timothy D.; Guarner, Jeannette; Derendorf, Hartmut; Peloquin, Charles A.; Blumberg, Henry M.; Vashakidze, Sergo

2017-01-01

ABSTRACT Improved knowledge regarding the tissue penetration of antituberculosis drugs may help optimize drug management. Patients with drug-resistant pulmonary tuberculosis undergoing adjunctive surgery were enrolled. Serial serum samples were collected, and microdialysis was performed using ex vivo lung tissue to measure pyrazinamide concentrations. Among 10 patients, the median pyrazinamide dose was 24.7 mg/kg of body weight. Imaging revealed predominant lung lesions as cavitary (n = 6 patients), mass-like (n = 3 patients), or consolidative (n = 1 patient). On histopathology examination, all tissue samples had necrosis; eight had a pH of ≤5.5. Tissue samples from two patients were positive for Mycobacterium tuberculosis by culture (pH 5.5 and 7.2). All 10 patients had maximal serum pyrazinamide concentrations within the recommended range of 20 to 60 μg/ml. The median lung tissue free pyrazinamide concentration was 20.96 μg/ml. The median tissue-to-serum pyrazinamide concentration ratio was 0.77 (range, 0.54 to 0.93). There was a significant inverse correlation between tissue pyrazinamide concentrations and the amounts of necrosis (R = −0.66, P = 0.04) and acid-fast bacilli (R = −0.75, P = 0.01) identified by histopathology. We found good penetration of pyrazinamide into lung tissue among patients with pulmonary tuberculosis with a variety of radiological lesion types. Our tissue pH results revealed that most lesions had a pH conducive to pyrazinamide activity. The tissue penetration of pyrazinamide highlights its importance in both drug-susceptible and drug-resistant antituberculosis treatment regimens. PMID:28373198

Lung Tissue Concentrations of Pyrazinamide among Patients with Drug-Resistant Pulmonary Tuberculosis.

Science.gov (United States)

Kempker, Russell R; Heinrichs, M Tobias; Nikolaishvili, Ketino; Sabulua, Irina; Bablishvili, Nino; Gogishvili, Shota; Avaliani, Zaza; Tukvadze, Nestani; Little, Brent; Bernheim, Adam; Read, Timothy D; Guarner, Jeannette; Derendorf, Hartmut; Peloquin, Charles A; Blumberg, Henry M; Vashakidze, Sergo

2017-06-01

Improved knowledge regarding the tissue penetration of antituberculosis drugs may help optimize drug management. Patients with drug-resistant pulmonary tuberculosis undergoing adjunctive surgery were enrolled. Serial serum samples were collected, and microdialysis was performed using ex vivo lung tissue to measure pyrazinamide concentrations. Among 10 patients, the median pyrazinamide dose was 24.7 mg/kg of body weight. Imaging revealed predominant lung lesions as cavitary ( n = 6 patients), mass-like ( n = 3 patients), or consolidative ( n = 1 patient). On histopathology examination, all tissue samples had necrosis; eight had a pH of ≤5.5. Tissue samples from two patients were positive for Mycobacterium tuberculosis by culture (pH 5.5 and 7.2). All 10 patients had maximal serum pyrazinamide concentrations within the recommended range of 20 to 60 μg/ml. The median lung tissue free pyrazinamide concentration was 20.96 μg/ml. The median tissue-to-serum pyrazinamide concentration ratio was 0.77 (range, 0.54 to 0.93). There was a significant inverse correlation between tissue pyrazinamide concentrations and the amounts of necrosis ( R = -0.66, P = 0.04) and acid-fast bacilli ( R = -0.75, P = 0.01) identified by histopathology. We found good penetration of pyrazinamide into lung tissue among patients with pulmonary tuberculosis with a variety of radiological lesion types. Our tissue pH results revealed that most lesions had a pH conducive to pyrazinamide activity. The tissue penetration of pyrazinamide highlights its importance in both drug-susceptible and drug-resistant antituberculosis treatment regimens. Copyright © 2017 American Society for Microbiology.

TRPA1 channels: expression in non-neuronal murine lung tissues and dispensability for hyperoxia-induced alveolar epithelial hyperplasia.

Science.gov (United States)

Kannler, Martina; Lüling, Robin; Yildirim, Ali Önder; Gudermann, Thomas; Steinritz, Dirk; Dietrich, Alexander

2018-05-12

Transient receptor potential A1 (TRPA1) channels were originally characterized in neuronal tissues but also identified in lung epithelium by staining with fluorescently coupled TRPA1 antibodies. Its exact function in non-neuronal tissues, however, is elusive. TRPA1 is activated in vitro by hypoxia and hyperoxia and is therefore a promising TRP candidate for sensing hyperoxia in pulmonary epithelial cells and for inducing alveolar epithelial hyperplasia. Here, we isolated tracheal, bronchial, and alveolar epithelial cells and show low but detectable TRPA1 mRNA levels in all these cells as well as TRPA1 protein by Western blotting in alveolar type II (AT II) cells. We quantified changes in intracellular Ca 2+ ([Ca 2+ ] i ) levels induced by application of hyperoxic solutions in primary tracheal epithelial, bronchial epithelial, and AT II cells isolated from wild-type (WT) and TRPA1-deficient (TRPA1-/-) mouse lungs. In all cell types, we detected hyperoxia-induced rises in [Ca 2+ ] i levels, which were not significantly different in TRPA1-deficient cells compared to WT cells. We also tested TRPA1 function in a mouse model for hyperoxia-induced alveolar epithelial hyperplasia. A characteristic significant increase in thickening of alveolar tissues was detected in mouse lungs after exposure to hyperoxia, but not in normoxic WT and TRPA1-/- controls. Quantification of changes in lung morphology in hyperoxic WT and TRPA1-/- mice, however, again revealed no significant changes. Therefore, TRPA1 expression does neither appear to be a key player for hyperoxia-induced changes in [Ca 2+ ] i levels in primary lung epithelial cells, nor being essential for the development of hyperoxia-induced alveolar epithelial hyperplasia.

Automating the expert consensus paradigm for robust lung tissue classification

Science.gov (United States)

Rajagopalan, Srinivasan; Karwoski, Ronald A.; Raghunath, Sushravya; Bartholmai, Brian J.; Robb, Richard A.

2012-03-01

Clinicians confirm the efficacy of dynamic multidisciplinary interactions in diagnosing Lung disease/wellness from CT scans. However, routine clinical practice cannot readily accomodate such interactions. Current schemes for automating lung tissue classification are based on a single elusive disease differentiating metric; this undermines their reliability in routine diagnosis. We propose a computational workflow that uses a collection (#: 15) of probability density functions (pdf)-based similarity metrics to automatically cluster pattern-specific (#patterns: 5) volumes of interest (#VOI: 976) extracted from the lung CT scans of 14 patients. The resultant clusters are refined for intra-partition compactness and subsequently aggregated into a super cluster using a cluster ensemble technique. The super clusters were validated against the consensus agreement of four clinical experts. The aggregations correlated strongly with expert consensus. By effectively mimicking the expertise of physicians, the proposed workflow could make automation of lung tissue classification a clinical reality.

Data-driven classification of ventilated lung tissues using electrical impedance tomography

International Nuclear Information System (INIS)

Gómez-Laberge, Camille; Hogan, Matthew J; Elke, Gunnar; Weiler, Norbert; Frerichs, Inéz; Adler, Andy

2011-01-01

Current methods for identifying ventilated lung regions utilizing electrical impedance tomography images rely on dividing the image into arbitrary regions of interest (ROI), manually delineating ROI, or forming ROI with pixels whose signal properties surpass an arbitrary threshold. In this paper, we propose a novel application of a data-driven classification method to identify ventilated lung ROI based on forming k clusters from pixels with correlated signals. A standard first-order model for lung mechanics is then applied to determine which ROI correspond to ventilated lung tissue. We applied the method in an experimental study of 16 mechanically ventilated swine in the supine position, which underwent changes in positive end-expiratory pressure (PEEP) and fraction of inspired oxygen (F I O 2 ). In each stage of the experimental protocol, the method performed best with k = 4 and consistently identified 3 lung tissue ROI and 1 boundary tissue ROI in 15 of the 16 subjects. When testing for changes from baseline in lung position, tidal volume, and respiratory system compliance, we found that PEEP displaced the ventilated lung region dorsally by 2 cm, decreased tidal volume by 1.3%, and increased the respiratory system compliance time constant by 0.3 s. F I O 2 decreased tidal volume by 0.7%. All effects were tested at p < 0.05 with n = 16. These findings suggest that the proposed ROI detection method is robust and sensitive to ventilation dynamics in the experimental setting

Radiation-induced changes in production of prostaglandins Fsub(2. cap alpha. ), E, and thromboxane B/sub 2/ in guinea pig parenchymal lung tissues

Energy Technology Data Exchange (ETDEWEB)

Steel, L K; Catravas, G N [Armed Forces Radiobiology Research Inst., Bethesda, MD (USA)

1982-11-01

At 1 hour to 4 days after unilateral exposure of guinea pigs to a single dose (0.5, 1.5, or 3.0 Gy) of gamma-radiation, changes were detected in prostaglandin and thromboxane concentrations in parenchymal lung tissues. At 1-3 hours after exposure, tissue levels of PGFsub(2..cap alpha..), PGE, and thromboxane B/sub 2/ were significantly elevated in animals receiving 3.0 Gy, with the magnitude of alteration revealing a radiation dose effect. By 24 hours, tissue prostaglandin and thromboxane levels returned to near control values. Lung tissue synthesis of prostaglandins in response to H-1 receptor stimulation by the exogenous addition of histamine revealed similar radiation dose effects. The carboxylic acid ionophore A23187, exogenously applied to lung tissues, revealed a transient peak of increased sensitivity to ionophore stimulation for TxB/sub 2/ synthesis at 24 hours and for PGFsub(2..cap alpha..) at 72 hours post-irradiation. The data suggest that significant alterations in prostaglandin and thromboxane concentrations in parenchymal lung tissues occur following irradiation, in a dose-dependent manner, and that altered responsiveness to H-1 receptor stimulation and divalent cation transport also occur.

Killing effect of EGFR-TKI combined with 125I seed implantation therapy on ⅢB-Ⅳ stage lung cancer tissue

Directory of Open Access Journals (Sweden)

Ai-Sheng Xiang

2016-12-01

Full Text Available Objective: To analyze the killing effect of EGFR-TKI combined with 125I seed implantation therapy on ⅢB-Ⅳ stage lung cancer tissue. Methods: A total of 78 patients with ⅢB-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 genes PDCD5, bax and bcl-xS mRNA expression levels in lung tissue of observation group after 1 month of treatment were higher than those of control group while Bag-1, survivin and bcl-xL mRNA expression levels were lower than those of control group; invasion genes CD147, EGFR and DDX17 mRNA expression levels were lower than those of control group while Bin1, E-cadherin and Ovol2 mRNA expression levels were higher than those of control group; autophagy genes ARHI, Beclin1, Atg5, LC3B, pULK and PI3KC3 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 with ⅢB-Ⅳ stage lung cancer, and contribute to the optimization of overall condition and the extension of survival time.

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.

Association Between RT-Induced Changes in Lung Tissue Density and Global Lung Function

International Nuclear Information System (INIS)

Ma Jinli; Zhang Junan; Zhou Sumin; Hubbs, Jessica L.; Foltz, Rodney J.; Hollis, Donna R.; Light, Kim L.; Wong, Terence Z.; Kelsey, Christopher R.; Marks, Lawrence B.

2009-01-01

Purpose: To assess the association between radiotherapy (RT)-induced changes in computed tomography (CT)-defined lung tissue density and pulmonary function tests (PFTs). Methods and Materials: Patients undergoing incidental partial lung RT were prospectively assessed for global (PFTs) and regional (CT and single photon emission CT [SPECT]) lung function before and, serially, after RT. The percent reductions in the PFT and the average changes in lung density were compared (Pearson correlations) in the overall group and subgroups stratified according to various clinical factors. Comparisons were also made between the CT- and SPECT-based computations using the Mann-Whitney U test. Results: Between 1991 and 2004, 343 patients were enrolled in this study. Of these, 111 patients had a total of 203 concurrent post-RT evaluations of changes in lung density and PFTs available for the analyses, and 81 patients had a total of 141 concurrent post-RT SPECT images. The average increases in lung density were related to the percent reductions in the PFTs, albeit with modest correlation coefficients (range, 0.20-0.43). The analyses also indicated that the association between lung density and PFT changes is essentially equivalent to the corresponding association with SPECT-defined lung perfusion. Conclusion: We found a weak quantitative association between the degree of increase in lung density as defined by CT and the percent reduction in the PFTs.

Differential N-glycan patterns identified in lung adenocarcinoma by N-glycan profiling of formalin-fixed paraffin-embedded (FFPE) tissue sections.

Science.gov (United States)

Wang, Xiaoning; Deng, Zaian; Huang, Chuncui; Zhu, Tong; Lou, Jiatao; Wang, Lin; Li, Yan

2018-02-10

N-glycan profiling is a powerful approach for analyzing the functional relationship between N-glycosylation and cancer. Current methods rely on either serum or fresh tissue samples; however, N-glycan patterns may differ between serum and tissue, as the proteins of serum originate from a variety of tissues. Furthermore, fresh tissue samples are difficult to ship and store. Here, we used a profiling method based on formalin-fixed paraffin-embedded (FFPE) tissue sections from lung adenocarcinoma patients. We found that our method was highly reproducible. We identified 58 N-glycan compositions from lung adenocarcinoma FFPE samples, 51 of which were further used for MS n -based structure prediction. We show that high mannose type N-glycans are upregulated, while sialylated N-glycans are downregulated in our FFPE lung adenocarcinoma samples, compared to the control samples. Our receiver operating characteristic (ROC) curve analysis shows that high mannose type and sialylated N-glycans are useful discriminators to distinguish between lung adenocarcinoma and control tissue. Together, our results indicate that expression levels of specific N-glycans correlate well with lung adenocarcinoma, and strongly suggest that our FFPE-based method will be useful for N-glycan profiling of cancer tissues. Glycosylation is one of the most important post-translational protein modifications, and is associated with several physiopathological processes, including carcinogenesis. In this study, we tested the feasibility of using formalin-fixed paraffin-embedded (FFPE) tissue sections to identify changes in N-glycan patterns and identified the differentially expressed N-glycans of lung adenocarcinoma. Our study shows that the FFPE-based N-glycan profiling method is useful for clinical diagnosis as well as identification of potential biomarkers, and our data expand current knowledge of differential N-glycan patterns of lung adenocarcinoma. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Lung involvement in systemic connective tissue diseases

Directory of Open Access Journals (Sweden)

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.

[Expression of high mobility group box-1 in the lung tissue and serum of patients with pulmonary tuberculosis].

Science.gov (United States)

Yang, Xiao-min; Yang, Hua

2013-07-01

To explore the expression of high mobility group box-1 (HMGB1) in the lung tissue and serum of patients with pulmonary tuberculosis and to explore its relationship with tumor necrosis factor (TNF)-α and interleukin(IL)-1β. Sixty samples of lung tissues were obtained from patients with pulmonary tuberculosis who had underwent pneumonectomy in Department of Chest Surgery, First Affiliated Hospital of Zunyi Medical College from June 2010 to December 2011. At the same period, 40 normal lung samples were also obtained from patients with pulmonary contusion and lung cancer by surgical resections as the control group. The mRNA expressions of HMGB1 was detected by reverse transcription-polymerase chain reaction (RT-PCR), and the protein level of HMGB1 was measured by immunohistochemical staining of tissue microarrays in lung tissue. Blood samples were taken from 89 patients with active pulmonary tuberculosis (pulmonary tuberculosis group), including hematogenous disseminated pulmonary tuberculosis (type II) in 35 cases and secondary pulmonary tuberculosis (type III) in 54 cases, and 50 healthy volunteers (control group). Furthermore, the 54 patients with secondary pulmonary tuberculosis were divided into different subgroups according to cavity formation and the lung fields involved: patients without lung cavity (35 cases) vs those with lung cavity (19 cases), patients with involvement of pulmonary tuberculosis (69 ± 29) was significantly higher than that in normal lung tissue (22 ± 12) (t = 2.389, P pulmonary tuberculosis (786 ± 86) was significantly higher than that in normal lung tissue (202 ± 60) (t = 3.872, P pulmonary tuberculosis group were (5.0 ± 3.2) µg/L, (118 ± 77) ng/L and (33 ± 20) ng/L, respectively, which were significantly higher than those in the control group [(1.7 ± 1.0) µg/L, (40 ± 11) ng/L and (18 ± 12) ng/L, respectively], the respective t values being -0.928, 4.268 and 11.064, all P pulmonary tuberculosis, the serum concentration of HMGB

Over-expression of thymosin β4 in granulomatous lung tissue with active pulmonary tuberculosis.

Science.gov (United States)

Kang, Yun-Jeong; Jo, Jin-Ok; Ock, Mee Sun; Yoo, Young-Bin; Chun, Bong-Kwon; Oak, Chul-Ho; Cha, Hee-Jae

2014-05-01

Recent studies have shown that thymosin β4 (Tβ4) stimulates angiogenesis by inducing vascular endothelial growth factor (VEGF) expression and stabilizing hypoxia inducible factor-1α (HIF-1α) protein. Pulmonary tuberculosis (TB), a type of granulomatous disease, is accompanied by intense angiogenesis and VEGF levels have been reported to be elevated in serum or tissue inflamed by pulmonary tuberculosis. We investigated the expression of Tβ4 in granulomatous lung tissues at various stages of active pulmonary tuberculosis, and we also examined the expression patterns of VEGF and HIF-1α to compare their Tβ4 expression patterns in patients' tissues and in the tissue microarray of TB patients. Tβ4 was highly expressed in both granulomas and surrounding lymphocytes in nascent granulomatous lung tissue, but was expressed only surrounding tissues of necrotic or caseous necrotic regions. The expression pattern of HIF-1α was similar to that of Tβ4. VEGF was expressed in both granulomas and blood vessels surrounding granulomas. The expression pattern of VEGF co-localized with CD31 (platelet endothelial cell adhesion molecule, PECAM-1), a blood endothelial cell marker, and partially co-localized with Tβ4. However, the expression of Tβ4 did not co-localize with alveolar macrophages. Stained alveolar macrophages were present surrounding regions of granuloma highly expressing Tβ4. We also analyzed mRNA expression in the sputum of 10 normal and 19 pulmonary TB patients. Expression of Tβ4 was significantly higher in patients with pulmonary tuberculosis than in normal controls. These data suggest that Tβ4 is highly expressed in granulomatous lung tissue with active pulmonary TB and is associated with HIF-1α- and VEGF-mediated inflammation and angiogenesis. Furthermore, the expression of Tβ4 in the sputum of pulmonary tuberculosis patients can be used as a potential marker for diagnosis. Copyright © 2014 Elsevier Ltd. All rights reserved.

[The effects of postconditioning with propofol on Toll-like receptor 4 expression in the lung tissue of rat with acute lung injury].

Science.gov (United States)

Li, Guo-Fu; Tong, Xin; Luan, Ting; Zang, Bin

2012-10-01

To investigate the effect of postconditioning with propofol on Toll-like receptor 4 (TLR4) expression in the lung tissue in lipopolysaccharide (LPS)-induced acute lung injury (ALI) rats. Thirty Sprague-Dawley (SD) rats were randomly assigned to control group, ALI group, and propofol postcondition group (each n=10). The model of ALI was reproduced by intravenous injection of LPS (8 mg/kg for 30 minutes) into the rats, equivalent normal saline was injected into the rats of control group. The rats were postconditioned with propofol injected intravenously by 20 mg/kg bolus dose and then continuously by 40 mg×kg(-1)×h(-1) with a constant speed for 1 hour. The rats were sacrificed 6 hours after drug injection. Lung wet/dry weight (W/D) ratio and lung permeability index (LPI) was taken. Tumor necrosis factor-α (TNF-α) level in bronchoalveolar lavage fluid (BALF) was detected using enzyme linked immunosorbent assay (ELISA) method and TLR4 mRNA expression in lung tissue was assessed by reverse transcription-polymerase chain reaction (RT-PCR). The lung W/D ratio, LPI, TLR4 mRNA and TNF-α in BALF were all increased in ALI group compared with control group [lung W/D ratio: 5.30±0.28 vs. 4.21±0.14, LPI (×10(-3)): 8.7±2.2 vs. 3.3±2.0, TLR4 mRNA: 2.451±0.028 vs. 0.998±0.021, TNF-α: 643.46±62.31 ng/L vs. 120.43±12.65 ng/L, all Pwaterfall-like inflammatory reaction.

Interstitial lung disease associated with connective tissue diseases

International Nuclear Information System (INIS)

Medina, Yimy F; Restrepo, Jose Felix; Iglesias, Antonio; Ojeda, Paulina; Matiz, Carlos

2007-01-01

An interstitial lung disease (ILD) belongs to a group of diffuse parenchyma lung diseases it should be differentiated from other pathologies among those are idiopathic and ILD associated to connective tissue diseases (CTD) New concepts have been developed in the last years and they have been classified in seven defined subgroups. It has been described the association of each one of these subgroups with CTD. Natural history and other aspects of its treatment is not known completely .For complete diagnose it is required clinical, image and histopathologic approaches. The biopsy lung plays an essential role. It is important to promote and to stimulate the subclasification of each subgroup with the purpose of knowing their natural history directing the treatment and to improve their outcome

Distribution of latex particles in lung and lymph node tissues of rats and dogs

International Nuclear Information System (INIS)

Mueller, H.L; Muggenburg, B.A.; Gillett, N.A.; Guilmette, R.A.

1988-01-01

The distribution of fluorescent poly sytrene microspheres in different lung compartments, with differing particle numbers within individual lung and lymph node cells was examined In methacrylate-embedded tissue slices. Rat tissues were analyzed at 1, 7 and 13 days after particle instillation, dog tissues at 7 and 13 days. A much higher fraction of particles was seen in the lung interstitium and in lung-associated lymph nodes in dogs than in rats. Particle concentrations in TBLN cells were generally very low in both species, but were high in free alveolar cells after high particle numbers were instilled, and increased from 1 to 13 days, suggesting that alveolar cells with few particles were cleared faster than those wth high ingested particle numbers. (author)

Influence of industrial dust of uranium ore on rats' lung tissue

International Nuclear Information System (INIS)

Jumasheva, R.T.

2010-01-01

Under the conditions of radiotoxic influence of uranium ore dust (UOD), the respiratory organs are the main system specifically responsible for adaptation to this factor. At the same time, there are not sufficient studies regarding the morphological aspects of structural lung distortions due to inhalational influence by UOD. To identify the nature of morphological changes in the animals' lung tissue at the cellular and subcellular levels under the influence of industrial dust of uranium ore in a dose of 50 MPC. Experimental studies were conducted on 80 white rats (tom) with a body mass of 120-180 g. The experimental animals were subjected to chronic inhalation of UOD in a dose of 50 MPC (107.75 mg/m 3 ). The animals that were kept in similar chambers but that were not exposed to UOD served as control animals. Material from the animals for research was withdrawn in 3, 7, 30 and 60 days after the beginning of the experiment. The animals were withdrawn from the experiment by decapitation after a brief ether anesthesia. The lung tissue was subjected to conventional histological processing. Sections were stained with haematoxylin and eosin according to van Gieson's method. For electronic microscopic examination the lung tissue slices were fixed and embedded by conventional methods. Obtained blocks were used to prepare ultrathin sections. An impact of UOD in a dose of 50 MPC was accompanied by the development of acute focal serous inflammation in the wall of the small bronchi and lung parenchyma in the early stages of the experiment (3-7 days), pneumonic foci of fibrosis, and the development of marked sclerotic changes in the peribronchial lymphoid tissue by the 30-th day. By the 60-th day, an increase of sclerotic changes in the bronchial wall accompanied by inhibition of the reaction on the part of interstitial macrophages and bronchus associated lymphoid tissue were reported. These indicate the intense course of the compensatory processes. Conducted electron

Biochemical and morphological changes in rat lung tissue under the influence of external ionizing radiation

International Nuclear Information System (INIS)

Uzlenkova, N.Je.; Mamotyuk, Je.M.; Gusakova, V.A.; Kononenko, O.K.

2006-01-01

Single external x-ray exposure at minimum and mean lethal doses was established to cause a long activation of biochemical processes in the connective tissue of the rat lungs. Morphological and ultrastructure changes in the tissue of the lungs at early terms after x-ray and gamma-radiation exposure were due to development of destructive and degenerative reactions. The long-term changes were characterized by growth of connective tissue and formation of areas of fibrous changes in the structure of the lungs

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

Three-dimensional simultaneous optical coherence tomography and confocal fluorescence microscopy for investigation of lung tissue.

Science.gov (United States)

Gaertner, Maria; Cimalla, Peter; Meissner, Sven; Kuebler, Wolfgang M; Koch, Edmund

2012-07-01

Although several strategies exist for a minimal-invasive treatment of patients with lung failure, the mortality rate of acute respiratory distress syndrome still reaches 30% at minimum. This striking number indicates the necessity of understanding lung dynamics on an alveolar level. To investigate the dynamical behavior on a microscale, we used three-dimensional geometrical and functional imaging to observe tissue parameters including alveolar size and length of embedded elastic fibers during ventilation. We established a combined optical coherence tomography (OCT) and confocal fluorescence microscopy system that is able to monitor the distension of alveolar tissue and elastin fibers simultaneously within three dimensions. The OCT system can laterally resolve a 4.9 μm line pair feature and has an approximately 11 μm full-width-half-maximum axial resolution in air. confocal fluorescence microscopy visualizes molecular properties of the tissue with a resolution of 0.75 μm (laterally), and 5.9 μm (axially) via fluorescence detection of the dye sulforhodamine B specifically binding to elastin. For system evaluation, we used a mouse model in situ to perform lung distension by application of different constant pressure values within the physiological regime. Our method enables the investigation of alveolar dynamics by helping to reveal basic processes emerging during artificial ventilation and breathing.

Metal concentrations in homing pigeon lung tissue as a biomonitor of atmospheric pollution.

Science.gov (United States)

Cui, Jia; Halbrook, Richard S; Zang, Shuying; Han, Shuang; Li, Xinyu

2018-03-01

Atmospheric pollution in urban areas is a major worldwide concern with potential adverse impacts on wildlife and humans. Biomonitoring can provide direct evidence of the bioavailability and bioaccumulation of toxic metals in the environment that is not available with mechanical air monitoring. The current study continues our evaluation of the usefulness of homing pigeon lung tissue as a biomonitor of atmospheric pollution. Homing pigeons (1-2, 5-6, and 9-10+ year old (yo)) collected from Guangzhou during 2015 were necropsied and concentrations of cadmium (Cd), lead (Pb), and mercury (Hg) were measured in lung tissue. Lung Cd and Pb concentrations were significantly greater in 9-10+-year-old pigeons compared with those in other age groups, indicating their bioavailability and bioaccumulation. Lung Pb and Cd concentrations measured in 5-yo pigeons collected from Guangzhou during 2015 were significantly lower than concentrations reported in 5-yo homing pigeons collected from Guangzhou during 2011 and correlated with concentrations measured using mechanical air monitoring. In addition to temporal differences, spatial differences in concentrations of Cd, Pb, and Hg reported in ambient air samples and in pigeon lung tissues collected from Beijing and Guangzhou are discussed.

Lung function testing according leptin levels in patients with chronic obstructive pulmonary disease

Directory of Open Access Journals (Sweden)

O. Radchenko

2017-02-01

Full Text Available Chronic obstructive pulmonary disease (COPD belongs to urgent medical and social problems of our time. Prognosis of COPD is often determined by a comorbidity, in particular obesity. The key chain, which unites COPD and obesity, is systemic inflammation, in the development of which the hormone of fatty tissue leptin plays an important role. The presence of receptors to leptin in the alveolar and bronchial epithelial cells, in smooth muscle tissue and submucous bronchial membrane allowes to assume that leptin takes pathogenetic part in COPD progression. The aim of our research was to estimate the leptin level in COPD patient and analyze changes of the respiratory function depending on it. Methods. We have been examined 26 patients with exacerbation of COPD (13 male and 13 female, 58 y.o. and 20 healthy people representative by gender, age and body mass. The level of serum leptin has been defined by the solid phase enzyme linked immunosorbent analysis, lung function – by computed testing. Results and conclusion. With the leptin level increase all of the lung function parameters progressively decreased, most significant - forced vital capacity and peak expiratory flow. Patients with hyperleptinemia had significantly lower measurements of forced expiratory volume in 1 second and vital lungs capacity. Severe degree of both obstructive and restrictive changes has been found more often among patients with hyperleptinemia and leptin level has been associated with the bronchial obstruction severity.

Human adipose tissue mesenchymal stromal cells and their extracellular vesicles act differentially on lung mechanics and inflammation in experimental allergic asthma.

Science.gov (United States)

de Castro, Ligia Lins; Xisto, Debora Gonçalves; Kitoko, Jamil Zola; Cruz, Fernanda Ferreira; Olsen, Priscilla Christina; Redondo, Patricia Albuquerque Garcia; Ferreira, Tatiana Paula Teixeira; Weiss, Daniel Jay; Martins, Marco Aurélio; Morales, Marcelo Marcos; Rocco, Patricia Rieken Macedo

2017-06-24

Asthma is a chronic inflammatory disease that can be difficult to treat due to its complex pathophysiology. Most current drugs focus on controlling the inflammatory process, but are unable to revert the changes of tissue remodeling. Human mesenchymal stromal cells (MSCs) are effective at reducing inflammation and tissue remodeling; nevertheless, no study has evaluated the therapeutic effects of extracellular vesicles (EVs) obtained from human adipose tissue-derived MSCs (AD-MSC) on established airway remodeling in experimental allergic asthma. C57BL/6 female mice were sensitized and challenged with ovalbumin (OVA). Control (CTRL) animals received saline solution using the same protocol. One day after the last challenge, each group received saline, 10 5 human AD-MSCs, or EVs (released by 10 5  AD-MSCs). Seven days after treatment, animals were anesthetized for lung function assessment and subsequently euthanized. Bronchoalveolar lavage fluid (BALF), lungs, thymus, and mediastinal lymph nodes were harvested for analysis of inflammation. Collagen fiber content of airways and lung parenchyma were also evaluated. In OVA animals, AD-MSCs and EVs acted differently on static lung elastance and on BALF regulatory T cells, CD3 + CD4 + T cells, and pro-inflammatory mediators (interleukin [IL]-4, IL-5, IL-13, and eotaxin), but similarly reduced eosinophils in lung tissue, collagen fiber content in airways and lung parenchyma, levels of transforming growth factor-β in lung tissue, and CD3 + CD4 + T cell counts in the thymus. No significant changes were observed in total cell count or percentage of CD3 + CD4 + T cells in the mediastinal lymph nodes. In this immunocompetent mouse model of allergic asthma, human AD-MSCs and EVs effectively reduced eosinophil counts in lung tissue and BALF and modulated airway remodeling, but their effects on T cells differed in lung and thymus. EVs may hold promise for asthma; however, further studies are required to elucidate the different

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

Directory of Open Access Journals (Sweden)

Xiaolin He

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

Ectopic Intrathoracic Hepatic Tissue and Accessory Lung Lobe Aplasia in a Dog.

Science.gov (United States)

Lande, Rachel; Dvorak, Laura; Gardiner, David W; Bahr, Anne

2015-01-01

A 6 yr old male Yorkshire terrier was presented for an ~6 yr history of progressive cough and dyspnea. Thoracic radiographs revealed a 6 cm diameter mass within the right caudal thorax. Thoracic ultrasound identified an intrathoracic mass ultrasonographically consistent with liver tissue and a chronic diaphragmatic hernia was suspected. Exploratory laparotomy was performed, but no evidence of a diaphragmatic hernia was identified. Thoracic exploration identified abnormal lung parenchyma. The accessory lung lobe was removed using a stapling devise near its base. The consolidated mass had the gross appearance of liver and was histologically identified as ectopic hepatic tissue. Ectopic hepatic tissue, unlike ectopic splenic and pancreatic tissue, is rare and generally has a subdiaphragmatic distribution. This solitary case report demonstrates that ectopic intrathoracic hepatic tissue should be considered a differential diagnosis for a caudal mediastinal mass.

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

International Nuclear Information System (INIS)

Rangel, M.P.; Sá, V.K. de; Martins, V.; Martins, J.R.M.; Parra, E.R.; Mendes, A.; Andrade, P.C.; Reis, R.M.; Longatto-Filho, A.; Oliveira, C.Z.; Takagaki, T.; Carraro, D.M.; Nader, H.B.; Capelozzi, V.L.

2015-01-01

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

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.

Soluble TGF-β type II receptor gene therapy reduces TGF-β activity in irradiated lung tissue and protects lungs from radiation-induced injury

International Nuclear Information System (INIS)

Vujaskovic, Z.; Rabbani, Z.; Zhang, X.; Samulski, T.V.; Li, C.-Y.; Anscher, M.S.

2003-01-01

Full text: The objective was to determine whether administration of recombinant human adenoviral vector carrying soluble TGF-β1 type II receptor (TβR-II) gene reduces availability of active TGFβ1 and protects lung from radiation-induced injury. Female Fisher-344 rats were randomized into four groups to receive: 1) Control 2) Adenoviral green fluorescent protein vector (AdGFP) alone 3) Radiation (RT) + Adenoviral vector with TGF-β1 type II receptor gene (AdexTβR-II-Fc) 4) RT alone. Animals were irradiated to right hemithorax using a single dose of 30 Gy. The packaging and production of a recombinant adenovirus carrying the fused human TβR-II-IgG1 Fc gene was achieved by use of the AdEasy system. The treatment vector AdexTbR-II-Fc (1.5*1010 PFU) and control vector AdGFP (1*109 PFU) were injected i.v. 24 hrs after RT. Respiratory rate was measured as an index of pulmonary function weekly for 5 weeks post RT. Structural damage was scored histologically. Immunohistochemistry was performed to identify activated macrophages. ELISA was used to quantify active TGF-β1 in tissue homogenate. Western blot was used to determine TβR-II expression in plasma and lung tissue. Animals receiving treatment vector AdexTbR-II-Fc have elevated plasma levels of soluble TβR-II at 24 and 48 hours after injection. In the RT+AdexTbR-II-Fc group, there was a significant reduction in respiratory rate (p = 0.002) at four weeks after treatment compared to RT alone group. Histology revealed a significant reduction in lung structural damage in animals receiving gene therapy after RT vs RT alone (p=0.0013). There was also a decrease in the number of activated macrophage (p= 0.02) in RT+AdexTbR-II-Fc group vs RT alone. The tissue protein expression of active TGF-β1 was significantly reduced in rats receiving RT+AdexTbR-II-Fc treatment (p<0.05). This study shows the ability of adenovirus mediated soluble TβR-II gene therapy to reduce tissue levels of active TGF-β1 and ameliorate radiation

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

Science.gov (United States)

2012-01-01

Background 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. Methods Elastin fragments were identified by mass-spectrometry and one sequence, generated by MMP-9 and -12 (ELN-441), was selected for monoclonal antibody generation and used in the development of an ELISA. Soluble and insoluble elastin from lung was cleaved in vitro and the time-dependent release of fragments was assessed in the ELN-441 assay. The release of ELN-441 in human serum from patients with chronic obstructive pulmonary disease (COPD) (n = 10) and idiopathic pulmonary fibrosis (IPF) (n = 29) were compared to healthy matched controls (n = 11). Results The sequence ELN-441 was exclusively generated by MMP-9 and -12 and was time-dependently released from soluble lung elastin. ELN-441 levels were 287% higher in patients diagnosed with COPD (p elastin. This fragment was elevated in serum from patients with the lung diseases IPF and COPD, however these data needs to be validated in larger clinical settings. PMID:22818364

A 3D Human Lung Tissue Model for Functional Studies on Mycobacterium tuberculosis Infection.

Science.gov (United States)

Braian, Clara; Svensson, Mattias; Brighenti, Susanna; Lerm, Maria; Parasa, Venkata R

2015-10-05

Tuberculosis (TB) still holds a major threat to the health of people worldwide, and there is a need for cost-efficient but reliable models to help us understand the disease mechanisms and advance the discoveries of new treatment options. In vitro cell cultures of monolayers or co-cultures lack the three-dimensional (3D) environment and tissue responses. Herein, we describe an innovative in vitro model of a human lung tissue, which holds promise to be an effective tool for studying the complex events that occur during infection with Mycobacterium tuberculosis (M. tuberculosis). The 3D tissue model consists of tissue-specific epithelial cells and fibroblasts, which are cultured in a matrix of collagen on top of a porous membrane. Upon air exposure, the epithelial cells stratify and secrete mucus at the apical side. By introducing human primary macrophages infected with M. tuberculosis to the tissue model, we have shown that immune cells migrate into the infected-tissue and form early stages of TB granuloma. These structures recapitulate the distinct feature of human TB, the granuloma, which is fundamentally different or not commonly observed in widely used experimental animal models. This organotypic culture method enables the 3D visualization and robust quantitative analysis that provides pivotal information on spatial and temporal features of host cell-pathogen interactions. Taken together, the lung tissue model provides a physiologically relevant tissue micro-environment for studies on TB. Thus, the lung tissue model has potential implications for both basic mechanistic and applied studies. Importantly, the model allows addition or manipulation of individual cell types, which thereby widens its use for modelling a variety of infectious diseases that affect the lungs.

Effect of ghrelin on inflammatory response in lung contusion

Directory of Open Access Journals (Sweden)

Berrak Guven

2013-02-01

Full Text Available The purpose of this study was to investigate the effects of ghrelin on inflammatory response and tissue damage following trauma-induced acute lung injury. Thirty male wistar albino rats (300–400 g were randomly assigned into three groups: control group (n = 6, lung contusion plus saline (saline-treated, n = 12, and lung contusion plus ghrelin (ghrelin-treated, n = 12. Saline- or ghrelin-treated traumatic rats were sacrificed at two time points (24 and 72 hours after lung contusion. Blood was collected for the analysis of serum adenosine deaminase (ADA. Tissue transforming growth factor-beta 1 (TGF-β1 and matrix metalloproteinase-2 (MMP-2 levels were measured by enzyme-linked immunosorbent assay and histopathological examination was performed on the lung tissue samples. Our results indicated that ghrelin significantly reduced morphologic damages. Serum ADA activities were significantly decreased after lung contusion and this decline started early with ghrelin treatment. TGF-β1 and MMP-2 levels in lung tissue were elevated at 72 hours after lung contusion and treatment with ghrelin significantly increased TGF-β1 level and reduced MMP-2 level. In conclusion, our study demonstrates that acute lung injury initiated proinflammatory responses and ghrelin administration showed an anti-inflammatory effect in lung contusion.

Oxidative DNA damage in lung tissue from patients with COPD is clustered in functionally significant sequences

Directory of Open Access Journals (Sweden)

Viktor M Pastukh

2011-03-01

Full Text Available Viktor M Pastukh1, Li Zhang2, Mykhaylo V Ruchko1, Olena Gorodnya1, Gina C Bardwell1, Rubin M Tuder2, Mark N Gillespie11Department of Pharmacology and Center for Lung Biology, University of South Alabama College of Medicine, Mobile, AL, USA; 2Program in Translational Lung Research, Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado at Denver, Aurora, CO, USAAbstract: Lung tissue from COPD patients displays oxidative DNA damage. The present study determined whether oxidative DNA damage was randomly distributed or whether it was localized in specific sequences in either the nuclear or mitochondrial genomes. The DNA damage-specific histone, gamma-H2AX, was detected immunohistochemically in alveolar wall cells in lung tissue from COPD patients but not control subjects. A PCR-based method was used to search for oxidized purine base products in selected 200 bp sequences in promoters and coding regions of the VEGF, TGF-β1, HO-1, Egr1, and β-actin genes while quantitative Southern blot analysis was used to detect oxidative damage to the mitochondrial genome in lung tissue from control subjects and COPD patients. Among the nuclear genes examined, oxidative damage was detected in only 1 sequence in lung tissue from COPD patients: the hypoxic response element (HRE of the VEGF promoter. The content of VEGF mRNA also was reduced in COPD lung tissue. Mitochondrial DNA content was unaltered in COPD lung tissue, but there was a substantial increase in mitochondrial DNA strand breaks and/or abasic sites. These findings show that oxidative DNA damage in COPD lungs is prominent in the HRE of the VEGF promoter and in the mitochondrial genome and raise the intriguing possibility that genome and sequence-specific oxidative DNA damage could contribute to transcriptional dysregulation and cell fate decisions in COPD.Keywords: DNA damage, VEGF hypoxic response element, mtDNA, COPD

N-isopropyl-p-iodoamphetamine receptors in normal and cancerous tissue of the human lung

Energy Technology Data Exchange (ETDEWEB)

Tanaka, Eiko; Mishima, Michiaki; Kawakami, Kenzo; Sakai, Naoki; Sugiura, Naoharu; Kuno, Kenshi [Kyoto Univ. (Japan). Dept. of Clinical Physiology; Taniguchi, Takashi [Kyoto Pharmaceutical Univ. (Japan). Dept. of Neurobiology

1993-04-01

N-Isopropyl-p-iodoamphetamine (IMP) receptors in normal human lung tissue were characterized using a radioligand binding assay with iodine-125 IMP as the ligand. Saturation binding studies revealed the presence of two binding sites with dissociation constant (K[sub d]) values of 53[+-]2 and 4687[+-]124 nM and maximum binding capacity (Bmax) values of 7[+-]1 and 133[+-]27 pmol/mg protein (n=5) respectively. The IC[sub 50] values of various amines were as follows: IMP, 9x10[sup -5] M; propranolol, 5x10[sup -4] M; haloperidol, 6x10[sup -4] M; ketamine, 9x10[sup -3] M; dopamine, 1x10[sup -2] M. The IMP receptors of cancerous tissue obtained from human lung also had two binding sites with K[sub d] values of 54[+-]2 and 5277[+-]652 nM and Bmax values of 7[+-]1 and 103[+-]21 pmol/mg protein (n=3) respectively. There was no significant difference in binding parameters between normal and cancerous lung tissue. These results demonstrate the existence of IMP receptors and suggest that cancer does not affect the nature of IMP receptors in human lung tissue. (orig.).

A morphological study of bronchi and lung tissues in long-term survived dogs

OpenAIRE

松本, 伸

1984-01-01

Morphological changes of the bronchus and lung tissue of ten adult dogs were examined at various intervals after sleeve resection of the left upper lobe was performed in combination with bronchoplasty and pulmonary artery angioplasty. Postoperative changes in the bronchus and pulmonary artery were investigated by bronchoscopy and pulmonary angiography 8 months to 14 months after the operation. The dogs were sacrificed 9 months to 32 months after the operation, and the bronchus and lung tissue...

Progress in Tissue Specimens Alternative for the Driver Genes Testing of Non-small Cell Lung Cancer

Directory of Open Access Journals (Sweden)

Yan SUN

2015-06-01

Full Text Available Target treatment based on driver genes in advanced non-small cell lung cancer is very important currently. Tumor tissues is the gold standard for driver genes testing. However, most of patients could not get the gene information for lack of enough tissues. To explore the tissue specimens alternatives is a hot spot in clinical work. This report reviews the tissue specimen alternatives of driver gene testing in non-small cell lung cancer.

Obesity And Laboratory Diets Affects Tissue Malondialdehyde (MDA) Levels In Obese Rats

Science.gov (United States)

Chowdhury, Parimal; Scott, Joseph; Holley, Andy; Hakkak, Reza

2010-04-01

This study was conducted to investigate the interaction of obesity and laboratory diets on tissue malondialdehyde levels in rats. Female Zucker obese and lean rats were maintained on either regular grain-based diet or purified casein diet for two weeks, orally gavaged at day 50 with 65 mg/kg DMBA and sacrificed 24 hrs later. Malondialdehyde (MDA) levels were measured in blood and harvested tissues. Data were recorded as mean ± SEM and analyzed statistically. Results show that the obese group on purified casein diet had reduction of MDA levels in the brain, duodenum, liver, lung and kidney tissues as compared to lean group, p <0.05. Obese group on grain-based diet showed significant increase in MDA levels only in the duodenum, p <0.05. We conclude that dietary intervention differentially affects the oxidative markers in obese rats. It appears that purified casein diets were more effective than grain-based diet in reduction of oxidative stress in obese rats.

Connective tissue-activating peptide III: a novel blood biomarker for early lung cancer detection.

Science.gov (United States)

Yee, John; Sadar, Marianne D; Sin, Don D; Kuzyk, Michael; Xing, Li; Kondra, Jennifer; McWilliams, Annette; Man, S F Paul; Lam, Stephen

2009-06-10

There are no reliable blood biomarkers to detect early lung cancer. We used a novel strategy that allows discovery of differentially present proteins against a complex and variable background. Mass spectrometry analyses of paired pulmonary venous-radial arterial blood from 16 lung cancer patients were applied to identify plasma proteins potentially derived from the tumor microenvironment. Two differentially expressed proteins were confirmed in 64 paired venous-arterial blood samples using an immunoassay. Twenty-eight pre- and postsurgical resection peripheral blood samples and two independent, blinded sets of plasma from 149 participants in a lung cancer screening study (49 lung cancers and 100 controls) and 266 participants from the National Heart Lung and Blood Institute Lung Health Study (45 lung cancer and 221 matched controls) determined the accuracy of the two protein markers to detect subclinical lung cancer. Connective tissue-activating peptide III (CTAP III)/ neutrophil activating protein-2 (NAP-2) and haptoglobin were identified to be significantly higher in venous than in arterial blood. CTAP III/NAP-2 levels decreased after tumor resection (P = .01). In two independent population cohorts, CTAP III/NAP-2 was significantly associated with lung cancer and improved the accuracy of a lung cancer risk prediction model that included age, smoking, lung function (FEV(1)), and an interaction term between FEV(1) and CTAP III/NAP-2 (area under the curve, 0.84; 95% CI, 0.77 to 0.91) compared to CAPIII/NAP-2 alone. We identified CTAP III/NAP-2 as a novel biomarker to detect preclinical lung cancer. The study underscores the importance of applying blood biomarkers as part of a multimodal lung cancer risk prediction model instead of as stand-alone tests.

Validation of freezing tissues and cells for analysis of DNA strand break levels by comet assay

Science.gov (United States)

Jackson, Petra

2013-01-01

The comet analysis of DNA strand break levels in tissues and cells has become a common method of screening for genotoxicity. The large majority of published studies have used fresh tissues and cells processed immediately after collection. However, we have used frozen tissues and cells for more than 10 years, and we believe that freezing samples improve efficiency of the method. We compared DNA strand break levels measured in fresh and frozen bronchoalveolar cells, and lung and liver tissues from mice exposed to the known mutagen methyl methanesulphonate (0, 25, 75, 112.5mg/kg). We used a high-throughput comet protocol with fully automated scoring of DNA strand break levels. The overall results from fresh and frozen samples were in agreement [R 2 = 0.93 for %DNA in tail (%TDNA) and R 2 = 0.78 for tail length (TL)]. A slightly increased %TDNA was observed in lung and liver tissue from vehicle controls; and TL was slightly reduced in bronchoalveolar lavage cells from the high-dose group. In our comet protocol, a small block of tissue designated for comet analysis is frozen immediately at tissue collection and kept deep frozen until rapidly homogenised and embedded in agarose. To demonstrate the feasibility of long-term freezing of samples, we analysed the day-to-day variation of our internal historical negative and positive comet assay controls collected over a 10-year period (1128 observations, 11 batches of frozen untreated and H2O2-treated A549 lung epithelial cells). The H2O2 treatment explained most of the variation 57–77% and the day-to-day variation was only 2–12%. The presented protocol allows analysis of samples collected over longer time span, at different locations, with reduced variation by reducing number of electrophoreses and is suitable for both toxicological and epidemiological studies. The use of frozen tissues; however, requires great care during preparation before analysis, with handling as a major risk factor. PMID:24136994

Losartan Attenuates Degradation of Aorta and Lung Tissue Micromechanics in a Mouse Model of Severe Marfan Syndrome.

Science.gov (United States)

Lee, Jia-Jye; Galatioto, Josephine; Rao, Satish; Ramirez, Francesco; Costa, Kevin D

2016-10-01

Marfan syndrome (MFS) is an autosomal dominant disease of the connective tissue due to mutations in the fibrillin-1 gene (FBN1). This study aimed at characterizing microelastic properties of the ascending aortic wall and lung parenchyma tissues from wild type (WT) and age-matched Fbn1 hypomorphic mice (Fbn1(mgR/mgR) mice) to identify tissue-specific biomechanical effects of aging and disease in MFS. Atomic force microscopy was used to indent lung parenchyma and aortic wall tissues, using Hybrid Eshelby Decomposition analysis to extract layer-specific properties of the intima and media. The intima stiffened with age and was not different between WT and Fbn1(mgR/mgR) tissues, whereas the media layer of MFS aortas showed progressive structural and mechanical degradation with a modulus that was 50% softer than WT by 3.5 months of age. Similarly, MFS mice displayed progressive structural and mechanical deterioration of lung tissue, which was over 85% softer than WT by 3.5 months of age. Chronic treatment with the angiotensin type I receptor antagonist, losartan, attenuated the aorta and lung tissue degradation, resulting in structural and mechanical properties not significantly different from age-matched WT controls. By revealing micromechanical softening of elastin-rich aorta and lung tissues with disease progression in fibrillin-1 deficient mice, our findings support the use of losartan as a prophylactic treatment that may abrogate the life-threatening symptoms of MFS.

Tracking lung tissue motion and expansion/compression with inverse consistent image registration and spirometry.

Science.gov (United States)

Christensen, Gary E; Song, Joo Hyun; Lu, Wei; El Naqa, Issam; Low, Daniel A

2007-06-01

Breathing motion is one of the major limiting factors for reducing dose and irradiation of normal tissue for conventional conformal radiotherapy. This paper describes a relationship between tracking lung motion using spirometry data and image registration of consecutive CT image volumes collected from a multislice CT scanner over multiple breathing periods. Temporal CT sequences from 5 individuals were analyzed in this study. The couch was moved from 11 to 14 different positions to image the entire lung. At each couch position, 15 image volumes were collected over approximately 3 breathing periods. It is assumed that the expansion and contraction of lung tissue can be modeled as an elastic material. Furthermore, it is assumed that the deformation of the lung is small over one-fifth of a breathing period and therefore the motion of the lung can be adequately modeled using a small deformation linear elastic model. The small deformation inverse consistent linear elastic image registration algorithm is therefore well suited for this problem and was used to register consecutive image scans. The pointwise expansion and compression of lung tissue was measured by computing the Jacobian of the transformations used to register the images. The logarithm of the Jacobian was computed so that expansion and compression of the lung were scaled equally. The log-Jacobian was computed at each voxel in the volume to produce a map of the local expansion and compression of the lung during the breathing period. These log-Jacobian images demonstrate that the lung does not expand uniformly during the breathing period, but rather expands and contracts locally at different rates during inhalation and exhalation. The log-Jacobian numbers were averaged over a cross section of the lung to produce an estimate of the average expansion or compression from one time point to the next and compared to the air flow rate measured by spirometry. In four out of five individuals, the average log

Tracking lung tissue motion and expansion/compression with inverse consistent image registration and spirometry

International Nuclear Information System (INIS)

Christensen, Gary E.; Song, Joo Hyun; Lu, Wei; Naqa, Issam El; Low, Daniel A.

2007-01-01

Breathing motion is one of the major limiting factors for reducing dose and irradiation of normal tissue for conventional conformal radiotherapy. This paper describes a relationship between tracking lung motion using spirometry data and image registration of consecutive CT image volumes collected from a multislice CT scanner over multiple breathing periods. Temporal CT sequences from 5 individuals were analyzed in this study. The couch was moved from 11 to 14 different positions to image the entire lung. At each couch position, 15 image volumes were collected over approximately 3 breathing periods. It is assumed that the expansion and contraction of lung tissue can be modeled as an elastic material. Furthermore, it is assumed that the deformation of the lung is small over one-fifth of a breathing period and therefore the motion of the lung can be adequately modeled using a small deformation linear elastic model. The small deformation inverse consistent linear elastic image registration algorithm is therefore well suited for this problem and was used to register consecutive image scans. The pointwise expansion and compression of lung tissue was measured by computing the Jacobian of the transformations used to register the images. The logarithm of the Jacobian was computed so that expansion and compression of the lung were scaled equally. The log-Jacobian was computed at each voxel in the volume to produce a map of the local expansion and compression of the lung during the breathing period. These log-Jacobian images demonstrate that the lung does not expand uniformly during the breathing period, but rather expands and contracts locally at different rates during inhalation and exhalation. The log-Jacobian numbers were averaged over a cross section of the lung to produce an estimate of the average expansion or compression from one time point to the next and compared to the air flow rate measured by spirometry. In four out of five individuals, the average log

Preanalytics in lung cancer.

Science.gov (United States)

Warth, Arne; Muley, Thomas; Meister, Michael; Weichert, Wilko

2015-01-01

Preanalytic sampling techniques and preparation of tissue specimens strongly influence analytical results in lung tissue diagnostics both on the morphological but also on the molecular level. However, in contrast to analytics where tremendous achievements in the last decade have led to a whole new portfolio of test methods, developments in preanalytics have been minimal. This is specifically unfortunate in lung cancer, where usually only small amounts of tissue are at hand and optimization in all processing steps is mandatory in order to increase the diagnostic yield. In the following, we provide a comprehensive overview on some aspects of preanalytics in lung cancer from the method of sampling over tissue processing to its impact on analytical test results. We specifically discuss the role of preanalytics in novel technologies like next-generation sequencing and in the state-of the-art cytology preparations. In addition, we point out specific problems in preanalytics which hamper further developments in the field of lung tissue diagnostics.

Detection of SiO2 nanoparticles in lung tissue by ToF-SIMS imaging and fluorescence microscopy.

Science.gov (United States)

Veith, Lothar; Vennemann, Antje; Breitenstein, Daniel; Engelhard, Carsten; Wiemann, Martin; Hagenhoff, Birgit

2017-07-10

The direct detection of nanoparticles in tissues at high spatial resolution is a current goal in nanotoxicology. Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) is widely used for the direct detection of inorganic and organic substances with high spatial resolution but its capability to detect nanoparticles in tissue sections is still insufficiently explored. To estimate the applicability of this technique for nanotoxicological questions, comparative studies with established techniques on the detection of nanoparticles can offer additional insights. Here, we compare ToF-SIMS imaging data with sub-micrometer spatial resolution to fluorescence microscopy imaging data to explore the usefulness of ToF-SIMS for the detection of nanoparticles in tissues. SiO 2 nanoparticles with a mean diameter of 25 nm, core-labelled with fluorescein isothiocyanate, were intratracheally instilled into rat lungs. Subsequently, imaging of lung cryosections was performed with ToF-SIMS and fluorescence microscopy. Nanoparticles were successfully detected with ToF-SIMS in 3D microanalysis mode based on the lateral distribution of SiO 3 - (m/z 75.96), which was co-localized with the distribution pattern that was obtained from nanoparticle fluorescence. In addition, the lateral distribution of protein (CN - , m/z 26.00) and phosphate based signals (PO 3 - , m/z 78.96) originating from the tissue material could be related to the SiO 3 - lateral distribution. In conclusion, ToF-SIMS is suitable to directly detect and laterally resolve SiO 2 nanomaterials in biological tissue at sufficient intensity levels. At the same time, information about the chemical environment of the nanoparticles in the lung tissue sections is obtained.

Cyclophosphamide for connective tissue disease-associated interstitial lung disease.

Science.gov (United States)

Barnes, Hayley; Holland, Anne E; Westall, Glen P; Goh, Nicole Sl; Glaspole, Ian N

2018-01-03

Approximately one-third of individuals with interstitial lung disease (ILD) have associated connective tissue disease (CTD). The connective tissue disorders most commonly associated with ILD include scleroderma/systemic sclerosis (SSc), rheumatoid arthritis, polymyositis/dermatomyositis, and Sjögren's syndrome. Although many people with CTD-ILD do not develop progressive lung disease, a significant proportion do progress, leading to reduced physical function, decreased quality of life, and death. ILD is now the major cause of death amongst individuals with systemic sclerosis.Cyclophosphamide is a highly potent immunosuppressant that has demonstrated efficacy in inducing and maintaining remission in autoimmune and inflammatory illnesses. However this comes with potential toxicities, including nausea, haemorrhagic cystitis, bladder cancer, bone marrow suppression, increased risk of opportunistic infections, and haematological and solid organ malignancies.Decision-making in the treatment of individuals with CTD-ILD is difficult; the clinician needs to identify those who will develop progressive disease, and to weigh up the balance between a high level of need for therapy in a severely unwell patient population against the potential for adverse effects from highly toxic therapy, for which only relatively limited data on efficacy can be found. Similarly, it is not clear whether histological subtype, disease duration, or disease extent can be used to predict treatment responsiveness. To assess the efficacy and adverse effects of cyclophosphamide in the treatment of individuals with CTD-ILD. We performed searches on CENTRAL, MEDLINE, Embase, CINAHL, and Web of Science up to May 2017. We handsearched review articles, clinical trial registries, and reference lists of retrieved articles. We included randomised controlled parallel-group trials that compared cyclophosphamide in any form, used individually or concomitantly with other immunomodulating therapies, versus non

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

BACKGROUND: Mesenchymal stem cells (MSC) have not only been implicated in the development of lung diseases, but they have also been proposed as a future cell-based therapy for lung diseases. However, the cellular identity of the primary MSC in human lung tissues has not yet been reported. This st......BACKGROUND: Mesenchymal stem cells (MSC) have not only been implicated in the development of lung diseases, but they have also been proposed as a future cell-based therapy for lung diseases. However, the cellular identity of the primary MSC in human lung tissues has not yet been reported...

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

[Effect of oxidative stress-associated damage to the lung tissue caused by different body mass index in the rat models].

Science.gov (United States)

Li, X Y; Zhang, X J; Zhao, J H; Xu, J Y

2016-12-12

Objective: To investigate the influence of different diets on serum protein expression levels of 4-hydroxynonenal (4-HNE), thioredoxin (Trx), thioredoxin reductase (TrxR) and the activities of Trx and TrxR, and to explore the effect of damage to the lung tissue and the underlying mechanisms of different body mass index caused by different diets in the rat models . Method: Healthy clean male SD rats were randomly divided into normal group, emaciation group and fat group, which were raised by different diets for 6 months.Then the rats were sacrificed and the serum and lung tissue were prepared. The levels of 4-HNE, Trx and TrxR in peripheral blood were quantitatively analyzed by enzyme-linked immunosorbent assay(ELISA), and the activities of Trx and TrxR were measured by chemical methods. Results: Compared with the normal group, the lung tissue had more apparent emphysema in the emaciation and the fat groups under light microscope, and more inflammatory cell infiltration in alveolar septum was observed in the fat group.The levels of 4-HNE in the fat group[(24.7±8.7)mg/L]was significantly higher than that in the normal group[(15.4±4.7)mg/L, P 0.05)in the levels of 4-HNE between the emaciation and the normal groups. The levels of TrxR in the emaciation group[(7.7±1.4)μg/ml]was significantly higher than that in the normal and the fat groups[(6.2±1.1), (4.9±1.4)μg/ml, all P 0.05). The activity of Trx in the emaciation group[(32.4±8.5)×10 -3 A ·min -1 ·mg -1 ]was significantly higher than that in the normal group[(19.6±3.3)×10 -3 A ·min -1 ·mg -1 ]and the fat group[(11.3±7.5)×10 -3 A ·min -1 ·mg -1 , all P 0.05). Conclusion: Both high BMI and low BMI can affect the oxidative stress of the body, resulting in increased oxidants and decreased antioxidants, and can cause damage to the lung tissue in the rat models.

Development of an experimental model of brain tissue heterotopia in the lung

Science.gov (United States)

Quemelo, Paulo Roberto Veiga; Sbragia, Lourenço; Peres, Luiz Cesar

2007-01-01

Summary The presence of heterotopic brain tissue in the lung is a rare abnormality. The cases reported thus far are usually associated with neural tube defects (NTD). As there are no reports of experimental models of NTD that present this abnormality, the objective of the present study was to develop a surgical method of brain tissue heterotopia in the lung. We used 24 pregnant Swiss mice divided into two groups of 12 animals each, denoted 17GD and 18GD according to the gestational day (GD) when caesarean section was performed to collect the fetuses. Surgery was performed on the 15th GD, one fetus was removed by hysterectomy and its brain tissue was cut into small fragments and implanted in the lung of its litter mates. Thirty-four live fetuses were obtained from the 17GD group. Of these, eight (23.5%) were used as control (C), eight (23.5%) were sham operated (S) and 18 (52.9%) were used for pulmonary brain tissue implantation (PBI). Thirty live fetuses were obtained from the females of the 18GD group. Of these, eight (26.6%) were C, eight (26.6%) S and 14 (46.6%) were used for PBI. Histological examination of the fetal trunks showed implantation of GFAP-positive brain tissue in 85% of the fetuses of the 17GD group and in 100% of those of the 18GD group, with no significant difference between groups for any of the parameters analysed. The experimental model proved to be efficient and of relatively simple execution, showing complete integration of the brain tissue with pulmonary and pleural tissue and thus representing a model that will permit the study of different aspects of cell implantation and interaction. PMID:17877535

Characterization of TLR-induced inflammatory responses in COPD and control lung tissue explants

Directory of Open Access Journals (Sweden)

Pomerenke A

2016-09-01

Full Text Available Anna Pomerenke,1 Simon R Lea,1 Sarah Herrick,2 Mark A Lindsay,3 Dave Singh1 1Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, Manchester Academic Health Science Centre, The University of Manchester and University Hospital of South Manchester, NHS Foundation Trust, 2Institute of Inflammation and Repair, Manchester Academic Health Science Centre, University of Manchester, Manchester, 3Department of Pharmacy and Pharmacology, University of Bath, Bath, UK Purpose: Viruses are a common cause of exacerbations in chronic obstructive pulmonary disease (COPD. They activate toll-like receptors (TLRs 3, 7, and 8, leading to a pro-inflammatory response. We have characterized the responses of TLR3 and TLR7/8 in lung tissue explants from COPD patients and control smokers.Methods: We prepared lung whole tissue explants (WTEs from patients undergoing surgery for confirmed or suspected lung cancer. In order to mimic the conditions of viral infection, we used poly(I:C for TLR3 stimulation and R848 for TLR7/8 stimulation. These TLR ligands were used alone and in combination. The effects of tumor necrosis factor α (TNFα neutralization and dexamethasone on TLR responses were examined. Inflammatory cytokine release was measured by enzyme-linked immunosorbent assay and gene expression by quantitative real-time polymerase chain reaction.Results: WTEs from COPD patients released higher levels of pro-inflammatory cytokines compared with WTEs from smokers. Activation of multiple TLRs led to a greater than additive release of TNFα and CCL5. TNFα neutralization and dexamethasone treatment decreased cytokine release.Conclusion: This WTE model shows an enhanced response of COPD compared with controls, suggesting an increased response to viral infection. There was amplification of innate immune responses with multiple TLR stimulation. Keywords: COPD, poly(I:C, R848, cytokines, lung explant

Serpine2 deficiency results in lung lymphocyte accumulation and bronchus-associated lymphoid tissue formation.

Science.gov (United States)

Solleti, Siva Kumar; Srisuma, Sorachai; Bhattacharya, Soumyaroop; Rangel-Moreno, Javier; Bijli, Kaiser M; Randall, Troy D; Rahman, Arshad; Mariani, Thomas J

2016-07-01

Serine proteinase inhibitor, clade E, member 2 (SERPINE2), is a cell- and extracellular matrix-associated inhibitor of thrombin. Although SERPINE2 is a candidate susceptibility gene for chronic obstructive pulmonary disease, the physiologic role of this protease inhibitor in lung development and homeostasis is unknown. We observed spontaneous monocytic-cell infiltration in the lungs of Serpine2-deficient (SE2(-/-)) mice, beginning at or before the time of lung maturity, which resulted in lesions that resembled bronchus-associated lymphoid tissue (BALT). The initiation of lymphocyte accumulation in the lungs of SE2(-/-) mice involved the excessive expression of chemokines, cytokines, and adhesion molecules that are essential for BALT induction, organization, and maintenance. BALT-like lesion formation in the lungs of SE2(-/-) mice was also associated with a significant increase in the activation of thrombin, a recognized target of SE2, and excess stimulation of NF-κB, a major regulator of chemokine expression and inflammation. Finally, systemic delivery of thrombin rapidly stimulated lung chemokine expression in vivo These data uncover a novel mechanism whereby loss of serine protease inhibition leads to lung lymphocyte accumulation.-Solleti, S. K., Srisuma, S., Bhattacharya, S., Rangel-Moreno, J., Bijli, K. M., Randall, T. D., Rahman, A., Mariani, T. J. Serpine2 deficiency results in lung lymphocyte accumulation and bronchus-associated lymphoid tissue formation. © FASEB.

Early and late effects of prenatal corticosteroid treatment on the microRNA profiles of lung tissue in rats

Science.gov (United States)

YU, HONG-REN; LI, SUNG-CHOU; TSENG, WAN-NING; TAIN, YOU-LIN; CHEN, CHIH-CHENG; SHEEN, JIUNN-MING; TIAO, MAO-MENG; KUO, HO-CHANG; HUANG, CHAO-CHENG; HSIEH, KAI-SHENG; HUANG, LI-TUNG

2016-01-01

Glucocorticoids have been administered to mothers at risk of premature delivery to induce maturation of preterm fetal lungs and prevent the development of respiratory distress syndrome. Micro (mi)RNAs serve various crucial functions in cell proliferation, differentiation and organ development; however, few studies have demonstrated an association between miRNAs and lung development. The aim of the present study was to investigate alterations in the miRNA profiles of rat lung tissue following prenatal glucocorticoid therapy for fetal lung development. The differences in miRNA expression profiles were compared between postnatal days 7 (D7) and 120 (D120) rat lung tissues, followed by validation using reverse transcription-quantitative polymerase chain reaction. The miRNA profiles of rat lung tissues following prenatal dexamethasone (DEX) therapy were also investigated. miRNAs with 2-fold changes were selected for further analysis. At D120, 6 upregulated and 6 downregulated miRNAs were detected, compared with D7. Among these differentially expressed miRNAs, miR-101-3p and miR-99b-5p were associated with the lowest and highest expressions of miRNA at D7, respectively. A limited impact on the miRNA profiles of rat lung tissues was observed following prenatal DEX treatment, which may help to further clarify the mechanisms underlying normal lung development. However, the results of the present study cannot entirely elucidate the effects of prenatal DEX treatment on the lung development of premature infants, and further studies investigating the impact of prenatal corticosteroids on fetal lung miRNA profiles are required. PMID:26997989

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

Science.gov (United States)

Kim, Kang-Hyun; Park, Tai Sun; Kim, You-Sun; Lee, Jae Seung; Oh, Yeon-Mok; Lee, Sang-Do; Lee, Sei Won

2016-01-01

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. 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. 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. RvD1 attenuated smoking-induced emphysema in vivo by reducing inflammation and promoting tissue regeneration. This result suggests that RvD1 may be useful in the prevention and treatment of emphysema.

Diagnostic value of combined determination of serum tumor markers (NSE, CA-242, TPA, CEA) levels in patients with lung cancer

International Nuclear Information System (INIS)

Liu Juzhen; Cai Tietie; Qin Shana

2007-01-01

Objective: To investigate the diagnostic value of combined determination of serum NSE, CA242, tissue polypeptide antigen (TPA) and CEA levels in patients with primary lung cancer. Methods: Serum NSE, CA242, TPA and CEA levels were determined with ELISA in (1) 102 patients with various types of primary lung carcinoma (adenocarcinoma 38, squamous cell carcinoma 32, small cell lung carcinoma 32) (2) 33 patients with open lung T. B. and (3) 30 controls. Results: (1) In patients with lung cancer, serum levels of all the four markers were increased and significantly higher than their respective values in patients with open lung T.B. and controls. (2) Positive rate of combined any two markers were 75% for adenocarcinoma, 50% for squamous cell carcinoma and 65% for small cell lung carcinoma, while false positive rate was only 9% for T.B patients and none for the controls. (3) The most appropriate single marker for each specific type of lung cancer was: NSE for SCLC (sensitivity 72%, specificity 97%, CA242 for adenocarcinoma sensitivity 62%, specificity 90%). Conclusion: Combined determination of these tumor markers would improve the sensitivity and specificity for diagnosis of primary lung carcinoma. (authors)

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

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

Response of rat lung tissue to short-term hyperoxia: a proteomic approach.

Science.gov (United States)

Spelten, Oliver; Wetsch, Wolfgang A; Wrettos, Georg; Kalenka, Armin; Hinkelbein, Jochen

2013-11-01

An inspiratory oxygen fraction of 1.0 is often required to avoid hypoxia both in many pre- and in-hospital situations. On the other hand, hyperoxia may lead to deleterious consequences (cell growth inhibition, inflammation, and apoptosis) for numerous tissues including the lung. Whereas clinical effects of hyperoxic lung injury are well known, its impact on the expression of lung proteins has not yet been evaluated sufficiently. The aim of this study was to analyze time-dependent alterations of protein expression in rat lung tissue after short-term normobaric hyperoxia (NH). After approval of the local ethics committee for animal research, N = 36 Wistar rats were randomized into six different groups: three groups with NH with exposure to 100 % oxygen for 3 h and three groups with normobaric normoxia (NN) with exposure to room air (21 % oxygen). After the end of the experiments, lungs were removed immediately (NH0 and NN0), after 3 days (NH3 and NN3) and after 7 days (NH7 and NN7). Lung lysates were analyzed by two-dimensional gel electrophoresis (2D-GE) followed by peptide mass fingerprinting using mass spectrometry. Statistical analysis was performed with Delta 2D (DECODON GmbH, Greifswald, Germany; ANOVA, Bonferroni correction, p pO2 was significantly higher in NH-groups compared to NN-groups (581 ± 28 vs. 98 ± 12 mmHg; p < 0.01), all other physiological parameters did not differ. Expression of 14 proteins were significantly altered: two proteins were up-regulated and 12 proteins were down-regulated. Even though NH was comparatively short termed, significant alterations in lung protein expression could be demonstrated up to 7 days after hyperoxia. The identified proteins indicate an association with cell growth inhibition, regulation of apoptosis, and approval of structural cell integrity.

CD4 T Cell Epitope Specificity and Cytokine Potential Are Preserved as Cells Transition from the Lung Vasculature to Lung Tissue following Influenza Virus Infection.

Science.gov (United States)

DiPiazza, Anthony; Laniewski, Nathan; Rattan, Ajitanuj; Topham, David J; Miller, Jim; Sant, Andrea J

2018-07-01

Pulmonary CD4 T cells are critical in respiratory virus control, both by delivering direct effector function and through coordinating responses of other immune cells. Recent studies have shown that following influenza virus infection, virus-specific CD4 T cells are partitioned between pulmonary vasculature and lung tissue. However, very little is known about the peptide specificity or functional differences of CD4 T cells within these two compartments. Using a mouse model of influenza virus infection in conjunction with intravascular labeling in vivo , the cell surface phenotype, epitope specificity, and functional potential of the endogenous polyclonal CD4 T cell response was examined by tracking nine independent CD4 T cell epitope specificities. These studies revealed that tissue-localized CD4 cells were globally distinct from vascular cells in expression of markers associated with transendothelial migration, residency, and micropositioning. Despite these differences, there was little evidence for remodeling of the viral epitope specificity or cytokine potential as cells transition from vasculature to the highly inflamed lung tissue. Our studies also distinguished cells in the pulmonary vasculature from peripheral circulating CD4 T cells, providing support for the concept that the pulmonary vasculature does not simply reflect circulating cells that are trapped within the narrow confines of capillary vessels but rather is enriched in transitional cells primed in the draining lymph node that have specialized potential to enter the lung tissue. IMPORTANCE CD4 T cells convey a multitude of functions in immunity to influenza, including those delivered in the lymph node and others conveyed by CD4 T cells that leave the lymph node, enter the blood, and extravasate into the lung tissue. Here, we show that the transition of recently primed CD4 cells detected in the lung vasculature undergo profound changes in expression of markers associated with tissue localization as

Dose-dependent induction of transforming growth factor β (TGF-β) in the lung tissue of fibrosis-prone mice after thoracic irradiation

International Nuclear Information System (INIS)

Ruebe, Claudia E.; Uthe, Daniela; Schmid, Kurt W.; Richter, Klaus D.; Wessel, Jan; Schuck, Andreas; Willich, Norman; Ruebe, Christian

2000-01-01

Purpose: The lung is the major dose-limiting organ for radiotherapy of cancer in the thoracic region. The pathogenesis of radiation-induced lung injury at the molecular level is still unclear. Immediate cellular damage after irradiation is supposed to result in cytokine-mediated multicellular interactions with induction and progression of fibrotic tissue reactions. The purpose of this investigation was to evaluate the acute and long-term effects of radiation on the gene expression of transforming growth factor beta (TGF-β) in a model of lung injury using fibrosis-sensitive C57BL/6 mice. Methods and Materials: The thoraces of C57BL/6 mice were irradiated with 6 and 12 Gy, respectively. Treated and sham-irradiated control mice were sacrificed at times corresponding to the latent period (1, 3, 6, 12, 24, 48, 72 hours and 1 week postirradiation), the pneumonic phase (2, 4, 8, and 16 weeks postirradiation), and the beginning of the fibrotic phase (24 weeks postirradiation). The lung tissue from three different mice per dosage and time point was analyzed by a combination of polymerase chain reaction (PCR), immunohistochemistry, and light microscopy. The mRNA expression of TGF-β was quantified by competitive reverse transcriptase/polymerase chain reaction (RT-PCR); the cellular origin of the TGF-β protein was identified by immunohistochemical staining (alkaline phosphatase-anti-alkaline phosphatase [APAAP]). The cytokine expression on mRNA and protein level was correlated with the histopathological alterations. Results: Following thoracic irradiation with a single dose of 12 Gy, radiation-induced TGF-β release in lung tissue was appreciable already within the first hours (1, 3, and 6 hours postirradiation) and reached a significant increase after 12 hours; subsequently (48 hours, 72 hours, and 1 week postirradiation) the TGF-β expression declined to basal levels. At the beginning of the pneumonic phase, irradiation-mediated stimulation of TGF-β release reached

5-Aza-2'-deoxycytidine protects against emphysema in mice via suppressing p16Ink4a expression in lung tissue

Directory of Open Access Journals (Sweden)

He ZH

2017-10-01

Full Text Available Zhi-Hui He,1 Yan Chen,2 Ping Chen,2 Sheng-Dong He,2 Hui-Hui Zeng,2 Ji-Ru Ye,2 Da Liu,2 Jun Cao3 1Intensive Care Unit, 2Department of Respiratory Medicine, Second Xiangya Hospital, Central South University, Changsha, 3Department of Respiratory Medicine, Hunan Provincial People’s Hospital, Changsha, China Background: There is a growing realization that COPD, or at least emphysema, involves several processes presenting in aging and cellular senescence. Endothelial progenitor cells (EPCs contribute to neovascularization and play an important role in the development of COPD. The gene for p16Ink4a is a major dominant senescence one. The aim of the present study was to observe changes in lung function, histomorphology of lung tissue, and expression of p16Ink4a in lung tissue and bone marrow-derived EPCs in emphysematous mice induced by cigarette-smoke extract (CSE, and further to search for a potential candidate agent protecting against emphysema induced by CSE. Materials and methods: An animal emphysema model was induced by intraperitoneal injection of CSE. 5-Aza-2'-deoxycytidine (5-Aza-CdR was administered to the emphysematous mice. Lung function and histomorphology of lung tissue were measured. The p16Ink4a protein and mRNA in EPCs and lung tissues were detected using Western blotting and quantitative reverse-transcription polymerase chain reaction, respectively. Results: CSE induced emphysema with increased p16Ink4a expression in lung tissue and bone marrow-derived EPCs. 5-Aza-CdR partly protected against emphysema, especially in the lung-morphology profile, and partly protest against the overexpression of p16Ink4a in EPCs and lung tissue induced by CSE. Conclusion: 5-Aza-CdR partly protected against emphysema in mice via suppressing p16Ink4a expression in EPCs and lung tissue. Keywords: 5-Aza-2'-deoxycytidine, cigarette smoke, emphysema, endothelial progenitor cells, p16Ink4a

The relationship among human papilloma virus infection, survivin, and p53 gene in lung squamous carcinoma tissue

International Nuclear Information System (INIS)

Yue-Hua Wang; De-jie Chen; Tie-Nan Yi

2010-01-01

To study the relationship between the infection of human papillomavirus (HPV) type 16, type 18, the expression of survivin, and the mutation of p53 gene in lung squamous carcinoma tissue for the research of pathogenesis of lung carcinoma.This study was carried out at the Laboratory of Molecular Biology, Xiangfan Central Hospital of Hubei Province, China from September 2008 to May 2010. Forty-five specimens of lung squamous carcinoma tissue confirmed by histopathology were the excisional specimens taken by the Thoracic Surgery of Xiangfan Central Hospital. Normal tissue, closely adjacent to the fresh carcinoma specimens, was used as the control group for p53 gene mutation analysis. Sixteen surgical excisional specimens of benign lung disease were used as a control group of non-carcinomatous diseases. Human papillomavirus DNA were detected by polymerase chain reaction (PCR), and we used the PCR-single-strand conformation polymorphism-ethidium bromide (PCR-SSCP-EB) method to detect the mutations of the p53 gene. The expression of the survivin gene was detected by immunohistochemistry methods. Approximately 68.9% of 45 lung squamous carcinoma tissue had p53 gene mutations. The mutation rate of exon 5-8 p53 were 15.6%, 17.8%, 15.6% and 20%. Approximately 42.2% of lung squamous cell carcinoma samples were shown to be positive for HPV DNA expression and 62.2% were positive for survivin expression. There was an inverse correlation between the presence of HPV infections and mutations of p53 gene; and the mutations of p53 gene and expression of survivin had a positive relationship. Mutation of p53 gene and HPV infection may facilitate each other in the generation of lung squamous cell carcinoma. Abnormal expression of the survivin gene may take part in the onset and progression of lung squamous cell carcinoma (Author).

Absorbed dose calculation of the energy deposition close to bone, lung and soft tissue interfaces in molecular radiotherapy

International Nuclear Information System (INIS)

Fernandez, M.; Lassman, M.

2015-01-01

Full text of publication follows. Aim: for voxel-based dosimetry in molecular radiotherapy (MRT) based on tabulated voxel S-values these values are usually obtained only for soft tissue. In order to study the changes in the dose deposition patterns at interfaces between different materials we have performed Monte Carlo simulations. Methods: the deposited energy patterns were obtained using the Monte-Carlo radiation code MCNPX v2.7 for Lu 177 (medium-energy) and Y 90 (high-energy). The following interfaces were studied: soft tissue-bone and soft tissue-lungs. For this purpose a volume of soft tissue homogeneously filled with Lu 177 or Y 90 was simulated at the interface to 3 different volumes containing no activity: soft tissue, lungs and bone. The emission was considered to be isotropic. The dimensions were chosen to ensure that the energy deposited by all generated particles was scored. The materials were defined as recommended by ICPR46; the decay schemes of Eckerman and Endo were used. With these data the absorbed dose patterns normalized to the maximum absorbed dose in the source region (soft tissue) were calculated. Results: the absorbed dose fractions in the boundary with soft tissue, bone and lungs are 50%, 47% and 57%, respectively, for Lu 177 and 50%, 47% and 51% for Y 90 . The distances to the interface at which the absorbed fractions are at 0.1% are 1.0, 0.6 and 3.0 mm for Lu 177 and 7.0, 4.0 and 24 mm for Y 90 , for soft tissue, bone and lungs respectively. Conclusions: in MRT, the changes in the absorbed doses at interfaces between soft tissue and bone/lungs need to be considered for isotopes emitting high energy particles. (authors)

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

Tissue spray ionization mass spectrometry for rapid recognition of human lung squamous cell carcinoma

Science.gov (United States)

Wei, Yiping; Chen, Liru; Zhou, Wei; Chingin, Konstantin; Ouyang, Yongzhong; Zhu, Tenggao; Wen, Hua; Ding, Jianhua; Xu, Jianjun; Chen, Huanwen

2015-05-01

Tissue spray ionization mass spectrometry (TSI-MS) directly on small tissue samples has been shown to provide highly specific molecular information. In this study, we apply this method to the analysis of 38 pairs of human lung squamous cell carcinoma tissue (cancer) and adjacent normal lung tissue (normal). The main components of pulmonary surfactants, dipalmitoyl phosphatidylcholine (DPPC, m/z 757.47), phosphatidylcholine (POPC, m/z 782.52), oleoyl phosphatidylcholine (DOPC, m/z 808.49), and arachidonic acid stearoyl phosphatidylcholine (SAPC, m/z 832.43), were identified using high-resolution tandem mass spectrometry. Monte Carlo sampling partial least squares linear discriminant analysis (PLS-LDA) was used to distinguish full-mass-range mass spectra of cancer samples from the mass spectra of normal tissues. With 5 principal components and 30 - 40 Monte Carlo samplings, the accuracy of cancer identification in matched tissue samples reached 94.42%. Classification of a tissue sample required less than 1 min, which is much faster than the analysis of frozen sections. The rapid, in situ diagnosis with minimal sample consumption provided by TSI-MS is advantageous for surgeons. TSI-MS allows them to make more informed decisions during surgery.

Decellularized Rat Lung Scaffolds Using Sodium Lauryl Ether Sulfate for Tissue Engineering.

Science.gov (United States)

Ma, Jinhui; Ju, Zhihai; Yu, Jie; Qiao, Yeru; Hou, Chenwei; Wang, Chen; Hei, Feilong

Perfusion decellularization with detergents is effective to maintain the architecture and proteins of extracellular matrix (ECM) for use in the field of lung tissue engineering (LTE). However, it is unclear which detergent is ideal to produce an acellular lung scaffold. In this study, we obtained two decellularized rat lung scaffolds using a novel detergent sodium lauryl ether sulfate (SLES) and a conventional detergent sodium dodecyl sulfate (SDS). Both decellularized lung scaffolds were assessed by histology, immunohistochemistry, scanning electron microscopy, DNA quantification, sulfated glycosaminoglycans (GAGs) quantification and western blot. Subsequently, the scaffolds were implanted subcutaneously in rats for 6 weeks and were evaluated via hematoxylin and eosin staining and Masson staining. Results indicated that SLES was effective to remove cells; moreover, lungs decellularized with SLES showed better preservation of sulfated GAGs, lung architecture, and ECM proteins than SDS. After 6 weeks, SLES scaffolds demonstrated a significantly greater potential for cell infiltration and blood vessel formation compared with SDS scaffolds. Taken together, we conclude that SLES is a promising detergent to produce an acellular scaffold using LTE for eventual transplantation.

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....

Reduced ischemia-reperfusion injury with isoproterenol in non-heart-beating donor lungs.

Science.gov (United States)

Jones, D R; Hoffmann, S C; Sellars, M; Egan, T M

1997-05-01

Transplantation of lungs retrieved from non-heart-beating donors could expand the donor pool. Recent studies suggest that the ischemia-reperfusion injury (IRI) to the lung can be attenuated by increasing intracellular cAMP concentrations. The purpose of this study was to determine the effect of IRI on capillary permeability, as measured by Kfc, in lungs retrieved from non-heart-beating donors and reperfused with or without isoproterenol (iso). Using an in situ isolated perfused lung model, lungs were retrieved from non-heart-beating donor rats ventilated with O2 or not at varying intervals after death. The lungs were reperfused with or without iso (10 microM). Kfc, lung viability, and pulmonary hemodynamics were measured, and tissue levels of adenine nucleotides and cAMP were measured by HPLC. Iso-reperfusion decreased Kfc significantly (P Kfc in non-iso-reperfused (r = 0.65) and iso-perfused (r = 0.84) lungs. cAMP levels increased significantly with iso-reperfusion. cAMP levels correlated with Kfc (r = 0.87) in iso-reperfused lungs. Iso-reperfusion of lungs retrieved from non-heart-beating donor rats results in decreased capillary permeability and increased lung tissue cAMP levels. Pharmacologic augmentation of tissue TAN and cAMP levels may further ameliorate the increased capillary permeability seen in lungs retrieved from non-heart-beating donors.

Real-time soft tissue motion estimation for lung tumors during radiotherapy delivery.

Science.gov (United States)

Rottmann, Joerg; Keall, Paul; Berbeco, Ross

2013-09-01

To provide real-time lung tumor motion estimation during radiotherapy treatment delivery without the need for implanted fiducial markers or additional imaging dose to the patient. 2D radiographs from the therapy beam's-eye-view (BEV) perspective are captured at a frame rate of 12.8 Hz with a frame grabber allowing direct RAM access to the image buffer. An in-house developed real-time soft tissue localization algorithm is utilized to calculate soft tissue displacement from these images in real-time. The system is tested with a Varian TX linear accelerator and an AS-1000 amorphous silicon electronic portal imaging device operating at a resolution of 512 × 384 pixels. The accuracy of the motion estimation is verified with a dynamic motion phantom. Clinical accuracy was tested on lung SBRT images acquired at 2 fps. Real-time lung tumor motion estimation from BEV images without fiducial markers is successfully demonstrated. For the phantom study, a mean tracking error real-time markerless lung tumor motion estimation from BEV images alone. The described system can operate at a frame rate of 12.8 Hz and does not require prior knowledge to establish traceable landmarks for tracking on the fly. The authors show that the geometric accuracy is similar to (or better than) previously published markerless algorithms not operating in real-time.

A 3D human tissue-engineered lung model to study influenza A infection.

Science.gov (United States)

Bhowmick, Rudra; Derakhshan, Mina; Liang, Yurong; Ritchey, Jerry; Liu, Lin; Gappa-Fahlenkamp, Heather

2018-05-05

Influenza A virus (IAV) claims approximately 250,000-500,000 lives annually worldwide. Currently, there are a few in vitro models available to study IAV immunopathology. Monolayer cultures of cell lines and primary lung cells (2D cell culture) is the most commonly used tool, however, this system does not have the in vivo-like structure of the lung and immune responses to IAV as it lacks the three-dimensional (3D) tissue structure. To recapitulate the lung physiology in vitro, a system that contains multiple cell types within a 3D environment that allows cell movement and interaction, would provide a critical tool. In this study, as a first step in designing a 3D-Human Tissue-Engineering Lung Model (3D-HTLM), we described the 3D culture of primary human small airway epithelial cells (HSAEpCs), and determined the immunophenotype of this system in response to IAV infections. We constructed a 3D chitosan-collagen scaffold and cultured HSAEpCs on these scaffolds at air-liquid interface (ALI). These 3D cultures were compared with 2D-cultured HSAEpCs for viability, morphology, marker protein expression, and cell differentiation. Results showed that the 3D-cultured HSAEpCs at ALI yielded maximum viable cells and morphologically resembled the in vivo lower airway epithelium. There were also significant increases in aquaporin-5 and cytokeratin-14 expression for HSAEpCs cultured in 3D compared to 2D. The 3D culture system was used to study the infection of HSAEpCs with two major IAV strains, H1N1 and H3N2.The HSAEpCs showed distinct changes in marker protein expression, both at mRNA and protein levels, and the release of proinflammatory cytokines. This study is the first step in the development of the 3D-HTLM, which will have wide applicability in studying pulmonary pathophysiology and therapeutics development.

Mesenchymal Stem Cells Adopt Lung Cell Phenotype in Normal and Radiation-induced Lung Injury Conditions.

Science.gov (United States)

Maria, Ola M; Maria, Ahmed M; Ybarra, Norma; Jeyaseelan, Krishinima; Lee, Sangkyu; Perez, Jessica; Shalaby, Mostafa Y; Lehnert, Shirley; Faria, Sergio; Serban, Monica; Seuntjens, Jan; El Naqa, Issam

2016-04-01

Lung tissue exposure to ionizing irradiation can invariably occur during the treatment of a variety of cancers leading to increased risk of radiation-induced lung disease (RILD). Mesenchymal stem cells (MSCs) possess the potential to differentiate into epithelial cells. However, cell culture methods of primary type II pneumocytes are slow and cannot provide a sufficient number of cells to regenerate damaged lungs. Moreover, effects of ablative radiation doses on the ability of MSCs to differentiate in vitro into lung cells have not been investigated yet. Therefore, an in vitro coculture system was used, where MSCs were physically separated from dissociated lung tissue obtained from either healthy or high ablative doses of 16 or 20 Gy whole thorax irradiated rats. Around 10±5% and 20±3% of cocultured MSCs demonstrated a change into lung-specific Clara and type II pneumocyte cells when MSCs were cocultured with healthy lung tissue. Interestingly, in cocultures with irradiated lung biopsies, the percentage of MSCs changed into Clara and type II pneumocytes cells increased to 40±7% and 50±6% at 16 Gy irradiation dose and 30±5% and 40±8% at 20 Gy irradiation dose, respectively. These data suggest that MSCs to lung cell differentiation is possible without cell fusion. In addition, 16 and 20 Gy whole thorax irradiation doses that can cause varying levels of RILD, induced different percentages of MSCs to adopt lung cell phenotype compared with healthy lung tissue, providing encouraging outlook for RILD therapeutic intervention for ablative radiotherapy prescriptions.

Investigating the bioavailability of graphene quantum dots in lung tissues via Fourier transform infrared spectroscopy.

Science.gov (United States)

Tabish, Tanveer A; Lin, Liangxu; Ali, Muhammad; Jabeen, Farhat; Ali, Muhammad; Iqbal, Rehana; Horsell, David W; Winyard, Paul G; Zhang, Shaowei

2018-06-06

Biomolecular fractions affect the fate and behaviour of quantum dots (QDs) in living systems but how the interactions between biomolecules and QDs affect the bioavailability of QDs is a major knowledge gap in risk assessment analysis. The transport of QDs after release into a living organism is a complex process. The majority accumulate in the lungs where they can directly affect the inhalation process and lung architecture. Here, we investigate the bioavailability of graphene quantum dots (GQDs) to the lungs of rats by measuring the alterations in macromolecular fractions via Fourier transform infrared spectroscopy (FTIR). GQDs were intravenously injected into the rats in a dose-dependent manner (low (5 mg kg -1 ) and high (15 mg kg -1 ) doses of GQDs per body weight of rat) for 7 days. The lung tissues were isolated, processed and haematoxylin-eosin stained for histological analysis to identify cell death. Key biochemical differences were identified by spectral signatures: pronounced changes in cholesterol were found in two cases of low and high doses; a change in phosphorylation profile of substrate proteins in the tissues was observed in low dose at 24 h. This is the first time biomolecules have been measured in biological tissue using FTIR to investigate the biocompatibility of foreign material. We found that highly accurate toxicological changes can be investigated with FTIR measurements of tissue sections. As a result, FTIR could form the basis of a non-invasive pre-diagnostic tool for predicting the toxicity of GQDs.

Metallic artifact mitigation and organ-constrained tissue assignment for Monte Carlo calculations of permanent implant lung brachytherapy

Energy Technology Data Exchange (ETDEWEB)

Sutherland, J. G. H.; Miksys, N.; Thomson, R. M., E-mail: rthomson@physics.carleton.ca [Carleton Laboratory for Radiotherapy Physics, Department of Physics, Carleton University, Ottawa, Ontario K1S 5B6 (Canada); Furutani, K. M. [Department of Radiation Oncology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905 (United States)

2014-01-15

Purpose: To investigate methods of generating accurate patient-specific computational phantoms for the Monte Carlo calculation of lung brachytherapy patient dose distributions. Methods: Four metallic artifact mitigation methods are applied to six lung brachytherapy patient computed tomography (CT) images: simple threshold replacement (STR) identifies high CT values in the vicinity of the seeds and replaces them with estimated true values; fan beam virtual sinogram replaces artifact-affected values in a virtual sinogram and performs a filtered back-projection to generate a corrected image; 3D median filter replaces voxel values that differ from the median value in a region of interest surrounding the voxel and then applies a second filter to reduce noise; and a combination of fan beam virtual sinogram and STR. Computational phantoms are generated from artifact-corrected and uncorrected images using several tissue assignment schemes: both lung-contour constrained and unconstrained global schemes are considered. Voxel mass densities are assigned based on voxel CT number or using the nominal tissue mass densities. Dose distributions are calculated using the EGSnrc user-code BrachyDose for{sup 125}I, {sup 103}Pd, and {sup 131}Cs seeds and are compared directly as well as through dose volume histograms and dose metrics for target volumes surrounding surgical sutures. Results: Metallic artifact mitigation techniques vary in ability to reduce artifacts while preserving tissue detail. Notably, images corrected with the fan beam virtual sinogram have reduced artifacts but residual artifacts near sources remain requiring additional use of STR; the 3D median filter removes artifacts but simultaneously removes detail in lung and bone. Doses vary considerably between computational phantoms with the largest differences arising from artifact-affected voxels assigned to bone in the vicinity of the seeds. Consequently, when metallic artifact reduction and constrained tissue

Modulation role of angelica sinensis on transforming growth factor beta 1 (TGF-β1) expression induced by radiation in the lung tissue

International Nuclear Information System (INIS)

Xie Conghua; Zhou Yunfeng; Peng Gang; Zhou Fuxiang; Zhang Gong; Liang Chen; Liu Hui; Chen Ji; Xia Mingtong

2005-01-01

Objective: To investigate the ability of Angelica Sinensis to affect the radiation- induced TGF-β 1 release in the animal model, so as to find an effective method to reduce the lung toxicity after thoracic irradiation. Methods: The thoraces of C57BL/6 mice were exposed to either sham irradiation or single fraction of 12 Gy. Four study groups were defined: those that received neither irradiation nor Angelica Sinensis (NT group), those that received Angelica Sinensis but no irradiation (AS group), those that underwent irradiation without Angelica Sinensis (XRT group) and those that received both Angelica Sinensis and irradiation (AS/XRT group). Treated and sham-irradiated control mice were sacrificed at times corresponding to the latent period (1, 24, 72 hours and 1 week postirradiation), the pneumonic phase (2, 4, 8, and 16 weeks postirradiation), and the beginning of the fibrotic phase (24 weeks postirradiation) . The TGF-β 1 mRNA expressions in the lung tissue were quantified by real-time quantitative reverse transcription polymerase chain reaction (RT-PCR). Immunohistochemical Streptavidin-Peroxidase method and positive cell counting were used for objective quantification of TGF-β 1 protein expression. Results: NT and AS groups exhibited low levels of TGF-β 1 protein expression with positive cell counts between 9 and 31. And there is an significantly elevated level of TGF-β 1 positive inflammatory cells in XRT group (P 1 in XRT group was significantly higher than the nonirradiated groups (P 1 response on mRNA level, but the statistical comparison of the TNF-αmRNA expression between the XRT and AS/XRT treatment-group was not significant (P=0.054). Conclusion: This study demonstrates a significant radiation-induced increase of TGF-β 1 (on mRNA and protein level) in the lung tissue, and the predominant localisation of TGF-β 1 in areas of inflammatory cell infiltrates suggests involvement of this cytokine in the pathogenesis of radiation-induced lung injury

Lung-protective perioperative mechanical ventilation

NARCIS (Netherlands)

Hemmes, S.N.T.

2015-01-01

Intraoperative ventilation has the potential to cause lung injury and possibly increase risk of pulmonary complications after surgery. Use of large tidal volumes could cause overdistension of lung tissue, which can be aggravated by too high levels of positive end-expiratory pressure (PEEP). Too low

HU deviation in lung and bone tissues: Characterization and a corrective strategy.

Science.gov (United States)

Ai, Hua A; Meier, Joseph G; Wendt, Richard E

2018-05-01

In the era of precision medicine, quantitative applications of x-ray Computed Tomography (CT) are on the rise. These require accurate measurement of the CT number, also known as the Hounsfield Unit. In this study, we evaluated the effect of patient attenuation-induced beam hardening of the x-ray spectrum on the accuracy of the HU values and a strategy to correct for the resulting deviations in the measured HU values. A CIRS electron density phantom was scanned on a Siemens Biograph mCT Flow CT scanner and a GE Discovery 710 CT scanner using standard techniques that are employed in the clinic to assess the HU deviation caused by beam hardening in different tissue types. In addition, an anthropomorphic ATOM adult male upper torso phantom was scanned on the GE Discovery 710 scanner. Various amounts of Superflab bolus material were wrapped around the phantoms to simulate different patient sizes. The mean HU values that were measured in the phantoms were evaluated as a function of the water-equivalent area (A w ), a parameter that is described in the report of AAPM Task Group 220. A strategy by which to correct the HU values was developed and tested. The variation in the HU values in the anthropomorphic ATOM phantom under different simulated body sizes, both before and after correction, were compared, with a focus on the lung and bone tissues. Significant HU deviations that depended on the simulated patient size were observed. A positive correlation between HU and A w was observed for tissue types that have an HU of less than zero, while a negative correlation was observed for tissue types with HU values that are greater than zero. The magnitude of the difference increases as the underlying attenuation property deviates further away from that of water. In the electron density phantom study, the maximum observed HU differences between the measured and reference values in the cortical bone and lung materials were 426 and 94 HU, respectively. In the anthropomorphic phantom

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.

Real-time soft tissue motion estimation for lung tumors during radiotherapy delivery

International Nuclear Information System (INIS)

Rottmann, Joerg; Berbeco, Ross; Keall, Paul

2013-01-01

Purpose: To provide real-time lung tumor motion estimation during radiotherapy treatment delivery without the need for implanted fiducial markers or additional imaging dose to the patient.Methods: 2D radiographs from the therapy beam's-eye-view (BEV) perspective are captured at a frame rate of 12.8 Hz with a frame grabber allowing direct RAM access to the image buffer. An in-house developed real-time soft tissue localization algorithm is utilized to calculate soft tissue displacement from these images in real-time. The system is tested with a Varian TX linear accelerator and an AS-1000 amorphous silicon electronic portal imaging device operating at a resolution of 512 × 384 pixels. The accuracy of the motion estimation is verified with a dynamic motion phantom. Clinical accuracy was tested on lung SBRT images acquired at 2 fps.Results: Real-time lung tumor motion estimation from BEV images without fiducial markers is successfully demonstrated. For the phantom study, a mean tracking error <1.0 mm [root mean square (rms) error of 0.3 mm] was observed. The tracking rms accuracy on BEV images from a lung SBRT patient (≈20 mm tumor motion range) is 1.0 mm.Conclusions: The authors demonstrate for the first time real-time markerless lung tumor motion estimation from BEV images alone. The described system can operate at a frame rate of 12.8 Hz and does not require prior knowledge to establish traceable landmarks for tracking on the fly. The authors show that the geometric accuracy is similar to (or better than) previously published markerless algorithms not operating in real-time

Real-time soft tissue motion estimation for lung tumors during radiotherapy delivery

Energy Technology Data Exchange (ETDEWEB)

Rottmann, Joerg; Berbeco, Ross [Brigham and Women' s Hospital, Dana Farber-Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115 (United States); Keall, Paul [Radiation Physics Laboratory, Sydney Medical School, University of Sydney, Sydney NSW 2006 (Australia)

2013-09-15

Purpose: To provide real-time lung tumor motion estimation during radiotherapy treatment delivery without the need for implanted fiducial markers or additional imaging dose to the patient.Methods: 2D radiographs from the therapy beam's-eye-view (BEV) perspective are captured at a frame rate of 12.8 Hz with a frame grabber allowing direct RAM access to the image buffer. An in-house developed real-time soft tissue localization algorithm is utilized to calculate soft tissue displacement from these images in real-time. The system is tested with a Varian TX linear accelerator and an AS-1000 amorphous silicon electronic portal imaging device operating at a resolution of 512 × 384 pixels. The accuracy of the motion estimation is verified with a dynamic motion phantom. Clinical accuracy was tested on lung SBRT images acquired at 2 fps.Results: Real-time lung tumor motion estimation from BEV images without fiducial markers is successfully demonstrated. For the phantom study, a mean tracking error <1.0 mm [root mean square (rms) error of 0.3 mm] was observed. The tracking rms accuracy on BEV images from a lung SBRT patient (≈20 mm tumor motion range) is 1.0 mm.Conclusions: The authors demonstrate for the first time real-time markerless lung tumor motion estimation from BEV images alone. The described system can operate at a frame rate of 12.8 Hz and does not require prior knowledge to establish traceable landmarks for tracking on the fly. The authors show that the geometric accuracy is similar to (or better than) previously published markerless algorithms not operating in real-time.

Significance of serum endostatin levels in patients with primary lung cancer

International Nuclear Information System (INIS)

Peng Qunxin; Ling Chunhua; Ji Cheng

2005-01-01

Objective: To investigate the relationship between the serum level of endostatin and the clinical pathophysiological characteristics in patients with primary lung cancer. Methods: The serum levels of endostatin were detected in 48 patients with primary lung cancer and 50 patients with benign pulmonary diseases by enzyme-linked immunosorbent assay (ELISA) method. Results: Serum endostatin level in patients with primary lung cancer was significantly higher than it in patients with benign pulmonary diseases (P<0.01). It was higher in adenocarcinoma group than that in squamous cell carcinoma and small cell carcinoma group (P<0.05). The level of serum endostatin in lung cancer with TNM stage III + IV was higher than that in patients in stage I + II (P<0.01). And it was also higher in patients suffering from lung cancer with metastasis than that in patients with no metastasis (P<0.05). However, there was not a significant relation between serum endostatin level the location of the tumor and lymph node metastasis. Conclusion: Serum endostatin level in expressed higher in patients with primary lung cancer. There is significant relationship between serum endostatin level, histological classification, TNM stage and metastasis of lung cancer. (authors)

Physical activity levels early after lung transplantation.

Science.gov (United States)

Wickerson, Lisa; Mathur, Sunita; Singer, Lianne G; Brooks, Dina

2015-04-01

Little is known of the early changes in physical activity after lung transplantation. The purposes of this study were: (1) to describe physical activity levels in patients up to 6 months following lung transplantation and (2) to explore predictors of the change in physical activity in that population. This was a prospective cohort study. Physical activity (daily steps and time spent in moderate-intensity activity) was measured using an accelerometer before and after transplantation (at hospital discharge, 3 months, and 6 months). Additional functional measurements included submaximal exercise capacity (measured with the 6-Minute Walk Test), quadriceps muscle torque, and health-related quality of life (measured with the Medical Outcomes Study 36-Item Short-Form Health Survey 36 [SF-36] and the St George's Respiratory Questionnaire). Thirty-six lung transplant recipients (18 men, 18 women; mean age=49 years, SD=14) completed posttransplant measurements. Before transplant, daily steps were less than a third of the general population. By 3 months posttransplant, the largest improvement in physical activity had occurred, and level of daily steps reached 55% of the general population. The change in daily steps (pretransplant to 3 months posttransplant) was inversely correlated with pretransplant 6-minute walk distance (r=-.48, P=.007), daily steps (r=-.36, P=.05), and SF-36 physical functioning (SF-36 PF) score (r=-.59, P=.0005). The SF-36 PF was a significant predictor of the change in physical activity, accounting for 35% of the variation in change in daily steps. Only individuals who were ambulatory prior to transplant and discharged from the hospital in less than 3 months were included in the study. Physical activity levels improve following lung transplantation, particularly in individuals with low self-reported physical functioning. However, the majority of lung transplant recipients remain sedentary between 3 to 6 months following transplant. The role of exercise

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

International Nuclear Information System (INIS)

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

2014-01-01

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

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.

Suppression subtractive hybridization identified differentially expressed genes in lung adenocarcinoma: ERGIC3 as a novel lung cancer-related gene

International Nuclear Information System (INIS)

Wu, Mingsong; Tu, Tao; Huang, Yunchao; Cao, Yi

2013-01-01

To understand the carcinogenesis caused by accumulated genetic and epigenetic alterations and seek novel biomarkers for various cancers, studying differentially expressed genes between cancerous and normal tissues is crucial. In the study, two cDNA libraries of lung cancer were constructed and screened for identification of differentially expressed genes. Two cDNA libraries of differentially expressed genes were constructed using lung adenocarcinoma tissue and adjacent nonmalignant lung tissue by suppression subtractive hybridization. The data of the cDNA libraries were then analyzed and compared using bioinformatics analysis. Levels of mRNA and protein were measured by quantitative real-time polymerase chain reaction (q-RT-PCR) and western blot respectively, as well as expression and localization of proteins were determined by immunostaining. Gene functions were investigated using proliferation and migration assays after gene silencing and gene over-expression. Two libraries of differentially expressed genes were obtained. The forward-subtracted library (FSL) and the reverse-subtracted library (RSL) contained 177 and 59 genes, respectively. Bioinformatic analysis demonstrated that these genes were involved in a wide range of cellular functions. The vast majority of these genes were newly identified to be abnormally expressed in lung cancer. In the first stage of the screening for 16 genes, we compared lung cancer tissues with their adjacent non-malignant tissues at the mRNA level, and found six genes (ERGIC3, DDR1, HSP90B1, SDC1, RPSA, and LPCAT1) from the FSL were significantly up-regulated while two genes (GPX3 and TIMP3) from the RSL were significantly down-regulated (P < 0.05). The ERGIC3 protein was also over-expressed in lung cancer tissues and cultured cells, and expression of ERGIC3 was correlated with the differentiated degree and histological type of lung cancer. The up-regulation of ERGIC3 could promote cellular migration and proliferation in vitro. The

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

Science.gov (United States)

Gorbunova, Vladlena; Lol, Pechin; Ashraf, Haseem; Dirksen, Asger; Nielsen, Mads; de Bruijne, Marleen

2008-01-01

We present a new image registration based method for monitoring regional disease progression in longitudinal image studies of lung disease. A free-form image registration technique is used to match a baseline 3D CT lung scan onto a following scan. Areas with lower intensity in the following scan compared with intensities in the deformed baseline image indicate local loss of lung tissue that is associated with progression of emphysema. To account for differences in lung intensity owing to differences in the inspiration level in the two scans rather than disease progression, we propose to adjust the density of lung tissue with respect to local expansion or compression such that the total weight of the lungs is preserved during deformation. Our method provides a good estimation of regional destruction of lung tissue for subjects with a significant difference in inspiration level between CT scans and may result in a more sensitive measure of disease progression than standard quantitative CT measures.

Isolation of Blastomyces dermatitidis yeast from lung tissue during murine infection for in vivo transcriptional profiling.

Science.gov (United States)

Marty, Amber J; Wüthrich, Marcel; Carmen, John C; Sullivan, Thomas D; Klein, Bruce S; Cuomo, Christina A; Gauthier, Gregory M

2013-07-01

Blastomyces dermatitidis belongs to a group of thermally dimorphic fungi that grow as sporulating mold in the soil and convert to pathogenic yeast in the lung following inhalation of spores. Knowledge about the molecular events important for fungal adaptation and survival in the host remains limited. The development of high-throughput analytic tools such as RNA sequencing (RNA-Seq) has potential to provide novel insight on fungal pathogenesis especially if applied in vivo during infection. However, in vivo transcriptional profiling is hindered by the low abundance of fungal cells relative to mammalian tissue and difficulty in isolating fungal cells from the tissues they infect. For the purpose of obtaining B. dermatitidis RNA for in vivo transcriptional analysis by RNA-Seq, we developed a simple technique for isolating yeast from murine lung tissue. Using a two-step approach of filtration and centrifugation following lysis of murine lung cells, 91% of yeast cells causing infection were isolated from lung tissue. B. dermatitidis recovered from the lung yielded high-quality RNA with minimal murine contamination and was suitable for RNA-Seq. Approximately 87% of the sequencing reads obtained from the recovered yeast aligned with the B. dermatitidis genome. This was similar to 93% alignment for yeast grown in vitro. The use of near-freezing temperature along with short ex vivo time minimized transcriptional changes that would have otherwise occurred with higher temperature or longer processing time. In conclusion, we have developed a technique that recovers the majority of yeast causing pulmonary infection and yields high-quality fungal RNA with minimal contamination by mammalian RNA. Copyright © 2013 Elsevier Inc. All rights reserved.

Abnormalities in lung volumes and airflow in children with newly diagnosed connective tissue disease.

Science.gov (United States)

Peradzyńska, Joanna; Krenke, Katarzyna; Szylling, Anna; Kołodziejczyk, Beata; Gazda, Agnieszka; Rutkowska-Sak, Lidia; Kulus, Marek

2016-01-01

Connective tissue diseases (CTDs) of childhood are rare inflammatory disorders, involving various organs and tissues including respiratory system. Pulmonary involvement in patients with CTDs is uncommon but may cause functional impairment. Data on prevalence and type of lung function abnormalities in children with CTDs are scarce. Thus, the aim of this study was to asses pulmonary functional status in children with newly diagnosed CTD and follow the results after two years of the disease course. There were 98 children (mean age: 13 ± 3; 76 girls), treated in Department of Pediatric Rheumatology, Institute of Rheumatology, Warsaw and 80 aged-matched, healthy controls (mean age 12.7 ± 2.4; 50 girls) included into the study. Study procedures included medical history, physical examination, chest radiograph and PFT (spirometry and whole body-plethysmography). Then, the assessment of PFT was performed after 24 months. FEV₁, FEV₁/FVC and MEF50 were significantly lower in CTD as compared to control group, there was no difference in FVC and TLC. The proportion of patients with abnormal lung function was significantly higher in the study group, 41 (42%) vs 9 (11%). 24-months observation didn't reveal progression in lung function impairment. Lung function impairment is relatively common in children with CTDs. Although restrictive ventilatory pattern is considered typical feature of lung involvement in CTDs, airflow limitation could also be an initial abnormality.

Sterilization of Lung Matrices by Supercritical Carbon Dioxide.

Science.gov (United States)

Balestrini, Jenna L; Liu, Angela; Gard, Ashley L; Huie, Janet; Blatt, Kelly M S; Schwan, Jonas; Zhao, Liping; Broekelmann, Tom J; Mecham, Robert P; Wilcox, Elise C; Niklason, Laura E

2016-03-01

Lung engineering is a potential alternative to transplantation for patients with end-stage pulmonary failure. Two challenges critical to the successful development of an engineered lung developed from a decellularized scaffold include (i) the suppression of resident infectious bioburden in the lung matrix, and (ii) the ability to sterilize decellularized tissues while preserving the essential biological and mechanical features intact. To date, the majority of lungs are sterilized using high concentrations of peracetic acid (PAA) resulting in extracellular matrix (ECM) depletion. These mechanically altered tissues have little to no storage potential. In this study, we report a sterilizing technique using supercritical carbon dioxide (ScCO2) that can achieve a sterility assurance level 10(-6) in decellularized lung matrix. The effects of ScCO2 treatment on the histological, mechanical, and biochemical properties of the sterile decellularized lung were evaluated and compared with those of freshly decellularized lung matrix and with PAA-treated acellular lung. Exposure of the decellularized tissue to ScCO2 did not significantly alter tissue architecture, ECM content or organization (glycosaminoglycans, elastin, collagen, and laminin), observations of cell engraftment, or mechanical integrity of the tissue. Furthermore, these attributes of lung matrix did not change after 6 months in sterile buffer following sterilization with ScCO2, indicating that ScCO2 produces a matrix that is stable during storage. The current study's results indicate that ScCO2 can be used to sterilize acellular lung tissue while simultaneously preserving key biological components required for the function of the scaffold for regenerative medicine purposes.

Role of heme in bromine-induced lung injury

Science.gov (United States)

Lam, Adam; Vetal, Nilam; Matalon, Sadis; Aggarwal, Saurabh

2016-01-01

Bromine (Br2) gas inhalation poses an environmental and occupational hazard resulting in high morbidity and mortality. In this review, we underline the acute lung pathology (within 24 hours of exposure) and potential therapeutic interventions that may be utilized to mitigate Br2-induced human toxicity. We will discuss our latest published data, which suggests that an increase in heme-dependent tissue injury underlies the pathogenesis of Br2 toxicity. Our study was based on previous findings that demonstrated that Br2 upregulates the heme-degrading enzyme heme oxygenase-1 (HO-1), which converts toxic heme into billiverdin. Interestingly, following Br2 inhalation, heme levels were indeed elevated in bronchoalveolar lavage fluid, plasma, and whole lung tissue in C57BL/6 mice. High heme levels correlated with increased lung oxidative stress, lung inflammation, respiratory acidosis, lung edema, higher airway resistance, and mortality. However, therapeutic reduction of heme levels, by either scavenging with hemopexin or degradation by HO-1, improved lung function and survival. Therefore, heme attenuation may prove a useful adjuvant therapy to treat patients after Br2 exposure. PMID:27244263

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.

The cryoablation of lung tissue using liquid nitrogen in gel and in the ex vivo pig lung.

Science.gov (United States)

Nomori, Hiroaki; Yamazaki, Ikuo; Kondo, Toshiya; Kanno, Masaya

2017-02-01

To examine the efficiency of cryoablation using liquid nitrogen in lung tissue, we measured the size and temperature distribution of the frozen area (iceball) in gel and in the ex vivo pig lungs. Cryoprobes with diameters of 2.4 and 3.4 mm (2.4D and 3.4D, respectively) were used. Three temperature sensors were positioned at the surface of the cryoprobe and at distances of 0.5 and 1.5 cm from the cryoprobe. The ex vivo pig lungs were perfused with 37 °C saline and inflated using ventilator to simulate in vivo lung conditions. In gel, the 2.4D and 3.4D probes made iceballs of 3.9 ± 0.1 and 4.8 ± 0.3 cm in diameter, respectively, and the temperature at 1.5 cm from those probes reached -32 ± 8 and -53 ± 5 °C, respectively. In the pig lung, the 2.4D and 3.4D probes made iceballs of 5.2 ± 0.1 and 5.5 ± 0.4 cm in diameter, respectively, and the temperature at 1.5 cm from these probes reached -49 ± 5 and -58 ± 3 °C, respectively. Liquid nitrogen cryoablation using both 2.4D and 3.4D probes made iceballs that were of sufficient size, and effective temperatures were reached in both gel and the ex vivo pig lung.

Cell structure and proliferative activity of organ cultures of normal embryonic lung tissue of mice resistant (C57BL) and predisposed (A) to lung tumors

International Nuclear Information System (INIS)

Kolesnichenko, T.S.; Gor'kova, T.G.

1985-01-01

Local factors such as proliferative activity and the numerical ratio between epithelial and mesenchymal cells, and also the character of interaction between the tissue components in ontogeny may play an important role in the realization of sensitivity of mice of a particular line to the development of lung tumors. These characteristics of lung tissue in mice of lines A and C57BL are investigated under normal conditions and during induced carcinogenesis. Results are given of a comparative study of the relative numbers of epithelial and mesenchymal cells in organ cultures of embryonic lungs. 3 H-thymidine was added to the cultures on the 14th day of the experiment in a concentration of 1 microCi/m1 medium. An autoradiographic study of the cultures was performed

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

A mast cell secretagogue, compound 48/80, prevents the accumulation of hyaluronan in lung tissue injured by ionizing irradiation

International Nuclear Information System (INIS)

Nilsson, K.; Bjermer, L.; Hellstroem, S.H.; Henriksson, R.; Haellgren, R.

1990-01-01

Irradiation with a single dose of 30 Grey on the basal regions of the lungs of Sprague-Dawley rats induced a peribronchial and alveolar inflammation. Infiltration of mast cells in the edematous alveolar interstitial tissue and also in the peribronchial tissue were characteristic features of the lesion. The appearance of mast cells was already seen 4 wk after irradiation and by weeks 6 to 8 there was a heavy infiltration. The staining properties suggested that they were connective tissue-type mast cells. The infiltration of mast cells was paralleled by an accumulation of hyaluronan (hyaluronic acid) in the alveolar interstitial tissue 6 and 8 wk after irradiation. The recovery of hyaluronan (HA) during bronchoalveolar lavage (BAL) of the lungs also increased at this time. Treatment with a mast cell secretagogue, compound 48/80, induced a distinct reduction of granulated mast cells in the alveolar tissue. Regular treatment with compound 48/80 from the time of irradiation considerably reduced the HA recovery during BAL and the HA accumulation in the interstitial tissue but did not affect the interstitial infiltration of mononuclear cells and polymorphonuclear leukocytes. By contrast, an accumulation of HA in the alveolar interstitial space was induced when compound 48/80 was given not until mast cell infiltration of the lung had started. The effects of compound 48/80 indicate that the connective tissue response after lung irradiation is dependent on whether or not mast cell degranulation is induced before or after the mast cell infiltration of the alveolar tissue

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

International Nuclear Information System (INIS)

Fukuzaki, Minoru; Shioya, Sumie; Haida, Munetaka

1997-01-01

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)

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.

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.

Does Three-Dimensional External Beam Partial Breast Irradiation Spare Lung Tissue Compared With Standard Whole Breast Irradiation?

International Nuclear Information System (INIS)

Jain, Anudh K.; Vallow, Laura A.; Gale, Ashley A.; Buskirk, Steven J.

2009-01-01

Purpose: To determine whether three-dimensional conformal partial breast irradiation (3D-PBI) spares lung tissue compared with whole breast irradiation (WBI) and to include the biologically equivalent dose (BED) to account for differences in fractionation. Methods and Materials: Radiotherapy treatment plans were devised for WBI and 3D-PBI for 25 consecutive patients randomized on the NSABP B-39/RTOG 0413 protocol at Mayo Clinic in Jacksonville, Florida. WBI plans were for 50 Gy in 25 fractions, and 3D-PBI plans were for 38.5 Gy in 10 fractions. Volume of ipsilateral lung receiving 2.5, 5, 10, and 20 Gy was recorded for each plan. The linear quadratic equation was used to calculate the corresponding dose delivered in 10 fractions and volume of ipsilateral lung receiving these doses was recorded for PBI plans. Ipsilateral mean lung dose was recorded for each plan and converted to BED. Results: There was a significant decrease in volume of lung receiving 20 Gy with PBI (median, 4.4% vs. 7.5%; p 3 vs 4.85 Gy 3 , p = 0.07). PBI plans exposed more lung to 2.5 and 5 Gy. Conclusions: 3D-PBI exposes greater volumes of lung tissue to low doses of radiation and spares the amount of lung receiving higher doses when compared with WBI.

Importance of serum levels of angiopoietin-2 and survivin biomarkers in non-small cell lung cancer

International Nuclear Information System (INIS)

Fawzy, A.; Gaafar, R.; Kasem, F.; Ali, Sh.S.; Elshafei, M.; Eldeib, M.

2012-01-01

Angio genesis is an essential process in cancer growth maintenance, and Lung cancer; metastasis. Appointing-2 promotes tumor angio genesis by priming the vasculature and potentiating the effects of cytokines at the front of active neovascularization. Enhanced expression of Angiopoietin-2 has been reported in lung cancer tissue. Survivin is one of the inhibitors of apoptosis Survivin; protein that has been shown to play a key role in cancer progression, and in tumor angio genesis. Also plays a key role in tumor cell resistance to anticancer agents and ionizing radiation. Aim: To measure the serum levels of angiopoietin-2 and survivin as possible angiogenic factors in lung cancer patients with the assessment of their interrelationships and clinical significance. Patients and methods: Patients with lung cancer as NSCLC (n = 70) and healthy volunteers (n = 10) were enrolled. Serum angiopoietin-2 and survivin concentrations were measured using enzyme-linked immunosorbent assay (ELIZA). Results: Median serum angiopoietin-2 levels with lung cancer (2730 pg/mL) ranged from 1171 to 6541 pg/mL was higher than the median of the control group (1795 pg/mL) ranged from 1076 to 2730/mL, p < 0.001. Median serum survivin levels were also higher in patients with lung cancer (53.0 pg/mL) ranged from 39.3 to 96.3 pg/mL than the median of the control group (48.8 pg/mL) ranged from 38.0 to 74.6pg/mL, but did not reach statistical significance p = 0.206. In all patients with lung cancer, serum angiopoietin-2 was not significantly correlated with survivin (r = 0.073, p = 0.657). Neither serum angiopoietin-2 nor survivin showed significant relation with the serum angiopoietin-2 or survivin levels depending on the cell types, stage progression, and metastasis among the patients with NSCLC. Conclusions: Our study suggests that serum angiopoietin-2 is a useful marker for the diagnosis of NSCLC by ELIZA technique

Protective ventilation reduces Pseudomonas aeruginosa growth in lung tissue in a porcine pneumonia model.

Science.gov (United States)

Sperber, Jesper; Nyberg, Axel; Lipcsey, Miklos; Melhus, Åsa; Larsson, Anders; Sjölin, Jan; Castegren, Markus

2017-08-31

Mechanical ventilation with positive end expiratory pressure and low tidal volume, i.e. protective ventilation, is recommended in patients with acute respiratory distress syndrome. However, the effect of protective ventilation on bacterial growth during early pneumonia in non-injured lungs is not extensively studied. The main objectives were to compare two different ventilator settings on Pseudomonas aeruginosa growth in lung tissue and the development of lung injury. A porcine model of severe pneumonia was used. The protective group (n = 10) had an end expiratory pressure of 10 cm H 2 O and a tidal volume of 6 ml x kg -1 . The control group (n = 10) had an end expiratory pressure of 5 cm H 2 O and a tidal volume of 10 ml x kg -1 . 10 11 colony forming units of Pseudomonas aeruginosa were inoculated intra-tracheally at baseline, after which the experiment continued for 6 h. Two animals from each group received only saline, and served as sham animals. Lung tissue samples from each animal were used for bacterial cultures and wet-to-dry weight ratio measurements. The protective group displayed lower numbers of Pseudomonas aeruginosa (p protective group was unchanged (p protective ventilation with lower tidal volume and higher end expiratory pressure has the potential to reduce the pulmonary bacterial burden and the development of lung injury.

Gene Expression Profiling in Lung Tissues from Rat Exposed to Lunar Dust Particles

Science.gov (United States)

Zhang, Ye; Lam, Chiu-Wing; Zalesak, Selina M.; Kidane, Yared H.; Feiveson, Alan H.; Ploutz-Snyder, Robert; Scully, Robert R.; Williams, Kyle; Wu, Honglu; James, John T.

2014-01-01

The Moon's surface is covered by a layer of fine, reactive dust. Lunar dust contain about 1-2% of very fine dust (gene expression changes in lung tissues from 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/m(exp 3) of lunar dust. Five rats per group were euthanized 1 day, and 3 months after the last inhalation exposure. The total RNAs were isolated from lung tissues after being lavaged. The Agilent Rat GE v3 microarray was used to profile global gene expression (44K). The genes with significant expression changes are identified and the gene expression data were further analyzed using various statistical tools.

Evaluating Superoxide Dismutase (SOD, Glutathione (GSH, Malondialdehyde (MDA and the Histological Changes of the Lung Tissue after γ-Irradiation in Rats

Directory of Open Access Journals (Sweden)

Abolhasan Rezaeyan

2016-09-01

Full Text Available Background & Objective: The lung is a radiosensitive organ and its damage is a dose-limiting factor in radiotherapy. Different side effects such as pneumonia and lung fibrosis are found in patients with thorax irradiation. The objective of the present study is to evaluate the effects of γ-irradiation on acute and chronic injuries of lung tissue in rats. Materials & Methods: 32 rats were divided into two groups. Control group consisted of 14 rats that underwent shame irradiation. In radiation group, 18 rats underwent γ-irradiation. The rats were exposed to γ-irradiation 18 Gy using a single fraction cobalt-60 unit. Eight rats in each group were sacrificed 24 hours after radiotherapy for determining Superoxide Dismutase (SOD, Glutathione (GSH, Malondialdehyde (MDA, and histopathological evaluations. Remained animals were sacrificed eight weeks after radiotherapy for histopathological evaluation. Results: Compared to control group, the level of SOD and GSH significantly decreased and MDA level significantly increased in radiation group 24 hours following irradiation, (p=0.001, p<0.001, p=0.001 respectively. Early histopathological results after 24 hours showed that radiation increases neutrophil, macrophage, and inflammation incidence compared to control group (p<0.05. Late histopathological evaluation after eight weeks revealed significant increase in factors including mast cells, pulmonary edema, vascular thickness, vascular damage, and also inflammation and fibrosis incidence in case group compared to radiation group  (p<0.05. Conclusion: Localized chest radiation with dose of 18 Gy induces changes in oxidative stress indices and histopathological lung tissue damage in short and long term.

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.

On Predicting lung cancer subtypes using ‘omic’ data from tumor and tumor-adjacent histologically-normal tissue

International Nuclear Information System (INIS)

Pineda, Arturo López; Ogoe, Henry Ato; Balasubramanian, Jeya Balaji; Rangel Escareño, Claudia; Visweswaran, Shyam; Herman, James Gordon; Gopalakrishnan, Vanathi

2016-01-01

Adenocarcinoma (ADC) and squamous cell carcinoma (SCC) are the most prevalent histological types among lung cancers. Distinguishing between these subtypes is critically important because they have different implications for prognosis and treatment. Normally, histopathological analyses are used to distinguish between the two, where the tissue samples are collected based on small endoscopic samples or needle aspirations. However, the lack of cell architecture in these small tissue samples hampers the process of distinguishing between the two subtypes. Molecular profiling can also be used to discriminate between the two lung cancer subtypes, on condition that the biopsy is composed of at least 50 % of tumor cells. However, for some cases, the tissue composition of a biopsy might be a mix of tumor and tumor-adjacent histologically normal tissue (TAHN). When this happens, a new biopsy is required, with associated cost, risks and discomfort to the patient. To avoid this problem, we hypothesize that a computational method can distinguish between lung cancer subtypes given tumor and TAHN tissue. Using publicly available datasets for gene expression and DNA methylation, we applied four classification tasks, depending on the possible combinations of tumor and TAHN tissue. First, we used a feature selector (ReliefF/Limma) to select relevant variables, which were then used to build a simple naïve Bayes classification model. Then, we evaluated the classification performance of our models by measuring the area under the receiver operating characteristic curve (AUC). Finally, we analyzed the relevance of the selected genes using hierarchical clustering and IPA® software for gene functional analysis. All Bayesian models achieved high classification performance (AUC > 0.94), which were confirmed by hierarchical cluster analysis. From the genes selected, 25 (93 %) were found to be related to cancer (19 were associated with ADC or SCC), confirming the biological relevance of our

Tissue Feature-Based and Segmented Deformable Image Registration for Improved Modeling of Shear Movement of Lungs

International Nuclear Information System (INIS)

Xie Yaoqin; Chao Ming; Xing Lei

2009-01-01

Purpose: To report a tissue feature-based image registration strategy with explicit inclusion of the differential motions of thoracic structures. Methods and Materials: The proposed technique started with auto-identification of a number of corresponding points with distinct tissue features. The tissue feature points were found by using the scale-invariant feature transform method. The control point pairs were then sorted into different 'colors' according to the organs in which they resided and used to model the involved organs individually. A thin-plate spline method was used to register a structure characterized by the control points with a given 'color.' The proposed technique was applied to study a digital phantom case and 3 lung and 3 liver cancer patients. Results: For the phantom case, a comparison with the conventional thin-plate spline method showed that the registration accuracy was markedly improved when the differential motions of the lung and chest wall were taken into account. On average, the registration error and standard deviation of the 15 points against the known ground truth were reduced from 3.0 to 0.5 mm and from 1.5 to 0.2 mm, respectively, when the new method was used. A similar level of improvement was achieved for the clinical cases. Conclusion: The results of our study have shown that the segmented deformable approach provides a natural and logical solution to model the discontinuous organ motions and greatly improves the accuracy and robustness of deformable registration.

Chronic exposure to microcystin-LR affected mitochondrial DNA maintenance and caused pathological changes of lung tissue in mice

International Nuclear Information System (INIS)

Li, Xinxiu; Xu, Lizhi; Zhou, Wei; Zhao, Qingya; Wang, Yaping

2016-01-01

Microcystin-LR (MC-LR), an important variant of cyanotoxin family, was frequently encountered in the contaminated aquatic environment and taken as a potent hepatotoxin. However, a little was known on the association between the long-term MC-LR exposure and lung damage. In this study, we investigated the changes of the pulmonary histopathology, mitochondrial DNA (mtDNA) integrity and the expression of mtDNA encoded genes in the mice with chronic exposed to MC-LR at different concentrations (1, 5, 10, 20 and 40 μg/L) for 12 months. Our results showed that the long-term and persistent exposure to MC-LR disturbed the balance of redox system, influenced mtDNA stability, changed the expression of mitochondrial genes in the lung cells. Notably, MC-LR exposure influenced the level of inflammatory cytokines and resulted in thickening of the alveolar septa. In conclusion, chronic exposure to MC-LR affected mtDNA maintenance, and caused lung impairment in mice. - Highlights: • A simulated natural exposure to MC-LR caused the lung pathological changes. • The chronic exposure disturbed the redox system balance of lung tissue cells. • The chronic exposure impaired the mtDNA stability and mitochondria function. • The lung was one of the vulnerable organs to MC-LR exposure in mice. - Long-term exposure to MC-LR in drinking water disturbed the balance of redox system, affected mitochondrial DNA maintenance and caused lung impairment in mice.

Local and systemic effects of fibrin and cyanoacrylate adhesives on lung lesions in rabbits

Directory of Open Access Journals (Sweden)

Marcus V.H. Carvalho

Full Text Available OBJECTIVES: Tissue adhesives can be used to prevent pulmonary air leaks, which frequently occur after lung interventions. The objective of this study is to evaluate local and systemic effects of fibrin and cyanoacrylate tissue adhesives on lung lesions in rabbits. METHODS: Eighteen rabbits were submitted to videothoracoscopy + lung incision alone (control or videothoracoscopy + lung incision + local application of fibrin or cyanoacrylate adhesive. Blood samples were collected and assessed for leukocyte, neutrophil and lymphocyte counts and interleukin-8 levels preoperatively and at 48 hours and 28 days post-operatively. After 28 days, the animals were euthanized for gross examination of the lung surface, and lung fragments were excised for histopathological analysis. RESULTS: Fibrin and cyanoacrylate produced similar adhesion scores of the lung to the parietal pleura. Microscopic analysis revealed uniform low-cellular tissue infiltration in the fibrin group and an intense tissue reaction characterized by dense inflammatory infiltration of granulocytes, giant cells and necrosis in the cyanoacrylate group. No changes were detected in the leukocyte, neutrophil or lymphocyte count at any time-point, while the interleukin-8 levels were increased in the fibrin and cyanoacrylate groups after 48 hours compared with the pre-operative control levels (p<0.01. CONCLUSION: Both adhesive agents promoted normal tissue healing, with a more pronounced local inflammatory reaction observed for cyanoacrylate. Among the serum markers of inflammation, only the interleukin-8 levels changed post-operatively, increasing after 48 hours and decreasing after 28 days to levels similar to those of the control group in both the fibrin and cyanoacrylate groups.

Micromechanical model of lung parenchyma hyperelasticity

Science.gov (United States)

Concha, Felipe; Sarabia-Vallejos, Mauricio; Hurtado, Daniel E.

2018-03-01

volumetric expansion, but also for three other anisotropic loading conditions for different levels of tissue porosity, while displaying superior computational efficiency and stability in estimating coarse-scale response when compared to direct numerical simulations of RVEs. Further, we find that the most influential microstructural parameters on the response of the micromechanical model are the reference porosity and the alveolar wall elasticity. We also show that the model can reproduce uniaxial experimental tests on lung tissue samples, and estimate the Poisson ratio to be 0.22. We envision that our model will enable predictive and efficient whole-organ simulations useful to study the normal and diseased lung.

Creation of lung-targeted dexamethasone immunoliposome and its therapeutic effect on bleomycin-induced lung injury in rats.

Directory of Open Access Journals (Sweden)

Xue-Yuan Chen

Full Text Available OBJECTIVE: Acute lung injury (ALI, is a major cause of morbidity and mortality, which is routinely treated with the administration of systemic glucocorticoids. The current study investigated the distribution and therapeutic effect of a dexamethasone(DXM-loaded immunoliposome (NLP functionalized with pulmonary surfactant protein A (SP-A antibody (SPA-DXM-NLP in an animal model. METHODS: DXM-NLP was prepared using film dispersion combined with extrusion techniques. SP-A antibody was used as the lung targeting agent. Tissue distribution of SPA-DXM-NLP was investigated in liver, spleen, kidney and lung tissue. The efficacy of SPA-DXM-NLP against lung injury was assessed in a rat model of bleomycin-induced acute lung injury. RESULTS: The SPA-DXM-NLP complex was successfully synthesized and the particles were stable at 4°C. Pulmonary dexamethasone levels were 40 times higher with SPA-DXM-NLP than conventional dexamethasone injection. Administration of SPA-DXM-NLP significantly attenuated lung injury and inflammation, decreased incidence of infection, and increased survival in animal models. CONCLUSIONS: The administration of SPA-DXM-NLP to animal models resulted in increased levels of DXM in the lungs, indicating active targeting. The efficacy against ALI of the immunoliposomes was shown to be superior to conventional dexamethasone administration. These results demonstrate the potential of actively targeted glucocorticoid therapy in the treatment of lung disease in clinical practice.

Age-dependent accumulation of heavy metals in liver, kidney and lung tissues of homing pigeons in Beijing, China.

Science.gov (United States)

Cui, Jia; Wu, Bin; Halbrook, Richard S; Zang, Shuying

2013-12-01

Biomonitoring provides direct evidence of the bioavailability and accumulation of toxic elements in the environment. In the current study, 1-2, 5-6, and 9-10+ year old homing pigeons collected from the Haidian District of Beijing during 2011 were necropsied and concentrations of cadmium, lead, and mercury were measured in liver, lung, and kidney tissue. At necropsy, gray/black discoloration of the margins of the lungs was observed in 98 % of the pigeons. There were no significant differences in metal concentrations as a function of gender. Cadmium concentrations in all tissues and Pb concentrations in the lung tissues were significantly greater in 9-10+ year old pigeons compared to other age groups indicating that Cd and Pb were bioavailable. Mercury concentrations were not significantly different among age groups. Cadmium concentrations in kidney and lung tissues of 9-10+ year old pigeons were similar to or exceeded concentrations of Cd reported in pigeons from another high traffic urban area and most wild avian species from Korea suggesting that Cd in this region of Beijing may be of concern. Homing pigeons provide valuable exposure and bioaccumulation data not readily available from air monitoring alone, thus providing information regarding potential health effects in wildlife and humans in urban areas. As environmental quality standards are implemented in China, homing pigeons will serve as a valuable bio-monitor of the efficacy of these actions.

Infection Rate and Tissue Localization of Murine IL-12p40-Producing Monocyte-Derived CD103+ Lung Dendritic Cells during Pulmonary Tuberculosis

Science.gov (United States)

Leepiyasakulchai, Chaniya; Taher, Chato; Chuquimia, Olga D.; Mazurek, Jolanta; Söderberg-Naucler, Cecilia; Fernández, Carmen; Sköld, Markus

2013-01-01

Non-hematopoietic cells, including lung epithelial cells, influence host immune responses. By co-culturing primary alveolar epithelial cells and monocytes from naïve donor mice, we show that alveolar epithelial cells support monocyte survival and differentiation in vitro, suggesting a role for non-hematopoietic cells in monocyte differentiation during the steady state in vivo. CD103+ dendritic cells (αE-DC) are present at mucosal surfaces. Using a murine primary monocyte adoptive transfer model, we demonstrate that αE-DC in the lungs and pulmonary lymph nodes are monocyte-derived during pulmonary tuberculosis. The tissue localization may influence the functional potential of αE-DC that accumulate in Mycobacterium tuberculosis-infected lungs. Here, we confirm the localization of αE-DC in uninfected mice beneath the bronchial epithelial cell layer and near the vascular wall, and show that αE-DC have a similar distribution in the lungs during pulmonary tuberculosis and are detected in the bronchoalveolar lavage fluid from infected mice. Lung DC can be targeted by M. tuberculosis in vivo and play a role in bacterial dissemination to the draining lymph node. In contrast to other DC subsets, only a fraction of lung αE-DC are infected with the bacterium. We also show that virulent M. tuberculosis does not significantly alter cell surface expression levels of MHC class II on infected cells in vivo and that αE-DC contain the highest frequency of IL-12p40+ cells among the myeloid cell subsets in infected lungs. Our results support a model in which inflammatory monocytes are recruited into the M. tuberculosis-infected lung tissue and, depending on which non-hematopoietic cells they interact with, differentiate along different paths to give rise to multiple monocyte-derived cells, including DC with a distinctive αE-DC phenotype. PMID:23861965

Infection rate and tissue localization of murine IL-12p40-producing monocyte-derived CD103(+) lung dendritic cells during pulmonary tuberculosis.

Science.gov (United States)

Leepiyasakulchai, Chaniya; Taher, Chato; Chuquimia, Olga D; Mazurek, Jolanta; Söderberg-Naucler, Cecilia; Fernández, Carmen; Sköld, Markus

2013-01-01

Non-hematopoietic cells, including lung epithelial cells, influence host immune responses. By co-culturing primary alveolar epithelial cells and monocytes from naïve donor mice, we show that alveolar epithelial cells support monocyte survival and differentiation in vitro, suggesting a role for non-hematopoietic cells in monocyte differentiation during the steady state in vivo. CD103(+) dendritic cells (αE-DC) are present at mucosal surfaces. Using a murine primary monocyte adoptive transfer model, we demonstrate that αE-DC in the lungs and pulmonary lymph nodes are monocyte-derived during pulmonary tuberculosis. The tissue localization may influence the functional potential of αE-DC that accumulate in Mycobacterium tuberculosis-infected lungs. Here, we confirm the localization of αE-DC in uninfected mice beneath the bronchial epithelial cell layer and near the vascular wall, and show that αE-DC have a similar distribution in the lungs during pulmonary tuberculosis and are detected in the bronchoalveolar lavage fluid from infected mice. Lung DC can be targeted by M. tuberculosis in vivo and play a role in bacterial dissemination to the draining lymph node. In contrast to other DC subsets, only a fraction of lung αE-DC are infected with the bacterium. We also show that virulent M. tuberculosis does not significantly alter cell surface expression levels of MHC class II on infected cells in vivo and that αE-DC contain the highest frequency of IL-12p40(+) cells among the myeloid cell subsets in infected lungs. Our results support a model in which inflammatory monocytes are recruited into the M. tuberculosis-infected lung tissue and, depending on which non-hematopoietic cells they interact with, differentiate along different paths to give rise to multiple monocyte-derived cells, including DC with a distinctive αE-DC phenotype.

HE4 Tissue Expression and Serum HE4 Levels in Healthy Individuals and Patients with Benign or Malignant Tumors

DEFF Research Database (Denmark)

Karlsen, Nikoline S; Karlsen, Mona A; Høgdall, Claus K

2014-01-01

, this review aims to systematically outline published results of HE4 tissue expression and serum HE4 levels in healthy individuals and patients with benign or malignant tumors. Our findings suggest scientific basis for a potential diagnostic ability of HE4 in gynecologic cancer and lung cancer, and further...

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.

Precision cut lung slices as an efficient tool for in vitro lung physio-pharmacotoxicology studies.

Science.gov (United States)

Morin, Jean-Paul; Baste, Jean-Marc; Gay, Arnaud; Crochemore, Clément; Corbière, Cécile; Monteil, Christelle

2013-01-01

1.We review the specific approaches for lung tissue slices preparation and incubation systems and the research application fields in which lung slices proved to be a very efficient alternative to animal experimentation for biomechanical, physiological, pharmacological and toxicological approaches. 2.Focus is made on air-liquid interface dynamic organ culture systems that allow direct tissue exposure to complex aerosol and that best mimic in vivo lung tissue physiology. 3.A compilation of research applications in the fields of vascular and airway reactivity, mucociliary transport, polyamine transport, xenobiotic biotransformation, chemicals toxicology and complex aerosols supports the concept that precision cut lung slices are a very efficient tool maintaining highly differentiated functions similar to in vivo lung organ when kept under dynamic organ culture. They also have been successfully used for lung gene transfer efficiency assessment, for lung viral infection efficiency assessment, for studies of tissue preservation media and tissue post-conditioning to optimize lung tissue viability before grafting. 4.Taken all together, the reviewed studies point to a great interest for precision cut lung slices as an efficient and valuable alternative to in vivo lung organ experimentation.

Low-level chromosome 12 amplification in a primary lipoma of the lung: evidence for a pathogenetic relationship with common adipose tissue tumors.

Science.gov (United States)

Bridge, J A; Roberts, C A; Degenhardt, J; Walker, C; Lackner, R; Linder, J

1998-02-01

Cytogenetic analysis of a primary lipoma of the lung removed from a 56-year-old woman revealed the presence of a supernumerary marker chromosome in all metaphase cells analyzed; namely, 47,XX,+mar. To the best of our knowledge, this is the first cytogenetic description of a primary lipoma of lung. Genetic analysis of intramuscular lipoma, atypical lipoma, and well-differentiated liposarcoma have revealed the presence of one to three supernumerary ring or giant marker chromosomes composed of chromosome 12 segments as the characteristic anomaly. The marker chromosome in the present case was shown to be composed entirely of chromosome 12 material by subsequent analysis with a chromosome 12-specific paint probe and fluorescence in situ hybridization. Thus, analogous to intramuscular lipoma, atypical lipoma, and well-differentiated liposarcoma, extra chromosome 12 material is present. These findings support a pathogenetic relationship between this lipoma of unusual anatomic location and common adipose tissue tumors.

Induction of Lipocalin2 in a Rat Model of Lung Irradiation

Directory of Open Access Journals (Sweden)

Sadaf Sultan

2016-04-01

Full Text Available Previously, we showed that lipocalin2 (LCN2 serum levels increased after liver irradiation and during acute-phase conditions. Here, we evaluate LCN2 expression and serum levels after single-dose lung irradiation with 25 Gy, percutaneously administered to the lung of randomly-paired male Wistar rats. Due to the concave anatomy of the lung recesses, the irradiation field included the upper part of the liver. No rat died due to irradiation. In control tissue, lung immunohistochemistry showed a high constitutive expression of LCN2+ granulocytes. LCN2 mRNA levels in lung tissue increased up to 24 h (9 ± 2.3-fold after irradiation. However, serum LCN2 levels remained undetectable after lung irradiation. LCN2 expression in the upper part of the liver increased up to 4.2-fold after lung irradiation, but the lower liver showed an early decrease. Acute-phase cytokines (IL-1β and TNF-α showed a significant increase on transcript level in both lung and upper liver, whilst the lower liver did not show any considerable increase. In conclusion, constitutive expression of LCN2 in local immune cells demonstrates its local role during stress conditions in the lung. The absence of LCN2 in the serum strengthens our previous findings that the liver is the key player in secreting LCN2 during stress conditions with liver involvement.

Hydrogels for lung tissue engineering: Biomechanical properties of thin collagen-elastin constructs.

Science.gov (United States)

Dunphy, Siobhán E; Bratt, Jessica A J; Akram, Khondoker M; Forsyth, Nicholas R; El Haj, Alicia J

2014-10-01

In this study, collagen-elastin constructs were prepared with the aim of producing a material capable of mimicking the mechanical properties of a single alveolar wall. Collagen has been used in a wide range of tissue engineering applications; however, due to its low mechanical properties its use is limited to non load-bearing applications without further manipulation using methods such as cross-linking or mechanical compression. Here, it was hypothesised that the addition of soluble elastin to a collagen hydrogel could improve its mechanical properties. Hydrogels made from collagen only and collagen plus varying amounts elastin were prepared. Young׳s modulus of each membrane was measured using the combination of a non-destructive indentation and a theoretical model previously described. An increase in Young׳s modulus was observed with increasing concentration of elastin. The use of non-destructive indentation allowed for online monitoring of the elastic moduli of cell-seeded constructs over 8 days. The addition of lung fibroblasts into the membrane increased the stiffness of the hydrogels further and cell-seeded collagen hydrogels were found to have a stiffness equal to the theoretical value for a single alveolar wall (≈5kPa). Through provision of some of the native extracellular matrix components of the lung parenchyma these scaffolds may be able to provide an initial building block toward the regeneration of new functional lung tissue. Copyright © 2014 Elsevier Ltd. All rights reserved.

Asthmatic inflammatory reaction in the lung tissues of juvenile rats following exposure to cyolane pesticide

International Nuclear Information System (INIS)

Nour el din, A.M.; Hassanin, M.M.

2004-01-01

The present study was carried out to evaluate the effect of the organophosphorus pesticide cyolane on the tissues of the respiratory system and the pro-inflammatory markers in the serum.The study was carried out on thirty juvenile Sprague Dawley rats. Animals were divided into three groups, one used as control and the other two groups, (Gr.I and Gr.Il) received daily diet contained cyolane equivalent to 1.0 mg/kg b.wt. for 2 and 4 weeks, respectively.Nitric oxide (No), immunoglobulins E(IgE) and G (IgG) were measured in the serum of control and treated rats as an important pro-inflammatory markers.The results revealed that nitric oxide was highly significantly increased in Gr.II (P< 0.001) and significantly increased in Gr.I (P< 0.01).As regards to serum immunoglobulins, the data obtained revealed significant increase in serum total IgE in both treated groups. The IgG, as an anaphylactic antibody, showed significant increase in both groups.Histopathological examination of lung tissue revealed increased inflammatory cells infiltration and congested blood vessels in Gr.I while Gr.II showed massive inflammatory cells infiltration and congestion of blood vessels which became more pronounced. In addition, the hypertrophied muscle fibers were increased in the sub-bronchial epithelium.We concluded that young adolescents and children must advised to avoid exposure to organophosphorus pesticides, even for short time, to prevent asthmatic inflammatory reaction, which by time destroy their lung tissues. Also, the study recommended importance of measuring No, IgE and IgG serum levels as inflammatory markers for early diagnosis and management of asthma

Weight preserving image registration for monitoring disease progression in lung CT

DEFF Research Database (Denmark)

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

2008-01-01

We present a new image registration based method for monitoring regional disease progression in longitudinal image studies of lung disease. A free-form image registration technique is used to match a baseline 3D CT lung scan onto a following scan. Areas with lower intensity in the following scan...... the density of lung tissue with respect to local expansion or compression such that the total weight of the lungs is preserved during deformation. Our method provides a good estimation of regional destruction of lung tissue for subjects with a significant difference in inspiration level between CT scans...

Significance of Lead Residues in Mallard Tissues

Science.gov (United States)

Longcore, J.R.; Locke, L.N.; Bagley, George E.; Andrews, R.

1974-01-01

Tissues of adult, lead-dosed mallards that either died or were sacrificed were analyzed for lead. Lead levels in brains, tibiae, and breast muscle of ducks that died and in tibiae of ducks that were sacrificed increased significantly from dosage until death. Lead in the heart, lung, and blood from sacrificed ducks decreased significantly from dosage until death. Lead concentrations in tissues from ducks in the two groups were not significantly different except for the liver, kidney, and lung. Average lead levels in the livers and kidneys of ducks that died were significantly higher than those in ducks that were sacrificed. The mean concentration of lead in the lungs of the ducks sacrificed was significantly higher than the mean level in the lungs of ducks that died. Measurements of the lead concentrations in this study, when compared with lead levels reported in the literature for avian and non-avian species, showed that arbitrary diagnostic levels indicating lead poisoning could be set. In mallard ducks, lead levels exceeding 3 ppm in the brain, 6 to 20 ppm in the kidney or liver, or 10 ppm in clotted blood from the heart indicated acute exposure to lead.

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

International Nuclear Information System (INIS)

Jala, Venkatakrishna Rao; Radde, Brandie N; Haribabu, Bodduluri; Klinge, Carolyn M

2012-01-01

G-protein-coupled estrogen receptor (GPER/GPR30) was reported to bind 17β-estradiol (E 2 ), 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. 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. 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. 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

[Correlation between EGLN1 gene, protein express in lung tissue of rats and pulmonary artery pressure at different altitude].

Science.gov (United States)

Li, S H; Li, S; Sun, L; Bai, Z Z; Yang, Q Y; Ga, Q; Jin, G E

2016-08-23

To investigate the correlation between pulmonary artery pressure (PAP) and the expression level of Egl nine homologue 1 (EGLN1) gene or its protein in lung tissue of rats at different altitudes. Totally 121 male Wistar rats were randomly divided into low altitude group (n=11), moderate altitude group and high altitude group, the rats in moderate altitude and high altitude group were further divided into 1(st) day, 3(rd) days, 7(th) days, 15(th) day and 30(th) day group according to the exposure time to hypoxic environment, each group 11 rats. The low altitude group, the PAP of rats were determined by physiological signal acquisition system, and tissue samples were collected in liquid nitrogen container for storage at an altitude of 498 m area. Moderate altitude group rats were placed in altitude of 2 260 meters of natural environment, 5 high altitude groups rats were placed in the hypobaric hypoxic chamber, simulating altitude of 4 500 meters. The PAP of rats in moderate altitude group and high altitude group were also determined by physiological signal acquisition system, and tissue samples were collected when rats were exposed to hypoxia at 1(st), 3(rd), 7(th), 15(th) and 30(th) day; Western blot was used to determine expression levels of EGLN1 protein, and person correlation analysis was used to analyze whether the protein was related to the formation of pulmonary arterial hypertension (PH) under hypoxia. Real-time quantitive PCR method determined expression levels of EGLN1 mRNA in lung tissues, and the relative expression method was used to analyze PCR data, and finally assess whether the EGLN1 gene was the initial cause of the formation of PH during hypoxia. The mean PAP of rats was (20.0±3.2) mmHg (1 mmHg=0.133 kPa) in low altitude group; in moderate altitude group, mean PAP began to increase slightly when rats were exposed to hypoxia on the 15(th) day and reached at (22.7±4.1) mmHg on hypoxic 30(th) day, but compared with the low altitude group, there was

Silica inhalation altered telomere length and gene expression of telomere regulatory proteins in lung tissue of rats.

Science.gov (United States)

Shoeb, Mohammad; Joseph, Pius; Kodali, Vamsi; Mustafa, Gul; Farris, Breanne Y; Umbright, Christina; Roberts, Jenny R; Erdely, Aaron; Antonini, James M

2017-12-11

Exposure to silica can cause lung fibrosis and cancer. Identification of molecular targets is important for the intervention and/or prevention of silica-induced lung diseases. Telomeres consist of tandem repeats of DNA sequences at the end of chromosomes, preventing chromosomal fusion and degradation. Regulator of telomere length-1 (RTEL1) and telomerase reverse transcriptase (TERT), genes involved in telomere regulation and function, play important roles in maintaining telomere integrity and length. The goal of this study was to assess the effect of silica inhalation on telomere length and the regulation of RTEL1 and TERT. Lung tissues and blood samples were collected from rats at 4, 32, and 44 wk after exposure to 15 mg/m 3 of silica × 6 h/d × 5 d. Controls were exposed to air. At all-time points, RTEL1 expression was significantly decreased in lung tissue of the silica-exposed animals compared to controls. Also, significant increases in telomere length and TERT were observed in the silica group at 4 and 32 wk. Telomere length, RTEL1 and TERT expression may serve as potential biomarkers related to silica exposure and may offer insight into the molecular mechanism of silica-induced lung disease and tumorigeneses.

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

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.

Incomplete Memories: The Natural Suppression of Tissue-Resident Memory CD8 T Cells in the Lung

Directory of Open Access Journals (Sweden)

Katie L. Reagin

2018-01-01

Full Text Available The yearly, cyclic impact of viruses like influenza on human health and the economy is due to the high rates of mutation of traditional antibody targets, which negate any preexisting humoral immunity. However, the seasonality of influenza infections can equally be attributed to an absent or defective memory CD8 T cell response since the epitopes recognized by these cells are derived from essential virus proteins that mutate infrequently. Experiments in mouse models show that protection from heterologous influenza infection is temporally limited and conferred by a population of tissue-resident memory (TRM cells residing in the lung and lung airways. TRM are elicited by a diverse set of pathogens penetrating mucosal barriers and broadly identified by extravascular staining and expression of the activation and adhesion molecules CD69 and CD103. Interestingly, lung TRM fail to express these molecules, which could limit tissue retention, resulting in airway expulsion or death with concomitant loss of heterologous protection. Here, we make the case that respiratory infections uniquely evoke a form of natural immunosuppression whereby specific cytokines and cell–cell interactions negatively impact memory cell programming and differentiation. Respiratory memory is not only short-lived but most of the memory cells in the lung parenchyma may not be bona fide TRM. Given the quantity of microbes humans inhale over a lifetime, limiting cellular residence could be a mechanism employed by the respiratory tract to preserve organismal vitality. Therefore, successful efforts to improve respiratory immunity must carefully and selectively breach these inherent tissue barriers.

Bone-marrow-derived mesenchymal stem cells inhibit gastric aspiration lung injury and inflammation in rats.

Science.gov (United States)

Zhou, Jing; Jiang, Liyan; Long, Xuan; Fu, Cuiping; Wang, Xiangdong; Wu, Xiaodan; Liu, Zilong; Zhu, Fen; Shi, Jindong; Li, Shanqun

2016-09-01

Gastric aspiration lung injury is one of the most common clinical events. This study investigated the effects of bone-marrow-derived mesenchymal stem cells (BMSCs) on combined acid plus small non-acidified particle (CASP)-induced aspiration lung injury. Enhanced green fluorescent protein (EGFP(+) ) or EGFP(-) BMSCs or 15d-PGJ2 were injected via the tail vein into rats immediately after CASP-induced aspiration lung injury. Pathological changes in lung tissues, blood gas analysis, the wet/dry weight ratio (W/D) of the lung, levels of total proteins and number of total cells and neutrophils in bronchoalveolar lavage fluid (BALF) were determined. The cytokine levels were measured using ELISA. Protein expression was determined by Western blot. Bone-marrow-derived mesenchymal stem cells treatment significantly reduced alveolar oedema, exudation and lung inflammation; increased the arterial partial pressure of oxygen; and decreased the W/D of the lung, the levels of total proteins and the number of total cells and neutrophils in BALF in the rats with CASP-induced lung injury. Bone-marrow-derived mesenchymal stem cells treatment decreased the levels of tumour necrosis factor-α and Cytokine-induced neutrophil chemoattractant (CINC)-1 and the expression of p-p65 and increased the levels of interleukin-10 and 15d-PGJ2 and the expression of peroxisome proliferator-activated receptor (PPAR)-γ in the lung tissue in CASP-induced rats. Tumour necrosis factor-α stimulated BMSCs to secrete 15d-PGJ2 . A tracking experiment showed that EGFP(+) BMSCs were able to migrate to local lung tissues. Treatment with 15d-PGJ2 also significantly inhibited CASP-induced lung inflammation and the production of pro-inflammatory cytokines. Our results show that BMSCs can protect lung tissues from gastric aspiration injury and inhibit lung inflammation in rats. A beneficial effect might be achieved through BMSC-derived 15d-PGJ2 activation of the PPAR-γ receptor, reducing the production of

Effect of radon and its progeny on the expression and mutation of p53 in lung tissues of mice

International Nuclear Information System (INIS)

Piao Chunnan; Tian Mei; Liu Jianxiang; Ruan Jianlei; Su Xu

2010-01-01

Objective: To explore the effect of radon and its progeny on the expression and mutations of p53 in lung tissue of mouse model. Methods: Apoptosis was detected by terminal deoxynucleotidy transferase-mediated dUTP-biotin nick end labeling. The expression of p53 gene was analyzed by immunohistochemistry, Western blot and realtime-PCR. PCR-SSCP was used to detect the mutation of p53 in lung tissues. Results: Compared with those in the control group, the apoptotic index were increased significantly in 30 WLM and 60 WLM groups (t=18.11, -10.30, P<0.05). The p53 protein was increased significantly (t=-11.08, P<0.05; t=-7.00, P<0.05) in 30 WLM and 60 WLM groups. The mutation of p53 gene was not detected in lungs of radon-exposure mice. Conclusions: Lung and bronchus might be the targets of radon and its progeny, and p53 gene plays an important role in the progression of radon-induced lung injury. (authors)

Accumulation of radium in ferruginous protein bodies formed in lung tissue. Association of resulting radiation hotspots with malignant mesothelioma and other malignancies

International Nuclear Information System (INIS)

Nakamura, Eizo; Makishima, Akio; Hagino, Kyoko; Okabe, Kazunori

2009-01-01

While exposure to fibers and particles has been proposed to be associated with several different lung malignancies including mesothelioma, the mechanism for the carcinogenesis is not fully understood. Along with mineralogical observation, we have analyzed forty-four major and trace elements in extracted asbestos bodies (fibers and proteins attached to them) with coexisting fiber-free ferruginous protein bodies from extirpative lungs of individuals with malignant mesothelioma. These observations together with patients' characteristics suggest that inhaled iron-rich asbestos fibers and dust particles, and excess iron deposited by continuous cigarette smoking would induce ferruginous protein body formation resulting in ferritin aggregates in lung tissue. Chemical analysis of ferruginous protein bodies extracted from lung tissues reveals anomalously high concentrations of radioactive radium, reaching millions of times higher concentration than that of seawater. Continuous and prolonged internal exposure to hotspot ionizing radiation from radium and its daughter nuclides could cause strong and frequent DNA damage in lung tissue, initiate different types of tumour cells, including malignant mesothelioma cells, and may cause cancers. (author)

Right ventricular systolic pressure measurements in combination with harvest of lung and immune tissue samples in mice.

Science.gov (United States)

Chen, Wen-Chi; Park, Sung-Hyun; Hoffman, Carol; Philip, Cecil; Robinson, Linda; West, James; Grunig, Gabriele

2013-01-16

The function of the right heart is to pump blood through the lungs, thus linking right heart physiology and pulmonary vascular physiology. Inflammation is a common modifier of heart and lung function, by elaborating cellular infiltration, production of cytokines and growth factors, and by initiating remodeling processes. Compared to the left ventricle, the right ventricle is a low-pressure pump that operates in a relatively narrow zone of pressure changes. Increased pulmonary artery pressures are associated with increased pressure in the lung vascular bed and pulmonary hypertension. Pulmonary hypertension is often associated with inflammatory lung diseases, for example chronic obstructive pulmonary disease, or autoimmune diseases. Because pulmonary hypertension confers a bad prognosis for quality of life and life expectancy, much research is directed towards understanding the mechanisms that might be targets for pharmaceutical intervention. The main challenge for the development of effective management tools for pulmonary hypertension remains the complexity of the simultaneous understanding of molecular and cellular changes in the right heart, the lungs and the immune system. Here, we present a procedural workflow for the rapid and precise measurement of pressure changes in the right heart of mice and the simultaneous harvest of samples from heart, lungs and immune tissues. The method is based on the direct catheterization of the right ventricle via the jugular vein in close-chested mice, first developed in the late 1990s as surrogate measure of pressures in the pulmonary artery. The organized team-approach facilitates a very rapid right heart catheterization technique. This makes it possible to perform the measurements in mice that spontaneously breathe room air. The organization of the work-flow in distinct work-areas reduces time delay and opens the possibility to simultaneously perform physiology experiments and harvest immune, heart and lung tissues. The

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.

FDG uptake in the fatty tissues of supraclavicular and the vascular structure of the lung hilum

International Nuclear Information System (INIS)

Dang Yaping; Liu Gang; Li Miao

2004-01-01

Objectives: To investigate FDG uptake on the sites of supraclavicular region (SR) and the lung hilum (LH) and find out the exact tissues of the uptake. Methods: Supraclavicular region (SR) and lung hilum (LH) are common sites for lymph node metastases. A commonly reported site of non-malignant FDG uptake on PET imaging in the SR is muscular uptake. PET/CT offers a unique technique to correlate PET findings with CT anatomy in the SR and EH. From September 2002 to March 2003, 147 consecutive clinical patients imaged by FDG PET/CT whole-body scan (GE Discovery LS, CT attenuation correction, OSEM reconstruction) were retrospectively reviewed. The presence of abnormal FDG uptake on PET images in the sites of SR and LH regions was evaluated and the corresponding CT findings on the same regions were also assessed. Results: Of 147 patients, 8 cases (2M, 6F and mean age 44 years) were found with increased symmetrical FDG uptake in the regions of the lower neck and shoulder as well as costo-vertebral articulations, the positive rates were 2.1% and 11.3 % for men and women respectively, and the average rate was 5.4%. However, no FDG uptake was seen in the greater muscular structures of the cervical or thoracic spine. FDG uptake was seen in the fatty tissue between the shoulder muscle and the dorsal thoracic wall, but not within the muscles itself. Five patients (3M, 2F, age 56-74 years,3.4%) showed abnormal LH FDG uptake, which were definitely localized in the vascular structure of the lung hilum by CT Conclusion: Co-registered PET/CT imaging shows that the FDG uptake been well known in the SR and LH regions are not fully located in greater muscular structures and lymph nodes, but in the costo-vertebral articulation complex of the thoracic spine and fatty tissue of the shoulders as well as in the vascular structure of both lung hilum. The FDG uptake in the fatty tissue of the shoulders was mostly seen in women, while the uptake in vascular structure of the lung hilum were

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

Statistical lung model for microdosimetry

International Nuclear Information System (INIS)

Fisher, D.R.; Hadley, R.T.

1984-03-01

To calculate the microdosimetry of plutonium in the lung, a mathematical description is needed of lung tissue microstructure that defines source-site parameters. Beagle lungs were expanded using a glutaraldehyde fixative at 30 cm water pressure. Tissue specimens, five microns thick, were stained with hematoxylin and eosin then studied using an image analyzer. Measurements were made along horizontal lines through the magnified tissue image. The distribution of air space and tissue chord lengths and locations of epithelial cell nuclei were recorded from about 10,000 line scans. The distribution parameters constituted a model of lung microstructure for predicting the paths of random alpha particle tracks in the lung and the probability of traversing biologically sensitive sites. This lung model may be used in conjunction with established deposition and retention models for determining the microdosimetry in the pulmonary lung for a wide variety of inhaled radioactive materials

Microdosimetric approach for lung dose assessments

International Nuclear Information System (INIS)

Hofmann, W.; Steinhausler, F.; Pohl, E.; Bernroider, G.

1980-01-01

In the macroscopic region the term ''organ dose'' is related to an uniform energy deposition within a homogeneous biological target. Considering the lung, inhaled radioactive nuclides, however, show a significant non-uniform distribution pattern throughout the respiratory tract. For the calculation of deposition and clearance of inhaled alpha-emitting radionuclides within different regions of this organ, a detailed compartment model, based on the Weibel model A was developed. Since biological effects (e.g. lung cancer initiation) are primarily caused at the cellular level, the interaction of alpha particles with different types of cells of the lung tissue was studied. The basic approach is to superimpose alpha particle tracks on magnified images of randomly selected tissue slices, simulating alpha emitting sources. Particle tracks are generated by means of a specially developed computer program and used as input data for an on-line electronic image analyzer (Quantimet-720). Using adaptive pattern recognition methods the different cells in the lung tissue can be identified and their distribution within the whole organ determined. This microdosimetric method is applied to soluble radon decay products as well as to insoluble, highly localized, plutonium particles. For a defined microdistribution of alpha emitters, the resulting dose, integrated over all cellular dose values, is compared to the compartmental doses of the ICRP lung model. Furthermore this methodology is also applicable to other organs and tissues of the human body for dose calculations in practical health physics. (author)

Microstructural Consequences of Blast Lung Injury Characterized with Digital Volume Correlation

Directory of Open Access Journals (Sweden)

Hari Arora

2017-12-01

Full Text Available This study focuses on microstructural changes that occur within the mammalian lung when subject to blast and how these changes influence strain distributions within the tissue. Shock tube experiments were performed to generate the blast injured specimens (cadaveric Sprague-Dawley rats. Blast overpressures of 100 and 180 kPa were studied. Synchrotron tomography imaging was used to capture volumetric image data of lungs. Specimens were ventilated using a custom-built system to study multiple inflation pressures during each tomography scan. These data enabled the first digital volume correlation (DVC measurements in lung tissue to be performed. Quantitative analysis was performed to describe the damaged architecture of the lung. No clear changes in the microstructure of the tissue morphology were observed due to controlled low- to moderate-level blast exposure. However, significant focal sites of injury were observed using DVC, which allowed the detection of bias and concentration in the patterns of strain level. Morphological analysis corroborated the findings, illustrating that the focal damage caused by a blast can give rise to diffuse influence across the tissue. It is important to characterize the non-instantly fatal doses of blast, given the transient nature of blast lung in the clinical setting. This research has highlighted the need for better understanding of focal injury and its zone of influence (alveolar interdependency and neighboring tissue burden as a result of focal injury. DVC techniques show great promise as a tool to advance this endeavor, providing a new perspective on lung mechanics after blast.

A multivariate analysis of serum nutrient levels and lung function

Directory of Open Access Journals (Sweden)

Smit Henriette A

2008-09-01

Full Text Available Abstract Background There is mounting evidence that estimates of intakes of a range of dietary nutrients are related to both lung function level and rate of decline, but far less evidence on the relation between lung function and objective measures of serum levels of individual nutrients. The aim of this study was to conduct a comprehensive examination of the independent associations of a wide range of serum markers of nutritional status with lung function, measured as the one-second forced expiratory volume (FEV1. Methods Using data from the Third National Health and Nutrition Examination Survey, a US population-based cross-sectional study, we investigated the relation between 21 serum markers of potentially relevant nutrients and FEV1, with adjustment for potential confounding factors. Systematic approaches were used to guide the analysis. Results In a mutually adjusted model, higher serum levels of antioxidant vitamins (vitamin A, beta-cryptoxanthin, vitamin C, vitamin E, selenium, normalized calcium, chloride, and iron were independently associated with higher levels of FEV1. Higher concentrations of potassium and sodium were associated with lower FEV1. Conclusion Maintaining higher serum concentrations of dietary antioxidant vitamins and selenium is potentially beneficial to lung health. In addition other novel associations found in this study merit further investigation.

Differential Serum Cytokine Levels and Risk of Lung Cancer between African and European Americans

Science.gov (United States)

Pine, Sharon R.; Mechanic, Leah E.; Enewold, Lindsey; Bowman, Elise D.; Ryan, Bríd M.; Cote, Michele L.; Wenzlaff, Angela S.; Loffredo, Christopher A.; Olivo-Marston, Susan; Chaturvedi, Anil; Caporaso, Neil E.; Schwartz, Ann G.; Harris, Curtis C.

2015-01-01

Background African Americans have a higher risk of developing lung cancer than European Americans. Previous studies suggested that certain circulating cytokines were associated with lung cancer. We hypothesized that variations in serum cytokine levels exist between African Americans and European Americans, and increased circulating cytokine levels contribute to lung cancer differently in the two races. Methods Differences in ten serum cytokine levels, interleukin (IL)-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, granulocyte macrophage colony-stimulating factor (GMCSF), interferon (IFN)-γ and tumor necrosis factor (TNF)-α between 170 African-American and 296 European-American controls from the National Cancer Institute-Maryland (NCI-MD) case-control study were assessed. Associations of the serum cytokine levels with lung cancer were analyzed. Statistically significant results were replicated in the prospective Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial and the Wayne State University (WSU) Karmanos Cancer Institute case-control study. Results Six cytokines: IL-4, IL-5, IL-8, IL-10, IFNγ, and TNFα, were significantly higher among European-American as compared to African-American controls. Elevated IL-6 and IL-8 levels were associated with lung cancer among both races in all three studies. Elevated IL-1β, IL-10 and TNFα levels were associated with lung cancer only among African Americans. The association between elevated TNFα levels and lung cancer among European Americans was significant after adjustment for additional factors. Conclusions Serum cytokine levels vary by race and might contribute to lung cancer differently between African Americans and European Americans. Impact Future work examining risk prediction models of lung cancer can measure circulating cytokines to accurately characterize risk within racial groups. PMID:26711330

The protective effect of propolis on damage to lung and blood in rats by inhaled radioactive radon and its progeny

International Nuclear Information System (INIS)

Ding Jiansong; Nie Jihua; Tong Jian

2006-01-01

Twenty-eight male wistar rats were randomly divided into seven groups, i.e. the radon groups (3), the propolis+radon groups (3) and the control (1). The propolis+radon groups were fed intragastrically with propolis 0.2 g/kg, before exposing them, together with the radon groups, to radon and its progeny with the cumulative dose up to 30, 67 and 111 working level month (WLM), respectively. The levels of SOD (superoxide dismutase) and MDA (Malonic dialdehyde) in blood and lung tissue were determined. The SOD level of in blood and lung tissues of the radon groups decreased significantly and the MDA level increased. The MDA level in lung tissue of the 30 WLM propolis+radon group was significantly higher than the 30 WLM radon group. The SOD level in lung tissue of the 67 WLM propolis+radon group was significantly higher, but the MDA level was significantly lower, than the 67 WLM radon group. Both the SOD and MDA levels in blood and lung tissue of the 111 WLM propolis+radon group were significantly higher than the 111 WLM radon group. In conclusion, the inhalation of radon and its progeny can lead to persistent disturbance of the redox state in rats. Propolis show some protective effects on the redox damage under the experimental conditions. (authors)

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....

The level of serum tumor makers and bone metastases of lung cancer correlation

International Nuclear Information System (INIS)

Li Li; Jin Jianhua

2014-01-01

Objective: To study the correlation between the level of serum tumor makers and bone metastases of lung cancer. Method: In 128 diagnosed patients with lung cancer, small cell lung cancer were 26 cases, non-small cell lung cancer were 102 cases which included 44 cases of adenocarcinoma, 50 cases of squamous cell carcinoma, 4 cases of large cell carcinoma, 4 cases of squamous adenocarcinoma. "9"9"mTc-MDP whole-body bone scanning was performed in 128 patients with lung cancer. over the same period, the serum samples were collected in these patients and 30 comparison controls. CEA, CA125, CA199, SCC, NSE, CA15-3, and AFP were measured by ELISA technique. Bone imaging findings analysis used t-test, and serum levels of tumor markers analysis used χ"2 test. Results: The diagnostic of 53 cases of lung cancer with bone metastasis was subject to clinical criteria of lung cancer with bone metastases. The positive ratio of patients with osseous metastasis was confirmed by "9"9"mTc-MDP whole-body bone scanning was 23.44% (30/128), including 16 cases of lung adenocarcinoma, 9 cases of squamous cell carcinoma, 3 cases of small cell lung cancer , 1 case of large cell lung cancer, 1 case of squamous adenocarcinoma and multiple bone metastases accounted for 66.67% (20/30). The levels of serum CEA, CA125, CA199, SCC, NSE and CA15-3 were higher than the control group (P < O.05). 29 cases of CEA positive and 21 cases of CA125 positive were included in 30 cases of lung cancer with bone metastasis. There was a significant difference between the levels of CEA, CA125, CA199, NSE in lung cancer with bone metastases and without bone metastases (P < 0.05). The sensitivity of "9"9"mTc-MDP whole-body bone scanning in diagnosis of lung cancer with bone metastasis was 84.91%. Conclusion: The average value of CEA, CA125, and CA199, SCC, NSE and CA15-3 in lung cancer patients were significantly higher than the control group. In addition, there is a significantly correlation between the occurrence

Importance of scatter compensation algorithm in heterogeneous tissue for the radiation dose calculation of small lung nodules. A clinical study

International Nuclear Information System (INIS)

Baba, Yuji; Murakami, Ryuji; Mizukami, Naohisa; Morishita, Shoji; Yamashita, Yasuyuki; Araki, Fujio; Moribe, Nobuyuki; Hirata, Yukinori

2004-01-01

The purpose of this study was to compare radiation doses of small lung nodules calculated with beam scattering compensation and those without compensation in heterogeneous tissues. Computed tomography (CT) data of 34 small (1-2 cm: 12 nodules, 2-3 cm 11 nodules, 3-4 cm 11 nodules) lung nodules were used in the radiation dose measurements. Radiation planning for lung nodule was performed with a commercially available unit using two different radiation dose calculation methods: the superposition method (with scatter compensation in heterogeneous tissues), and the Clarkson method (without scatter compensation in heterogeneous tissues). The energy of the linac photon used in this study was 10 MV and 4 MV. Monitor unit (MU) to deliver 10 Gy at the center of the radiation field (center of the nodule) calculated with the two methods were compared. In 1-2 cm nodules, MU calculated by Clarkson method (MUc) was 90.0±1.1% (4 MV photon) and 80.5±2.7% (10 MV photon) compared to MU calculated by superposion method (MUs), in 2-3 cm nodules, MUc was 92.9±1.1% (4 MV photon) and 86.6±2.8% (10 MV photon) compared to MUs, and in 3-4 cm nodules, MUc was 90.5±2.0% (4 MV photon) and 90.1±1.7% (10 MV photon) compared to MUs. In 1-2 cm nodules, MU calculated without lung compensation (MUn) was 120.6±8.3% (4 MV photon) and 95.1±4.1% (10 MV photon) compared to MU calculated by superposion method (MUs), in 2-3 cm nodules, MUc was 120.3±11.5% (4 MV photon) and 100.5±4.6% (10 MV photon) compared to MUs, and in 3-4 cm nodules, MUc was 105.3±9.0% (4 MV photon) and 103.4±4.9% (10 MV photon) compared to MUs. The MU calculated without lung compensation was not significantly different from the MU calculated by superposition method in 2-3 cm nodules. We found that the conventional dose calculation algorithm without scatter compensation in heterogeneous tissues substantially overestimated the radiation dose of small nodules in the lung field. In the calculation of dose distribution of small

Lung segmentation from HRCT using united geometric active contours

Science.gov (United States)

Liu, Junwei; Li, Chuanfu; Xiong, Jin; Feng, Huanqing

2007-12-01

Accurate lung segmentation from high resolution CT images is a challenging task due to various detail tracheal structures, missing boundary segments and complex lung anatomy. One popular method is based on gray-level threshold, however its results are usually rough. A united geometric active contours model based on level set is proposed for lung segmentation in this paper. Particularly, this method combines local boundary information and region statistical-based model synchronously: 1) Boundary term ensures the integrality of lung tissue.2) Region term makes the level set function evolve with global characteristic and independent on initial settings. A penalizing energy term is introduced into the model, which forces the level set function evolving without re-initialization. The method is found to be much more efficient in lung segmentation than other methods that are only based on boundary or region. Results are shown by 3D lung surface reconstruction, which indicates that the method will play an important role in the design of computer-aided diagnostic (CAD) system.

Innate lymphoid cells: the role in respiratory infections and lung tissue damage.

Science.gov (United States)

Głobińska, Anna; Kowalski, Marek L

2017-10-01

Innate lymphoid cells (ILCs) represent a diverse family of cells of the innate immune system, which play an important role in regulation of tissue homeostasis, immunity and inflammation. Emerging evidence has highlighted the importance of ILCs in both protective immunity to respiratory infections and their pathological roles in the lungs. Therefore, the aim of this review is to summarize the current knowledge, interpret and integrate it into broader perspective, enabling greater insight into the role of ILCs in respiratory diseases. Areas covered: In this review we highlighted the role of ILCs in the lungs, citing the most recent studies in this area. PubMed searches (2004- July 2017) were conducted using the term 'innate lymphoid cells respiratory viral infections' in combination with other relevant terms including various respiratory viruses. Expert commentary: Since studies of ILCs have opened new areas of investigation, understanding the role of ILCs in respiratory infections may help to clarify the mechanisms underlying viral-induced exacerbations of lung diseases, providing the basis for novel therapeutic strategies. Potential therapeutic targets have already been identified. So far, the most promising strategy is cytokine-targeting, although further clinical trials are needed to verify its effectiveness.

Lung vitamin E transport processes are affected by both age and environmental oxidants in mice

International Nuclear Information System (INIS)

Valacchi, Giuseppe; Vasu, Vihas T.; Yokohama, Wallace; Corbacho, Ana M.; Phung, Anh; Lim, Yunsook; Aung, Hnin Hnin; Cross, Carroll E.; Davis, Paul A.

2007-01-01

Despite the physiological importance of alpha-tocopherol (AT), the molecular mechanisms involved in maintaining cellular and tissue tocopherol levels remain to be fully characterized. Scavenger receptor B1 (SRB1), one of a large family of scavenger receptors, has been shown to facilitate AT transfer from HDL to peripheral tissues via apo A-1-mediated processes and to be important in the delivery of AT to the lung cells. In the present studies the effects of age and two environmental oxidants ozone (O 3 ) (0.25 ppm 6 h/day) and cigarette smoke (CS) (60 mg/m 3 6 h/day) for 4 days on selected aspects of AT transport in murine lung tissues were assessed. While AT levels were 25% higher (p 3 or CS at the doses used had no effect. Gene expression levels, determined by RT-PCR of AT transport protein (ATTP), SRB1, CD36, ATP binding cassette 3 (ABCA3) and ABCA1 and protein levels, determined by Western blots for SRB1, ATTP and ABCA1 were assessed. Aged mouse lung showed a lower levels of ATTP, ABCA3 and SRB1 and a higher level CD36 and ABCA1. Acute exposure to either O 3 or CS induced declines in ATTP and SRB1 in both aged and young mice lung. CD36 increased in both young and aged mice lung upon exposure to O 3 and CS. These findings suggest that both age and environmental oxidant exposure affect pathways related to lung AT homeostasis and do so in a way that favors declines in lung AT. However, given the approach taken, the effects cannot be traced to changes in these pathways or AT content in any specific lung associated cell type and thus highlight the need for further follow-up studies looking at specific lung associated cell types

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.

Fibrocytes in the Fibrotic Lung: Altered Phenotype Detected by Flow Cytometry

Directory of Open Access Journals (Sweden)

Charles eReese

2014-06-01

Full Text Available Fibrocytes are bone marrow hematopoietic-derived cells that also express a mesenchymal cell marker (commonly collagen I and participate in fibrotic diseases of multiple organs. Given their origin, they or their precursors must be circulating cells before recruitment into target tissues. While most previous studies focused on circulating fibrocytes, here we focus on the fibrocyte phenotype in fibrotic tissue. The study’s relevance to human disease is heightened by use of a model in which bleomycin is delivered systemically, recapitulating several features of human scleroderma including multi-organ fibrosis not observed when bleomycin is delivered directly into the lungs. Using flow cytometry, we find in the fibrotic lung a large population of CD45high fibrocytes (called Region I rarely found in vehicle-treated control mice. A second population of CD45+ fibrocytes (called Region II is observed in both control and fibrotic lung. The level of CD45 in circulating fibrocytes is far lower than in either Region I or II lung fibrocytes. The chemokine receptors CXCR4 and CCR5 are expressed at higher levels in Region I than in Region II and are present at very low levels in all other lung cells including CD45+/collagen I- leucocytes. The collagen chaperone HSP47 is present at similar high levels in both Regions I and II, but at a higher level in fibrotic lung than in control lung. There is also a major population of HSP47high/CD45- cells in fibrotic lung not present in control lung. CD44 is present at higher levels in Region I than in Region II and at much lower levels in all other cells including CD45+/collagen I- leucocytes. When lung fibrosis is inhibited by restoring caveolin-1 activity using a caveolin-1 scaffolding domain peptide (CSD, a strong correlation is observed between fibrocyte number and fibrosis score. In summary, the distinctive phenotype of fibrotic lung fibrocytes suggests that fibrocyte differentiation occurs primarily within the

Chitinase mRNA Levels Determined by QPCR in Crab-Eating Monkey (Macaca fascicularis) Tissues: Species-Specific Expression of Acidic Mammalian Chitinase and Chitotriosidase.

Science.gov (United States)

Uehara, Maiko; Tabata, Eri; Ishii, Kazuhiro; Sawa, Akira; Ohno, Misa; Sakaguchi, Masayoshi; Matoska, Vaclav; Bauer, Peter O; Oyama, Fumitaka

2018-05-09

Mice and humans express two active chitinases: acidic mammalian chitinase (AMCase) and chitotriosidase (CHIT1). Both chitinases are thought to play important roles in specific pathophysiological conditions. The crab-eating monkey ( Macaca fascicularis ) is one of the most frequently used nonhuman primate models in basic and applied biomedical research. Here, we performed gene expression analysis of two chitinases in normal crab-eating monkey tissues by way of quantitative real-time polymerase chain reaction (qPCR) using a single standard DNA molecule. Levels of AMCase and CHIT1 messenger RNAs (mRNAs) were highest in the stomach and the lung, respectively, when compared to other tissues. Comparative gene expression analysis of mouse, monkey, and human using monkey⁻mouse⁻human hybrid standard DNA showed that the AMCase mRNA levels were exceptionally high in mouse and monkey stomachs while very low in the human stomach. As for the CHIT1 mRNA, we detected higher levels in the monkey lung when compared with those of mouse and human. The differences of mRNA expression between the species in the stomach tissues were basically reflecting the levels of the chitinolytic activities. These results indicate that gene expression of AMCase and CHIT1 differs between mammalian species and requiring special attention in handling data in chitinase-related studies in particular organisms.

The novel human influenza A(H7N9) virus is naturally adapted to efficient growth in human lung tissue.

Science.gov (United States)

Knepper, Jessica; Schierhorn, Kristina L; Becher, Anne; Budt, Matthias; Tönnies, Mario; Bauer, Torsten T; Schneider, Paul; Neudecker, Jens; Rückert, Jens C; Gruber, Achim D; Suttorp, Norbert; Schweiger, Brunhilde; Hippenstiel, Stefan; Hocke, Andreas C; Wolff, Thorsten

2013-10-08

A novel influenza A virus (IAV) of the H7N9 subtype has been isolated from severely diseased patients with pneumonia and acute respiratory distress syndrome and, apparently, from healthy poultry in March 2013 in Eastern China. We evaluated replication, tropism, and cytokine induction of the A/Anhui/1/2013 (H7N9) virus isolated from a fatal human infection and two low-pathogenic avian H7 subtype viruses in a human lung organ culture system mimicking infection of the lower respiratory tract. The A(H7N9) patient isolate replicated similarly well as a seasonal IAV in explanted human lung tissue, whereas avian H7 subtype viruses propagated poorly. Interestingly, the avian H7 strains provoked a strong antiviral type I interferon (IFN-I) response, whereas the A(H7N9) virus induced only low IFN levels. Nevertheless, all viruses analyzed were detected predominantly in type II pneumocytes, indicating that the A(H7N9) virus does not differ in its cellular tropism from other avian or human influenza viruses. Tissue culture-based studies suggested that the low induction of the IFN-β promoter correlated with an efficient suppression by the viral NS1 protein. These findings demonstrate that the zoonotic A(H7N9) virus is unusually well adapted to efficient propagation in human alveolar tissue, which most likely contributes to the severity of lower respiratory tract disease seen in many patients. Humans are usually not infected by avian influenza A viruses (IAV), but this large group of viruses contributes to the emergence of human pandemic strains. Transmission of virulent avian IAV to humans is therefore an alarming event that requires assessment of the biology as well as pathogenic and pandemic potentials of the viruses in clinically relevant models. Here, we demonstrate that an early virus isolate from the recent A(H7N9) outbreak in Eastern China replicated as efficiently as human-adapted IAV in explanted human lung tissue, whereas avian H7 subtype viruses were unable to

Bothrops jararaca venom metalloproteinases are essential for coagulopathy and increase plasma tissue factor levels during envenomation.

Directory of Open Access Journals (Sweden)

Karine M Yamashita

2014-05-01

Full Text Available BACKGROUND/AIMS: Bleeding tendency, coagulopathy and platelet disorders are recurrent manifestations in snakebites occurring worldwide. We reasoned that by damaging tissues and/or activating cells at the site of the bite and systemically, snake venom toxins might release or decrypt tissue factor (TF, resulting in activation of blood coagulation and aggravation of the bleeding tendency. Thus, we addressed (a whether TF and protein disulfide isomerase (PDI, an oxireductase involved in TF encryption/decryption, were altered in experimental snake envenomation; (b the involvement and significance of snake venom metalloproteinases (SVMP and serine proteinases (SVSP to hemostatic disturbances. METHODS/PRINCIPAL FINDINGS: Crude Bothrops jararaca venom (BjV was preincubated with Na2-EDTA or AEBSF, which are inhibitors of SVMP and SVSP, respectively, and injected subcutaneously or intravenously into rats to analyze the contribution of local lesion to the development of hemostatic disturbances. Samples of blood, lung and skin were collected and analyzed at 3 and 6 h. Platelet counts were markedly diminished in rats, and neither Na2-EDTA nor AEBSF could effectively abrogate this fall. However, Na2-EDTA markedly reduced plasma fibrinogen consumption and hemorrhage at the site of BjV inoculation. Na2-EDTA also abolished the marked elevation in TF levels in plasma at 3 and 6 h, by both administration routes. Moreover, increased TF activity was also noticed in lung and skin tissue samples at 6 h. However, factor VII levels did not decrease over time. PDI expression in skin was normal at 3 h, and downregulated at 6 h in all groups treated with BjV. CONCLUSIONS: SVMP induce coagulopathy, hemorrhage and increased TF levels in plasma, but neither SVMP nor SVSP are directly involved in thrombocytopenia. High levels of TF in plasma and TF decryption occur during snake envenomation, like true disseminated intravascular coagulation syndrome, and might be implicated in

Lung cancer in connective tissue disease-associated interstitial lung disease: clinical features and impact on outcomes.

Science.gov (United States)

Watanabe, Satoshi; Saeki, Keigo; Waseda, Yuko; Murata, Akari; Takato, Hazuki; Ichikawa, Yukari; Yasui, Masahide; Kimura, Hideharu; Hamaguchi, Yasuhito; Matsushita, Takashi; Yamada, Kazunori; Kawano, Mitsuhiro; Furuichi, Kengo; Wada, Takashi; Kasahara, Kazuo

2018-02-01

Lung cancer (LC) adversely impacts survival in patients with idiopathic pulmonary fibrosis. However, little is known about LC in patients with connective tissue disease-associated interstitial lung disease (CTD-ILD). The aim of this study was to evaluate the prevalence of and risk factors for LC in CTD-ILD, and the clinical characteristics and survival of CTD-ILD patients with LC. We conducted a single-center, retrospective review of patients with CTD-ILD from 2003 to 2016. Patients with pathologically diagnosed LC were identified. The prevalence, risk factors, and clinical features of LC and the impact of LC on CTD-ILD patient outcomes were observed. Of 266 patients with CTD-ILD, 24 (9.0%) had LC. CTD-ILD with LC was more likely in patients who were older, male, and smokers; had rheumatoid arthritis, a usual interstitial pneumonia pattern, emphysema on chest computed tomography scan, and lower diffusing capacity of the lung carbon monoxide (DLco)% predicted; and were not receiving immunosuppressive therapy. Multivariate analysis indicated that the presence of emphysema [odds ratio (OR), 8.473; 95% confidence interval (CI), 2.241-32.033] and nonuse of immunosuppressive therapy (OR, 8.111; 95% CI, 2.457-26.775) were independent risk factors for LC. CTD-ILD patients with LC had significantly worse survival than patients without LC (10-year survival rate: 28.5% vs. 81.8%, P<0.001). LC is associated with the presence of emphysema and nonuse of immunosuppressive therapy, and contributes to increased mortality in patients with CTD-ILD.

P38 pathway as a key downstream signal of connective tissue growth factor to regulate metastatic potential in non-small-cell lung cancer.

Science.gov (United States)

Kato, Shinichiro; Yokoyama, Satoru; Hayakawa, Yoshihiro; Li, Luhui; Iwakami, Yusuke; Sakurai, Hiroaki; Saiki, Ikuo

2016-10-01

Although the secretory matricellular protein connective tissue growth factor (CTGF) has been reported to be related to lung cancer metastasis, the precise mechanism by which CTGF regulates lung cancer metastasis has not been elucidated. In the present study, we show the molecular link between CTGF secretion and the p38 pathway in the invasive and metastatic potential of non-small-cell lung cancer (NSCLC). Among three different human NSCLC cell lines (PC-14, A549, and PC-9), their in vitro invasiveness was inversely correlated with the level of CTGF secretion. By supplementing or reducing CTGF secretion in NSCLC culture, dysregulation of the invasive and metastatic potential of NSCLC cell lines was largely compensated. By focusing on the protein kinases that are known to be regulated by CTGF, we found that the p38 pathway is a key downstream signal of CTGF to regulate the metastatic potential of NSCLC. Importantly, a negative correlation between CTGF and phosphorylation status of p38 was identified in The Cancer Genome Atlas lung adenocarcinoma dataset. In the context of the clinical importance of our findings, we showed that p38 inhibitor, SB203580, reduced the metastatic potential of NSCLC secreting low levels of CTGF. Collectively, our present findings indicate that the CTGF/p38 axis is a novel therapeutic target of NSCLC metastasis, particularly NSCLC secreting low levels of CTGF. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Decreased expression of connective tissue growth factor in non-small cell lung cancer is associated with clinicopathological variables and can be restored by epigenetic modifiers.

Science.gov (United States)

Drzewiecka, Hanna; Gałęcki, Bartłomiej; Jarmołowska-Jurczyszyn, Donata; Kluk, Andrzej; Dyszkiewicz, Wojciech; Jagodziński, Paweł P

2016-09-01

Recent studies indicated undisputed contribution of connective tissue growth factor (CTGF) in the development of many cancers, including non-small cell lung cancer (NSCLC). However, the functional role and regulation of CTGF expression during tumorigenesis remain elusive. Our goal was to determine CTGF transcript and protein levels in tumoral and matched control tissues from 98 NSCLC patients, to correlate the results with clinicopathological features and to investigate whether the CTGF expression can be epigenetically regulated in NSCLC. We used quantitative PCR, Western blotting and immunohistochemistry to evaluate CTGF expression in lung cancerous and histopathologically unchanged tissues. We tested the impact of 5-Aza-2'-deoxycytidine (5-dAzaC) and trichostatin A (TSA) on CTGF transcript and protein levels in NSCLC cells (A549, Calu-1). DNA methylation status of the CTGF regulatory region was evaluated by bisulfite sequencing. The influence of 5-dAzaC and TSA on NSCLC cells viability and proliferation was monitored by the trypan blue assay. We found significantly decreased levels of CTGF mRNA and protein (both p cancerous tissues of NSCLC patients. Down-regulation of CTGF occurred regardless of gender in all histological subtypes of NSCLC. Moreover, we showed that 5-dAzaC and TSA were able to restore CTGF mRNA and protein contents in NSCLC cells. However, no methylation within CTGF regulatory region was detected. Both compounds significantly reduced NSCLC cells proliferation. Decreased expression of CTGF is a common feature in NSCLC; however, it can be restored by the chromatin-modifying agents such as 5-dAzaC or TSA and consequently restrain cancer development.

FDG uptake in the fatty tissues of supraclavicular and the vascular structure of the lung hilum

International Nuclear Information System (INIS)

Dang Yaping; Liu Gang; Li Miao

2004-01-01

Full text: Supraclavicular region (SR) and lung hilum (LH) are common sites for lymph node metastases. A commonly reported site of non-malignant FDG uptake on PET imaging in the SR is muscular uptake. PET/CT offers a unique technique to correlate PET findings with CT anatomy in the SR and LH. We carried out this study to investigate FDG uptake in SR and LH to find out the exact tissues of FDG uptake. From September 2002 to March 2003, 147 consecutive patients imaged by FDG PET/CT whole-body scan (GE Discovery LS, CT attenuation correction, OSEM reconstruction) were retrospectively reviewed. The presence of abnormal FDG uptake on PET images in SR and LH regions was evaluated and the corresponding CT findings on the same regions were also assessed. Of the 147 patients, 8 cases (2M, 6F and mean age 44 years) were found with increased symmetrical FDG uptake in the regions of the lower neck and shoulder as well as costo-vertebral articulations. The positive rates were 2.1% and 11.3% for men and women respectively, and the average rate was 5.4%. However, no FDG uptake was seen in the greater muscular structures of the cervical or thoracic spine. FDG uptake was seen in the fatty tissue between the shoulder muscle and the dorsal thoracic wall, but not within the muscles itself. Five patients (3M, 2F, age 56-74 years, 3.4%) showed abnormal FDG uptake in LH, which were definitely localized in the vascular structure of the lung hilum by CT. Co-registered PET/CT imaging shows that the FDG uptake, though well known in the SR and LH regions, is not fully located in greater muscular structures and lymph nodes, but in the costo-vertebral articulation complex of the thoracic spine and fatty tissue of the shoulders as well as in the vascular structure of both lung hilum. The FDG uptake in the fatty tissue of the shoulders was mostly seen in women, while the uptake in vascular structure of the lung hilum were found in aged people. (author)

Maintenance of cAMP in non-heart-beating donor lungs reduces ischemia-reperfusion injury.

Science.gov (United States)

Hoffmann, S C; Bleiweis, M S; Jones, D R; Paik, H C; Ciriaco, P; Egan, T M

2001-06-01

Studies suggest that pulmonary vascular ischemia-reperfusion injury (IRI) can be attenuated by increasing intracellular cAMP concentrations. The purpose of this study was to determine the effect of IRI on capillary permeability, assessed by capillary filtration coeficient (Kfc), in lungs retrieved from non-heart-beating donors (NHBDs) and reperfused with the addition of the beta(2)-adrenergic receptor agonist isoproterenol (iso), and rolipram (roli), a phosphodiesterase (type IV) inhibitor. Using an in situ isolated perfused lung model, lungs were retrieved from NHBD rats at varying intervals after death and either ventilated with O(2) or not ventilated. The lungs were reperfused with Earle's solution with or without a combination of iso (10 microM) and roli (2 microM). Kfc, lung viability, and pulmonary hemodynamics were measured. Lung tissue levels of adenine nucleotides and cAMP were measured by HPLC. Combined iso and roli (iso/roli) reperfusion decreased Kfc significantly (p Kfc in non-iso/roli-reperfused (r = 0.89) and iso/roli-reperfused (r = 0.97) lungs. cAMP levels correlated with Kfc (r = 0.93) in iso/roli-reperfused lungs. Pharmacologic augmentation of tissue TAN and cAMP levels might ameliorate the increased capillary permeability observed in lungs retrieved from NHBDs.

Prognostic significance of tissue polypeptidespecific antigen (TPS) in patients with advanced non-small cell lung cancer

NARCIS (Netherlands)

A. van der Gaast (Ate); C.H.H. Schoenmakers (Christian); T.C. Kok (Tjebbe); B.G. Blijenberg (Bert); W.C.J. Hop (Wim); T.A.W. Splinter (Ted)

1994-01-01

textabstractIn this study, we evaluated the prognostic value of the tumour marker, tissue polypeptide-specific antigen (TPS), in 203 patients with non-small cell lung cancer (NSCLC), and related this to several other known prognostic factors. TPS was significantly correlated with lactate

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.

Computer program modifications for lung microdosimetry

International Nuclear Information System (INIS)

Harty, R.; Hadley, R.T.

1983-01-01

A lung model based on statistical studies of beagle dog lung microstructure was incorporated to describe the distributions of tissue, air space, and cell nuclei in pulmonary lung tissue was modified from basic to FORTRAN to shorten time and increase flexibility

Dosimetric lung models

International Nuclear Information System (INIS)

James, A.C.; Roy, M.

1986-01-01

The anatomical and physiological factors that vary with age and influence the deposition of airborne radionuclides in the lung are reviewed. The efficiency with which aerosols deposit in the lung for a given exposure at various ages from birth to adulthood is evaluated. Deposition within the lung is considered in relation to the clearance mechanisms acting in different regions or compartments. The procedure for evaluating dose to sensitive tissues in lung and transfer to other organs that is being considered by the Task Group established by ICRP to review the Lung Model is outlined. Examples of the application of this modelling procedure to evaluate lung dose as a function of age are given, for exposure to radon daughters in dwellings, and for exposure to an insoluble 239 Pu aerosol. The former represents exposure to short-lived radionuclides that deliver relatively high doses to bronchial tissue. In this case, dose rates are marginally higher in children than in adults. Plutonium exposure represents the case where dose is predominantly delivered to respiratory tissue and lymph nodes. In this case, the life-time doses tend to be lower for exposure in childhood. Some of the uncertainties in this modelling procedure are noted

MMP-10 Is Overexpressed, Proteolytically Active, and a Potential Target for Therapeutic Intervention in Human Lung Carcinomas

Directory of Open Access Journals (Sweden)

Jason H. Gill

2004-11-01

Full Text Available Matrix metalloproteinase (MMP-mediated degradation of the extracellular matrix is a major factor for tumor development and expansion. This study analysed MMP-10 protein expression and activity in human lung tumors of various grade, stage, and type to address the relationship between MMP-10 and tumor characteristics and to evaluate MMP-10 as a therapeutic target in non small cell lung carcinoma (NSCLC. Unlike the majority of MMPs, MMP-10 was located in the tumor mass as opposed to tumor stroma. MMP-10 protein was observed at low levels in normal human lung tissues and at significantly higher levels in all types of NSCLC. No correlation was observed between MMP-10 protein expression and tumor type, stage, or lymph node invasion. To discriminate between active and inactive forms of MMP-10 in samples of human NSCLC, we have developed an ex vivo fluorescent assay. Measurable MMP-10 activity was detected in 42 of 50 specimens of lung cancer and only 2 of 10 specimens of histologically normal lung tissue. No relationship was observed between MMP-10 activity levels and clinicopathologic characteristics. Our results suggest that MMP-10 is expressed and active at high levels in human NSCLC compared to normal lung tissues, and, as such, is a potential target for the development of novel therapeutics for lung cancer treatment.

[Elevated expression of endothelin 2 in lung tissues of asthmatic rats after exposed to cigarette smoke and its mechanism].

Science.gov (United States)

Han, Fangfang; Zhu, Shuyang; Chen, Bi; Li, Jingjing

2017-08-01

Objective To study the effect of cigarette smoke exposure on the expression of endothelin 2 (ET-2) in bronchial epithelium of asthmatic rats. Methods Asthma models were established through intraperitoneal injection of 1 mL chicken ovalbumin (OVA)/Al(OH) 3 mixture (asthma model group, n=6); based on the asthma models, exposure to smoking gas lasted four weeks with 10 cigarettes per day (smoke-exposed asthma group, n=6); based on the smoke-exposed asthma models, the rats were treated with intraperitoneal injection of dexamethasone 2 mg/(kg.d), intragastric administration of ET receptor inhibitor bosentan 100 mg/(kg.d) and combined use, respectively named dexamethasone treated group, bosentan treated group, and dexamethasone-bosentan treated group, 6 rats in every group. What's more, other 6 rats were only subjected to intraperitoneal injection of 1 mL normal saline as normal controls; in addition to the injection of saline, cigarette smoke control group (n=6) was set up by the exposure to smoking gas for four weeks with 10 cigarettes per day. Bronchoalveolar lavage fluid (BALF) was collected from the upper lobe of the left lung for cell counting and classification. Pathological changes of the right upper lung lobe tissues were observed by HE staining. In other lung tissues, the expression of JNK1/2 was detected by Western blotting; ET-2 was tested by Western blotting and immunohistochemistry; thiobarbituric acid reactive substances (TBARS) assay and trace enzyme standard method were used to measure malondialdehyde (MDA) and glutathione (GSH), respectively. Results Compared with normal control group, the number of airway inflammation cells increased in the BALF, and the expressions of ET-2, JNK1/2, MDA and GSH increased in the lung tissues of cigarette smoke control group, asthma model group and cigarette smoke-exposed asthma group. Compared with cigarette smoke-exposed asthma group, the number of airway inflammation cells decreased in the BALF, and the expressions of

Effect of chest wall radiotherapy in different manners using tissue equivalent bolus on skin and lung of cavia cobayas

International Nuclear Information System (INIS)

Huang Wei; Qu Yaqin; Song Xiangfu; Liu Shixin; Jia Xiaojing; Guo He; Yang Lei

2009-01-01

Objective: To probe the influence of electron beam radiotherapy in different manners using different tissue equivalent boluses on skin and lung. Methods: Adult female cavia cobayas were randomly divided into four groups as control group, half-time with bolus group, half-time with bolus group and without bolus group. Acute-irradiation animal models were established using electron beam in different manners with or without 0.5 cm tissue equivalent bolus. Pathological changes in lung, hair vesicle and fibroblast cell count were analyzed 40 clays after irradiation. Results: The radiation dermatitis in the group with bolus was slighter than that of the group without bolus, but the radiation pneumonia was reverse. With bolus, the radiation dermatitis of haft-time group was slighter than that of full-time group. The injury repair of half-time group was more active than full-time group. Conclusions: The treatment of haft-time bolus could protect lung without serious skin complications. (authors)

Overexpression of K-p21Ras play a prominent role in lung cancer

Science.gov (United States)

Zhang, Peng-bo; Zhou, Xin-liang; Yang, Ju-lun

2018-06-01

The proto-oncogene ras product, p21Ras, has been found overexpression in many human tumors. However, the subtypes of overexpressed p21Ras still remain unclear. The purpose of this study was to investigate overexpressed isoforms of p21Ras and their roles in the progress of lung cancer. Method: The expression of total p21Ras in normal lung tissues and lung cancers was determined by immunohistochemically staining with monoclonal antibody (Mab) KGHR-1 which could recognize and broad spectrum reaction with the (K/H/N) ras protein. Then, the isoforms of p21Ras was examined by specific Mab for each p21Ras subtypes. Results: Low expression of total p21Ras was found in 26.67% (8/30) of normal lung tissues, and 81.31% (87/107) of adenocarcinoma harbored overexpressed total p21Ras. Besides, 70.00% (35/50) of squamous cell carcinoma were detected overexpressed total p21Ras. In addition, 122 lung cancer tissues from overexpression of total p21Ras protein were selected to detect the expression of each subtype. And all the 122 lung cancer tissues were K-p21Ras overexpression. Moreover, there was a statistical significance difference between the expression level of total p21Ras and differentiation, and the same results were observed between the expression level of total p21Ras and lymph node metastasis (P0.05). Conclusions: Overexpression of K-p21Ras plays a prominent role in the progress of lung cancer and it is suggested that the p21Ras could serve as a promising treatment target in lung cancer.

Expected indoor 222Rn levels in counties with very high and very low lung cancer rates

International Nuclear Information System (INIS)

Cohen, B.L.

1989-01-01

Counties in the US with high lung cancer rates should have higher average 222 Rn levels than counties with low lung cancer rates, assuming the average 222 Rn level in a county is not correlated with other factors that cause lung cancer. The magnitude of this effect was calculated, using the absolute risk model, the relative risk model, and an intermediate model, for females who died in 1950-1969. The results were similar for all three models. We concluded that, ignoring migration, the average Rn level in the highest lung cancer counties should be about three times higher than in the lowest lung cancer counties according to the theory. Preliminary data are presented indicating that the situation is quite the opposite: The average Rn level in the highest lung cancer counties was only about one-half that in the lowest lung cancer counties

Desferrioxamine Reduces Oxidative Stress in the Lung Contusion

Directory of Open Access Journals (Sweden)

Umit Nusret Basaran

2013-01-01

Full Text Available Our hypothesis in this study is that desferrioxamine (DFX has therapeutic effects on experimental lung contusions in rats. The rats were divided into four groups (n=8: control, control+DFX, contusion, and contusion+DFX. In the control+DFX and contusion+DFX groups, 100 mg/kg DFX was given intraperitoneally once a day just after the contusion and the day after the contusion. Contusions led to a meaningful rise in the malondialdehyde (MDA level in lung tissue. MDA levels in the contusion+DFX group experienced a significant decline. Glutathione levels were significantly lower in the contusion group than in the control group and significantly higher in the contusion+DFX group. Glutathione peroxidase (GPx and superoxide dismutase (SOD levels in the contusion group were significantly lower than those in the control group. In the contusion+DFX group, SOD and GPx levels were significantly higher than those in the contusion group. In light microscopic evaluation, the contusion and contusion+DFX groups showed edema, hemorrhage, alveolar destruction, and leukocyte infiltration. However, histological scoring of the contusion+DFX group was significantly more positive than that of the contusion group. The iNOS staining in the contusion group was significantly more intensive than that in all other groups. DFX reduced iNOS staining significantly in comparison to the contusion group. This study showed that DFX reduced oxidative stress in lung contusions in rats and histopathologically ensured the recovery of the lung tissue.

Concentration of mercury and selenium in tissues of five cetacean species from Croatian coastal waters

Directory of Open Access Journals (Sweden)

Bilandžić Nina

2015-01-01

Full Text Available Mercury (Hg and selenium (Se concentrations were measured in muscle, liver, kidney, spleen and lung tissues of five cetacean species, three dolphin (Stenella coeruleoalba, Tursiops truncatus and Grampus griseus and two whale species (Balaenoptera physalus and Ziphius cavirostris, stranded along the Croatian coast during the period 1999-2002. Statistically significant differences in Hg concentrations in muscle, spleen and lung, and Se in liver and lung of the different dolphin species were observed. Mercury levels in liver and spleen and Se levels in liver differed between young and adult T. truncatus species. A significant positive correlation between different tissue types for Hg and Se concentrations was observed. In all tissues tested, the lowest Hg and Se concentrations were found in B. physalus. Mercury concentrations were positively correlated with Se in all tissues. The results present one of few studies related to lung and spleen tissues in these mammals, particularly in the Adriatic Sea. Since very little data are available, this research provides new data on concentrations of Hg and Se in five cetacean species from the Adriatic Sea basin.

Kaempferol attenuates acute lung injury in caecal ligation and puncture model of sepsis in mice.

Science.gov (United States)

Rabha, Dipankar Jyoti; Singh, Thakur Uttam; Rungsung, Soya; Kumar, Tarun; Parida, Subhashree; Lingaraju, Madhu Cholenahalli; Paul, Avishek; Sahoo, Monalisa; Kumar, Dinesh

2018-03-01

Kaempferol is a flavonoid and important part of the diet. Kaempferol has shown antioxidant, antiinflammatory and antidiabetic activities in various studies. However, protective potential of kaempferol in acute lung injury induced by sepsis and its mechanism remains unclear. The present study was undertaken to evaluate the effect of kaempferol in sepsis-induced acute lung injury in mice and its possible mechanism of action. Acute lung injury was induced by CLP surgery in mice. Kaempferol (100 mg/kg bw) was administered orally one hour before caecal ligation and puncture surgery in mice. Mice were divided into four groups sham, KEM+sham, sepsis (CLP), and KEM+sepsis. Assessment of lung injury was done by estimation of protein content in lung tissue, lung edema, proinflammatory cytokines in plasma and lung tissue, oxidative stress, antioxidant enzymes, nitrite production, and histopathology. Kaempferol pretreated mice showed significant (P Kaempferol pretreatment showed reduction in cytokines IL-6, IL-1β, and TNF-α in plasma as well as in lung tissue in comparison with septic mice without pretreatment. Pretreatment with kaempferol did not show any reduction in MDA level in comparison with septic mice. Antioxidant enzymes SOD and catalase and nonenzymatic antioxidant GSH activities were also increased with kaempferol pretreatment in septic mice. Further, kaempferol pretreatment reduced the lung tissue nitrite level (P Kaempferol pretreatment did not decrease bacterial load in septic mice. Mice pretreated with kaempferol followed by sepsis showed lesser infiltration of cells and more arranged alveolar structure in histopathological analysis. The study suggests that kaempferol showed attenuation in sepsis-induced acute lung injury in mice through suppression of oxidative stress, iNOS, and ICAM-1 pathways.

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

International Nuclear Information System (INIS)

Samet, J.; Gilliland, F.D.

1998-01-01

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

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.

86Rb Distribution in the Lung of the Rabbit with Pneumothorax

International Nuclear Information System (INIS)

Huh, Kap To

1972-01-01

86 Rb uptake of some organs and tissues, eg. both lungs, both renal cortices. small intestine, liver and skeletal muscle were studied in the control and the rabbit subjected to pneumothorax. 86 Rb in the form of chloride mixed with physiological saline was intravenously injected. The doses were 100 μc for a rabbit. The rabbits were sacrificed at intervals of 10, 20, 40, and 60 seconds after the injection of 86 Rb, by the injection of saturated KCI solution. After scarification, the organ and tissue sample were quickly removed. 86 Rb uptake in gm of the organs and tissues were measured. On the basis of uptake value, administered doses and body weight, % dose/gm tissues per 200 gm body weight was calculated. Followings were the results: 1. Pneumothorax resulted in a marked elevation in 86 Rb uptake value of collapsed lung and returned to normal level lately. 2. Contralateral lung of pneumothorax also showed marked elevation in 86 Rb uptake value and recovered to normal level. 3. Initial 86 Rb uptake value of liver, small intestine of the rabbit with pneumothorax showed some elevation as compared to control, but that of late stage were similar with control. 4. Local blood flow determination by means of 86 Rb uptake were inadequate in the collapsed lung of pneumothorax. 5. It was suggested that the mechanism for the initial elevation of 86 Rb uptake value in each organs and tissue were different from each other.

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.

Functional capacities of lungs and thorax in beagles after prolonged residence at 3,100 m.

Science.gov (United States)

Johnson, R L; Cassidy, S S; Grover, R F; Schutte, J E; Epstein, R H

1985-12-01

Functional capacities of the lungs and thorax in beagles taken to high altitude as adults for 33 mo or in beagles raised from puppies at high altitude were compared with functional capacities in corresponding sets of beagles kept simultaneously at sea level. Comparisons were made after reacclimatization to sea level. Lung volumes, airway pressures, esophageal pressures, CO diffusing capacities (DLCO), pulmonary blood flow, and lung tissue volume (Vt) were measured by a rebreathing technique at inspired volumes ranging from 15 to 90 ml/kg. In beagles raised from puppies we measured anatomical distribution of intrathoracic air and tissue using X-ray computed tomography at transpulmonary pressures of 20 cm H2O. Lung and thoracic distensibility, DLCO, and Vt were not different between beagles that had been kept at high altitude for 33 mo as adults and control subjects kept simultaneously at sea level. Lung distensibility, DLCO, and Vt were significantly greater in beagles raised at high altitude than control subjects raised simultaneously at sea level. Thoracic distensibility was not increased in beagles raised at high altitude; the larger lung volume was accommodated by a lower diaphragm, not a larger rib cage.

HOXA9 inhibits migration of lung cancer cells and its hypermethylation is associated with recurrence in non-small cell lung cancer.

Science.gov (United States)

Hwang, Jung-Ah; Lee, Bo Bin; Kim, Yujin; Hong, Seung-Hyun; Kim, Young-Ho; Han, Joungho; Shim, Young Mog; Yoon, Chae-Yeong; Lee, Yeon-Su; Kim, Duk-Hwan

2015-06-01

This study was aimed at understanding the clinicopathological significance of HOXA9 hypermethylation in non-small cell lung cancer (NSCLC). HOXA9 hypermethylation was characterized in six lung cancer cell lines, and its clinicopathological significance was analyzed using methylation-specific PCR in 271 formalin-fixed paraffin-embedded tissues and 27 fresh-frozen tumor and matched normal tissues from 298 NSCLC patients, and Ki-67 expression was analyzed using immunohistochemistry. The promoter region of HOXA9 was highly methylated in six lung cancer cell lines, but not in normal bronchial epithelial cells. The loss of expression was restored by treatment of the cells with a demethylating agent, 5-aza-2'-deoxycytidine (5-Aza-dC). Transient transfection of HOXA9 into H23 lung cancer cells resulted in the inhibition of cell migration but not proliferation. Conversely, sequence-specific siRNA-mediated knockdown of HOXA9 enhanced cell migration. The mRNA levels of HOXA9 in 27 fresh-frozen tumor tissues were significantly lower than in matched normal tissues (Precurrence-free survival (hazard ratio=3.98, 95% confidence interval = 1.07-17.09, P=0.01) in never-smokers, after adjusting for age, sex, tumor size, adjuvant therapy, pathologic stage, and histology. In conclusion, the present study suggests that HOXA9 inhibits migration of lung cancer cells and its hypermethylation is an independent prognostic factor for recurrence-free survival in never-smokers with NSCLC. © 2014 Wiley Periodicals, Inc.

Mechanical phenotyping of cells and extracellular matrix as grade and stage markers of lung tumor tissues.

Science.gov (United States)

Panzetta, Valeria; Musella, Ida; Rapa, Ida; Volante, Marco; Netti, Paolo A; Fusco, Sabato

2017-07-15

The mechanical cross-talk between cells and the extra-cellular matrix (ECM) regulates the properties, functions and healthiness of the tissues. When this is disturbed it changes the mechanical state of the tissue components, singularly or together, and cancer, along with other diseases, may start and progress. However, the bi-univocal mechanical interplay between cells and the ECM is still not properly understood. In this study we show how a microrheology technique gives us the opportunity to evaluate the mechanics of cells and the ECM at the same time. The mechanical phenotyping was performed on the surgically removed tissues of 10 patients affected by adenocarcinoma of the lung. A correlation between the mechanics and the grade and stage of the tumor was reported and compared to the mechanical characteristics of the healthy tissue. Our findings suggest a sort of asymmetric modification of the mechanical properties of the cells and the extra-cellular matrix in the tumor, being the more compliant cell even though it resides in a stiffer matrix. Overall, the simultaneous mechanical characterization of the tissues constituents (cells and ECM) provided new support for diagnosis and offered alternative points of analysis for cancer mechanobiology. When the integrity of the mechanical cross-talk between cells and the extra-cellular matrix is disturbed cancer, along with other diseases, may initiate and progress. Here, we show how a new technique gives the opportunity to evaluate the mechanics of cells and the ECM at the same time. It was applied on surgically removed tissues of 10 patients affected by adenocarcinoma of the lung and a correlation between the mechanics and the grade and stage of the tumor was reported and compared to the mechanical characteristics of the healthy tissue. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Bmi-1 expression modulates non-small cell lung cancer progression

Science.gov (United States)

Xiong, Dan; Ye, Yunlin; Fu, Yujie; Wang, Jinglong; Kuang, Bohua; Wang, Hongbo; Wang, Xiumin; Zu, Lidong; Xiao, Gang; Hao, Mingang; Wang, Jianhua

2015-01-01

Previous studies indicate that the role of B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1) is responsible for multiple cancer progression. However, Bmi-1 in controlling gene expression in non-small cell lung cancer (NSCLC) development is not well explored. Here we report that the Bmi-1 level is highly increased in primary NSCLC tissues compared to matched adjacent non-cancerous tissues and required for lung tumor growth in xenograft model. Furthermore, we also demonstrate that Bmi-1 level is lower in matched involved lymph node cancerous tissues than the respective primary NSCLC tissues. We find that Bmi-1 does not affect cell cycle and apoptosis in lung cancer cell lines as it does not affect the expression of p16/p19, Pten, AKT and P-AKT. Mechanistic analyses note that reduction of Bmi-1 expression inversely regulates invasion and metastasis of NSCLC cells in vitro and in vivo, followed by induction of epithelial-mesenchymal transition (EMT). Using genome microarray assays, we find that RNAi-mediated silence of Bmi-1 modulates some important molecular genetics or signaling pathways, potentially associated with NSCLC development. Taken together, our findings disclose for the first time that Bmi-1 level accumulates strongly in early stage and then declines in late stage, which is potentially important for NSCLC cell invasion and metastasis during progression. PMID:25880371

LungMAP: The Molecular Atlas of Lung Development Program.

Science.gov (United States)

Ardini-Poleske, Maryanne E; Clark, Robert F; Ansong, Charles; Carson, James P; Corley, Richard A; Deutsch, Gail H; Hagood, James S; Kaminski, Naftali; Mariani, Thomas J; Potter, Steven S; Pryhuber, Gloria S; Warburton, David; Whitsett, Jeffrey A; Palmer, Scott M; Ambalavanan, Namasivayam

2017-11-01

The National Heart, Lung, and Blood Institute is funding an effort to create a molecular atlas of the developing lung (LungMAP) to serve as a research resource and public education tool. The lung is a complex organ with lengthy development time driven by interactive gene networks and dynamic cross talk among multiple cell types to control and coordinate lineage specification, cell proliferation, differentiation, migration, morphogenesis, and injury repair. A better understanding of the processes that regulate lung development, particularly alveologenesis, will have a significant impact on survival rates for premature infants born with incomplete lung development and will facilitate lung injury repair and regeneration in adults. A consortium of four research centers, a data coordinating center, and a human tissue repository provides high-quality molecular data of developing human and mouse lungs. LungMAP includes mouse and human data for cross correlation of developmental processes across species. LungMAP is generating foundational data and analysis, creating a web portal for presentation of results and public sharing of data sets, establishing a repository of young human lung tissues obtained through organ donor organizations, and developing a comprehensive lung ontology that incorporates the latest findings of the consortium. The LungMAP website (www.lungmap.net) currently contains more than 6,000 high-resolution lung images and transcriptomic, proteomic, and lipidomic human and mouse data and provides scientific information to stimulate interest in research careers for young audiences. This paper presents a brief description of research conducted by the consortium, database, and portal development and upcoming features that will enhance the LungMAP experience for a community of users. Copyright © 2017 the American Physiological Society.

Lung dose and lung cancer risk by inhalation of radon daughters

International Nuclear Information System (INIS)

Jacobi, W.

1983-01-01

The inhalation of short-lived radon daughters constitutes the most important occupational radiation exposure in mines, particularly in uranium mines. Among some groups of miners exposed in the past to relatively high radon levels, an excess lung cancer incidence has been observed. In addition to this occupational hazard, the observed radon levels in domestic houses indicate that the inhalation of short-lived radon daughters seems to be the most important component of the radiation exposure of the population from natural sources. For the quantification and judgment of the radiological impact by inhalation of radon daughters in mines as well as in houses, it is necessary to estimate the relationships between the inhaled activity or potential alpha (α) energy of these radionuclides, the dose to target tissues in the lung, and the possible associated lung cancer (LC) risk. It is the purpose of this paper to give a condensed review of our present knowledge in this field and to indicate the main gaps and uncertainties where future research seems necessary

Guards at the gate: physiological and pathological roles of tissue-resident innate lymphoid cells in the lung.

Science.gov (United States)

Cheng, Hang; Jin, Chengyan; Wu, Jing; Zhu, Shan; Liu, Yong-Jun; Chen, Jingtao

2017-12-01

The lung is an important open organ and the primary site of respiration. Many life-threatening diseases develop in the lung, e.g., pneumonia, asthma, chronic obstructive pulmonary diseases (COPDs), pulmonary fibrosis, and lung cancer. In the lung, innate immunity serves as the frontline in both anti-irritant response and anti-tumor defense and is also critical for mucosal homeostasis; thus, it plays an important role in containing these pulmonary diseases. Innate lymphoid cells (ILCs), characterized by their strict tissue residence and distinct function in the mucosa, are attracting increased attention in innate immunity. Upon sensing the danger signals from damaged epithelium, ILCs activate, proliferate, and release numerous cytokines with specific local functions; they also participate in mucosal immune-surveillance, immune-regulation, and homeostasis. However, when their functions become uncontrolled, ILCs can enhance pathological states and induce diseases. In this review, we discuss the physiological and pathological functions of ILC subsets 1 to 3 in the lung, and how the pathogenic environment affects the function and plasticity of ILCs.

Low Level Laser Therapy Reduces the Development of Lung Inflammation Induced by Formaldehyde Exposure.

Directory of Open Access Journals (Sweden)

Cristiane Miranda da Silva

Full Text Available Lung diseases constitute an important public health problem and its growing level of concern has led to efforts for the development of new therapies, particularly for the control of lung inflammation. Low Level Laser Therapy (LLLT has been highlighted as a non-invasive therapy with few side effects, but its mechanisms need to be better understood and explored. Considering that pollution causes several harmful effects on human health, including lung inflammation, in this study, we have used formaldehyde (FA, an environmental and occupational pollutant, for the induction of neutrophilic lung inflammation. Our objective was to investigate the local and systemic effects of LLLT after FA exposure. Male Wistar rats were exposed to FA (1% or vehicle (distillated water during 3 consecutive days and treated or not with LLLT (1 and 5 hours after each FA exposure. Non-manipulated rats were used as control. 24 h after the last FA exposure, we analyzed the local and systemic effects of LLLT. The treatment with LLLT reduced the development of neutrophilic lung inflammation induced by FA, as observed by the reduced number of leukocytes, mast cells degranulated, and a decreased myeloperoxidase activity in the lung. Moreover, LLLT also reduced the microvascular lung permeability in the parenchyma and the intrapulmonary bronchi. Alterations on the profile of inflammatory cytokines were evidenced by the reduced levels of IL-6 and TNF-α and the elevated levels of IL-10 in the lung. Together, our results showed that LLLT abolishes FA-induced neutrophilic lung inflammation by a reduction of the inflammatory cytokines and mast cell degranulation. This study may provide important information about the mechanisms of LLLT in lung inflammation induced by a pollutant.

Napsin A levels in epithelial lining fluid as a diagnostic biomarker of primary lung adenocarcinoma.

Science.gov (United States)

Uchida, Akifumi; Samukawa, Takuya; Kumamoto, Tomohiro; Ohshige, Masahiro; Hatanaka, Kazuhito; Nakamura, Yoshihiro; Mizuno, Keiko; Higashimoto, Ikkou; Sato, Masami; Inoue, Hiromasa

2017-12-12

It is crucial to develop novel diagnostic approaches for determining if peripheral lung nodules are malignant, as such nodules are frequently detected due to the increased use of chest computed tomography scans. To this end, we evaluated levels of napsin A in epithelial lining fluid (ELF), since napsin A has been reported to be an immunohistochemical biomarker for histological diagnosis of primary lung adenocarcinoma. In consecutive patients with indeterminate peripheral lung nodules, ELF samples were obtained using a bronchoscopic microsampling (BMS) technique. The levels of napsin A and carcinoembryonic antigen (CEA) in ELF at the nodule site were compared with those at the contralateral site. A final diagnosis of primary lung adenocarcinoma was established by surgical resection. We performed BMS in 43 consecutive patients. Among patients with primary lung adenocarcinoma, the napsin A levels in ELF at the nodule site were markedly higher than those at the contralateral site, while there were no significant differences in CEA levels. Furthermore, in 18 patients who were undiagnosed by bronchoscopy and finally diagnosed by surgery, the napsin A levels in ELF at the nodule site were identically significantly higher than those at the contralateral site. In patients with non-adenocarcinoma, there were no differences in napsin A levels in ELF. The area under the receiver operator characteristic curve for identifying primary lung adenocarcinoma was 0.840 for napsin A and 0.542 for CEA. Evaluation of napsin A levels in ELF may be useful for distinguishing primary lung adenocarcinoma.

An immune response manifested by the common occurrence of annexins I and II autoantibodies and high circulating levels of IL-6 in lung cancer

Science.gov (United States)

Brichory, Franck M.; Misek, David E.; Yim, Anne-Marie; Krause, Melissa C.; Giordano, Thomas J.; Beer, David G.; Hanash, Samir M.

2001-01-01

The identification of circulating tumor antigens or their related autoantibodies provides a means for early cancer diagnosis as well as leads for therapy. The purpose of this study was to identify proteins that commonly induce a humoral response in lung cancer by using a proteomic approach and to investigate biological processes that may be associated with the development of autoantibodies. Aliquots of solubilized proteins from a lung adenocarcinoma cell line (A549) and from lung tumors were subjected to two-dimensional PAGE, followed by Western blot analysis in which individual sera were tested for primary antibodies. Sera from 54 newly diagnosed patients with lung cancer and 60 patients with other cancers and from 61 noncancer controls were analyzed. Sera from 60% of patients with lung adenocarcinoma and 33% of patients with squamous cell lung carcinoma but none of the noncancer controls exhibited IgG-based reactivity against proteins identified as glycosylated annexins I and/or II. Immunohistochemical analysis showed that annexin I was expressed diffusely in neoplastic cells in lung tumor tissues, whereas annexin II was predominant at the cell surface. Interestingly, IL-6 levels were significantly higher in sera of antibody-positive lung cancer patients compared with antibody-negative patients and controls. We conclude that an immune response manifested by annexins I and II autoantibodies occurs commonly in lung cancer and is associated with high circulating levels of an inflammatory cytokine. The proteomic approach we have implemented has utility for the development of serum-based assays for cancer diagnosis as we report in this paper on the discovery of antiannexins I and/or II in sera from patients with lung cancer. PMID:11504947

Late regional density changes of the lung after radiotherapy for breast cancer

International Nuclear Information System (INIS)

Vagane, Randi; Danielsen, Turi; Fossa, Sophie Dorothea; Lokkevik, Erik; Olsen, Dag Rune

2009-01-01

Background and purpose: To investigate density changes in lung tissue, 3-4 years after postoperative adjuvant radiotherapy for breast cancer, based on dose dependence and regional differences. Material and methods: Sixty-one breast cancer patients, who had received computed tomography (CT) based postoperative radiotherapy, were included. CT scans were performed 35-51 months after start of radiotherapy. Dose information and CT scans from before and after radiotherapy were geometrically aligned in order to analyse changes in air-filled fraction (derived from CT density) as a function of dose for different regions of the lung. Results: Dose-dependent reduction of the air-filled fraction was shown to vary between the different regions of the lung. For lung tissue receiving about 50 Gy, the largest reduction in air-filled fraction was found in the cranial part of the lung. An increased air-filled fraction was observed for lung tissue irradiated to doses below 20 Gy, indicating compensatory response. Conclusions: The treatment-induced change in whole-lung density is a weighted response, involving the different regions, the irradiated volumes, and dose levels to these volumes. Simplistic models may therefore not be appropriate for describing the whole-lung dose-volume-response relationship following inhomogeneous irradiation

iASPP is over-expressed in human non-small cell lung cancer and regulates the proliferation of lung cancer cells through a p53 associated pathway

International Nuclear Information System (INIS)

Chen, Jinfeng; Xie, Fei; Zhang, Lijian; Jiang, Wen G

2010-01-01

iASPP is a key inhibitor of tumour suppressor p53 and is found to be up-regulated in certain malignant conditions. The present study investigated the expression of iASPP in clinical lung cancer, a leading cancer type in the world, and the biological impact of this molecule on lung cancer cells. iASPP protein levels in lung cancer tissues were evaluated using an immunohistochemical method. In vitro, iASPP gene expression was suppressed with a lentvirus-mediated shRNA method and the biological impact after knocking down iASSP on lung cancer cell lines was investigated in connection with the p53 expression status. We showed here that the expression of iASPP was significantly higher in lung cancer tissues compared with the adjacent normal tissues. iASPP shRNA treatment resulted in a down-regulation of iASPP in lung cancer cells. There was a subsequent reduction of cell proliferation of the two lung tumour cell lines A459 and 95D both of which had wild-type p53 expression. In contrast, reduction of iASPP in H1229 cells, a cell with little p53 expression, had no impact on its growth rate. iASPP regulates the proliferation and motility of lung cancer cells. This effect is intimately associated with the p53 pathway. Together with the pattern of the over-expression in clinical lung cancers, it is concluded that iASPP plays an pivotal role in the progression of lung cancer and is a potential target for lung cancer therapy

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

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

The Effects of Dexmedetomidine on Secondary Acute Lung and Kidney Injuries in the Rat Model of Intra-Abdominal Sepsis

Directory of Open Access Journals (Sweden)

Uğur Koca

2013-01-01

Full Text Available In the present study, the effects of dexmedetomidine on secondary lung and kidney injuries were studied in the rat model of intra-abdominal sepsis by immunohistological and biochemical examinations. We measured serum creatinine, kidney tissue malondialdehide and plasma neutrophil gelatinase-associated lipocalin levels. In order to evaluate tissue injury we determined kidney tissue mononuclear cell infiltration score, alveolar macrophage count, histological kidney and lung injury scores and kidney and lung tissue immunoreactivity scores. We demonstrated that dexmedetomidine attenuates sepsis-induced lung and kidney injuries and apoptosis in the rat model of sepsis. There is still need for comparative studies in order to determine the effects of dexmedetomidine on organ functions in early human sepsis.

Lipase member H is a novel secreted protein selectively upregulated in human lung adenocarcinomas and bronchioloalveolar carcinomas

Energy Technology Data Exchange (ETDEWEB)

Seki, Yasuhiro [Graduate School of Arts and Sciences, The University of Tokyo, Tokyo (Japan); Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba (Japan); Yoshida, Yukihiro [Department of Surgery, Asahi General Hospital, Chiba (Japan); Department of Thoracic Surgery, The University of Tokyo, Graduate School of Medicine, Tokyo (Japan); Ishimine, Hisako [Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba (Japan); Graduate School of Life and Environmental Sciences, The University of Tsukuba, Tsukuba, Ibaraki (Japan); Shinozaki-Ushiku, Aya [Department of Pathology, Graduate School of Medicine, The University of Tokyo, Hongo, Tokyo (Japan); Ito, Yoshimasa [Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba (Japan); Sumitomo, Kenya [Department of Internal Medicine, JA Kochi Hospital, Kochi (Japan); Nakajima, Jun [Department of Thoracic Surgery, The University of Tokyo, Graduate School of Medicine, Tokyo (Japan); Fukayama, Masashi [Department of Pathology, Graduate School of Medicine, The University of Tokyo, Hongo, Tokyo (Japan); Michiue, Tatsuo [Graduate School of Arts and Sciences, The University of Tokyo, Tokyo (Japan); Asashima, Makoto, E-mail: asashi@bio.c.u-tokyo.ac.jp [Graduate School of Arts and Sciences, The University of Tokyo, Tokyo (Japan); Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba (Japan); Life Science Center of Tsukuba Advanced Research Alliance (TARA), The University of Tsukuba, Tsukuba, Ibaraki (Japan); Kurisaki, Akira, E-mail: akikuri@hotmail.com [Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba (Japan); Graduate School of Life and Environmental Sciences, The University of Tsukuba, Tsukuba, Ibaraki (Japan)

2014-01-24

Highlights: • Most of the adenocarcinomas and bronchioloalveolar carcinomas were LIPH-positive. • LIPH is necessary for the proliferation of lung cancer cells in vitro. • A high level of LIPH in serum is correlated with better survival in early phase lung-cancer patients after surgery. - Abstract: Lung cancer is one of the most frequent causes of cancer-related death worldwide. However, molecular markers for lung cancer have not been well established. To identify novel genes related to lung cancer development, we surveyed publicly available DNA microarray data on lung cancer tissues. We identified lipase member H (LIPH, also known as mPA-PLA1) as one of the significantly upregulated genes in lung adenocarcinoma. LIPH was expressed in several adenocarcinoma cell lines when they were analyzed by quantitative real-time polymerase chain reaction (qPCR), western blotting, and sandwich enzyme-linked immunosorbent assay (ELISA). Immunohistochemical analysis detected LIPH expression in most of the adenocarcinomas and bronchioloalveolar carcinomas tissue sections obtained from lung cancer patients. LIPH expression was also observed less frequently in the squamous lung cancer tissue samples. Furthermore, LIPH protein was upregulated in the serum of early- and late-phase lung cancer patients when they were analyzed by ELISA. Interestingly, high serum level of LIPH was correlated with better survival in early phase lung cancer patients after surgery. Thus, LIPH may be a novel molecular biomarker for lung cancer, especially for adenocarcinoma and bronchioloalveolar carcinoma.

Lipase member H is a novel secreted protein selectively upregulated in human lung adenocarcinomas and bronchioloalveolar carcinomas

International Nuclear Information System (INIS)

Seki, Yasuhiro; Yoshida, Yukihiro; Ishimine, Hisako; Shinozaki-Ushiku, Aya; Ito, Yoshimasa; Sumitomo, Kenya; Nakajima, Jun; Fukayama, Masashi; Michiue, Tatsuo; Asashima, Makoto; Kurisaki, Akira

2014-01-01

Highlights: • Most of the adenocarcinomas and bronchioloalveolar carcinomas were LIPH-positive. • LIPH is necessary for the proliferation of lung cancer cells in vitro. • A high level of LIPH in serum is correlated with better survival in early phase lung-cancer patients after surgery. - Abstract: Lung cancer is one of the most frequent causes of cancer-related death worldwide. However, molecular markers for lung cancer have not been well established. To identify novel genes related to lung cancer development, we surveyed publicly available DNA microarray data on lung cancer tissues. We identified lipase member H (LIPH, also known as mPA-PLA1) as one of the significantly upregulated genes in lung adenocarcinoma. LIPH was expressed in several adenocarcinoma cell lines when they were analyzed by quantitative real-time polymerase chain reaction (qPCR), western blotting, and sandwich enzyme-linked immunosorbent assay (ELISA). Immunohistochemical analysis detected LIPH expression in most of the adenocarcinomas and bronchioloalveolar carcinomas tissue sections obtained from lung cancer patients. LIPH expression was also observed less frequently in the squamous lung cancer tissue samples. Furthermore, LIPH protein was upregulated in the serum of early- and late-phase lung cancer patients when they were analyzed by ELISA. Interestingly, high serum level of LIPH was correlated with better survival in early phase lung cancer patients after surgery. Thus, LIPH may be a novel molecular biomarker for lung cancer, especially for adenocarcinoma and bronchioloalveolar carcinoma

Serum selenium level and risk of lung cancer mortality

DEFF Research Database (Denmark)

Suadicani, P; Hein, H O; Gyntelberg, F

2011-01-01

Serum selenium has been implicated as a risk factor for lung cancer, but the issue remains unsettled. We tested in a cohort of 3,333 males aged 53 to 74 years the hypothesis that a low serum selenium would be associated with an increased risk of lung cancer mortality.During 16 years, 167 subjects(5.......1%) died from lung cancer; 48 males (5.0%) among males with low serum selenium, 0.4-1.0 μmol·l(-1), n=965, 57 males (5.1%) among males with medium serum selenium, 1.1-1.2 μmol·l(-1), n=1,141, and 62 males (5.1%) among males with high serum selenium, 1.3-3.0 μmol·l(-1), n=1,227. After adjustment for age...... (chronic bronchitis and peak flow), referencing the lowest level of serum selenium HRs were 1.17(0.79-1.75), and 1.43(0.96-2.14), respectively. Among heavy smokers a high serum selenium was associated with a significantly increased risk of lung cancer mortality after taking into account all potential...

Effects of lung elasticity on the sound propagation in the lung

International Nuclear Information System (INIS)

Yoneda, Takahiro; Wada, Shigeo; Nakamura, Masanori; Horii, Noriaki; Mizushima, Koichiro

2011-01-01

Sound propagation in the lung was simulated for gaining insight into its acoustic properties. A thorax model consisting of lung parenchyma, thoracic bones, trachea and other tissues was made from human CT images. Acoustic nature of the lung parenchyma and bones was expressed with the Biot model of poroelastic material, whereas trachea and tissues were modeled with gas and an elastic material. A point sound source of white noises was placed in the first bifurcation of trachea. The sound propagation in the thorax model was simulated in a frequency domain. The results demonstrated the significant attenuation of sound especially in frequencies larger than 1,000 Hz. Simulations with a stiffened lung demonstrated suppression of the sound attenuation for higher frequencies observed in the normal lung. These results indicate that the normal lung has the nature of a low-pass filter, and stiffening helps the sound at higher frequencies to propagate without attenuations. (author)

Interstitial Lung Disease

Science.gov (United States)

... propranolol (Inderal, Innopran), may harm lung tissue. Some antibiotics. Nitrofurantoin (Macrobid, Macrodantin, others) and ethambutol (Myambutol) can cause lung damage. Anti-inflammatory drugs. Certain anti-inflammatory drugs, such as rituximab ( ...

SU-F-T-150: Comparing Normal Tissue Irradiated Volumes for Proton Vs. Photon Treatment Plans On Lung Patients

Energy Technology Data Exchange (ETDEWEB)

Liu, A; Mohan, R; Liao, Z [UT MD Anderson Cancer Center, Houston, TX (United States)

2016-06-15

Purpose: The aim of this work is to compare the “irradiated volume” (IRV) of normal tissues receiving 5, 20, 50, 80 and 90% or higher of the prescription dose with passively scattered proton therapy (PSPT) vs. IMRT of lung cancer patients. The overall goal of this research is to understand the factors affecting outcomes of a randomized PSPT vs. IMRT lung trial. Methods: Thirteen lung cancer patients, selected randomly, were analyzed. Each patient had PSPT and IMRT 74 Gy (RBE) plans meeting the same normal tissue constraints generated. IRVs were created for pairs of IMRT and PSPT plans on each patient. The volume of iGTV, (respiratory motion-incorporated GTV) was subtracted from each IRV to create normal tissue irradiated volume IRVNT. The average of IRVNT DVHs over all patients was also calculated for both modalities and inter-compared as were the selected dose-volume indices. Probability (p value) curves were calculated based on the Wilcoxon matched-paired signed-rank test to determine the dose regions where the statistically significant differences existed. Results: As expected, the average 5, 20 and 50% IRVNT’s for PSPT was found to be significantly smaller than for IMRT (p < 0.001, 0.01, and 0.001 respectively). However, the average 90% IRVNT for PSPT was greater than for IMRT (p = 0.003) presumably due to larger penumbra of protons and the long range of protons in lower density media. The 80% IRVNT for PSPT was also larger but not statistically distinguishable (p = .224). Conclusion: PSPT modality has smaller irradiated volume at lower doses, but larger volume at high doses. A larger cohort of lung patients will be analyzed in the future and IRVNT of patients treated with PSPT and IMRT will be compared to determine if the irradiated volumes (the magnitude of “dose bath”) correlate with outcomes.

Expression of livin protein in lung cancer and its relation with the expression of pro-caspase3 protein

Directory of Open Access Journals (Sweden)

Hongru LI

2008-10-01

Full Text Available Background and objective Livin is a novel inhibitor of apoptosis protein (IAP, recent studies showed it overexpresses in a variety of carcinomas including lung cancer and contributes much to the cancerous development. The objective of this study is to explore the expression of livin in tissues of lung cancer and its relationshipwith histological types, chemotherapy, Lymph node metastasis and to study its correlation with the expression of pro-caspase3 as well. Methods Expressions of Livin and caspase3 were detected by Western blot assay in lung cancer tissues as well as in controls. Results Livin was expressed in 15 of 27 lung cancer, significantly more than those in lung para-cancerous (1/5 or benign disease lung tissues (2/12 (P 0.05. Conclusion Livin are differently expressed in different histological types of lung cancer; High levels of livin expression do not relate to chemotherapy, lymph node metastasis (P >0.05. The levels of livin tends to be positively associated with those of accordingly pro-caspase3, it is presumed that livin could bind pro-caspase3 and suppress its activation.

Comparison of single, fractionated and hyperfractionated irradiation on the development of normal tissue damage in rat lung

International Nuclear Information System (INIS)

Giri, P.G.S.; Kimler, B.F.; Giri, U.P.; Cox, G.G.; Reddy, E.K.

1985-01-01

The effect of fractionated thoracic irradiation on the development of normal tissue damage in rats was compared to that produced by single doses. Animals received a single dose of 15 Gy, 30 Gy in 10 daily fractions of 3 Gy each (fractionation), or 30 Gy in 30 fractions of 1 Gy each 3 times a day (hyperfractionation). The treatments produced minimal lethality since a total of only 6 animals died between days 273 and 475 after the initiation of treatment, with no difference in survival observed between the control and any of the 3 treated groups. Despite the lack of lethality, evidence of lung damage was obtained by histological examination. Animals that had received either single doses or fractionated doses had more of the pulmonary parenchyma involved than did animals that had received hyperfractionated doses. The authors conclude that, in the rat lung model, a total radiation dose of 30 Gy fractionated over 14 days produces no more lethality nor damage to lung tissue than does 15 Gy delivered as a single dose. However, long-term effects as evidenced by deposits of collagen and development of fibrosis are significantly reduced by hyperfractionation when compared to single doses and daily fractionation

Systematic Assessment of Strategies for Lung-targeted Delivery of MicroRNA Mimics

Science.gov (United States)

Schlosser, Kenny; Taha, Mohamad; Stewart, Duncan J.

2018-01-01

There is considerable interest in the use of synthetic miRNA mimics (or inhibitors) as potential therapeutic agents in pulmonary vascular disease; however, the optimal delivery method to achieve high efficiency, selective lung targeting has not been determined. Here, we sought to investigate the relative merits of different lung-targeted strategies for delivering miRNA mimics in rats. Methods: Tissue levels of a synthetic miRNA mimic, cel-miR-39-3p (0.5 nmol in 50 µL invivofectamine/PBS vehicle) were compared in male rats (n=3 rats/method) after delivery by commonly used lung-targeting strategies including intratracheal liquid instillation (IT-L), intratracheal aerosolization with (IT-AV) or without ventilator assistance (IT-A), intranasal liquid instillation (IN-L) and intranasal aerosolization (IN-A). Intravenous (IV; via jugular vein), intraperitoneal (IP) and subcutaneous (SC) delivery served as controls. Relative levels of cel-miR-39 were quantified by RT-qPCR. Results: At 2 h post delivery, IT-L showed the highest lung mimic level, which was significantly higher than levels achieved by all other methods (from ~10- to 10,000-fold, pMimic levels remained detectable in the lung 24 h after delivery, but were 10- to 100-fold lower. The intrapulmonary distribution of cel-miR-39 was comparable when delivered as either a liquid or aerosol, with evidence of mimic distribution to both the left and right lung lobes and penetration to distal regions. All lung-targeted strategies showed lung-selective mimic uptake, with mimic levels 10- to 100-fold lower in heart and 100- to 10,000-fold lower in liver, kidney and spleen. In contrast, IV, SC and IP routes showed comparable or higher mimic levels in non-pulmonary tissues. Conclusions: miRNA uptake in the lungs differed markedly by up to 4 orders of magnitude, demonstrating that the choice of delivery strategy could have a significant impact on potential therapeutic outcomes in preclinical investigations of miRNA-based drug

Identification of radiation response genes and proteins from mouse pulmonary tissues after high-dose per fraction irradiation of limited lung volumes.

Science.gov (United States)

Jin, Hee; Jeon, Seulgi; Kang, Ga-Young; Lee, Hae-June; Cho, Jaeho; Lee, Yun-Sil

2017-02-01

The molecular effects of focal exposure of limited lung volumes to high-dose per fraction irradiation (HDFR) such as stereotactic body radiotherapy (SBRT) have not been fully characterized. In this study, we used such an irradiation system and identified the genes and proteins after HDFR to mouse lung, similar to those associated with human therapy. High focal radiation (90 Gy) was applied to a 3-mm volume of the left lung of C57BL6 mice using a small-animal stereotactic irradiator. As well as histological examination for lungs, a cDNA micro array using irradiated lung tissues and a protein array of sera were performed until 4 weeks after irradiation, and radiation-responsive genes and proteins were identified. For comparison, the long-term effects (12 months) of 20 Gy radiation wide-field dose to the left lung were also investigated. The genes ermap, epb4.2, cd200r3 (up regulation) and krt15, hoxc4, gdf2, cst9, cidec, and bnc1 (down-regulation) and the proteins of AIF, laminin, bNOS, HSP27, β-amyloid (upregulation), and calponin (downregulation) were identified as being responsive to 90 Gy HDFR. The gdf2, cst9, and cidec genes also responded to 20 Gy, suggesting that they are universal responsive genes in irradiated lungs. No universal proteins were identified in both 90 Gy and 20 Gy. Calponin, which was downregulated in protein antibody array analysis, showed a similar pattern in microarray data, suggesting a possible HDFR responsive serum biomarker that reflects gene alteration of irradiated lung tissue. These genes and proteins also responded to the lower doses of 20 Gy and 50 Gy HDFR. These results suggest that identified candidate genes and proteins are HDFR-specifically expressed in lung damage induced by HDFR relevant to SBRT in humans.

Lung cancer and angiogenesis imaging using synchrotron radiation

International Nuclear Information System (INIS)

Liu Xiaoxia; Zhao Jun; Xu, Lisa X; Sun Jianqi; Gu Xiang; Liu Ping; Xiao Tiqiao

2010-01-01

Early detection of lung cancer is the key to a cure, but a difficult task using conventional x-ray imaging. In the present study, synchrotron radiation in-line phase-contrast imaging was used to study lung cancer. Lewis lung cancer and 4T1 breast tumor metastasis in the lung were imaged, and the differences were clearly shown in comparison to normal lung tissue. The effect of the object-detector distance and the energy level on the phase-contrast difference was investigated and found to be in good agreement with the theory of in-line phase-contrast imaging. Moreover, 3D image reconstruction of lung tumor angiogenesis was obtained for the first time using a contrast agent, demonstrating the feasibility of micro-angiography with synchrotron radiation for imaging tumor angiogenesis deep inside the body.

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

956.54 than that in ΔlasRΔrhlR group (28 861.99±10 826.96, P<0.05; the level of IL-10 was significantly higher in the two Ps. aer infected groups than in that of sterile control group (57.43±22.13ng/ ml, and significantly higher in PAO1 group (188.07±57.01ng/ml than in ΔlasRΔrhlR group (93.31±17.26ng/ml, P<0.05. Conclusion 　Ps. aer QS system lasR/rhlR gene may promote inflammation, up-regulate the Foxp3 expression and increase the TGF-β1 and IL-10 levels in lung tissue, which may prompt the protraction and persistence of infection. DOI: 10.11855/j.issn.0577-7402.2016.02.04

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

Ischemia postconditioning and mesenchymal stem cells engraftment synergistically attenuate ischemia reperfusion-induced lung injury in rats.

Science.gov (United States)

Chen, Shuchen; Chen, Liangwan; Wu, Xiaonan; Lin, Jiangbo; Fang, Jun; Chen, Xiangqi; Wei, Shijin; Xu, Jianxin; Gao, Qin; Kang, Mingqiang

2012-11-01

It has been reported that ischemic postconditioning (IPO) or mesenchymal stem cell (MSC) engraftment could protect organs from ischemia/reperfusion (I/R) injury. We investigated the synergetic effects of combined treatment on lung injury induced by I/R. Adult Sprague-Dawley rats were randomly assigned to one of the following groups: sham-operated control, I/R, IPO, MSC engraftment, and IPO plus MSC engraftment. Lung injury was assessed by arterial blood gas analysis, the wet/dry lung weight ratio, superoxide dismutase level, malondialdehyde content, myeloperoxidase activity, and tissue histologic changes. Cytokine expression was detected using real-time polymerase chain reaction, Western blotting, and enzyme-linked immunosorbent assay. Cell apoptosis was determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end assay and annexin V staining. MSC engraftment or IPO alone markedly attenuated the lung wet/dry weight ratio, malondialdehyde and myeloperoxidase production, and lung pathologic injury and enhanced arterial partial oxygen pressure, superoxide dismutase content, inhibited pro-inflammatory cytokine levels, and decreased cell apoptosis in lung tissue, compared with the I/R group. In contrast, IPO pretreatment enhanced the protective effects of MSC on I/R-induced lung injury compared with treatment alone. Moreover, in the combined treatment group, the number of MSC engraftments in the lung tissue was increased, associated with enhanced survival of MSCs compared with MSC treatment alone. Additional investigation showed that IPO treatment increased expression of vascular endothelial growth factor and stromal cell-derived factor-1 in I/R lung tissue. IPO might contribute to the homing and survival of transplanted MSCs and enhance their therapeutic effects through improvement of the microenvironment of I/R injury. Copyright © 2012 Elsevier Inc. All rights reserved.

The -271 G>A polymorphism of kinase insert domain-containing receptor gene regulates its transcription level in patients with non-small cell lung cancer

International Nuclear Information System (INIS)

An, She-Juan; Chen, Zhi-Hong; Lin, Qiu-Xiong; Su, Jian; Chen, Hua-Jun; Lin, Jia-Ying; Wu, Yi-Long

2009-01-01

Kinase insert domain-containing receptor (KDR) plays a critical role in the metastasis of cancer and is used as a molecular target in cancer therapy. We investigated the characteristics of the -271 G>A polymorphism of the KDR gene to gain information that may benefit the development of individualized therapies for patients with non-small cell lung cancer (NSCLC). The -271 G>A polymorphism of the KDR gene in 106 lung cancer patients and 203 healthy control individuals was analyzed by polymerase chain reaction (PCR) and DNA sequencing methods. Real-time quantitative PCR and immunohistochemical methods were used to evaluate KDR mRNA and protein expression levels, respectively, in frozen tumor specimens. The -271 G>A polymorphism was associated with the mRNA expression level of the KDR gene in tumor tissues (t = 2.178, P = 0.032, independent samples t-test). Compared with the AG/GG genotype, the AA genotype was associated with higher KDR mRNA expression in tumor tissues. We found no relationship between the genotype and the KDR protein expression level and no significant difference in the distribution of the KDR gene polymorphism genotypes between lung cancer patients and the control group (χ 2 = 1.269, P = 0.264, Fisher's exact test). This study is the first to show that the -271 G>A polymorphism of the KDR gene may be a functional polymorphism related to the regulation of gene transcription. These findings may have important implications for therapies targeting KDR in patients with NSCLC

Hydroxysafflor yellow A suppress oleic acid-induced acute lung injury via protein kinase A

International Nuclear Information System (INIS)

Wang, Chaoyun; Huang, Qingxian; Wang, Chunhua; Zhu, Xiaoxi; Duan, Yunfeng; Yuan, Shuai; Bai, Xianyong

2013-01-01

Inflammation response and oxidative stress play important roles in acute lung injury (ALI). Activation of the cAMP/protein kinase A (PKA) signaling pathway may attenuate ALI by suppressing immune responses and inhibiting the generation of reactive oxygen species (ROS). Hydroxysafflor yellow A (HSYA) is a natural flavonoid compound that reduces oxidative stress and inflammatory cytokine-mediated damage. In this study, we examined whether HSYA could protect the lungs from oleic acid (OA)-induced injury, which was used to mimic ALI, and determined the role of the cAMP/PKA signaling pathway in this process. Arterial oxygen tension (PaO 2 ), carbon dioxide tension, pH, and the PaO 2 /fraction of inspired oxygen ratio in the blood were detected using a blood gas analyzer. We measured wet/dry lung weight ratio and evaluated tissue morphology. The protein and inflammatory cytokine levels in the bronchoalveolar lavage fluid and serum were determined using enzyme-linked immunoassay. The activities of superoxide dismutase, glutathione peroxidase, PKA, and nicotinamide adenine dinucleotide phosphate oxidase, and the concentrations of cAMP and malondialdehyde in the lung tissue were detected using assay kits. Bcl-2, Bax, caspase 3, and p22 phox levels in the lung tissue were analyzed using Western blotting. OA increased the inflammatory cytokine and ROS levels and caused lung dysfunction by decreasing cAMP synthesis, inhibiting PKA activity, stimulating caspase 3, and reducing the Bcl-2/Bax ratio. H-89 increased these effects. HSYA significantly increased the activities of antioxidant enzymes, inhibited the inflammatory response via cAMP/PKA pathway activation, and attenuated OA-induced lung injury. Our results show that the cAMP/PKA signaling pathway is required for the protective effect of HSYA against ALI. - Highlights: • Oleic acid (OA) cause acute lung injury (ALI) via inhibiting cAMP/PKA signal pathway. • Blocking protein kinase A (PKA) activation may enhance Cytokine

Esophagus and contralateral lung-sparing IMRT for locally advanced lung cancer in the community hospital setting

Directory of Open Access Journals (Sweden)

Johnny eKao

2015-06-01

Full Text Available Background: The optimal technique for performing lung IMRT remains poorly defined. We hypothesize that improved dose distributions associated with normal tissue sparing IMRT can allow for safe dose escalation resulting in decreased acute and late toxicity. Methods: We performed a retrospective analysis of 82 consecutive lung cancer patients treated with curative intent from 1/10 to 9/14. From 1/10 to 4/12, 44 patients were treated with the community standard of 3-dimensional conformal radiotherapy or IMRT without specific esophagus or contralateral lung constraints (standard RT. From 5/12 to 9/14, 38 patients were treated with normal tissue-sparing IMRT with selective sparing of contralateral lung and esophagus. The study endpoints were dosimetry, toxicity and overall survival.Results: Despite higher mean prescribed radiation doses in the normal tissue-sparing IMRT cohort (64.5 Gy vs. 60.8 Gy, p=0.04, patients treated with normal tissue-sparing IMRT had significantly lower lung V20, V10, V5, mean lung, maximum esophagus and mean esophagus doses compared to patients treated with standard RT (p≤0.001. Patients in the normal tissue-sparing IMRT group had reduced acute grade ≥3 esophagitis (0% vs. 11%, p<0.001, acute grade ≥2 weight loss (2% vs. 16%, p=0.04, late grade ≥2 pneumonitis (7% vs. 21%, p=0.02. The 2-year overall survival was 52% with normal tissue-sparing IMRT arm compared to 28% for standard RT (p=0.015.Conclusion: These data provide proof of principle that suboptimal radiation dose distributions are associated with significant acute and late lung and esophageal toxicity that may result in hospitalization or even premature mortality. Strict attention to contralateral lung and esophageal dose volume constraints are feasible in the community hospital setting without sacrificing disease control.

Comparative biology of decellularized lung matrix: Implications of species mismatch in regenerative medicine.

Science.gov (United States)

Balestrini, Jenna L; Gard, Ashley L; Gerhold, Kristin A; Wilcox, Elise C; Liu, Angela; Schwan, Jonas; Le, Andrew V; Baevova, Pavlina; Dimitrievska, Sashka; Zhao, Liping; Sundaram, Sumati; Sun, Huanxing; Rittié, Laure; Dyal, Rachel; Broekelmann, Tom J; Mecham, Robert P; Schwartz, Martin A; Niklason, Laura E; White, Eric S

2016-09-01

Lung engineering is a promising technology, relying on re-seeding of either human or xenographic decellularized matrices with patient-derived pulmonary cells. Little is known about the species-specificity of decellularization in various models of lung regeneration, or if species dependent cell-matrix interactions exist within these systems. Therefore decellularized scaffolds were produced from rat, pig, primate and human lungs, and assessed by measuring residual DNA, mechanical properties, and key matrix proteins (collagen, elastin, glycosaminoglycans). To study intrinsic matrix biologic cues, human endothelial cells were seeded onto acellular slices and analyzed for markers of cell health and inflammation. Despite similar levels of collagen after decellularization, human and primate lungs were stiffer, contained more elastin, and retained fewer glycosaminoglycans than pig or rat lung scaffolds. Human endothelial cells seeded onto human and primate lung tissue demonstrated less expression of vascular cell adhesion molecule and activation of nuclear factor-κB compared to those seeded onto rodent or porcine tissue. Adhesion of endothelial cells was markedly enhanced on human and primate tissues. Our work suggests that species-dependent biologic cues intrinsic to lung extracellular matrix could have profound effects on attempts at lung regeneration. Copyright © 2016 Elsevier Ltd. All rights reserved.

Irradiation induces a biphasic expression of pro-inflammatory cytokines in the lung

International Nuclear Information System (INIS)

Ruebe, C.E.; Wilfert, F.; Palm, J.; Burdak-Rothkamm, S.; Ruebe, C.; Koenig, J.; Liu Li; Schuck, A.; Willich, N.

2004-01-01

Background and purpose: the precise pathophysiological mechanisms of radiation-induced lung injury are poorly understood, but have been shown to correlate with dysregulation of different cytokines. The purpose of this study was to evaluate the time course of the pro-inflammatory cytokines tumor necrosis factor-(TNF-)α, interleukin-(IL)-1α and IL-6 after whole-lung irradiation. Material and methods: the thoraces of C57BL/6J mice were irradiated with 12 Gy. Treated and control mice were sacrificed at 0.5, 1, 3, 6, 12, 24, 48, 72 h, 1, 2, 4, 8, 16, and 24 weeks post irradiation (p.i.). Real-time multiplex RT-PCR (reverse transcriptase polmyerase chain reaction) was established to evaluate the expression of TNF-α, IL-1α and IL-6 in the lung tissue of the mice. For histological analysis, lung tissue sections were stained by hematoxylin and eosin. Results: multiplex RT-PCR analysis revealed a biphasic expression of these pro-inflammatory cytokines in the lung tissue after irradiation. After an initial increase at 1 h p.i. for TNF-α and at 6 h p.i. for IL-1α and IL-6, the mRNA expression of these pro-inflammatory cytokines returned to basal levels (48 h, 72 h, 1 week, 2 weeks p.i.). During the pneumonic phase, TNF-α, IL-1α and IL-6 were significantly elevated and revealed their maximum at 8 weeks p.i. Histopathologic evaluation of the lung sections obtained within 4 weeks p.i. revealed only minor lung damage in 5-30% of the lung tissue. By contrast, at 8, 16, and 24 weeks p.i., 70-90% of the lung tissue revealed histopathologically detectable organizing alveolitis. Conclusion: irradiation induces a biphasic expression of pro-inflammatory cytokines in the lung. The initial transitory cytokine response occurred within the first hours after lung irradiation with no detectable histopathologic alterations. The second, more persistent cytokine elevation coincided with the onset of histologically discernible organizing acute pneumonitis. (orig.)

Irradiation induces a biphasic expression of pro-inflammatory cytokines in the lung

Energy Technology Data Exchange (ETDEWEB)

Ruebe, C.E.; Wilfert, F.; Palm, J.; Burdak-Rothkamm, S.; Ruebe, C. [Dept. of Radiotherapy - Radiooncology, Saarland Univ., Homburg/Saar (Germany); Koenig, J. [Inst. of Medical Biometrics, Epidemiology and Medical Informatics, Saarland Univ., Homburg/Saar (Germany); Liu Li [Dept. of Radiotherapy - Radiooncology, Saarland Univ., Homburg/Saar (Germany); Cancer Center, Union Hospital Tongji Medical Coll., Huazhong Univ. of Science and Technology, Wuhan (China); Schuck, A.; Willich, N. [Dept. of Radiotherapy - Radiooncology, Univ. of Muenster (Germany)

2004-07-01

Background and purpose: the precise pathophysiological mechanisms of radiation-induced lung injury are poorly understood, but have been shown to correlate with dysregulation of different cytokines. The purpose of this study was to evaluate the time course of the pro-inflammatory cytokines tumor necrosis factor-(TNF-){alpha}, interleukin-(IL)-1{alpha} and IL-6 after whole-lung irradiation. Material and methods: the thoraces of C57BL/6J mice were irradiated with 12 Gy. Treated and control mice were sacrificed at 0.5, 1, 3, 6, 12, 24, 48, 72 h, 1, 2, 4, 8, 16, and 24 weeks post irradiation (p.i.). Real-time multiplex RT-PCR (reverse transcriptase polmyerase chain reaction) was established to evaluate the expression of TNF-{alpha}, IL-1{alpha} and IL-6 in the lung tissue of the mice. For histological analysis, lung tissue sections were stained by hematoxylin and eosin. Results: multiplex RT-PCR analysis revealed a biphasic expression of these pro-inflammatory cytokines in the lung tissue after irradiation. After an initial increase at 1 h p.i. for TNF-{alpha} and at 6 h p.i. for IL-1{alpha} and IL-6, the mRNA expression of these pro-inflammatory cytokines returned to basal levels (48 h, 72 h, 1 week, 2 weeks p.i.). During the pneumonic phase, TNF-{alpha}, IL-1{alpha} and IL-6 were significantly elevated and revealed their maximum at 8 weeks p.i. Histopathologic evaluation of the lung sections obtained within 4 weeks p.i. revealed only minor lung damage in 5-30% of the lung tissue. By contrast, at 8, 16, and 24 weeks p.i., 70-90% of the lung tissue revealed histopathologically detectable organizing alveolitis. Conclusion: irradiation induces a biphasic expression of pro-inflammatory cytokines in the lung. The initial transitory cytokine response occurred within the first hours after lung irradiation with no detectable histopathologic alterations. The second, more persistent cytokine elevation coincided with the onset of histologically discernible organizing acute

Eosinophilic Lung Disorders

Science.gov (United States)

... problems characterized by having an increased number of eosinophils (white blood cells) in the lungs. These white ... category of pneumonias that feature increased numbers of eosinophils in the lung tissue. Pneumonia is an inflammatory ...

Pharmacokinetics of WR-1065 in mouse tissue following treatment with WR-2721

International Nuclear Information System (INIS)

Utley, J.F.; Seaver, N.; Newton, G.L.; Fahey, R.C.

1984-01-01

Levels of reduced glutathione (GSH) and N-(2-mercaptoethyl)-1,3-diaminopropane (WR-1065) were measured in tissues of Balb/c mouse bearing EMT 6 tumors at time intervals ranging from 5 min to 48 hr after i.v. injection of S-2-(3-aminopropylamino)ethyl phosphorothioate (WR-2721) at 500 mg per kg. In all tissues examined (liver, kidney, lung, heart, muscle, brain, tumor, spleen, and salivary gland), maximal WR-1065 levels occurred 5-15 min after injection, with levels in liver, kidney, lung, and salivary gland exceeding one μmole per gm. The post-maximum decline in WR-1065 varied markedly with tissue, lung exhibiting a 6-fold drop by 30 min and salivary gland falling only 15% after 3 hr. In a mouse treated with carbon-14 labeled WR-2721 it was found after 15 min that WR-1065 accounted for over half of the total drug in all tissues except tumor, where it accounted for a third of the total drug. There was no evidence that GSH levels were substantially altered by WR-2721 treatment. The results provide the first direct evidence supporting the widely held view that WR-2721 treatment results in intracellular WR-1065 and they demonstrate that high levels of WR-1065 occur very soon after i.v. injection

Ultrastructural changes in lung tissue after acute lead intoxication in the rat.

Science.gov (United States)

Kaczynska, Katarzyna; Walski, Michał; Szereda-Przestaszewska, Małgorzata

2011-01-01

Pulmonary toxicity of lead was studied in rats after an intraperitoneal administration of lead acetate at a dose of 25 mg/kg. Three consecutive days of treatment increased lead content in the whole blood to 2.1 µg/dl and in lung homogenate it attained 9.62 µg/g w.w. versus control values of 0.17 µg/dl and 0.78 µg/g w.w., respectively. At the ultrastructural level, the effects of lead toxicity were observed in lung capillaries, interstitium, epithelial cells and alveolar lining layer. Accumulation of aggregated platelets, leucocytic elements and monocytes was found within capillaries. Interstitium comprised a substantial number of collagen, elastin filaments and lipofibroblasts. Lamellar bodies of type II pneumocytes contained phospolipid lamellae, which stratified into an irregular arrangement. Pulmonary alveoli were filled with macrophages. The extracellular lining layer of lung alveoli was partially destroyed. This study provided evidence that acute lead intoxication affects the whole lung parenchyma and by impairing production of the surfactant might disturb the regular respiratory function.

Peripheral ovine progressive pneumonia provirus levels correlate with and predict histological tissue lesion severity in naturally infected sheep.

Science.gov (United States)

Herrmann-Hoesing, Lynn M; Noh, Susan M; White, Stephen N; Snekvik, Kevin R; Truscott, Thomas; Knowles, Donald P

2009-04-01

Studies were undertaken to determine whether anti-ovine progressive pneumonia virus (OPPV) antibody responses in serum or OPP provirus levels in peripheral blood associate with the degree of histologically measured tissue lesions in naturally OPPV-infected sheep. Sections of formalin-fixed, paraffin-embedded, and hematoxylin- and eosin-stained lung, mammary gland, carpal synovial membrane, and brain tissues from 11 OPPV-infected ewes (mean age of 8.6 years) and 5 OPPV-uninfected ewes (mean age of 6 years) were evaluated for lesion severity. Ovine progressive pneumonia (OPP) provirus levels and anti-OPPV antibody titers in peripheral blood and serum samples, respectively, were measured upon euthanasia and 3 years prior to euthanasia. Both mean peripheral OPP provirus levels and mean serum anti-surface envelope glycoprotein (anti-SU) antibody titers at the time of euthanasia were significantly higher in ewes with moderate to severe histological lesions than in ewes with no to mild histological lesions. However, although mean peripheral blood OPP provirus levels at euthanasia and 3 years prior to euthanasia significantly correlated with the highest histological lesion score for any affected tissue (two-tailed P values, 0.03 and 0.02), mean serum anti-SU antibody titers, anti-capsid antibody titers, and anti-transmembrane 90 antibody titers at euthanasia did not show a significant correlation with the highest histological lesion score for any tissue (two-tailed P values, 0.32, 0.97, and 0.18, respectively). These data are the first to show that OPP provirus levels predict and correlate with the extent of OPPV-related histological lesions in various OPPV-affected tissues. These findings suggest that peripheral OPP provirus levels quantitatively contribute more to the development of histological lesions than the systemic anti-SU antibody host immune response.

Mass Preserving Registration for lung CT

DEFF Research Database (Denmark)

Gorbunova, Vladlena; Lo, Pechin Chien Pau; Loeve, Martin

2009-01-01

intensities due to differences in inspiration level, we propose to adjust the intensity of lung tissue according to the local expansion or compression. An image registration method without intensity adjustment is compared to the proposed method. Both approaches are evaluated on a set of 10 pairs of expiration...... and inspiration CT scans of children with cystic fibrosis lung disease. The proposed method with mass preserving adjustment results in significantly better alignment of the vessel trees. Analysis of local volume change for regions with trapped air compared to normally ventilated regions revealed larger...

Level-set-based reconstruction algorithm for EIT lung images: first clinical results.

Science.gov (United States)

Rahmati, Peyman; Soleimani, Manuchehr; Pulletz, Sven; Frerichs, Inéz; Adler, Andy

2012-05-01

We show the first clinical results using the level-set-based reconstruction algorithm for electrical impedance tomography (EIT) data. The level-set-based reconstruction method (LSRM) allows the reconstruction of non-smooth interfaces between image regions, which are typically smoothed by traditional voxel-based reconstruction methods (VBRMs). We develop a time difference formulation of the LSRM for 2D images. The proposed reconstruction method is applied to reconstruct clinical EIT data of a slow flow inflation pressure-volume manoeuvre in lung-healthy and adult lung-injury patients. Images from the LSRM and the VBRM are compared. The results show comparable reconstructed images, but with an improved ability to reconstruct sharp conductivity changes in the distribution of lung ventilation using the LSRM.

Level-set-based reconstruction algorithm for EIT lung images: first clinical results

International Nuclear Information System (INIS)

Rahmati, Peyman; Adler, Andy; Soleimani, Manuchehr; Pulletz, Sven; Frerichs, Inéz

2012-01-01

We show the first clinical results using the level-set-based reconstruction algorithm for electrical impedance tomography (EIT) data. The level-set-based reconstruction method (LSRM) allows the reconstruction of non-smooth interfaces between image regions, which are typically smoothed by traditional voxel-based reconstruction methods (VBRMs). We develop a time difference formulation of the LSRM for 2D images. The proposed reconstruction method is applied to reconstruct clinical EIT data of a slow flow inflation pressure–volume manoeuvre in lung-healthy and adult lung-injury patients. Images from the LSRM and the VBRM are compared. The results show comparable reconstructed images, but with an improved ability to reconstruct sharp conductivity changes in the distribution of lung ventilation using the LSRM. (paper)

Effects of acute and chronic administration of methylprednisolone on oxidative stress in rat lungs

Directory of Open Access Journals (Sweden)

Ronaldo Lopes Torres

2014-06-01

Full Text Available Objective: To determine the effects of acute and chronic administration of methylprednisolone on oxidative stress, as quantified by measuring lipid peroxidation (LPO and total reactive antioxidant potential (TRAP, in rat lungs. Methods: Forty Wistar rats were divided into four groups: acute treatment, comprising rats receiving a single injection of methylprednisolone (50 mg/kg i.p.; acute control, comprising rats i.p. injected with saline; chronic treatment, comprising rats receiving methylprednisolone in drinking water (6 mg/kg per day for 30 days; and chronic control, comprising rats receiving normal drinking water. Results: The levels of TRAP were significantly higher in the acute treatment group rats than in the acute control rats, suggesting an improvement in the pulmonary defenses of the former. The levels of lung LPO were significantly higher in the chronic treatment group rats than in the chronic control rats, indicating oxidative damage in the lung tissue of the former. Conclusions: Our results suggest that the acute use of corticosteroids is beneficial to lung tissue, whereas their chronic use is not. The chronic use of methylprednisolone appears to increase lung LPO levels.

SARS – Lung Pathology

Indian Academy of Sciences (India)

Dry nonproductive cough – may show minimal lung infiltration. Recovery; * Lungs get fluid in bronchi- droplets infective and +ve for virus in culture and PCR. May also have co-infection with chlamydia/metapneumoviruses. Recovery; * Lung tissue destroyed due to ? immunological/cytokine mediated damage-Recovery ...

Inducible Bronchus-Associated Lymphoid Tissue: Taming Inflammation in the Lung.

Science.gov (United States)

Hwang, Ji Young; Randall, Troy D; Silva-Sanchez, Aaron

2016-01-01

Following pulmonary inflammation, leukocytes that infiltrate the lung often assemble into structures known as inducible Bronchus-Associated Lymphoid Tissue (iBALT). Like conventional lymphoid organs, areas of iBALT have segregated B and T cell areas, specialized stromal cells, high endothelial venules, and lymphatic vessels. After inflammation is resolved, iBALT is maintained for months, independently of inflammation. Once iBALT is formed, it participates in immune responses to pulmonary antigens, including those that are unrelated to the iBALT-initiating antigen, and often alters the clinical course of disease. However, the mechanisms that govern immune responses in iBALT and determine how iBALT impacts local and systemic immunity are poorly understood. Here, we review our current understanding of iBALT formation and discuss how iBALT participates in pulmonary immunity.

Lung inflammation biomarkers and lung function in children chronically exposed to arsenic

Energy Technology Data Exchange (ETDEWEB)

Olivas-Calderón, Edgar, E-mail: edgar_olivascalderon@hotmail.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); School of Medicine, University Juarez of Durango, Gomez Palacio, Durango (Mexico); Recio-Vega, Rogelio, E-mail: rrecio@yahoo.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); Gandolfi, A. Jay, E-mail: gandolfi@pharmacy.arizona.edu [Southwest Environmental Health Science Center, University of Arizona, Tucson, AZ (United States); Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ (United States); Lantz, R. Clark, E-mail: lantz@email.arizona.edu [Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ (United States); Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ (United States); González-Cortes, Tania, E-mail: taniagc2201@hotmail.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); Gonzalez-De Alba, Cesar, E-mail: cesargonzalezalba@hotmail.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); Froines, John R., E-mail: jfroines@ucla.edu [Center for Environmental and Occupational Health, School of Public Health, University of California at Los Angeles, Los Angeles, CA (United States); Espinosa-Fematt, Jorge A., E-mail: dr.jorge.espinosa@gmail.com [School of Medicine, University Juarez of Durango, Gomez Palacio, Durango (Mexico)

2015-09-01

Evidence suggests that exposure to arsenic in drinking water during early childhood or in utero has been associated with an increase in respiratory symptoms or diseases in the adulthood, however only a few studies have been carried out during those sensitive windows of exposure. Recently our group demonstrated that the exposure to arsenic during early childhood or in utero in children was associated with impairment in the lung function and suggested that this adverse effect could be due to a chronic inflammation response to the metalloid. Therefore, we designed this cross-sectional study in a cohort of children associating lung inflammatory biomarkers and lung function with urinary As levels. A total of 275 healthy children were partitioned into four study groups according with their arsenic urinary levels. Inflammation biomarkers were measured in sputum by ELISA and the lung function was evaluated by spirometry. Fifty eight percent of the studied children were found to have a restrictive spirometric pattern. In the two highest exposed groups, the soluble receptor for advanced glycation end products' (sRAGE) sputum level was significantly lower and matrix metalloproteinase-9 (MMP-9) concentration was higher. When the biomarkers were correlated to the urinary arsenic species, negative associations were found between dimethylarsinic (DMA), monomethylarsonic percentage (%MMA) and dimethylarsinic percentage (%DMA) with sRAGE and positive associations between %DMA with MMP-9 and with the MMP-9/tissue inhibitor of metalloproteinase (TIMP-1) ratio. In conclusion, chronic arsenic exposure of children negatively correlates with sRAGE, and positively correlated with MMP-9 and MMP-9/TIMP-1 levels, and increases the frequency of an abnormal spirometric pattern. Arsenic-induced alterations in inflammatory biomarkers may contribute to the development of restrictive lung diseases. - Highlights: • First study in children evaluating lung inflammatory biomarkers and As levels

Identification and validation of differentially expressed transcripts by RNA-sequencing of formalin-fixed, paraffin-embedded (FFPE) lung tissue from patients with Idiopathic Pulmonary Fibrosis.

Science.gov (United States)

Vukmirovic, Milica; Herazo-Maya, Jose D; Blackmon, John; Skodric-Trifunovic, Vesna; Jovanovic, Dragana; Pavlovic, Sonja; Stojsic, Jelena; Zeljkovic, Vesna; Yan, Xiting; Homer, Robert; Stefanovic, Branko; Kaminski, Naftali

2017-01-12

Idiopathic Pulmonary Fibrosis (IPF) is a lethal lung disease of unknown etiology. A major limitation in transcriptomic profiling of lung tissue in IPF has been a dependence on snap-frozen fresh tissues (FF). In this project we sought to determine whether genome scale transcript profiling using RNA Sequencing (RNA-Seq) could be applied to archived Formalin-Fixed Paraffin-Embedded (FFPE) IPF tissues. We isolated total RNA from 7 IPF and 5 control FFPE lung tissues and performed 50 base pair paired-end sequencing on Illumina 2000 HiSeq. TopHat2 was used to map sequencing reads to the human genome. On average ~62 million reads (53.4% of ~116 million reads) were mapped per sample. 4,131 genes were differentially expressed between IPF and controls (1,920 increased and 2,211 decreased (FDR < 0.05). We compared our results to differentially expressed genes calculated from a previously published dataset generated from FF tissues analyzed on Agilent microarrays (GSE47460). The overlap of differentially expressed genes was very high (760 increased and 1,413 decreased, FDR < 0.05). Only 92 differentially expressed genes changed in opposite directions. Pathway enrichment analysis performed using MetaCore confirmed numerous IPF relevant genes and pathways including extracellular remodeling, TGF-beta, and WNT. Gene network analysis of MMP7, a highly differentially expressed gene in both datasets, revealed the same canonical pathways and gene network candidates in RNA-Seq and microarray data. For validation by NanoString nCounter® we selected 35 genes that had a fold change of 2 in at least one dataset (10 discordant, 10 significantly differentially expressed in one dataset only and 15 concordant genes). High concordance of fold change and FDR was observed for each type of the samples (FF vs FFPE) with both microarrays (r = 0.92) and RNA-Seq (r = 0.90) and the number of discordant genes was reduced to four. Our results demonstrate that RNA sequencing of RNA

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.

CT-guided needle biopsy in the diagnosis of lung adenocarcinoma accompanied by extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue: a rare combination.

Science.gov (United States)

Tian, Panwen; Wang, Ye; Wan, Chun; Shen, Yongchun; Wen, Fuqiang

2015-01-01

We represent a rare case of lung adenocarcinoma accompanied by extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT). The patient was a 66-year-old male presented with 1 month history of recurrent cough and hemoptysis. Chest CT showed solitary ground-glass opacity (GGO) in the upper lobe of the right lung and mediastinal lymph node enlargement in station 3p. A CT-guided transthoracic needle biopsy was performed. Tissue specimens of the GGO revealed a typical adenocarcinoma. Histopathologic diagnosis of mediastinal lymph node was extranodal marginal zone lymphoma of MALT. Because of its rarity, extranodal marginal zone lymphoma of MALT should be considered in the differential diagnosis when we encounter mediastinal lymphadenopathy in patients with lung adenocarcinoma.

Illumina MiSeq 16S amplicon sequence analysis of bovine respiratory disease associated bacteria in lung and mediastinal lymph node tissue.

Science.gov (United States)

Johnston, Dayle; Earley, Bernadette; Cormican, Paul; Murray, Gerard; Kenny, David Anthony; Waters, Sinead Mary; McGee, Mark; Kelly, Alan Kieran; McCabe, Matthew Sean

2017-05-02

Bovine respiratory disease (BRD) is caused by growth of single or multiple species of pathogenic bacteria in lung tissue following stress and/or viral infection. Next generation sequencing of 16S ribosomal RNA gene PCR amplicons (NGS 16S amplicon analysis) is a powerful culture-independent open reference method that has recently been used to increase understanding of BRD-associated bacteria in the upper respiratory tract of BRD cattle. However, it has not yet been used to examine the microbiome of the bovine lower respiratory tract. The objective of this study was to use NGS 16S amplicon analysis to identify bacteria in post-mortem lung and lymph node tissue samples harvested from fatal BRD cases and clinically healthy animals. Cranial lobe and corresponding mediastinal lymph node post-mortem tissue samples were collected from calves diagnosed as BRD cases by veterinary laboratory pathologists and from clinically healthy calves. NGS 16S amplicon libraries, targeting the V3-V4 region of the bacterial 16S rRNA gene were prepared and sequenced on an Illumina MiSeq. Quantitative insights into microbial ecology (QIIME) was used to determine operational taxonomic units (OTUs) which corresponded to the 16S rRNA gene sequences. Leptotrichiaceae, Mycoplasma, Pasteurellaceae, and Fusobacterium were the most abundant OTUs identified in the lungs and lymph nodes of the calves which died from BRD. Leptotrichiaceae, Fusobacterium, Mycoplasma, Trueperella and Bacteroides had greater relative abundances in post-mortem lung samples collected from fatal cases of BRD in dairy calves, compared with clinically healthy calves without lung lesions. Leptotrichiaceae, Mycoplasma and Pasteurellaceae showed higher relative abundances in post-mortem lymph node samples collected from fatal cases of BRD in dairy calves, compared with clinically healthy calves without lung lesions. Two Leptotrichiaceae sequence contigs were subsequently assembled from bacterial DNA-enriched shotgun sequences

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.

Forcing lateral electron disequilibrium to spare lung tissue: a novel technique for stereotactic body radiation therapy of lung cancer

International Nuclear Information System (INIS)

Disher, Brandon; Hajdok, George; Gaede, Stewart; Mulligan, Matthew; Battista, Jerry J

2013-01-01

by considering the extent of tumour motion over the patient's breathing cycle and set-up uncertainties. All patient dose results were normalized such that at least 95% of the PTV received at least 54 Gy (i.e. D95 = 54 Gy). Further, we introduce ‘LED maps’ as a novel clinical tool to compare the magnitude of LED resulting from the various SBRT arc plans. Results from the phantom simulation suggest that the best lung sparing occurred for RT parameters that cause severe LED. For equal tumour dose coverage, normal lung dose (2 cm outside the target region) was reduced from 92% to 23%, comparing results between the 18 MV (5 × 5 cm 2 ) and 18 MV (1 × 1 cm 2 ) arc simulations. In addition to reduced lung dose for the 18 MV (1 × 1 cm 2 ) arc, maximal tumour dose increased beyond 125%. Thus, LED can create steep dose gradients to spare normal lung, while increasing tumour dose levels (if desired). In the patient simulation, a LED-optimized arc plan was designed using either 18 MV (3 × 1 cm 2 ) or 6 MV (3 × 3cm 2 ) beams. Both plans met the D95 dose coverage requirement for the target. However, the LED-optimized plan increased the maximum, mean, and minimum dose within the PTV by as much as 80 Gy, 11 Gy, and 3 Gy, respectively. Despite increased tumour dose levels, the 18 MV (3 × 1 cm 2 ) arc plan improved or maintained the V20, V5, and mean lung dose metrics compared to the 6 MV (3 × 3 cm 2 ) simulation. We conclude that LED-SBRT has the potential to increase dose gradients, and dose levels within a small lung tumour. The magnitude of tumour dose increase or lung sparing can be optimized through manipulation of RT parameters (e.g. beam energy and field size). (paper)

Deep inspiration breath-hold technique for lung tumors: the potential value of target immobilization and reduced lung density in dose escalation

International Nuclear Information System (INIS)

Hanley, J.; Debois, M.M.; Raben, A.; Mageras, G.S.; Lutz, W.R.; Mychalczak, B.; Schwartz, L.H.; Gloeggler, P.J.; Leibel, S.A.; Fuks, Z.; Kutcher, G.J.

1996-01-01

Purpose/Objective: Lung tumors are subject to movement due to respiratory motion. Conventionally, a margin is applied to the clinical target volume (CTV) to account for this and other treatment uncertainties. The purpose of this study is to evaluate the dosimetric benefits of a deep inspiration breath-hold (DIBH) technique which has two distinct features - deep inspiration which reduces lung density and breath-hold which immobilizes lung tumors. Both properties can potentially reduce the mass of normal lung tissue in the high dose region, thus improving the possibility of dose escalation. Methods and Materials: To study the efficacy of the DIBH technique, CT scans are acquired for each patient under 4 respiration conditions: free-breathing; DIBH; shallow inspiration breath-hold; shallow expiration breath-hold. The free-breathing and DIBH scans are used to generate treatment plans for comparison of standard and DIBH techniques, while the shallow inspiration and expiration scans provide information on the maximum extent of tumor motion under free-breathing conditions. To acquire the breath-hold scans, the patients are brought to reproducible respiration levels using spirometry and slow vital capacity maneuvers. For the treatment plan comparison free-breathing and DIBH planning target volumes (PTVs) are constructed consisting of the CTV plus a margin for setup error and lung tumor motion. For both plans the margin for setup error is the same while the margin for lung tumor motion differs. The margin for organ motion in free-breathing is determined by the maximum tumor excursions in the shallow inspiration and expiration CT scans. For the DIBH, tumor motion is reduced to the extent to which DIBH can be maintained and the margin for any residual tumor motion is determined from repeat fluoroscopic movies, acquired with the patient monitored using spirometry. Three-dimensional treatment plans, generated using apertures based on the free-breathing and DIBH PTVs, are

Telomerase in lung cancer diagnostics

International Nuclear Information System (INIS)

Kovkarova, E.; Stefanovski, T.; Dimov, A.; Naumovski, J.

2003-01-01

Background. Telomerase is a ribonucleoprotein that looks after the telomeric cap of the linear chromosomes maintaining its length. It is over expressed in tumour tissues, but not in normal somatic cells. Therefore the aim of this study was to determine the telomerase activity in lung cancer patients as novel marker for lung cancer detection evaluating the influence of tissue/cell obtaining technique. Material and methods. Using the TRAP (telomeric repeat amplification protocol), telomerase activity was determined in material obtained from bronchobiopsy (60 lung cancer patients compared with 20 controls) and washings from transthoracic fine needle aspiration biopsy performed in 10 patients with peripheral lung tumours. Results. Telomerase activity was detected in 75% of the lung cancer bronchobyopsies, and in 100% in transthoracic needle washings. Conclusions. Measurement of telomerase activity can contribute in fulfilling the diagnosis of lung masses and nodules suspected for lung cancer. (author)

Clinical significance of preoperative serum albumin level for prognosis in surgically resected patients with non-small cell lung cancer: Comparative study of normal lung, emphysema, and pulmonary fibrosis.

Science.gov (United States)

Miura, Kentaro; Hamanaka, Kazutoshi; Koizumi, Tomonobu; Kitaguchi, Yoshiaki; Terada, Yukihiro; Nakamura, Daisuke; Kumeda, Hirotaka; Agatsuma, Hiroyuki; Hyogotani, Akira; Kawakami, Satoshi; Yoshizawa, Akihiko; Asaka, Shiho; Ito, Ken-Ichi

2017-09-01

This study was performed to clarify whether preoperative serum albumin level is related to the prognosis of non-small cell lung cancer patients undergoing surgical resection, and the relationships between serum albumin level and clinicopathological characteristics of lung cancer patients with emphysema or pulmonary fibrosis. We retrospectively evaluated 556 patients that underwent surgical resection for non-small cell lung cancer. The correlation between preoperative serum albumin level and survival was evaluated. Patients were divided into three groups according to the findings on chest high-resolution computed tomography (normal lung, emphysema, and pulmonary fibrosis), and the relationships between serum albumin level and clinicopathological characteristics, including prognosis, were evaluated. The cut-off value of serum albumin level was set at 4.2g/dL. Patients with low albumin levels (albumin emphysema group (n=48) and pulmonary fibrosis group (n=45) were significantly lower than that in the normal lung group (n=463) (p=0.009 and pulmonary fibrosis groups, but not in the emphysema group. Preoperative serum albumin level was an important prognostic factor for overall survival and recurrence-free survival in patients with resected non-small cell lung cancer. Divided into normal lung, emphysema, and pulmonary fibrosis groups, serum albumin level showed no influence only in patients in the emphysema group. Copyright © 2017 Elsevier B.V. All rights reserved.

Expression of TMPRSS4 in non-small cell lung cancer and its modulation by hypoxia

Science.gov (United States)

NGUYEN, TRI-HUNG; WEBER, WILLIAM; HAVARI, EVIS; CONNORS, TIMOTHY; BAGLEY, REBECCA G.; McLAREN, RAJASHREE; NAMBIAR, PRASHANT R.; MADDEN, STEPHEN L.; TEICHER, BEVERLY A.; ROBERTS, BRUCE; KAPLAN, JOHANNE; SHANKARA, SRINIVAS

2012-01-01

Overexpression of TMPRSS4, a cell surface-associated transmembrane serine protease, has been reported in pancreatic, colorectal and thyroid cancers, and has been implicated in tumor cell migration and metastasis. Few reports have investigated both TMPRSS4 gene expression levels and the protein products. In this study, quantitative RT-PCR and protein staining were used to assess TMPRSS4 expression in primary non-small cell lung carcinoma (NSCLC) tissues and in lung tumor cell lines. At the transcriptional level, TMPRSS4 message was significantly elevated in the majority of human squamous cell and adenocarcinomas compared with normal lung tissues. Staining of over 100 NSCLC primary tumor and normal specimens with rabbit polyclonal anti-TMPRSS4 antibodies confirmed expression at the protein level in both squamous cell and adenocarcinomas with little or no staining in normal lung tissues. Human lung tumor cell lines expressed varying levels of TMPRSS4 mRNA in vitro. Interestingly, tumor cell lines with high levels of TMPRSS4 mRNA failed to show detectable TMPRSS4 protein by either immunoblotting or flow cytometry. However, protein levels were increased under hypoxic culture conditions suggesting that hypoxia within the tumor microenvironment may upregulate TMPRSS4 protein expression in vivo. This was supported by the observation of TMPRSS4 protein in xenograft tumors derived from the cell lines. In addition, staining of human squamous cell carcinoma samples for carbonic anhydrase IX (CAIX), a hypoxia marker, showed TMPRSS4 positive cells adjacent to CAIX positive cells. Overall, these results indicate that the cancer-associated TMPRSS4 protein is overexpressed in NSCLC and may represent a potential therapeutic target. PMID:22692880

Cordycepin alleviates lipopolysaccharide-induced acute lung injury via Nrf2/HO-1 pathway.

Science.gov (United States)

Qing, Rui; Huang, Zezhi; Tang, Yufei; Xiang, Qingke; Yang, Fan

2018-04-24

The present study is to investigate the protective effect of cordycepin on inflammatory reactions in rats with acute lung injury (ALI) induced by lipopolysaccharide (LPS), as well as the underlying mechanism. Wistar rat model of ALI was induced by intravenous injection of LPS (30 mg/kg body weight). One hour later, intravenous injection of cordycepin (1, 10 or 30 mg/kg body weight) was administered. The wet-to-dry weight ratio of lung tissues and myeloperoxidase activity in the lung tissues were measured. The contents of nitrite and nitrate were measured by reduction method, while chemiluminescence was used to determine the content of superoxide. Quantitative real-time polymerase chain reaction and Western blotting were used to determine the expression of mRNA and protein, respectively. Colorimetry was performed to determine the enzymatic activity of heme oxygenase-1 (HO-1). Nuclear translocation of Nrf2 was identified by Western blotting. The plasma contents of cytokines were measured by enzyme-linked immunosorbent assay. Cordycepin enhanced the expression and enzymatic activity of HO-1 in ALI rats, and activated Nrf2 by inducing the translocation of Nrf2 from cytoplasm to nucleus. In addition, cordycepin regulated the secretion of TNF-α, IL-6 and IL-10 via HO-1, and suppressed inflammation in lung tissues of ALI rats by inducing the expression of HO-1. HO-1 played important roles in the down-regulation of superoxide levels in lung tissues by cordycepin, and HO-1 expression induced by cordycepin affected nitrite and nitrate concentrations in plasma and iNOS protein expression in lung tissues. Cordycepin showed protective effect on injuries in lung tissues. The present study demonstrates that cordycepin alleviates inflammation induced by LPS via the activation of Nrf2 and up-regulation of HO-1 expression. Copyright © 2018. Published by Elsevier B.V.

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

Science.gov (United States)

2011-07-01

glucose , hematocrit (Hct), hemoglobin (Hb), sodium (Na+), potassium (K+), and ionized calcium (iCa2+) using i-STAT cartridges ( Abbott Laboratories...animals were observed for 200 minutes. Blood chemistry and physiological parameters were recorded. Tissue samples from lung and small intestine were...seemingly acceptable medical therapy and surgical intervention.4 The first physiologic response to severe blood loss is activation of the neuroendocrine

SAMHD1 is down regulated in lung cancer by methylation and inhibits tumor cell proliferation

International Nuclear Information System (INIS)

Wang, Jia-lei; Lu, Fan-zhen; Shen, Xiao-Yong; Wu, Yun; Zhao, Li-ting

2014-01-01

Highlights: • SAMHD1 expression level is down regulated in lung adenocarcinoma. • The promoter of SAMHD1 is methylated in lung adenocarcinoma. • Over expression of SAMHD1 inhibits the proliferation of lung cancer cells. - Abstract: The function of dNTP hydrolase SAMHD1 as a viral restriction factor to inhibit the replication of several viruses in human immune cells was well established. However, its regulation and function in lung cancer have been elusive. Here, we report that SAMHD1 is down regulated both on protein and mRNA levels in lung adenocarcinoma compared to adjacent normal tissue. We also found that SAMHD1 promoter is highly methylated in lung adenocarcinoma, which may inhibit its gene expression. Furthermore, over expression of the SAMHD1 reduces dNTP level and inhibits the proliferation of lung tumor cells. These results reveal the regulation and function of SAMHD1 in lung cancer, which is important for the proliferation of lung tumor cells

Receiver Operating Characteristic (ROC to Determine Cut-Off Points of Biomarkers in Lung Cancer Patients

Directory of Open Access Journals (Sweden)

Heidi L. Weiss

2004-01-01

Full Text Available The role of biomarkers in disease prognosis continues to be an important investigation in many cancer studies. In order for these biomarkers to have practical application in clinical decision making regarding patient treatment and follow-up, it is common to dichotomize patients into those with low vs. high expression levels. In this study, receiver operating characteristic (ROC curves, area under the curve (AUC of the ROC, sensitivity, specificity, as well as likelihood ratios were calculated to determine levels of growth factor biomarkers that best differentiate lung cancer cases versus control subjects. Selected cut-off points for p185erbB-2 and EGFR membrane appear to have good discriminating power to differentiate control tissues versus uninvolved tissues from patients with lung cancer (AUC = 89% and 90%, respectively; while AUC increased to at least 90% for selected cut-off points for p185erbB-2 membrane, EGFR membrane, and FASE when comparing between control versus carcinoma tissues from lung cancer cases. Using data from control subjects compared to patients with lung cancer, we presented a simple and intuitive approach to determine dichotomized levels of biomarkers and validated the value of these biomarkers as surrogate endpoints for cancer outcome.

Seawater immersion aggravates burn-associated lung injury and inflammatory and oxidative-stress responses.

Science.gov (United States)

Ma, Jun; Wang, Ying; Wu, Qi; Chen, Xiaowei; Wang, Jiahan; Yang, Lei

2017-08-01

With the increasing frequency of marine development activities and local wars at sea, the incidence of scald burns in marine accidents or wars has been increasing yearly. Various studies have indicated that immersion in seawater has a systemic impact on some organs of animals or humans with burn. Thus, for burn/scald injuries after immersion in seawater, it is desirable to study the effects and mechanisms of action on important organs. In the present study, we aimed to investigate the effect of immersion in seawater on lung injury, inflammatory and oxidative-stress responses in scalded rats. The structural damage to lungs was detected by hematoxylin and eosin staining and the results showed that seawater immersion aggravated structural lung injury in scalded rats. The expression of HMGB1 in lung tissues was detected by immunohistochemical analysis and the results showed that seawater immersion increased HMGB1 expression in lung tissues of scalded rats. Apoptosis in lung tissues was detected by terminal deoxynucleotidyl transfer-mediated dUTP nick end-labeling (TUNEL) staining and the results showed that seawater immersion increased apoptosis rate in lung tissues of scalded rats. In addition, the expression levels of TNF-α, IL-6, IL-8, SOD, and MDA in serum were analyzed by enzyme-linked immunosorbent assays (ELISAs) and the results showed that seawater immersion induced secretion of proinflammatory factors (TNF-α, IL-6, and IL-8), increased MDA protein level, and suppressed SOD activity in the serum of scalded rats. Furthermore, measurement of plasma volume and pH showed that seawater immersion decreased plasma volume and pH value. Overall, the results indicated that all effects induced by immersion in seawater in scalded rats are more pronounced than those induced by freshwater. In conclusion, seawater immersion may aggravate lung injury and enhance inflammatory and oxidative-stress responses after burn. Copyright © 2017 Elsevier Ltd and ISBI. All rights

Plutonium deposits in lung tissues of Filipinos

International Nuclear Information System (INIS)

Natera, E.S.; Palad, L.J.H.; Ignacio, L.M.

1989-01-01

This initial report on the plutonium concentration in lungs of Filipino adults is based on four samples. The data obtained suggest that the average of concentration in lungs of Filipinos is similar to that observed in other countries. This could be attributed to fallout resulting from nuclear test explosions conducted by neighboring countries. The result of this study will be useful in initiating the establishment of plutonium burden of Filipinos. (ELC). 2 tabs

Automated diagnosis of interstitial lung diseases and emphysema in MDCT imaging

Science.gov (United States)

Fetita, Catalin; Chang Chien, Kuang-Che; Brillet, Pierre-Yves; Prêteux, Françoise

2007-09-01

Diffuse lung diseases (DLD) include a heterogeneous group of non-neoplasic disease resulting from damage to the lung parenchyma by varying patterns of inflammation. Characterization and quantification of DLD severity using MDCT, mainly in interstitial lung diseases and emphysema, is an important issue in clinical research for the evaluation of new therapies. This paper develops a 3D automated approach for detection and diagnosis of diffuse lung diseases such as fibrosis/honeycombing, ground glass and emphysema. The proposed methodology combines multi-resolution 3D morphological filtering (exploiting the sup-constrained connection cost operator) and graph-based classification for a full characterization of the parenchymal tissue. The morphological filtering performs a multi-level segmentation of the low- and medium-attenuated lung regions as well as their classification with respect to a granularity criterion (multi-resolution analysis). The original intensity range of the CT data volume is thus reduced in the segmented data to a number of levels equal to the resolution depth used (generally ten levels). The specificity of such morphological filtering is to extract tissue patterns locally contrasting with their neighborhood and of size inferior to the resolution depth, while preserving their original shape. A multi-valued hierarchical graph describing the segmentation result is built-up according to the resolution level and the adjacency of the different segmented components. The graph nodes are then enriched with the textural information carried out by their associated components. A graph analysis-reorganization based on the nodes attributes delivers the final classification of the lung parenchyma in normal and ILD/emphysematous regions. It also makes possible to discriminate between different types, or development stages, among the same class of diseases.

[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.

Cytokine levels in pleural fluid as markers of acute rejection after lung transplantation

Directory of Open Access Journals (Sweden)

Priscila Cilene León Bueno de Camargo

2014-08-01

Full Text Available Our objective was to determine the levels of lactate dehydrogenase, IL-6, IL-8, and VEGF, as well as the total and differential cell counts, in the pleural fluid of lung transplant recipients, correlating those levels with the occurrence and severity of rejection. We analyzed pleural fluid samples collected from 18 patients at various time points (up to postoperative day 4. The levels of IL-6, IL-8, and VEGF tended to elevate in parallel with increases in the severity of rejection. Our results suggest that these levels are markers of acute graft rejection in lung transplant recipients.

Use of radioimmunodetection of carcinoembryonic antigen (CEA) and ferritin in diagnosis of lung cancer

International Nuclear Information System (INIS)

Zamyatin, S.S.; Zakharychev, V.D.

1989-01-01

To study the diagnostic value of radioimmunoassay (RIA) of carcinoembryonic antigen (CEA) and ferritin the level of this markers under lung cancer depending on the tumor localization and the process stage is determined. It is shown that determination of CEA and ferritin level in a number of patients with the peripheral lung cancer allows on the confirm the diagnosis. In case of the central cancer an increase of CEA level testifies to the tumor germination into the adjacent organs and lung tissue and allows one to determine the stage and operability of the disease. 10 refs.; 3 tabs

Method to characterize inorganic particulates in lung tissue biopsies using field emission scanning electron microscopy

Science.gov (United States)

Lowers, Heather; Breit, George N.; Strand, Matthew; Pillers, Renee M.; Meeker, Gregory P.; Todorov, Todor I.; Plumlee, Geoffrey S.; Wolf, Ruth E.; Robinson, Maura; Parr, Jane; Miller, Robert J.; Groshong, Steve; Green, Francis; Rose, Cecile

2018-01-01

Humans accumulate large numbers of inorganic particles in their lungs over a lifetime. Whether this causes or contributes to debilitating disease over a normal lifespan depends on the type and concentration of the particles. We developed and tested a protocol for in situ characterization of the types and distribution of inorganic particles in biopsied lung tissue from three human groups using field emission scanning electron microscopy (FE-SEM) combined with energy dispersive spectroscopy (EDS). Many distinct particle types were recognized among the 13 000 particles analyzed. Silica, feldspars, clays, titanium dioxides, iron oxides and phosphates were the most common constituents in all samples. Particles were classified into three general groups: endogenous, which form naturally in the body; exogenic particles, natural earth materials; and anthropogenic particles, attributed to industrial sources. These in situ results were compared with those using conventional sodium hypochlorite tissue digestion and particle filtration. With the exception of clays and phosphates, the relative abundances of most common particle types were similar in both approaches. Nonetheless, the digestion/filtration method was determined to alter the texture and relative abundances of some particle types. SEM/EDS analysis of digestion filters could be automated in contrast to the more time intensive in situ analyses.

Polyhexamethyleneguanidine phosphate induces severe lung inflammation, fibrosis, and thymic atrophy.

Science.gov (United States)

Song, Jeong Ah; Park, Hyun-Ju; Yang, Mi-Jin; Jung, Kyung Jin; Yang, Hyo-Seon; Song, Chang-Woo; Lee, Kyuhong

2014-07-01

Polyhexamethyleneguanidine phosphate (PHMG-P) has been widely used as a disinfectant because of its strong bactericidal activity and low toxicity. However, in 2011, the Korea Centers for Disease Control and Prevention and the Ministry of Health and Welfare reported that a suspicious outbreak of pulmonary disease might have originated from humidifier disinfectants. The purpose of this study was to assess the toxicity of PHMG-P following direct exposure to the lung. PHMG-P (0.3, 0.9, or 1.5 mg/kg) was instilled into the lungs of mice. The levels of proinflammatory markers and fibrotic markers were quantified in lung tissues and flow cytometry was used to evaluate T cell distribution in the thymus. Administration of PHMG-P induced proinflammatory cytokines elevation and infiltration of immune cells into the lungs. Histopathological analysis revealed a dose-dependent exacerbation of both inflammation and pulmonary fibrosis on day 14. PHMG-P also decreased the total cell number and the CD4(+)/CD8(+) cell ratio in the thymus, with the histopathological examination indicating severe reduction of cortex and medulla. The mRNA levels of biomarkers associated with T cell development also decreased markedly. These findings suggest that exposure of lung tissue to PHMG-P leads to pulmonary inflammation and fibrosis as well as thymic atrophy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Lung Regeneration: Endogenous and Exogenous Stem Cell Mediated Therapeutic Approaches.

Science.gov (United States)

Akram, Khondoker M; Patel, Neil; Spiteri, Monica A; Forsyth, Nicholas R

2016-01-19

The tissue turnover of unperturbed adult lung is remarkably slow. However, after injury or insult, a specialised group of facultative lung progenitors become activated to replenish damaged tissue through a reparative process called regeneration. Disruption in this process results in healing by fibrosis causing aberrant lung remodelling and organ dysfunction. Post-insult failure of regeneration leads to various incurable lung diseases including chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis. Therefore, identification of true endogenous lung progenitors/stem cells, and their regenerative pathway are crucial for next-generation therapeutic development. Recent studies provide exciting and novel insights into postnatal lung development and post-injury lung regeneration by native lung progenitors. Furthermore, exogenous application of bone marrow stem cells, embryonic stem cells and inducible pluripotent stem cells (iPSC) show evidences of their regenerative capacity in the repair of injured and diseased lungs. With the advent of modern tissue engineering techniques, whole lung regeneration in the lab using de-cellularised tissue scaffold and stem cells is now becoming reality. In this review, we will highlight the advancement of our understanding in lung regeneration and development of stem cell mediated therapeutic strategies in combating incurable lung diseases.

Isoproterenol reduces ischemia-reperfusion lung injury despite beta-blockade.

Science.gov (United States)

Takashima, Seiki; Schlidt, Scott A; Koukoulis, Giovanna; Sevala, Mayura; Egan, Thomas M

2005-06-01

If lungs could be retrieved from non-heart-beating donors (NHBDs), the shortage of lungs for transplantation could be alleviated. The use of lungs from NHBDs is associated with a mandatory warm ischemic interval, which results in ischemia-reperfusion injury upon reperfusion. In an earlier study, rat lungs retrieved 2-h postmortem from NHBDs had reduced capillary leak measured by filtration coefficient (Kfc) when reperfused with isoproterenol (iso), associated with an increase in lung tissue levels of cyclic AMP (cAMP). The objective was to determine if this decrease in Kfc was because of beta-stimulation, or would persist despite beta-blockade. Donor rats were treated intraperitoneally with beta-blockade (propranolol or pindolol) or carrier, sacrificed, and lungs were retrieved immediately or 2 h postmortem. The lungs were reperfused with or without iso and the beta-blockers in the reperfusate. Outcome measures were Kfc, wet:dry weight ratio (W/D), lung levels of adenine nucleotides and cAMP. Lungs retrieved immediately after death had normal Kfc and W/D. After 2 h of ischemia, Kfc and W/D were markedly elevated in controls (no drug) and lungs reperfused with beta-blockers alone. Isoproterenol-reperfusion decreased Kfc and W/D significantly (P < 0.01) even in the presence of beta-blockade. Lung cAMP levels were increased only with iso in the absence of beta-blockade. The attenuation of ischemia-reperfusion injury because of iso occurs even in the presence of beta-blockade, and may not be a result of beta-stimulated increased cAMP.

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.

Fibulin-1 functions as a prognostic factor in lung adenocarcinoma.

Science.gov (United States)

Cui, Yuan; Liu, Jian; Yin, Hai-Bing; Liu, Yi-Fei; Liu, Jun-Hua

2015-09-01

Fibulin-1 is a member of the fibulin gene family, characterized by tandem arrays of epidermal growth factor-like domains and a C-terminal fibulin-type module. Fibulin-1 plays important roles in a range of cellular functions including morphology, growth, adhesion and mobility. It acts as a tumor suppressor gene in cutaneous melanoma, prostate cancer and gastric cancer. However, whether fibulin-1 also acts as a tumor suppressor gene in lung adenocarcinoma remains unknown. We also determined the association of fibulin-1 expression with various clinical and pathological parameters, which would show its potential role in clinical prognosis. We investigated and followed up 140 lung adenocarcinoma patients who underwent lung resection without pre- and post-operative systemic chemotherapy at the Affiliated Hospital of Nantong University from 2009 to 2013. Western blot assay and immunohistochemistry were used to evaluate the expression of fibulin-1 in lung adenocarcinoma tissues. We then analyzed the correlations between fibulin-1 expression and clinicopathological variables as well as the patients' overall survival rate. Both western blot assay and immunohistochemistry demonstrated that the level of fibulin-1 was downregulated in human lung adenocarcinoma tissues compared with that of normal lung tissues. Fibulin-1 expression significantly correlated with histological differentiation (P = 0.046), clinical stage (P< 0.01), lymph node status (P = 0.038) and expression of Ki-67 (P = 0.013). More importantly, multivariate analysis revealed that fibulin-1 was an independent prognostic marker for lung adenocarcinoma, and high expression of fibulin-1 was significantly associated with better prognosis of lung adenocarcinoma patients. The results supported our hypothesis that fibulin-1 can act as a prognostic factor in lung adenocarcinoma progression. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Ruscogenin inhibits lipopolysaccharide-induced acute lung injury in mice: involvement of tissue factor, inducible NO synthase and nuclear factor (NF)-κB.

Science.gov (United States)

Sun, Qi; Chen, Ling; Gao, Mengyu; Jiang, Wenwen; Shao, Fangxian; Li, Jingjing; Wang, Jun; Kou, Junping; Yu, Boyang

2012-01-01

Acute lung injury is still a significant clinical problem with a high mortality rate and there are few effective therapies in clinic. Here, we studied the inhibitory effect of ruscogenin, an anti-inflammatory and anti-thrombotic natural product, on lipopolysaccharide (LPS)-induced acute lung injury in mice basing on our previous studies. The results showed that a single oral administration of ruscogenin significantly decreased lung wet to dry weight (W/D) ratio at doses of 0.3, 1.0 and 3.0 mg/kg 1 h prior to LPS challenge (30 mg/kg, intravenous injection). Histopathological changes such as pulmonary edema, coagulation and infiltration of inflammatory cells were also attenuated by ruscogenin. In addition, ruscogenin markedly decreased LPS-induced myeloperoxidase (MPO) activity and nitrate/nitrite content, and also downregulated expression of tissue factor (TF), inducible NO synthase (iNOS) and nuclear factor (NF)-κB p-p65 (Ser 536) in the lung tissue at three doses. Furthermore, ruscogenin reduced plasma TF procoagulant activity and nitrate/nitrite content in LPS-induced ALI mice. These findings confirmed that ruscogenin significantly attenuate LPS-induced acute lung injury via inhibiting expressions of TF and iNOS and NF-κB p65 activation, indicating it as a potential therapeutic agent for ALI or sepsis. Copyright © 2011 Elsevier B.V. All rights reserved.

Spatial distribution patterns of energy deposition and cellular radiation effects in lung tissue following simulated exposure to alpha particles

International Nuclear Information System (INIS)

Hofmann, W.; Crawford-Brown, D.J.

1990-01-01

Randomly oriented sections of rat tissue have been digitised to provide the contours of tissue-air interfaces and the locations of individual cell nuclei in the alveolated region of the lung. Sources of alpha particles with varying irradiation geometries and densities are simulated to compute the resulting random pattern of cellular irradiation, i.e. spatial coordinates, frequency, track length, and energy of traversals by the emitted alpha particles. Probabilities per unit track lengths, derived from experimental data on in vitro cellular inactivation and transformation, are then applied to the results of the alpha exposure simulations to yield an estimate of the number of both dead and viable transformed cells and their spatial distributions. If lung cancer risk is linearly related to the number of transformed cells, the carcinogenic risk for hot particles is always smaller than that for a uniform nuclide distribution of the same activity. (author)

Effect of diet on tissue levels of palmitoylethanolamide

DEFF Research Database (Denmark)

Hansen, Harald S.

2013-01-01

small intestine, PEA, oleoylethanolamide and linoleoylethanolamide have anorectic properties. Of other dietary components, only ethanol is known to influence tissue levels of PEA. Thus, an acute intoxicating dose of ethanol will decrease PEA levels in various areas in the brain of rats. The mechanism......Palmitoylethanolamide (PEA) as well as the other N-acylethanolamines (NAEs), e.g. anandamide, oleoylethanolamide, stearoylethanolamide and linoleoylethanolamide, appear to exist in every mammalian cell at low levels, e.g. a few hundred pmol/g tissue for PEA. Their formation can be stimulated...... by cellular injury and inflammation. In the brain PEA and other NAEs may have neuroprotective functions. PEA levels in tissues seem hardly to be influenced by variation in intake of dietary fatty acids, except in the small intestine where dietary fat results in decreased levels of PEA and other NAEs. In rat...

Mass preserving image registration for lung CT

DEFF Research Database (Denmark)

Gorbunova, Vladlena; Sporring, Jon; Lo, Pechin Chien Pau

2012-01-01

This paper presents a mass preserving image registration algorithm for lung CT images. To account for the local change in lung tissue intensity during the breathing cycle, a tissue appearance model based on the principle of preservation of total lung mass is proposed. This model is incorporated...... on four groups of data: 44 pairs of longitudinal inspiratory chest CT scans with small difference in lung volume; 44 pairs of longitudinal inspiratory chest CT scans with large difference in lung volume; 16 pairs of expiratory and inspiratory CT scans; and 5 pairs of images extracted at end exhale and end...

Reduced generation of lung tissue–resident memory T cells during infancy

Science.gov (United States)

Zens, Kyra D.; Chen, Jun Kui; Wu, Felix L.; Cvetkovski, Filip

2017-01-01

Infants suffer disproportionately from respiratory infections and generate reduced vaccine responses compared with adults, although the underlying mechanisms remain unclear. In adult mice, lung-localized, tissue-resident memory T cells (TRMs) mediate optimal protection to respiratory pathogens, and we hypothesized that reduced protection in infancy could be due to impaired establishment of lung TRM. Using an infant mouse model, we demonstrate generation of lung-homing, virus-specific T effectors after influenza infection or live-attenuated vaccination, similar to adults. However, infection during infancy generated markedly fewer lung TRMs, and heterosubtypic protection was reduced compared with adults. Impaired TRM establishment was infant–T cell intrinsic, and infant effectors displayed distinct transcriptional profiles enriched for T-bet–regulated genes. Notably, mouse and human infant T cells exhibited increased T-bet expression after activation, and reduction of T-bet levels in infant mice enhanced lung TRM establishment. Our findings reveal that infant T cells are intrinsically programmed for short-term responses, and targeting key regulators could promote long-term, tissue-targeted protection at this critical life stage. PMID:28855242

USP1 regulates AKT phosphorylation by modulating the stability of PHLPP1 in lung cancer cells.

Science.gov (United States)

Zhiqiang, Zhang; Qinghui, Yang; Yongqiang, Zhang; Jian, Zhang; Xin, Zhao; Haiying, Ma; Yuepeng, Guo

2012-07-01

Hyperactivation of phosphatidylinositol 3-kinase/Akt signaling is commonly associated with human tumors including lung cancers. PH domain leucine-rich repeat protein phosphatase 1 (PHLPP1), which terminates Akt signaling by directly dephosphorylating and inactivating Akt, has been identified as a tumor suppressor. The protein level of PHLPP1 is regulated by E3 ligase beta-TRCP, however, the deubiquitinase for PHLPP1 is still not known. The mRNA levels of USP1 and PHLPP1 in lung cancer cells and tissues were determined by real-time PCR. The half-life of PHLPP1 was detected by CHX assay. The interaction between USP1 and PHLPP1 was examined by immunoprecipitation and GST pull-down assay. Both USP1 and PHLPP1 are low expressed in lung cancer cells and tissues and silencing of USP1 by RNA interference significantly decreased the half-life of PHLPP1, which in turn amplified Akt1 phosphorylation. Our data identified a novel USP1-PHLPP1-Akt signaling axis, and decreased USP1 level in lung cancer cells may play an important role in lung cancer progress.

SU-E-T-92: Achieving Desirable Lung Doses in Total Body Irradiation Based On in Vivo Dosimetry and Custom Tissue Compensation

International Nuclear Information System (INIS)

Cui, G; Shiu, A; Zhou, S; Cui, J; Ballas, L

2015-01-01

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

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.

Small cell lung cancer presenting as dermatomyositis: mistaken for single connective tissue disease.

Science.gov (United States)

Chao, Guanqun; Fang, Lizheng; Lu, Chongrong; Chen, Zhouwen

2012-06-01

Dermatomyositis (DM) is well-known to be associated with several types of malignancy. This case emphasizes the importance of a thorough examination for an underlying cancer, in patients with the symptoms of dermatomyositis. We report the case of a 62-year-old Chinese man who presented with a two-month history of edema of face and neck, together with erythema of the eyelids diagnosed of small cell lung cancer. Initially, it was thought to be single connective tissue disease such as DM. This study highlights the importance of a thorough physical examination when visiting a patient.

Gene Expression Profiling of Lung Tissue of Rats Exposed to Lunar Dust Particles

Science.gov (United States)

Zhang, Ye; Feiveson, Alan H.; Lam, Chiu-Wing; Kidane, Yared H.; Ploutz-Snyder Robert; Yeshitla, Samrawit; Zalesak, Selina M.; Scully, Robert R.; Wu, Honglu; James, John T.

2014-01-01

The purpose of the study is to analyze the dynamics of global gene expression changes in the lung tissue of rats exposed to lunar dust particles. Multiple pathways and transcription factors were identified using the Ingenuity Pathway Analysis tool, showing the potential networks of these signaling regulations involved in lunar dust-induced prolonged proflammatory response and toxicity. The data presented in this study, for the first time, explores the molecular mechanisms of lunar dust induced toxicity. This work contributes not only to the risk assessment for future space exploration, but also to the understanding of the dust-induced toxicity to humans on earth.

Serological assessment of neutrophil elastase activity on elastin during lung ECM remodeling.

Science.gov (United States)

Kristensen, Jacob H; Karsdal, Morten A; Sand, Jannie Mb; Willumsen, Nicholas; Diefenbach, Claudia; Svensson, Birte; Hägglund, Per; Oersnes-Leeming, Diana J

2015-05-03

During the pathological destruction of lung tissue, neutrophil elastase (NE) degrades elastin, one of the major constituents of lung parenchyma. However there are no non-invasive methods to quantify NE degradation of elastin. We selected specific elastin fragments generated by NE for antibody generation and developed an ELISA assay (EL-NE) for the quantification of NE-degraded elastin. Monoclonal antibodies were developed against 10 NE-specific cleavage sites on elastin. One EL-NE assay was tested for analyte stability, linearity and intra- and inter-assay variation. The NE specificity was demonstrated using elastin cleaved in vitro with matrix metalloproteinases (MMPs), cathepsin G (CatG), NE and intact elastin. Clinical relevance was assessed by measuring levels of NE-generated elastin fragments in serum of patients diagnosed with idiopathic pulmonary fibrosis (IPF, n = 10) or lung cancer (n = 40). Analyte recovery of EL-NE for human serum was between 85% and 104%, the analyte was stable for four freeze/thaw cycles and after 24 h storage at 4°C. EL-NE was specific for NE-degraded elastin. Levels of NE-generated elastin fragments for elastin incubated in the presence of NE were 900% to 4700% higher than those seen with CatG or MMP incubation or in intact elastin. Serum levels of NE-generated elastin fragments were significantly increased in patients with IPF (137%, p = 0.002) and in patients with lung cancer (510%, p elastin. The EL-NE assay was able to specifically quantify NE-degraded elastin in serum. Serum levels of NE-degraded elastin might be used to detect excessive lung tissue degradation in lung cancer and IPF.

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

Science.gov (United States)

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

2014-01-01

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 bleomycin-induced pulmonary fibrosis in rats and the relation to the expression of metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1). 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). 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 pulmonary fibrosis, which is associated with decreased expression of MMP-9 and TIMP-1.

[Altered expressions of alkane monooxygenase and hypoxia inducible factor-1α expression in lung tissue of rat hypoxic pulmonary hypertension].

Science.gov (United States)

Deng, Hua-jun; Yuan, Ya-dong

2013-10-29

To explore the altered expressions of alkane monooxygenase (AlkB) and hypoxia-inducible factor-1α (HIF-1α) in a rat model of hypoxic pulmonary arterial hypertension. Twenty Wistar rats were divided randomly into normal control and hypoxia groups after 1-week adaptive feeding. Hypoxia group was raised in a homemade organic glass tank with a 24-h continuous supply of air and nitrogen atmospheric mixed gas. And the oxygen concentration of (10.0 ± 0.5)% was controlled by oxygen monitoring control system. The control group was maintained in room air. Both groups stayed in the same room with the same diet. After 8 weeks, the level of mean pulmonary pressure (mPAP) was measured by right-heart catheterization, right ventricular hypertrophy index (RVHI) calculated by the ratio of right ventricle to left ventricle plus septum and hypoxic pulmonary vascular remodeling (HPSR) observed under microscope. And the levels of AlkB and HIF-1α mRNA and protein in lungs were measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot. At 8 weeks post-hypoxia, compared with the control group [11.0 ± 0.7 mm Hg (1 mm Hg = 0.133 kPa), 0.210 ± 0.035], the levels of mPAP and RVHI in hypoxia group (33.3 ± 1.3 mm Hg, 0.448 ± 0.013) increased significantly (both P < 0.05), the expressions of AlkB mRNA and protein in pulmonary tissue decreased significantly (0.338 ± 0.085 vs 0.688 ± 0.020, P < 0.01) (0.483 ± 0.052 vs 0.204 ± 0.010, P < 0.01), and the expressions of HIF-1α mRNA and protein increased significantly (0.790 ± 0.161 vs 0.422 ± 0.096, P < 0.01) (0.893 ± 0.080 vs 0.346 ± 0.008, P < 0.01). The down-regulation of AlkB in lung tissue may increase the activity of HIF-1 to participate in the occurrence and development of pulmonary hypertension.

Temporary dosal characteristics of processes of Krebs cycle of lungs tissue of rats under prolonged inhalation of uranium dust

International Nuclear Information System (INIS)

Bekenova, Zh. M.; Mustafina, R. Kh.; Kazymbet, P. K.

2010-01-01

Effect of industrial uranium ore dust (UOD) in extrasmall doses have been studied after prolonged inhalation. It has been established that prolonged inhalation influence of the uranium ore dust (UOD) at the dose equal to 5 threshold limit value (TLV) gradually raised a content of isocitric acid (ICA) - the original product of the Cycle of Tricarbon Acid (NOA). However by the end of the observation already on the 120-th day the peak of increasing ICA started to come down and its indicators exceeded the control level by only 57%. At the same time it has been established that the aqueos licorice root extract facilitates raising a content of ICA which is the product of initial stages in Krebs cycle by 3 times in comparison with the control data and it was by 71% more than under UOD influence. In this case it is the evolution of examined compound ratio, determined as a balance coefficient isocitric acid/malic acid at different periods of UOD effect. It has been identified that at different times of examination its indicators have decreased almost two fold. Also, in the lung tissue of the animals, primed with UOD dose equal to 5 OLV, absolute content of malic acid (MA) practically has not been changing, unless consider the raising of its indicators by 27% and 20% on the 60-th and 120-th days respctively, e.g. in the period of. It has been identified that the licorice root extract has increased concentration indicators of the malic acid in the lung tissue by the average of 4-5%. In this situation particular significance is acquired by dynamics of ratio variation in compounds under investigation determined through a balance coefficient ICA/AA at different periods of UOD effect. It is established that the value of it is lowed by almost 2 times in different terms of observation. Additionally with noticed data in lung tissue activity inhibition of 4-Dehydrogenases in Krebs cycle is revealed. Maximal inhibition is characteristic for Isocitrate- and alphakethoglutarate

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

EXSPRESSION OF MDR-GENES AND MONORESISTANCE GENES IN NON-SMALL-CELL LUNG CANCER

Directory of Open Access Journals (Sweden)

E. L. Yumov

2014-01-01

Full Text Available We studied the expression of multidrug resistance genes (MDR and monoresistance genes in normal bronchial tissue and tumor tissue of the non-small cell lung cancer (NSCLC after neoadjuvant chemotherapy (NACT (vinorelbine-carboplatine. The study included 30 patients with NSCLC (Т2–4N0–3M0. Normal bronchial tissue, normal lung tissue and tumor tissue collected during surgery following neoadjuvant chemotherapy (NACT served as a material of the study. The expression levels of MDR genes (ABCB1, ABCB2, ABCC1, ABCC2, ABCС5, ABCG1, ABCG2, GSTP and MVP, and monoresistance genes (BRCA1, ERCC1, RRM1, TOP1, TOP2A, TUBB3 and TYMS were estimated by quantitative reverse transcriptase PCR (RT-qPCR. The expression levels of some MDR genes and monoresistance genes (АВСВ1, АВСВ2, ABCG1, ERCC1, GSTP1 and MVP were significantly higher in the bronchi than in tumor tissue. The expression of ABCG1, ABCG2 and ERCC1 genes was higher in patients with T1-2 cancer than in patients with T3-4 cancer. Patients with adenocarcinoma had higher expression of BRCA1, MVP and ABCB1 genes than patients with squamous cell lung cancer. A tendency towards reduction in the expression level of MDR-genes and monoresistance genes was observed in patients with partial tumor regression compared to that observed in patients with stable disease. These findings were consistent with the previous data on reduction in the MDR-gene expression after chemotherapy with a good response in breast cancer patients.

Intravenous immunoglobulin prevents murine antibody-mediated acute lung injury at the level of neutrophil reactive oxygen species (ROS production.

Directory of Open Access Journals (Sweden)

John W Semple

Full Text Available Transfusion-related acute lung injury (TRALI is a leading cause of transfusion-associated mortality that can occur with any type of transfusion and is thought to be primarily due to donor antibodies activating pulmonary neutrophils in recipients. Recently, a large prospective case controlled clinical study of cardiac surgery patients demonstrated that despite implementation of male donors, a high incidence of TRALI still occurred and suggested a need for additional interventions in susceptible patient populations. To examine if intravenous immunoglobulin (IVIg may be effective, a murine model of antibody-mediated acute lung injury that approximates human TRALI was examined. When BALB/c mice were injected with the anti-major histocompatibility complex class I antibody 34-1-2s, mild shock (reduced rectal temperature and respiratory distress (dyspnea were observed and pre-treatment of the mice with 2 g/kg IVIg completely prevented these symptoms. To determine IVIg's usefulness to affect severe lung damage, SCID mice, previously shown to be hypersensitive to 34-1-2s were used. SCID mice treated with 34-1-2s underwent severe shock, lung damage (increased wet/dry ratios and 40% mortality within 2 hours. Treatment with 2 g/kg IVIg 18 hours before 34-1-2s administration completely protected the mice from all adverse events. Treatment with IVIg after symptoms began also reduced lung damage and mortality. While the prophylactic IVIg administration did not affect 34-1-2s-induced pulmonary neutrophil accumulation, bone marrow-derived neutrophils from the IVIg-treated mice displayed no spontaneous ROS production nor could they be stimulated in vitro with fMLP or 34-1-2s. These results suggest that IVIg prevents murine antibody-mediated acute lung injury at the level of neutrophil ROS production and thus, alleviating tissue damage.

Estimation of lung tissue doses following exposure to low-LET radiation in the Canadian study of cancer following multiple fluoroscopies

International Nuclear Information System (INIS)

Howe, G.R.; Yaffe, M.

1992-02-01

Lung tissue doses from exposure to external low-LET radiation have been estimated for each year between 1930 and 1960 for 92,707 tuberculosis patients first treated in Canadian institutions between 1930 and 1952. Many of these patients received multiple chest fluoroscopies together with treatment by artificial pneumothorax, and thus accumulated doses up to 15.7 grays. The estimated doses have been used in a statistical analysis of lung cancer mortality between 1950 and 1987 occurring among 64,698 patients known to be alive at the start of 1950, and followed by linkage to the Canadian national mortality data base. There were substantial variations in the total cumulative lung tissue dose received by the cohort, with 2,490 individuals having doses in excess of 1.7 grays. A total of 1,156 lung cancer deaths was observed in the cohort, and these have been used to estimate relative risks. The most appropriate risk model appears to be a simple linear relative risk function, with an excess relative risk coefficient of 0.089 for an absorbed dose of 1 gray. This contrasts with estimates of relative risk based on the atomic bomb survivors study, for which the excess relative risk coefficient for males 20 years after the first exposure is estimated to be 0.64. The difference is statistically significant. It is postulated that fractionation and dose rate effectiveness factors may account for some of the discrepancy. (Modified author abstract) (14 refs., 20 tabs.)

Effects of puerarin combined with edaravone on inhalation lung injury induced by black gunpowder smog in rats

Directory of Open Access Journals (Sweden)

Zheng-guan WANG

2015-04-01

Full Text Available Objective　To explore the protective effects of puerarin combined with edaravone on inhalation lung injury induced by black gunpowder smog in rats. Methods　Forty healthy male Wistar rats were randomly divided into normal control group (group N, inhalation group (group X, puerarin group (group P, edaravone group (group E and edaravone combined with puerarin group (group L, with 8 rats in each group. Rat model of inhalation lung injury was reproduced by a self-made smoke generator. Rats in group E were given intraperitoneal injections of edaravone (9 mg/kg at 30 minutes and 1 day after modeling (twice totally. Rats in group P were given intraperitoneal injections of puerarin (100 mg/kg at 30 minutes and 1, 2, 3, 4, 5 days after modeling (6 times totally. Rats in group L were treated the way of both group E and P. The rats in group N and group X were given intraperitoneal injections of normal saline (12 ml/kg at the time-points above. The animals were sacrificed 6 days after modeling, and the blood samples were collected from abdominal aorta to assess arterial blood gas values, meanwhile the serum levels of tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6, interleukin-10 (IL-10 were determined by ELISA. Lung tissue homogenates were prepared to determine the protein content and myeloperoxidase (MPO activity. The pathological changes in the lung tissue with HE staining were observed under light microscope. Results　Arterial blood gas analysis revealed that the PaO2 levels in groups P, E and L were higher than that in group X (P<0.05, and the PaO2 levels in groups E and L were higher than that in group P (P<0.05, while the PaCO2 level in group L was lower than that in groups X and E (P<0.05. The TNF-α, IL-6 and IL-10 levels in serum, the protein content and MPO activity in lung tissue homogenate in groups P, E and L were lower than those of group X (P<0.05. The TNF-α and IL-6 levels in serum and protein content and MPO activity in lung

Positron emission tomography of the lung

International Nuclear Information System (INIS)

Wollmer, P.

1984-01-01

Positron emission tomography enables the distribution of positron emitting isotopes to be imaged in a transverse plane through the body and the regional concentration of the isotope to be measured quantitatively. This thesis reports some applications of positron emission tomography to studies of pulmonary pathophysiology. Measurements in lung phantoms showed that regional lung density could be measured from a transmission tomogram obtained with an external source of positron emitting isotope. The regional, fractional blood volume was measured after labelling the blood with carbon-11-monoxide. Regional extravascular lung density (lung tissue and interstitial water per unit thoracic volume) was obtained by subtracting fractional blood volume from lung density. Measurements in normal subjects revealed large regional variations in lung density and fractional blood volume in the supine posture. Extravascular lung density showed a more uniform distribution. The technique has been used to study patients with chronic interstitial pulmonary oedema, pulmonary sarcoidosis and fibrosis, pulmonary arterial hypertension and patients with intracardiac, left-to-right shunt. Tomographic measurements of pulmonary tissue concentration of radionuclides are difficult, since corrections for the blood content and the inflation of the lung must be applied. A simultaneous measurement of lung density and fractional blood volume allows such corrections to be made and the extravascular tracer concentration to be calculated. This has been applied to measurements of the tissue penetration of carbon-11-labelled erythromycin in patients with lobar pneumonia. (author)

Concentrations of metallic elements in kidney, liver, and lung tissue of Indo-Pacific bottlenose dolphin Tursiops aduncus from coastal waters of Zanzibar, Tanzania.

Science.gov (United States)

Mapunda, Edgar C; Othman, Othman C; Akwilapo, Leonard D; Bouwman, Hindrik; Mwevura, Haji

2017-09-15

Concentrations of metallic elements in kidney, liver and lung tissues of Indo-Pacific bottlenose dolphins Tursiops aduncus from coastal waters of Zanzibar were determined using inductively coupled plasma - optical emission spectroscopy. Cadmium, chromium, copper, and zinc were quantifiable in all tissues at concentration ranges of 0.10-150, 0.08-3.2, 1.1-88 and 14-210μg/g dry mass, respectively. Copper and zinc was significantly higher in liver, and females had significantly higher Cd in liver, and chromium in lung. Generally, T. aduncus dolphins from coastal waters around Zanzibar carry low concentrations of metals compared with dolphins from other areas. Cadmium increased significantly with age in kidney and lung. Copper decreased significantly with age in liver, probably due to foetal metallothionein. This study supplied baseline data against which future trends in marine mammals in the Indian Ocean, the world's third largest, can be assessed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Validation of SCT Methylation as a Hallmark Biomarker for Lung Cancers.

Science.gov (United States)

Zhang, Yu-An; Ma, Xiaotu; Sathe, Adwait; Fujimoto, Junya; Wistuba, Ignacio; Lam, Stephen; Yatabe, Yasushi; Wang, Yi-Wei; Stastny, Victor; Gao, Boning; Larsen, Jill E; Girard, Luc; Liu, Xiaoyun; Song, Kai; Behrens, Carmen; Kalhor, Neda; Xie, Yang; Zhang, Michael Q; Minna, John D; Gazdar, Adi F

2016-03-01

The human secretin gene (SCT) encodes secretin, a hormone with limited tissue distribution. Analysis of the 450k methylation array data in The Cancer Genome Atlas (TCGA) indicated that the SCT promoter region is differentially hypermethylated in lung cancer. Our purpose was to validate SCT methylation as a potential biomarker for lung cancer. We analyzed data from TCGA and developed and applied SCT-specific bisulfite DNA sequencing and quantitative methylation-specific polymerase chain reaction assays. The analyses of TCGA 450K data for 801 samples showed that SCT hypermethylation has an area under the curve (AUC) value greater than 0.98 that can be used to distinguish lung adenocarcinomas or squamous cell carcinomas from nonmalignant lung tissue. Bisulfite sequencing of lung cancer cell lines and normal blood cells allowed us to confirm that SCT methylation is highly discriminative. By applying a quantitative methylation-specific polymerase chain reaction assay, we found that SCT hypermethylation is frequently detected in all major subtypes of malignant non-small cell lung cancer (AUC = 0.92, n = 108) and small cell lung cancer (AUC = 0.93, n = 40) but is less frequent in lung carcinoids (AUC = 0.54, n = 20). SCT hypermethylation appeared in samples of lung carcinoma in situ during multistage pathogenesis and increased in invasive samples. Further analyses of TCGA 450k data showed that SCT hypermethylation is highly discriminative in most other types of malignant tumors but less frequent in low-grade malignant tumors. The only normal tissue with a high level of methylation was the placenta. Our findings demonstrated that SCT methylation is a highly discriminative biomarker for lung and other malignant tumors, is less frequent in low-grade malignant tumors (including lung carcinoids), and appears at the carcinoma in situ stage. Copyright © 2015 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Expression of coding (mRNA) and non-coding (microRNA) RNA in lung tissue and blood isolated from pigs suffering from bacterial pleuropneumonia

DEFF Research Database (Denmark)

Skovgaard, Kerstin; Schou, Kirstine Klitgaard; Wendt, Karin Tarp

2010-01-01

MicroRNAs are small non-coding RNA molecules (18-23 nt), that regulate the activity of other genes at the post-transcriptional level. Recently it has become evident that microRNA plays an important role in modulating and fine tuning innate and adaptive immune responses. Still, little is known about...... the impact of microRNAs in the development and pathogenesis of lung infections. Expression of microRNA 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 and in blood from pigs experimentally infected...... with Actinobacillus pleuropneumoniae (AP). Expression differences of mRNA and microRNA were quantified at different time points (6h, 12h, 24h, 48h PI) using reverse transcription quantitative real-time PCR (Rotor-Gene and Fluidigm). Expression profiles of miRNA in blood of seven animals were further studied using mi...

Gender, Estrogen, and Obliterative Lesions in the Lung

Directory of Open Access Journals (Sweden)

Hamza Assaggaf

2017-01-01

Full Text Available Gender has been shown to impact the prevalence of several lung diseases such as cancer, asthma, chronic obstructive pulmonary disease, and pulmonary arterial hypertension (PAH. Controversy over the protective effects of estrogen on the cardiopulmonary system should be of no surprise as clinical trials of hormone replacement therapy have failed to show benefits observed in experimental models. Potential confounders to explain these inconsistent estrogenic effects include the dose, cellular context, and systemic versus local tissue levels of estrogen. Idiopathic PAH is disproportionately found to be up to 4 times more common in females than in males; however, estrogen levels cannot explain why males develop PAH sooner and have poorer survival. Since the sex steroid hormone 17β-estradiol is a mitogen, obliterative processes in the lung such as cell proliferation and migration may impact the growth of pulmonary tissue or vascular cells. We have reviewed evidence for biological differences of sex-specific lung obliterative lesions and highlighted cell context-specific effects of estrogen in the formation of vessel lumen-obliterating lesions. Based on this information, we provide a biological-based mechanism to explain the sex difference in PAH severity as well as propose a mechanism for the formation of obliterative vascular lesions by estrogens.

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

An experimental study on the radiation-induced injury of the rabbit lung: Correlation of soft-tissue radiograph and high- resolution CT findings with pathologic findings

International Nuclear Information System (INIS)

Lee, Ki Nam; Nam, Kyung Jin; Park, Byeoung Ho; Jeong, Jin Sook; Lee, Hyung Sik

1994-01-01

To describe soft-tissue radiographic and high-resolution CT findings of radiation-induced lung injury of rabbit over time and to correlate them with pathologic findings. 15 rabbits were irradiated in the right lung with one fracture of 2000 cGy. After 4, 6, 12, 20, 24 weeks 3 rabbits in each group were sacrificed and soft-tissue radiographs and high-resolution CT of their lung tissue were obtained. Radiological findings were correlated with pathologic findings. On soft-tissue radiogram, radiation pneumonitis shown as consolidation with air- bronchogram occurred in 3 cases after 6 weeks , and in 1 case after 12 weeks of irradiation. In addition, pneumonic consolidation with adjacent pleural contraction was seen in 2 cases after 12 weeks of irradiation. Fibrotic changes indicated by decreased volume occurred after 20 weeks and combined bronchiectatic change and bronchial wall thickening appeared after 20 weeks(N=1), and 24 weeks(N=3). HRCT findings of radiation pneumonitis were homogeneous, increased attention after 4 weeks(N=3), 6 and 12 weeks(each N=1), patchy consolidation after 6 and 12 weeks(each N=2), discrete consolidation after 12, 20 and 24 weeks(each N=1) and solid consolidation after 20 and 24 weeks(each N=2). Pathologically radiation pneumonitis and pulmonary congestion were seen after 4 and 6 weeks. After 6 weeks, collagen and reticulin fibers were detected along alveolar wall. Mixed radiation pneumonitis and fibrosis were detected after 12 weeks. 20 weeks after irradiation, fibrosis was well defined in interstitium and in 24 weeks, decreased number of alveoli and thickening of bronchial wall were defined. Radiation pneumonitis was provoked 4 weeks after irradiation on rabbit lung and progressed into radiation fibrosis 20 weeks after irradiation on soft-tissue radiographs and high-resolution CT. High-resolution CT is more precise in detecting early radiation pneumonitis and detailed pathologic findings

Tissue Distribution Of Chloroaluminium Sulfonated Phthalocyanine In Dogs

Science.gov (United States)

M. M.; H. C.; Newman

1989-06-01

Chloroaluminum sulfonated phthalocyanine (A1PCS) was administered intravenously to clinically normal dogs, and A1PCS levels were determined in tissues using a sensitive assay. A1PCS accumulated to high levels in liver, spleen, bone marrow, kidney, and lung. These tissue levels confirm previous determinations in mice and rats. Only a small amount of dye was retained in skin and very small amounts in muscle and brain. A1PCS was cleared from the blood within 24 h, and excreted primarily by urine. Serum clearance was faster in males than in females. There were also significant tissue distribution differences between the genders, particularly during the first 12 h. The low levels of A1PCS in skin suggest that cutaneous photosensitivity and toxic skin reactions using this photosensitizer in photodynamic therapy of cancer may be eliminated. The difference in tissue distribution between genders is not only intriguing, but indicates that the optimal time window for treatment of various tissue sites may vary by gender.

Traditional Chinese medicine, Qing Ying Tang, ameliorates the severity of acute lung injury induced by severe acute pancreatitis in rats via the upregulation of aquaporin-1.

Science.gov (United States)

Gao, Zhenming; Xu, Junfeng; Sun, Deguang; Zhang, Rixin; Liang, Rui; Wang, Liming; Fan, Rong

2014-12-01

Aquaporin-1 (AQP-1) is expressed in lung endothelial cells and regulates water transport; thus, AQP-1 plays an important role in a number of edema-associated lung diseases. Qing Yin Tang (QYT), a traditional Chinese medicine, has been shown to effectively reduce the mortality rate of acute lung injury (ALI) induced by severe acute pancreatitis (SAP). The current study aimed to investigate the detailed mechanisms underlying the effects of QYT on ALI induced by SAP, particularly the effects on the expression levels of AQP-1 in the lung tissue. ALI was established in Wister rats who were subsequently divided into four groups: SHAM, ALI, dexamethasone (DEX) and QYT groups (n=8 per group). In the QYT group, 20 ml/kg QYT was administered by gavage immediately following the induction of SAP. Blood and lung tissues were collected 8 h following the induction of pancreatitis. The lung wet/dry ratio, as well as the levels of blood gases, serum amylase and tumor necrosis factor-α (TNF-α), were measured at 4, 8 and 12 h following SAP-associated ALI induction surgery. The expression levels of AQP-1 in the lung tissue were detected by quantitative polymerase chain reaction, immunohistochemistry and western blot analysis. No statistically significant differences were observed with regard to the levels of serum amylase, wet/dry ratio, partial pressure of oxygen, serum TNF-α and pathological changes in the pulmonary tissue between the QYT and DEX groups; however, a statistically significant difference was observed when compared with the ALI group. The expression levels of AQP-1 significantly increased (P<0.05) and lung edema was alleviated in the QYT and DEX groups, when compared with ALI group. Therefore, the expression level of AQP-1 is associated with pulmonary edema. QYT protects the lungs from injury induced by SAP via the upregulation of AQP-1, which suppresses TNF-α expression.

Autofluorescence Imaging and Spectroscopy of Human Lung Cancer

Directory of Open Access Journals (Sweden)

Mengyan Wang

2016-12-01

Full Text Available Lung cancer is one of the most common cancers, with high mortality rate worldwide. Autofluorescence imaging and spectroscopy is a non-invasive, label-free, real-time technique for cancer detection. In this study, lung tissue sections excised from patients were detected by laser scan confocal microscopy and spectroscopy. The autofluorescence images demonstrated the cellular morphology and tissue structure, as well as the pathology of stained images. Based on the spectra study, it was found that the majority of the patients showed discriminating fluorescence in tumor tissues from normal tissues. Therefore, autofluorescence imaging and spectroscopy may be a potential method for aiding the diagnosis of lung cancer.

Movie prediction of lung tumor for precise chasing radiation therapy

International Nuclear Information System (INIS)

Chhatkuli, Ritu Bhusal; Demachi, Kazuyuki; Kawai, Masaki; Sakakibara, Hiroshi; Uesaka, Mitsuru

2012-01-01

In recent years, precision for radiation therapy is a major challenge in the field of cancer treatment. When it comes to a moving organ like lungs, limiting the radiation to the target and sparing the surrounding healthy tissue is always a concern. It can induce the limit in the accuracy of area irradiated during lung cancer radiation therapy. Many methods have been introduced to compensate the motion in order to reduce the effect of radiation to healthy tissue due to respiratory motion. The motion of lung along with the tumor makes it very difficult to spare the healthy tissue during radiation therapy. The fear of this unintended damage to the neighboring tissue often limits the dose that can be applied to the tumor. The purpose of this research is the prediction of future motion images for the improvement of tumor tracking method. We predict the motion images by using principal component analysis (PCA) and multi-channel singular spectral analysis (MSSA) method. Time series x-ray images are used as training images. The motion images were successfully predicted and verified using the developed algorithm. The real time implementation of this method in future is believed to be significant for higher level of real time tumor tracking during radiation therapy. (author)

The role of high airway pressure and dynamic strain on ventilator-induced lung injury in a heterogeneous acute lung injury model.

Science.gov (United States)

Jain, Sumeet V; Kollisch-Singule, Michaela; Satalin, Joshua; Searles, Quinn; Dombert, Luke; Abdel-Razek, Osama; Yepuri, Natesh; Leonard, Antony; Gruessner, Angelika; Andrews, Penny; Fazal, Fabeha; Meng, Qinghe; Wang, Guirong; Gatto, Louis A; Habashi, Nader M; Nieman, Gary F

2017-12-01

Acute respiratory distress syndrome causes a heterogeneous lung injury with normal and acutely injured lung tissue in the same lung. Improperly adjusted mechanical ventilation can exacerbate ARDS causing a secondary ventilator-induced lung injury (VILI). We hypothesized that a peak airway pressure of 40 cmH 2 O (static strain) alone would not cause additional injury in either the normal or acutely injured lung tissue unless combined with high tidal volume (dynamic strain). Pigs were anesthetized, and heterogeneous acute lung injury (ALI) was created by Tween instillation via a bronchoscope to both diaphragmatic lung lobes. Tissue in all other lobes was normal. Airway pressure release ventilation was used to precisely regulate time and pressure at both inspiration and expiration. Animals were separated into two groups: (1) over-distension + high dynamic strain (OD + H DS , n = 6) and (2) over-distension + low dynamic strain (OD + L DS , n = 6). OD was caused by setting the inspiratory pressure at 40 cmH 2 O and dynamic strain was modified by changing the expiratory duration, which varied the tidal volume. Animals were ventilated for 6 h recording hemodynamics, lung function, and inflammatory mediators followed by an extensive necropsy. In normal tissue (N T ), OD + L DS caused minimal histologic damage and a significant reduction in BALF total protein (p < 0.05) and MMP-9 activity (p < 0.05), as compared with OD + H DS . In acutely injured tissue (ALI T ), OD + L DS resulted in reduced histologic injury and pulmonary edema (p < 0.05), as compared with OD + H DS . Both N T and ALI T are resistant to VILI caused by OD alone, but when combined with a H DS , significant tissue injury develops.

Intercomparison of JAERI Torso Phantom lung sets

International Nuclear Information System (INIS)

Kramer, Gary H.; Hauck, Barry M.

2000-01-01

During the course of an IAEA sponsored In Vivo intercomparison using the JAERI phantom the Human Monitoring Laboratory was able to intercompare thirteen lung sets made by three suppliers. One set consisted of sliced lungs with planar inserts containing different radionuclides. The others consisted of whole lung sets with the activity homogeneously distributed throughout the tissue substitute material. Radionuclides in the study were: natural uranium, 3% enriched uranium, 241 Am, 238 Pu, 239 Pu, 152 Eu, and 232 Th Except for the 241 Am (59.5 keV) and occasionally one of the 232 Th (209 keV) photopeaks, the lung sets that had radioactivity homogeneously distributed throughout the tissue equivalent lung tissue material showed good agreement. The 241 Am lung set gave a counting efficiency that appeared 25% too high for all overlay plate configurations. This was observed by other participants. It exemplifies that the manufacture of tissue substitute lung sets is still something of a black art. Despite all precautions, this lung set is either inhomogeneous or has had the wrong activity added. Heterogeneity can lead to an error in the activity estimate of a factor of three if the activity was severely localised due to improper mixing. A factor of 1.25, which appears to be the discrepancy, could easily be explained in this way. It will not be known for some time, however, what the true reason is as the participants are still waiting for the destructive analysis of this lung set to determine the 'true' activity. The sliced lungs ( 241 Am, 152 Eu, and U-nat) manufactured by the Human Monitoring Laboratory are in excellent agreement with the other lung sets. The advantages of sliced lung sets and planar sources are manifold. Activity can be distributed in a known and reproducible manner to mimic either a homogeneous or heterogeneous distribution in the lung. Short lived radionuclides can be used. Cost is much less than purchasing or manufacturing lung sets that have the

Diurnal levels of immunoreactive erythropoietin in normal subjects and subjects with chronic lung disease

Energy Technology Data Exchange (ETDEWEB)

Miller, M.E.; Garcia, J.F.; Cohen, R.A.; Cronkite, E.P.; Moccia, G.; Acevedo, J.

1981-10-01

Serum levels of immunoreactive erythropoietin (Ep) were measured in 48 normal male and female volunteers, ages 20-60 years, to establish a control value for Ep of 18.5 +/- 5.0 (mean +/- SD) mU/ml. Levels of the hormone were also measured sequentially over a 24 h period of time in an additional 17 normal volunteers with no diurnal variation. Diurnal levels of immunoreactive Ep were also measured in 30 subjects, with chronic lung disease. These patients, in contrast to normal subjects exhibited a diurnal variation in the level of immunoreactive Ep with peak levels occurring at midnight. The only variable measured which correlated with the serum immunoreactive Ep level in subjects with chronic lung disease was the level of carboxyhaemoglobin (P less than 0.02).

Influence of Manufacturing Processes on the Performance of Phantom Lungs

International Nuclear Information System (INIS)

Traub, Richard J.

2008-01-01

Chest counting is an important tool for estimating the radiation dose to individuals who have inhaled radioactive materials. Chest counting systems are calibrated by counting the activity in the lungs of phantoms where the activity in the phantom lungs is known. In the United States a commonly used calibration phantom was developed at the Lawrence Livermore National Laboratory and is referred to as the Livermore Torso Phantom. An important feature of this phantom is that the phantom lungs can be interchanged so that the counting system can be challenged by different combinations of radionuclides and activity. Phantom lungs are made from lung tissue substitutes whose constituents are foaming plastics and various adjuvants selected to make the lung tissue substitute similar to normal healthy lung tissue. Some of the properties of phantom lungs cannot be readily controlled by phantom lung manufacturers. Some, such as density, are a complex function of the manufacturing process, while others, such as elemental composition of the bulk plastic are controlled by the plastics manufacturer without input, or knowledge of the phantom manufacturer. Despite the fact that some of these items cannot be controlled, they can be measured and accounted for. This report describes how manufacturing processes can influence the performance of phantom lungs. It is proposed that a metric that describes the brightness of the lung be employed by the phantom lung manufacturer to determine how well the phantom lung approximates the characteristics of a human lung. For many purposes, the linear attenuation of the lung tissue substitute is an appropriate surrogate for the brightness

Evidence for reduced arterial plasma input, prolonged lung retention and reduced lung monoamine oxidase in smokers

International Nuclear Information System (INIS)

Logan, Jean; Fowler, Joanna S.

2005-01-01

, we estimated the ratio of MAO subtypes A and B in normal lung tissue to be on the order of 3 to 1 (MAO A to B) and that smokers have reduced MAO levels for both subtypes as measured by the model parameter, k 3 . The values of k 3 are insensitive to model assumptions of variations in air and tissue fraction in the PET voxel. Most of the effects of changes in these fractions are absorbed into the parameter K 1 , which governs the plasma-to-tissue transfer of tracer and is a function of blood flow. K 1 was found to be larger in smokers, although the values depend upon model assumptions of air and tissue fractions. k 3 was found to be significantly lower in smokers; for CLG, a 50% reduction in MAO A for both CLG and D CLG was observed. For DEP, k 3 was also significantly lower in smokers with a reduction of ∼80% in lung MAO B, although there was a very large coefficient of variation in the smoker's k 3 . We also found larger values of λ (K 1 /k 2 ) for smokers relative to nonsmokers for all tracers consistent with a longer lung retention of the nonenzyme-bound tracer, which explains the slower decline in uptake from peak radioactivity for smokers. Conclusions: The measured arterial input function values for smokers and nonsmokers are significantly different for these two tracer pairs for nonsmokers and smokers particularly for the first few minutes after radiotracer injection. Model estimates of k 3 that indicate that smokers have lower lung MAO A and B activity than nonsmokers are robust and insensitive to variations in model assumptions for relative fractions of lung tissue, blood and air in the PET voxel. Although we have only investigated the behavior of [ 11 C]clorgyline and [ 11 C]L-deprenyl and their deuterium-substituted analogs in this report, the extent to which reduced arterial input and longer lung retention also hold for other tracers for subjects who smoke merits investigation

Protective mechanical ventilation does not exacerbate lung function impairment or lung inflammation following influenza A infection.

Science.gov (United States)

Zosky, Graeme R; Cannizzaro, Vincenzo; Hantos, Zoltan; Sly, Peter D

2009-11-01

The degree to which mechanical ventilation induces ventilator-associated lung injury is dependent on the initial acute lung injury (ALI). Viral-induced ALI is poorly studied, and this study aimed to determine whether ALI induced by a clinically relevant infection is exacerbated by protective mechanical ventilation. Adult female BALB/c mice were inoculated with 10(4.5) plaque-forming units of influenza A/Mem/1/71 in 50 microl of medium or medium alone. This study used a protective ventilation strategy, whereby mice were anesthetized, tracheostomized, and mechanically ventilated for 2 h. Lung mechanics were measured periodically throughout the ventilation period using a modification of the forced oscillation technique to obtain measures of airway resistance and coefficients of tissue damping and tissue elastance. Thoracic gas volume was measured and used to obtain specific airway resistance, tissue damping, and tissue elastance. At the end of the ventilation period, a bronchoalveolar lavage sample was collected to measure inflammatory cells, macrophage inflammatory protein-2, IL-6, TNF-alpha, and protein leak. Influenza infection caused significant increases in inflammatory cells, protein leak, and deterioration in lung mechanics that were not exacerbated by mechanical ventilation, in contrast to previous studies using bacterial and mouse-specific viral infection. This study highlighted the importance of type and severity of lung injury in determining outcome following mechanical ventilation.

Prostate tissue metal levels and prostate cancer recurrence in smokers.

Science.gov (United States)

Neslund-Dudas, Christine; Kandegedara, Ashoka; Kryvenko, Oleksandr N; Gupta, Nilesh; Rogers, Craig; Rybicki, Benjamin A; Dou, Q Ping; Mitra, Bharati

2014-02-01

Although smoking is not associated with prostate cancer risk overall, smoking is associated with prostate cancer recurrence and mortality. Increased cadmium (Cd) exposure from smoking may play a role in progression of the disease. In this study, inductively coupled plasma mass spectrometry was used to determine Cd, arsenic (As), lead (Pb), and zinc (Zn) levels in formalin-fixed paraffin embedded tumor and tumor-adjacent non-neoplastic tissue of never- and ever-smokers with prostate cancer. In smokers, metal levels were also evaluated with regard to biochemical and distant recurrence of disease. Smokers (N = 25) had significantly higher Cd (median ppb, p = 0.03) and lower Zn (p = 0.002) in non-neoplastic tissue than never-smokers (N = 21). Metal levels were not significantly different in tumor tissue of smokers and non-smokers. Among smokers, Cd level did not differ by recurrence status. However, the ratio of Cd ppb to Pb ppb was significantly higher in both tumor and adjacent tissue of cases with distant recurrence when compared with cases without distant recurrence (tumor tissue Cd/Pb, 6.36 vs. 1.19, p = 0.009, adjacent non-neoplastic tissue Cd/Pb, 6.36 vs. 1.02, p = 0.038). Tissue Zn levels were also higher in smokers with distant recurrence (tumor, p = 0.039 and adjacent non-neoplastic, p = 0.028). These initial findings suggest that prostate tissue metal levels may differ in smokers with and without recurrence. If these findings are confirmed in larger studies, additional work will be needed to determine whether variations in metal levels are drivers of disease progression or are simply passengers of the disease process.

The emphysematous lung is abnormally sensitive to TRAIL-mediated apoptosis

Directory of Open Access Journals (Sweden)

Milot Julie

2011-08-01

Full Text Available Abstract Background Alveolar apoptosis is increased in the emphysematous lung. However, mechanisms involved are not fully understood. Recently, we demonstrated that levels of TRAIL receptor 1 and 2, levels of p53, and Bax/Bcl-xL ratio were elevated in the lung of subjects with emphysema, despite smoking cessation. Thus, we postulate that due to chronic pulmonary oxidative stress, the emphysematous lung would be abnormally sensitive to TRAIL-mediated apoptosis. Methodology A549 cells were exposed to rTRAIL, cigarette smoke extract, and/or H2O2 prior to caspase-3 activity measurement and annexin V staining assessment. In addition, freshly resected lung samples were obtained from non-emphysematous and emphysematous subjects and exposed ex vivo to rTRAIL for up to 18 hours. Lung samples were harvested and levels of active caspase-3 and caspase-8 were measured from tissue lysates. Results Both cigarette smoke extract and H2O2 were able to sensitize A549 cells to TRAIL-mediated apoptosis. Moreover, following exposure to rTRAIL, caspase-3 and -8 were activated in lung explants from emphysematous subjects while being decreased in lung explants from non-emphysematous subjects. Significance of the study Alveolar sensitivity to TRAIL-mediated apoptosis is strongly increased in the emphysematous lung due to the presence of oxidative stress. This might be a new mechanism leading to increased alveolar apoptosis and persistent alveolar destruction following smoking cessation.

Multiple image x-radiography for functional lung imaging

Science.gov (United States)

Aulakh, G. K.; Mann, A.; Belev, G.; Wiebe, S.; Kuebler, W. M.; Singh, B.; Chapman, D.

2018-01-01

Detection and visualization of lung tissue structures is impaired by predominance of air. However, by using synchrotron x-rays, refraction of x-rays at the interface of tissue and air can be utilized to generate contrast which may in turn enable quantification of lung optical properties. We utilized multiple image radiography, a variant of diffraction enhanced imaging, at the Canadian light source to quantify changes in unique x-ray optical properties of lungs, namely attenuation, refraction and ultra small-angle scatter (USAXS or width) contrast ratios as a function of lung orientation in free-breathing or respiratory-gated mice before and after intra-nasal bacterial endotoxin (lipopolysaccharide) instillation. The lung ultra small-angle scatter and attenuation contrast ratios were significantly higher 9 h post lipopolysaccharide instillation compared to saline treatment whereas the refraction contrast decreased in magnitude. In ventilated mice, end-expiratory pressures result in an increase in ultra small-angle scatter contrast ratio when compared to end-inspiratory pressures. There were no detectable changes in lung attenuation or refraction contrast ratio with change in lung pressure alone. In effect, multiple image radiography can be applied towards following optical properties of lung air-tissue barrier over time during pathologies such as acute lung injury.

Nucleic Acid Amplification Testing and Sequencing Combined with Acid-Fast Staining in Needle Biopsy Lung Tissues for the Diagnosis of Smear-Negative Pulmonary Tuberculosis.

Directory of Open Access Journals (Sweden)

Faming Jiang

Full Text Available Smear-negative pulmonary tuberculosis (PTB is common and difficult to diagnose. In this study, we investigated the diagnostic value of nucleic acid amplification testing and sequencing combined with acid-fast bacteria (AFB staining of needle biopsy lung tissues for patients with suspected smear-negative PTB.Patients with suspected smear-negative PTB who underwent percutaneous transthoracic needle biopsy between May 1, 2012, and June 30, 2015, were enrolled in this retrospective study. Patients with AFB in sputum smears were excluded. All lung biopsy specimens were fixed in formalin, embedded in paraffin, and subjected to acid-fast staining and tuberculous polymerase chain reaction (TB-PCR. For patients with positive AFB and negative TB-PCR results in lung tissues, probe assays and 16S rRNA sequencing were used for identification of nontuberculous mycobacteria (NTM. The sensitivity, specificity, positive predictive value (PPV, negative predictive value (NPV, and diagnostic accuracy of PCR and AFB staining were calculated separately and in combination.Among the 220 eligible patients, 133 were diagnosed with TB (men/women: 76/57; age range: 17-80 years, confirmed TB: 9, probable TB: 124. Forty-eight patients who were diagnosed with other specific diseases were assigned as negative controls, and 39 patients with indeterminate final diagnosis were excluded from statistical analysis. The sensitivity, specificity, PPV, NPV, and accuracy of histological AFB (HAFB for the diagnosis of smear-negative were 61.7% (82/133, 100% (48/48, 100% (82/82, 48.5% (48/181, and 71.8% (130/181, respectively. The sensitivity, specificity, PPV, and NPV of histological PCR were 89.5% (119/133, 95.8% (46/48, 98.3% (119/121, and 76.7% (46/60, respectively, demonstrating that histological PCR had significantly higher accuracy (91.2% [165/181] than histological acid-fast staining (71.8% [130/181], P < 0.001. Parallel testing of histological AFB staining and PCR showed the

[THE ROLE OF ESTROGENS IN THE CARCINOGENESIS OF LUNG CANCER].

Science.gov (United States)

Uchikova, E; Uchikov, A; Dimitrakova, E; Uchikov, P

2016-01-01

Morbidity and mortality from lung cancer has dramatically increased in women as compared to men over the past few years. Historically, smoking has been considered the major risk factor for lung cancer regardless of gender. Several recent lines of evidence implicate gender differences in the observed differences in prevalence and histologic type which cannot be explained based on the carcinogenic action of nicotine. Several recent studies underscore the importance of reproductive and hormonal factors in the carcinogenesis of lung cancer Lung cancer morbidity and mortality in Bulgaria was 16.2/100000 women and 14.6/ 100000 women, resp. Lung cancer morbidity in Europe was 39/100000 women. Lung cancer is extremely sensitive to estrogens. The latter act directly or as effect modifiers for the relationship between smoking and lung cancer. Further research examining the relationship between serum estrogen levels and the estrogen receptor expression in normal and tumor lung tissue samples can help elucidate the importance of reproductive and hormonal (exogenous and endogenous) factors in the carcinogenesis of lung cancer.

Histological evaluation of lung cancer with T2-weighted magnetic resonance images

International Nuclear Information System (INIS)

Ohta, Takashi; Matsuura, Yoshifumi; Shioya, Sumie; Ohta, Yasuyo

1995-01-01

We investigated the differences in signal intensity of lung cancer tissue and non-cancerous lung tissues on T 2 -weighted magnetic resonance (MR) images. MR images were obtained from patients with squamous cell carcinoma (n=6), adenocarcinoma (n=5), small cell carcinoma (n=5), and large cell carcinoma (n=1). To compare the MR signal intensity between tissues, we calculated the signal intensity ratios for tumor/skeletal muscle and lung/skeletal muscle. The MR signal intensity for each tissue was measured with a densitometer and T 2 -weighted MR images with a similar window and a center. The value of the signal intensity ratio for squamous cell carcinoma (3.26±0.76) was greater than those for adenocarcinoma (1.99±0.50, p<0.05), small cell carcinoma (2.35±0.60), large cell carcinoma (2.46), and non-cancerous lung tissues (1.70±0.68, p<0.02). The values of the MR signal intensity ratio for non-cancerous lung tissues were 2.00 for a collapsed lung, 0.93 for a fibrotic lung, and 2.18 for a fibrotic lung with obstructive pneumonia. The results suggest that the MR signal intensity ratio for pathologic tissues/normal skeletal muscle can be a useful indicator for qualitative and quantitative MR imaging diagnosis. (author)

Follistatin is a novel biomarker for lung adenocarcinoma in humans.

Directory of Open Access Journals (Sweden)

Fangfang Chen

Full Text Available Follistatin (FST, a single chain glycoprotein, is originally isolated from follicular fluid of ovary. Previous studies have revealed that serum FST served as a biomarker for pregnancy and ovarian mucinous tumor. However, whether FST can serve as a biomarker for diagnosis in lung adenocarcinoma of humans remains unclear.The study population consisted of 80 patients with lung adenocarcinoma, 40 patients with ovarian adenocarcinoma and 80 healthy subjects. Serum FST levels in patients and healthy subjects were measured using ELISA. The results showed that the positive ratio of serum FST levels was 51.3% (41/80, which was comparable to the sensitivity of FST in 40 patients with ovarian adenocarcinoma (60%, 24/40 using the 95th confidence interval for the healthy subject group as the cut-off value. FST expressions in lung adenocarcinoma were examined by immunohistochemical staining, we found that lung adenocarcinoma could produce FST and there was positive correlation between the level of FST expression and the differential degree of lung adenocarcinoma. Furthermore, the results showed that primary cultured lung adenocarcinoma cells could secrete FST, while cells derived from non-tumor lung tissues almost did not produce FST. In addition, the results of CCK8 assay and flow cytometry showed that using anti-FST monoclonal antibody to neutralize endogenous FST significantly augmented activin A-induced lung adenocarcinoma cells apoptosis.These data indicate that lung adenocarcinoma cells can secret FST into serum, which may be beneficial to the survival of adenocarcinoma cells by neutralizing activin A action. Thus, FST can serve as a promising biomarker for diagnosis of lung adenocarcinoma and a useful biotherapy target for lung adenocarcinoma.

Uncovering growth-suppressive MicroRNAs in lung cancer

DEFF Research Database (Denmark)

Liu, Xi; Sempere, Lorenzo F; Galimberti, Fabrizio

2009-01-01

PURPOSE: MicroRNA (miRNA) expression profiles improve classification, diagnosis, and prognostic information of malignancies, including lung cancer. This study uncovered unique growth-suppressive miRNAs in lung cancer. EXPERIMENTAL DESIGN: miRNA arrays were done on normal lung tissues...... and adenocarcinomas from wild-type and proteasome degradation-resistant cyclin E transgenic mice to reveal repressed miRNAs in lung cancer. Real-time and semiquantitative reverse transcription-PCR as well as in situ hybridization assays validated these findings. Lung cancer cell lines were derived from each......-malignant human lung tissue bank. RESULTS: miR-34c, miR-145, and miR-142-5p were repressed in transgenic lung cancers. Findings were confirmed by real-time and semiquantitative reverse transcription-PCR as well as in situ hybridization assays. Similar miRNA profiles occurred in human normal versus malignant lung...

Dosimetric verification of small fields in the lung using lung-equivalent polymer gel and Monte Carlo simulation

Directory of Open Access Journals (Sweden)

Nahideh Gharehaghaji

2018-01-01

Conclusion: Our study showed that the dose reduction with small fields in the lung was very high. Thus, inaccurate prediction of absorbed dose inside the lung and also lung/soft-tissue interfaces with small photon beams may lead to critical consequences for treatment outcome.

Focal exposure of limited lung volumes to high-dose irradiation down-regulated organ development-related functions and up-regulated the immune response in mouse pulmonary tissues.

Science.gov (United States)

Kim, Bu-Yeo; Jin, Hee; Lee, Yoon-Jin; Kang, Ga-Young; Cho, Jaeho; Lee, Yun-Sil

2016-01-27

Despite the emergence of stereotactic body radiotherapy (SBRT) for treatment of medically inoperable early-stage non-small-cell lung cancer patients, the molecular effects of focal exposure of limited lung volumes to high-dose radiation have not been fully characterized. This study was designed to identify molecular changes induced by focal high-dose irradiation using a mouse model of SBRT. Central areas of the mouse left lung were focally-irradiated (3 mm in diameter) with a single high-dose of radiation (90 Gy). Temporal changes in gene expression in the irradiated and non-irradiated neighboring lung regions were analyzed by microarray. For comparison, the long-term effect (12 months) of 20 Gy radiation on a diffuse region of lung was also measured. The majority of genes were down-regulated in the focally-irradiated lung areas at 2 to 3 weeks after irradiation. This pattern of gene expression was clearly different than gene expression in the diffuse region of lungs exposed to low-dose radiation. Ontological and pathway analyses indicated these down-regulated genes were mainly associated with organ development. Although the number was small, genes that were up-regulated after focal irradiation were associated with immune-related functions. The temporal patterns of gene expression and the associated biological functions were also similar in non-irradiated neighboring lung regions, although statistical significance was greatly reduced when compared with those from focally-irradiated areas of the lung. From network analysis of temporally regulated genes, we identified inter-related modules associated with diverse functions, including organ development and the immune response, in both the focally-irradiated regions and non-irradiated neighboring lung regions. Focal exposure of lung tissue to high-dose radiation induced expression of genes associated with organ development and the immune response. This pattern of gene expression was also observed in non

Serum tocopherol levels and vitamin E intake are associated with lung function in the normative aging study.

Science.gov (United States)

Hanson, Corrine; Lyden, Elizabeth; Furtado, Jeremy; Campos, Hannia; Sparrow, David; Vokonas, Pantel; Litonjua, Augusto A

2016-02-01

The results of studies assessing relationships between vitamin E intake and status and lung function are conflicting. This study aimed to evaluate the effect of vitamin E intake and serum levels of tocopherol isoforms on lung function in a cross-sectional sample of 580 men from the Normative Aging Study, a longitudinal aging study. Regression models were used to look at associations of serum tocopherol isoform levels and vitamin E intake with lung function parameters after adjustment for confounders. Vitamin E intake was measured using a food frequency questionnaire and serum levels of γ, α, and δ-tocopherol levels were measured using high-performance liquid chromatography. After adjustment for potential confounders, serum γ-tocopherol had a significant inverse association with forced vital capacity (β = -0.10, p = 0.05). Alpha and δ-tocopherol were not associated with any lung function parameter. After classifying COPD status according to Global Initiative for Obstructive Lung Disease (GOLD) stage criteria, serum levels of δ-tocopherol were lower in participants with more severe COPD (p = 0.01). Serum levels of δ-tocopherol were also lower in participants with greater levels of smoking (p = 0.02). Both vitamin E intake (β = 0.03, p = 0.02; β = 0.03, p = 0.01) and use of vitamin E supplements (β = 0.05, p = 0.03; β = 0.06. p = 0.02) were positively associated with FEV1 and FVC, after adjusting for confounders. Subjects who took vitamin E supplements had significantly higher α-tocopherol levels (p tocopherol levels (p tocopherol and lung function. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Inhibition of thromboxane synthase induces lung cancer cell death via increasing the nuclear p27

Energy Technology Data Exchange (ETDEWEB)

Leung, Kin Chung; Hsin, Michael K.Y.; Chan, Joey S.Y.; Yip, Johnson H.Y.; Li, Mingyue; Leung, Billy C.S. [Department of Surgery, The Chinese University of Hong Kong, Shatin, New Territories (Hong Kong); Mok, Tony S.K. [Department of Clinical Oncology, The Chinese University of Hong Kong, Shatin, New Territories (Hong Kong); Warner, Timothy D. [The William Harvey Research Institute, Queen Mary University of London, London (United Kingdom); Underwood, Malcolm J. [Department of Surgery, The Chinese University of Hong Kong, Shatin, New Territories (Hong Kong); Chen, George G., E-mail: gchen@cuhk.edu.hk [Department of Surgery, The Chinese University of Hong Kong, Shatin, New Territories (Hong Kong)

2009-10-15

The role of thromboxane in lung carcinogenesis is not clearly known, though thromboxane B2 (TXB{sub 2}) level is increased and antagonists of thromboxane receptors or TXA2 can induce apoptosis of lung cancer cells. p27, an atypical tumor suppressor, is normally sequestered in the nucleus. The increased nuclear p27 may result in apoptosis of tumor cells. We hypothesize that the inhibition of thromboxane synthase (TXS) induces the death of lung cancer cells and that such inhibition is associated with the nuclear p27 level. Our experiment showed that the inhibition of TXS significantly induced the death or apoptosis in lung cancer cells. The activity of TXS was increased in lung cancer. The nuclear p27 was remarkably reduced in lung cancer tissues. The inhibition of TXS caused the cell death and apoptosis of lung cancer cells, likely via the elevation of the nuclear p27 since the TXS inhibition promoted the nuclear p27 level and the inhibition of p27 by its siRNA recovered the cell death induced by TXS inhibition. Collectively, lung cancer cells produce high levels of TXB{sub 2} but their nuclear p27 is markedly reduced. The inhibition of TXS results in the p27-related induction of cell death in lung cancer cells.

Inhibition of thromboxane synthase induces lung cancer cell death via increasing the nuclear p27

International Nuclear Information System (INIS)

Leung, Kin Chung; Hsin, Michael K.Y.; Chan, Joey S.Y.; Yip, Johnson H.Y.; Li, Mingyue; Leung, Billy C.S.; Mok, Tony S.K.; Warner, Timothy D.; Underwood, Malcolm J.; Chen, George G.

2009-01-01

The role of thromboxane in lung carcinogenesis is not clearly known, though thromboxane B2 (TXB 2 ) level is increased and antagonists of thromboxane receptors or TXA2 can induce apoptosis of lung cancer cells. p27, an atypical tumor suppressor, is normally sequestered in the nucleus. The increased nuclear p27 may result in apoptosis of tumor cells. We hypothesize that the inhibition of thromboxane synthase (TXS) induces the death of lung cancer cells and that such inhibition is associated with the nuclear p27 level. Our experiment showed that the inhibition of TXS significantly induced the death or apoptosis in lung cancer cells. The activity of TXS was increased in lung cancer. The nuclear p27 was remarkably reduced in lung cancer tissues. The inhibition of TXS caused the cell death and apoptosis of lung cancer cells, likely via the elevation of the nuclear p27 since the TXS inhibition promoted the nuclear p27 level and the inhibition of p27 by its siRNA recovered the cell death induced by TXS inhibition. Collectively, lung cancer cells produce high levels of TXB 2 but their nuclear p27 is markedly reduced. The inhibition of TXS results in the p27-related induction of cell death in lung cancer cells.

Elevated plasma angiopoietin-2 levels and primary graft dysfunction after lung transplantation.

Directory of Open Access Journals (Sweden)

Joshua M Diamond

Full Text Available Primary graft dysfunction (PGD is a significant contributor to early morbidity and mortality after lung transplantation. Increased vascular permeability in the allograft has been identified as a possible mechanism leading to PGD. Angiopoietin-2 serves as a partial antagonist to the Tie-2 receptor and induces increased endothelial permeability. We hypothesized that elevated Ang2 levels would be associated with development of PGD.We performed a case-control study, nested within the multi-center Lung Transplant Outcomes Group cohort. Plasma angiopoietin-2 levels were measured pre-transplant and 6 and 24 hours post-reperfusion. The primary outcome was development of grade 3 PGD in the first 72 hours. The association of angiopoietin-2 plasma levels and PGD was evaluated using generalized estimating equations (GEE.There were 40 PGD subjects and 79 non-PGD subjects included for analysis. Twenty-four PGD subjects (40% and 47 non-PGD subjects (59% received a transplant for the diagnosis of idiopathic pulmonary fibrosis (IPF. Among all subjects, GEE modeling identified a significant change in angiopoietin-2 level over time in cases compared to controls (p = 0.03. The association between change in angiopoietin-2 level over the perioperative time period was most significant in patients with a pre-operative diagnosis of IPF (p = 0.02; there was no statistically significant correlation between angiopoietin-2 plasma levels and the development of PGD in the subset of patients transplanted for chronic obstructive pulmonary disease (COPD (p = 0.9.Angiopoietin-2 levels were significantly associated with the development of PGD after lung transplantation. Further studies examining the regulation of endothelial cell permeability in the pathogenesis of PGD are indicated.

Characteristic patterns in the fibrotic lung. Comparing idiopathic pulmonary fibrosis with chronic lung allograft dysfunction.

Science.gov (United States)

Fernandez, Isis E; Heinzelmann, Katharina; Verleden, Stijn; Eickelberg, Oliver

2015-03-01

Tissue fibrosis, a major cause of death worldwide, leads to significant organ dysfunction in any organ of the human body. In the lung, fibrosis critically impairs gas exchange, tissue oxygenation, and immune function. Idiopathic pulmonary fibrosis (IPF) is the most detrimental and lethal fibrotic disease of the lung, with an estimated median survival of 50% after 3-5 years. Lung transplantation currently remains the only therapeutic alternative for IPF and other end-stage pulmonary disorders. Posttransplant lung function, however, is compromised by short- and long-term complications, most importantly chronic lung allograft dysfunction (CLAD). CLAD affects up to 50% of all transplanted lungs after 5 years, and is characterized by small airway obstruction with pronounced epithelial injury, aberrant wound healing, and subepithelial and interstitial fibrosis. Intriguingly, the mechanisms leading to the fibrotic processes in the engrafted lung exhibit striking similarities to those in IPF; therefore, antifibrotic therapies may contribute to increased graft function and survival in CLAD. In this review, we focus on these common fibrosis-related mechanisms in IPF and CLAD, comparing and contrasting clinical phenotypes, the mechanisms of fibrogenesis, and biomarkers to monitor, predict, or prognosticate disease status.

OPTICAL IMAGING OF LIPOPOLYSACCHARIDE-INDUCED OXIDATIVE STRESS IN ACUTE LUNG INJURY FROM HYPEROXIA AND SEPSIS

Directory of Open Access Journals (Sweden)

REYHANEH SEPEHR

2013-07-01

Full Text Available Reactive oxygen species (ROS have been implicated in the pathogenesis of many acute and chronic pulmonary disorders such as acute lung injury (ALI in adults and bronchopulmonary dysplasia (BPD in premature infants. Bacterial infection and oxygen toxicity, which result in pulmonary vascular endothelial injury, contribute to impaired vascular growth and alveolar simplification seen in the lungs of premature infants with BPD. Hyperoxia induces ALI, reduces cell proliferation, causes DNA damage and promotes cell death by causing mitochondrial dysfunction. The objective of this study was to use an optical imaging technique to evaluate the variations in fluorescence intensities of the auto-fluorescent mitochondrial metabolic coenzymes, NADH and FAD in four different groups of rats. The ratio of these fluorescence signals (NADH/FAD, referred to as NADH redox ratio (NADH RR has been used as an indicator of tissue metabolism in injuries. Here, we investigated whether the changes in metabolic state can be used as a marker of oxidative stress caused by hyperoxia and bacterial lipopolysaccharide (LPS exposure in neonatal rat lungs. We examined the tissue redox states of lungs from four groups of rat pups: normoxic (21% O2 pups, hyperoxic (90% O2 pups, pups treated with LPS (normoxic + LPS, and pups treated with LPS and hyperoxia (hyperoxic + LPS. Our results show that hyperoxia oxidized the respiratory chain as reflected by a ~ 31% decrease in lung tissue NADH RR as compared to that for normoxic lungs. LPS treatment alone or with hyperoxia had no significant effect on lung tissue NADH RR as compared to that for normoxic or hyperoxic lungs, respectively. Thus, NADH RR serves as a quantitative marker of oxidative stress level in lung injury caused by two clinically important conditions: hyperoxia and LPS exposure.

The effect of pregnant rat swimming on hypoxia-inducible factor-1α levels of neonatal lung

Directory of Open Access Journals (Sweden)

Mirdar Shadmehr

2012-03-01

Conclusion: Our research suggests that HIF-1α level is an essential element for the development of the lungs of embryos. Moreover, further studies on the lung HIF-1α levels at post-natal period with different modes of exercise will provide more clear insight into the mechanisms of the findings resulting from this study.

The significance of PIWI family expression in human lung embryogenesis and non-small cell lung cancer.

Science.gov (United States)

Navarro, Alfons; Tejero, Rut; Viñolas, Nuria; Cordeiro, Anna; Marrades, Ramon M; Fuster, Dolors; Caritg, Oriol; Moises, Jorge; Muñoz, Carmen; Molins, Laureano; Ramirez, Josep; Monzo, Mariano

2015-10-13

The expression of Piwi-interacting RNAs, small RNAs that bind to PIWI proteins, was until recently believed to be limited to germinal stem cells. We have studied the expression of PIWI genes during human lung embryogenesis and in paired tumor and normal tissue prospectively collected from 71 resected non-small-cell lung cancer patients. The mRNA expression analysis showed that PIWIL1 was highly expressed in 7-week embryos and downregulated during the subsequent weeks of development. PIWIL1 was expressed in 11 of the tumor samples but in none of the normal tissue samples. These results were validated by immunohistochemistry, showing faint cytoplasmic reactivity in the PIWIL1-positive samples. Interestingly, the patients expressing PIWIL1 had a shorter time to relapse (TTR) (p = 0.006) and overall survival (OS) (p = 0.0076) than those without PIWIL1 expression. PIWIL2 and 4 were downregulated in tumor tissue in comparison to the normal tissue (p < 0.001) and the patients with lower levels of PIWIL4 had shorter TTR (p = 0.048) and OS (p = 0.033). In the multivariate analysis, PIWIL1 expression emerged as an independent prognostic marker. Using 5-Aza-dC treatment and bisulfite sequencing, we observed that PIWIL1 expression could be regulated in part by methylation. Finally, an in silico study identified a stem-cell expression signature associated with PIWIL1 expression.

Association of alpha-1 antitrypsin level and lung function in patients with chronic obstructive pulmonary disease

Directory of Open Access Journals (Sweden)

Serapinas Danielius

2017-01-01

Full Text Available Introduction/Objective. Alpha-1 antitrypsin deficiency is a well established inherited risk factor for chronic obstructive pulmonary disease (COPD; however, alpha-1 antitrypsin level may result in different lung function reduction. The aim of our study was to evaluate possible associations of alpha-1 antitrypsin level and lung function in COPD patients with different alpha-1 antitrypsin phenotypes. Methods. Serum alpha-1 antitrypsin concentration from patients (n = 1,167 with COPD, defined according to the GOLD criteria, were analyzed by nephelometry, and alpha-1 antitrypsin phenotype was determined by means of isoelectric-focusing. Results. In COPD patients without alpha-1 antitrypsin deficiency (MM, a significant negative association of lung function (FEV1 with serum alpha-1 antitrypsin (r = -0.511; p < 0.05 and C-reactive protein (CRP concentrations (r = -0.583; p < 0.05 was detected; moreover, the level of alpha-1 antitrypsin positively correlated with CRP concentration (r = 0.667; p < 0.05. Conclusions. In patients without alpha-1 antitrypsin deficiency, detected negative association of alpha-1 antitrypsin level with FEV1 and positive association with the CRP level defined the importance of alpha-1 antitrypsin for lung function in COPD patients.

Expression of Angiotensin II and Aldosterone in Radiation-induced Lung Injury.

Science.gov (United States)

Cao, Shuo; Wu, Rong

2012-12-01

Radiation-induced lung injury (RILI) is the most common, dose-limiting complication in thoracic malignancy radiotherapy. Considering its negative impact on patients and restrictions to efficacy, the mechanism of RILI was studied. Wistar rats were locally irradiated with a single dose of 0, 16, and 20 Gy to the right half of the lung to establish a lung injury model. Two and six months after irradiation, the right half of the rat lung tissue was removed, and the concentrations of TGF-β1, angiotensin II, and aldosterone were determined via enzyme-linked immunosorbent assay. Statistical differences were observed in the expression levels of angiotensin II and aldosterone between the non-irradiation and irradiation groups. Moreover, the expression level of the angiotensin II-aldosterone system increased with increasing doses, and the difference was still observed as time progressed. Angiotensin II-aldosterone system has an important pathophysiological function in the progression of RILI.

Expression of Angiotensin II and Aldosterone in Radiation-induced Lung Injury

International Nuclear Information System (INIS)

Cao, Shuo; Wu, Rong

2012-01-01

Radiation-induced lung injury (RILI) is the most common, dose-limiting complication in thoracic malignancy radiotherapy. Considering its negative impact on patients and restrictions to efficacy, the mechanism of RILI was studied. Wistar rats were locally irradiated with a single dose of 0, 16, and 20 Gy to the right half of the lung to establish a lung injury model. Two and six months after irradiation, the right half of the rat lung tissue was removed, and the concentrations of TGF-β1, angiotensin II, and aldosterone were determined via enzyme-linked immunosorbent assay. Statistical differences were observed in the expression levels of angiotensin II and aldosterone between the non-irradiation and irradiation groups. Moreover, the expression level of the angiotensin II-aldosterone system increased with increasing doses, and the difference was still observed as time progressed. Angiotensin II-aldosterone system has an important pathophysiological function in the progression of RILI

Improved application of the electrophoretic tissue clearing technology, CLARITY, to intact solid organs including brain, pancreas, liver, kidney, lung, and intestine.

Science.gov (United States)

Lee, Hyunsu; Park, Jae-Hyung; Seo, Incheol; Park, Sun-Hyun; Kim, Shin

2014-12-21

Mapping of tissue structure at the cellular, circuit, and organ-wide scale is important for understanding physiological and biological functions. A bio-electrochemical technique known as CLARITY used for three-dimensional anatomical and phenotypical mapping within transparent intact tissues has been recently developed. This method provided a major advance in understanding the structure-function relationships in circuits of the nervous system and organs by using whole-body clearing. Thus, in the present study, we aimed to improve the original CLARITY procedure and developed specific CLARITY protocols for various intact organs. We determined the optimal conditions for reducing bubble formation, discoloration, and depositing of black particles on the surface of tissue, which allowed production of clearer organ images. We also determined the appropriate replacement cycles of clearing solution for each type of organ, and convincingly demonstrated that 250-280 mA is the ideal range of electrical current for tissue clearing. We then acquired each type of cleared organs including brain, pancreas, liver, lung, kidney, and intestine. Additionally, we determined the images of axon fibers of hippocampal region, the Purkinje layer of cerebellum, and vessels and cellular nuclei of pancreas. CLARITY is an innovative biochemical technology for the structural and molecular analysis of various types of tissue. We developed improved CLARITY methods for clearing of the brain, pancreas, lung, intestine, liver, and kidney, and identified the appropriate experimental conditions for clearing of each specific tissue type. These optimized methods will be useful for the application of CLARITY to various types of organs.

Nebulized hyaluronan ameliorates lung inflammation in cystic fibrosis mice.

Science.gov (United States)

Gavina, Manuela; Luciani, Alessandro; Villella, Valeria R; Esposito, Speranza; Ferrari, Eleonora; Bressani, Ilaria; Casale, Alida; Bruscia, Emanuela M; Maiuri, Luigi; Raia, Valeria