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Sample records for beas-2b normal lung

  1. Propofol inhibits LPS-induced apoptosis in lung epithelial cell line, BEAS-2B.

    Science.gov (United States)

    Lv, Xiang; Zhou, Xuhui; Yan, Jia; Jiang, Jue; Jiang, Hong

    2017-03-01

    Lipopolysaccharide (LPS) plays an important role in lung endothelial apoptosis which is crucial for lung fibrogenesis in ARDS progression. Reactive oxygen species (ROS) has been reported to be involved in LPS-induced lung epithelial cell apoptosis. Propofol is a commonly used intravenous anesthetic agent in clinic and it could attenuate LPS-induced epithelial cells oxidation and apoptosis. However, the mechanisms are still obscure. In this study, we examined whether and how propofol attenuates LPS-induced oxidation and apoptosis in BEAS-2B cells. Compared with control group, LPS up-regulated Pin-1, phosphatase A2 (PP2A) expression, induced p66 Shc -Ser 36 phosphorylation, and facilitated p66 Shc mitochondrial translocation, thus leading to superoxide anion (O 2 - ) generation, mitochondrial cytochrome c release, active caspase 3 over-expression and cell viability inhibition. Importantly, propofol was shown to down-regulate LPS-induced PP2A expression, limit p66 Shc mitochondrial translocation, decrease O 2 - generation, inhibit mitochondrial cytochrome c release, reduce active caspase 3 expression, and recover cells viability, while propofol had no effects on LPS-induced Pin-1 expression and p66 Shc -Ser 36 phosphorylation. Moreover, the protective effects of propofol on LPS-induced BEAS-2B cells apoptosis were similar to that of calyculin A, which is an inhibitor of PP2A. We also found that FTY720, which is an activator of PP2A, can effectively reverse the protective function of propofol. Our data illustrated that propofol could alleviate LPS-induced BEAS-2B cells oxidation and apoptosis through down-regulating PP2A expression, limiting p66 Shc -Ser 36 dephosphorylation and p66 Shc mitochondrial translocation, decreasing O 2 - generation, mitochondrial cytochrome c release, activating caspase 3 expression. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-01-09

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

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

    International Nuclear Information System (INIS)

    Zhang, Zhuo; Pratheeshkumar, Poyil; Budhraja, Amit; Son, Young-Ok; Kim, Donghern; Shi, Xianglin

    2015-01-01

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

  4. The Effect of Sodium Fluoride on Cell Apoptosis and the Mechanism of Human Lung BEAS-2B Cells In Vitro.

    Science.gov (United States)

    Ying, Jun; Xu, Jie; Shen, Liping; Mao, Zhijie; Liang, Jingchen; Lin, Shuangxiang; Yu, Xinyan; Pan, Ruowang; Yan, Chunxia; Li, Shengbin; Bao, Qiyu; Li, Peizhen

    2017-09-01

    Sodium fluoride (NaF) is a source of fluoride ions used in many applications. Previous studies found that NaF suppressed the proliferation of osteoblast MC3T3 E1 cells and induced the apoptosis of chondrocytes. However, little is known about the effects of NaF on human lung BEAS-2B cells. Therefore, we investigated the mode of cell death induced by NaF and its underlying molecular mechanisms. BEAS-2B cells were treated with NaF at concentrations of 0, 0.25, 0.5, 1.0, 2.0, and 4.0 mmol/L. Cell viability decreased and apoptotic cells significantly increased as concentrations of NaF increased over specific periods of time. The IC 50 of NaF was 1.9 and 0.9 mM after 24 and 48 h, respectively. The rates of apoptosis increased from 4.8 to 37.7% after NaF exposure. HE staining, electron microscopy, and single cell gel electrophoresis revealed that morphological changes of apoptosis increased with exposure concentrations. RT-PCR and Western blotting were used to detect the apoptotic pathways. The expressions of bax, caspase-3, caspase-9, p53, and the cytoplasmic CytC of the NaF groups increased, while bcl-2 and mitochondrial CytC decreased compared with that of the control group (P < 0.05). Further, the fluorescence intensities of ROS in the NaF groups were higher than those in the control group, and the membrane potential of mitochondria in the NaF group was significantly lower than that of the control group (P < 0.05). These findings suggested that NaF induced apoptosis in the BEAS-2B cells through mitochondria-mediated signal pathways. Our study provides the theoretical foundation and experimental basis for exploring the mechanisms of human lung epithelial cell damage and cytotoxicity induced by fluorine.

  5. Silica Nanoparticle-induced Cytokine Responses in BEAS-2B and HBEC3-KT Cells: Significance of Particle Size and Signalling Pathways in Different Lung Cell Cultures.

    Science.gov (United States)

    Låg, Marit; Skuland, Tonje; Godymchuk, Anna; Nguyen, Thu H T; Pham, Hang L T; Refsnes, Magne

    2018-01-15

    We have previously reported that silica nanoparticles (SiNPs) of nominal size 50 nm (Si50) induce the pro-inflammatory cytokines CXCL8 and IL-6 in BEAS-2B cells, via mechanisms involving MAPK p38, TACE-mediated TGF-α release and the NF-κB pathway. In this study, we examined whether these findings are cell specific or might be extended to another epithelial lung cell model, HBEC3-KT, and also to SiNPs of a smaller size (nominal size of 10 nm; Si10). The TEM average size of Si10 and Si50 was 10.9 and 34.7 nm, respectively. The surface area (BET) of Si10 was three times higher than for Si50 per mass unit. With respect to hydrodynamic size (DLS), Si10 in exposure medium showed a higher z-average for the main peak than Si50, indicating more excessive agglomeration. Si10 strongly induced CXCL8 and IL-6, as assessed by ELISA and RT-PCR, and was markedly more potent than Si50, even when adjusted to equal surface area. Furthermore, Si10 was far more cytotoxic, measured as lactate dehydrogenase (LDH) release, than Si50 in both epithelial cell cultures. With respect to signalling pathways, Western analysis and experiments with and without inhibition of MAPK, TACE and NF-κB (synthetic inhibitors) revealed that p38-phosphorylation, TACE-mediated TGF-α release and NF-κB activation seem to be important triggering mechanisms for both Si50 and Si10 in the two different lung epithelial cell cultures. In conclusion, the identified signalling pathways are suggested to be important in inducing cytokine responses in different epithelial cell types and also for various sizes of silica nanoparticles. © 2018 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-09-15

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

  7. Oxidative stress induced by cerium oxide nanoparticles in cultured BEAS-2B cells

    International Nuclear Information System (INIS)

    Park, Eun-Jung; Choi, Jinhee; Park, Young-Kwon; Park, Kwangsik

    2008-01-01

    Cerium oxide nanoparticles of different sizes (15, 25, 30, 45 nm) were prepared by the supercritical synthesis method, and cytotoxicity was evaluated using cultured human lung epithelial cells (BEAS-2B). Exposure of the cultured cells to nanoparticles (5, 10, 20, 40 μg/ml) led to cell death, ROS increase, GSH decrease, and the inductions of oxidative stress-related genes such as heme oxygenase-1, catalase, glutathione S-transferase, and thioredoxin reductase. The increased ROS by cerium oxide nanoparticles triggered the activation of cytosolic caspase-3 and chromatin condensation, which means that cerium oxide nanoparticles exert cytotoxicity by an apoptotic process. Uptake of the nanoparticles to the cultured cells was also tested. It was observed that cerium oxide nanoparticles penetrated into the cytoplasm and located in the peri-region of the nucleus as aggregated particles, which may induce the direct interaction between nanoparticles and cellular molecules to cause adverse cellular responses

  8. MiR-146a regulates PM1 -induced inflammation via NF-κB signaling pathway in BEAS-2B cells.

    Science.gov (United States)

    Liu, Limin; Wan, Chong; Zhang, Wei; Guan, Longfei; Tian, Guoxiong; Zhang, Fang; Ding, Wenjun

    2018-04-18

    Exposure to particulate matter (PM) leads to kinds of cardiopulmonary diseases, such as asthma, COPD, arrhythmias, lung cancer, etc., which are related to PM-induced inflammation. We have found that PM 2.5 (aerodynamics diameter <2.5 µm) exposure induces inflammatory response both in vivo and in vitro. Since the toxicity of PM is tightly associated with its size and components, PM 1 (aerodynamics diameter <1.0 µm) is supposed to be more toxic than PM 2.5 . However, the mechanism of PM 1 -induced inflammation is not clear. Recently, emerging evidences prove that microRNAs play a vital role in regulating inflammation. Therefore, we studied the regulation of miR-146a in PM 1 -induced inflammation in human lung bronchial epithelial BEAS-2B cells. The results show that PM 1 induces the increase of IL-6 and IL-8 in BEAS-2B cells and up-regulates the miR-146a expression by activating NF-κB signaling pathway. Overexpressed miR-146a prevents the nuclear translocation of p65 through inhibiting the IRAK1/TRAF6 expression, and downregulates the expression of IL-6 and IL-8. Taken together, these results demonstrate that miR-146a can negatively feedback regulate PM 1 -induced inflammation via NF-κB signaling pathway in BEAS-2B cells. © 2018 Wiley Periodicals, Inc.

  9. A Cross-Talk Between NFAT and NF-κB Pathways is Crucial for Nickel-Induced COX-2 Expression in Beas-2B Cells

    Science.gov (United States)

    Cai, T.; Li, X.; Ding, J.; Luo, W.; Li, J.; Huang, C.

    2013-01-01

    Cyclooxygenase-2 (COX-2) is a critical enzyme implicated in chronic inflammation-associated cancer development. Our studies have shown that the exposure of Beas-2B cells, a human bronchial epithelial cell line, to lung carcinogenic nickel compounds results in increased COX-2 expression. However, the signaling pathways leading to nickel-induced COX-2 expression are not well understood. In the current study, we found that the exposure of Beas-2B cells to nickel compounds resulted in the activation of both nuclear factor of activated T cell (NFAT) and nuclear factor-κB (NF-κB). The expression of COX-2 induced upon nickel exposure was inhibited by either a NFAT pharmacological inhibitor or the knockdown of NFAT3 by specific siRNA. We further found that the activation of NFAT and NF-κB was dependent on each other. Since our previous studies have shown that NF-κB activation is critical for nickel-induced COX-2 expression in Beas-2B cells exposed to nickel compounds under same experimental condition, we anticipate that there might be a cross-talk between the activation of NFAT and NF-κB for the COX-2 induction due to nickel exposure in Beas-2B cells. Furthermore, we showed that the scavenging of reactive oxygen species (ROS) by introduction of mitochondrial catalase inhibited the activation of both NFAT and NF-κB, and the induction of COX-2 due to nickel exposure. Taken together, our results defining the evidence showing a key role of the cross-talk between NFAT and NF-κB pathways in regulating nickel-induced COX-2 expression, further provide insight into the understanding of the molecular mechanisms linking nickel exposure to its lung carcinogenic effects. PMID:21486220

  10. Cellular effects in an in vitro human 3D cellular airway model and A549/BEAS-2B in vitro cell cuultures following air exposure to cerium oxide particles at an air-liquid interface

    NARCIS (Netherlands)

    Kooter, I.M.; Grollers-Mulderij, M.; Steenhof, M.; Duistermaat, E.; Acker, F.A.A. van; Staal, Y.C.M.; Tromp, P.C.; Schoen, E.D.; Kuiper, C.F.; Someren, E.P. van

    2016-01-01

    There is a need for representative in vitro models to assess the effects of airborne particles on lung health. The ob-jective of this study was to assess the cellular effects of cerium oxide (Ce02) particles exposed via an air—liquid interface in three relevant cell models in parallel. BEAS-2B,

  11. The crosstalk between α-irradiated Beas-2B cells and its bystander U937 cells through MAPK and NF-κB signaling pathways

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Jiamei; Yuan, Dexiao; Xiao, Linlin; Tu, Wenzhi; Dong, Chen; Liu, Weili; Shao, Chunlin, E-mail: clshao@shmu.edu.cn

    2016-01-15

    Highlights: • α-irradiated Beas-2B cells induced bystander effects in macrophage U937 cells. • The neighboring macrophages enhanced the damage of α-irradiated Beas-2B cells. • MAPK and NF-κB pathways were activated in U937 cells after cell co-culture. • NF-κB and MAPK pathways participated in the bilateral bystander responses. - Abstract: Although accumulated evidence suggests that α-particle irradiation induced bystander effect may relevant to lung injury and cancer risk assessment, the exact mechanisms are not yet elucidated. In the present study, a cell co-culture system was used to investigate the interaction between α-particle irradiated human bronchial epithelial cells (Beas-2B) and its bystander macrophage U937 cells. It was found that the cell co-culture amplified the detrimental effects of α-irradiation including cell viability decrease and apoptosis promotion on both irradiated cells and bystander cells in a feedback loop which was closely relevant to the activation of MAPK and NF-κB pathways in the bystander U937 cells. When these two pathways in U937 cells were disturbed by special pharmacological inhibitors before cell co-culture, it was found that a NF-κB inhibitor of BAY 11-7082 further enhanced the proliferation inhibition and apoptosis induction in bystander U937 cells, but MAPK inhibitors of SP600125 and SB203580 protected cells from viability loss and apoptosis and U0126 presented more beneficial effect on cell protection. For α-irradiated epithelial cells, the activation of NF-κB and MAPK pathways in U937 cells participated in detrimental cellular responses since the above inhibitors could largely attenuate cell viability loss and apoptosis of irradiated cells. Our results demonstrated that there are bilateral bystander responses between irradiated lung epithelial cells and macrophages through MAPK and NF-κB signaling pathways, which accounts for the enhancement of α-irradiation induced damage.

  12. Induction of pro-inflammatory signals by 1-nitropyrene in cultured BEAS-2B cells.

    Science.gov (United States)

    Park, Eun-Jung; Park, Kwangsik

    2009-01-30

    Nitropyrene (1-NP) is classified as Group 2B carcinogen and is one of the main components of diesel exhaust particles (DEP), which are generated from incomplete combustion of automobile engines to cause human cancer or inflammatory diseases. Although many reports on the mutagenesis or carcinogenesis of 1-NP have been released, non-carcinogenic toxicities of 1-NP have not been widely studied. In this study, induction of pro-inflammatory signals by 1-NP was investigated using cultured human bronchial epithelial cells, BEAS-2B. By using microarray analysis and RT-PCR technique, it was found that 1-NP induced the expression of genes related to the pro-inflammatory responses such as pentaxin, IL-1beta, IL-6, IL-8, C-X-C motif ligand 2 (CXCL2), and TNF-alpha. 1-NP was also found to induce ROS generation and intracellular GSH decrease. It suggested that 1-NP may be a pivotal component of DEP to cause inflammatory diseases.

  13. Effects of Size-Fractionated Particulate Matter on Cellular Oxidant Radical Generation in Human Bronchial Epithelial BEAS-2B Cells

    Directory of Open Access Journals (Sweden)

    Longfei Guan

    2016-05-01

    Full Text Available The aim of the present study was to investigate the effects of size-fractionated (i.e., <1; 1–2.5, and 2.5–10 µm in an aerodynamic diameter ambient particulate matter (PM on reactive oxygen species (ROS activity and cell viability in human bronchial epithelial cells (BEAS-2B. The PM samples were collected from an urban site (uPM in Beijing and a steel factory site (sPM in Anshan, China, from March 2013 to December 2014. Metal elements, organic and elemental carbon, and water-soluble inorganic ions in the uPM and sPM were analyzed. The cell viability and ROS generation in PM-exposed BEAS-2B cells were measured by MTS and DCFH-DA. The results showed that both uPM and sPM caused a decrease in the cell viability and an increase in ROS generation. The level of ROS measured in sPM1.0 was approximately triple that in uPM1.0. The results of correlation analysis showed that the ROS activity and cytotoxicity were related to different PM composition. Moreover, deferoxamine (DFO significantly prevented the increase of ROS generation and the decrease of cell viability. Taken together, our results suggest that the metals absorbed on PM induced oxidant radical generation in BEAS-2B cells that could lead to impairment of pulmonary function.

  14. Genotoxicity of polyvinylpyrrolidone-coated silver nanoparticles in BEAS 2B cells.

    Science.gov (United States)

    Nymark, Penny; Catalán, Julia; Suhonen, Satu; Järventaus, Hilkka; Birkedal, Renie; Clausen, Per Axel; Jensen, Keld Alstrup; Vippola, Minnamari; Savolainen, Kai; Norppa, Hannu

    2013-11-08

    Silver nanoparticles (AgNPs) are widely utilized in various consumer products and medical devices, especially due to their antimicrobial properties. However, several studies have associated these particles with toxic effects, such as inflammation and oxidative stress in vivo and cytotoxic and genotoxic effects in vitro. Here, we assessed the genotoxic effects of AgNPs coated with polyvinylpyrrolidone (PVP) (average diameter 42.5±14.5 nm) on human bronchial epithelial BEAS 2B cells in vitro. AgNPs were dispersed in bronchial epithelial growth medium (BEGM) with 0.6 mg/ml bovine serum albumin (BSA). The AgNP were partially well-dispersed in the medium and only limited amounts (ca. 0.02 μg Ag(+) ion/l) could be dissolved after 24h. The zeta-potential of the AgNPs was found to be highly negative in pure water but was at least partially neutralized in BEGM with 0.6 mg BSA/ml. Cytotoxicity was measured by cell number count utilizing Trypan Blue exclusion and by an ATP-based luminescence cell viability assay. Genotoxicity was assessed by the alkaline single cell gel electrophoresis (comet) assay, the cytokinesis-block micronucleus (MN) assay, and the chromosomal aberration (CA) assay. The cells were exposed to various doses (0.5-48 μg/cm(2) corresponding to 2.5-240 μg/ml) of AgNPs for 4 and 24 h in the comet assay, for 48 h in the MN assay, and for 24 and 48 h in the CA assay. DNA damage measured by the percent of DNA in comet tail was induced in a dose-dependent manner after both the 4-h and the 24-h exposures to AgNPs, with a statistically significant increase starting at 16 μg/cm(2) (corresponding to 60.8 μg/ml) and doubling of the percentage of DNA in tail at 48 μg/cm(2). However, no induction of MN or CAs was observed at any of the doses or time points. The lack of induction of chromosome damage by the PVP-coated AgNPs is possibly due to the coating which may protect the cells from direct interaction with the AgNPs, either by reducing ion leaching from the

  15. Nickel compounds induce apoptosis in human bronchial epithelial Beas-2B cells by activation of c-Myc through ERK pathway

    International Nuclear Information System (INIS)

    Li Qin; Suen, T.-C.; Sun Hong; Arita, Adriana; Costa, Max

    2009-01-01

    Nickel compounds are carcinogenic to humans and have been shown to alter epigenetic homeostasis. The c-Myc protein controls 15% of human genes and it has been shown that fluctuations of c-Myc protein alter global epigenetic marks. Therefore, the regulation of c-Myc by nickel ions in immortalized but not tumorigenic human bronchial epithelial Beas-2B cells was examined in this study. It was found that c-Myc protein expression was increased by nickel ions in non-tumorigenic Beas-2B and human keratinocyte HaCaT cells. The results also indicated that nickel ions induced apoptosis in Beas-2B cells. Knockout of c-Myc and its restoration in a rat cell system confirmed the essential role of c-Myc in nickel ion-induced apoptosis. Further studies in Beas-2B cells showed that nickel ion increased the c-Myc mRNA level and c-Myc promoter activity, but did not increase c-Myc mRNA and protein stability. Moreover, nickel ion upregulated c-Myc in Beas-2B cells through the MEK/ERK pathway. Collectively, the results demonstrate that c-Myc induction by nickel ions occurs via an ERK-dependent pathway and plays a crucial role in nickel-induced apoptosis in Beas-2B cells

  16. Signaling factors and pathways of α-particle irradiation induced bilateral bystander responses between Beas-2B and U937 cells

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Jiamei; Wang, Juan; Wang, Xiangdong; Wang, Ping; Xu, Jinping; Zhou, Cuiping; Bai, Yang; Shao, Chunlin, E-mail: clshao@shmu.edu.cn

    2016-07-15

    Highlights: • Radiation damage of Beas-2B cells was enhanced by macrophage-mediated bilateral bystander responses. • Expressions of TNF-α and IL-8 in the α-irradiated Beas-2B cells were dependent on ERK and p38 pathways. • The neighboring U937 cells further increased the generation of TNF-α and IL-8 in the α-irradiated Beas-2B cells. • NF-κB dependent upregulation of TNF-α and IL-8 was induced in the bystander U937 cells. - Abstract: Although radiation induced bystander effects (RIBE) have been investigated for decades for their potential health risk, the underlying gene regulation is still largely unclear, especially the roles of immune system and inflammatory response in RIBE. In the present study, macrophage U937 cells and epithelial Beas-2B cells were co-cultured to disclose the cascades of bystander signaling factors and intercellular communications. After α-particle irradiation, both ERK and p38 pathways were activated in Beas-2B cells and were associated with the autocrine and paracrine signaling of TNF-α and IL-8, resulting in direct damage to the irradiated cells. Similar upregulation of TNF-α and IL-8 was induced in the bystander U937 cells after co-culture with α-irradiated Beas-2B cells. This upregulation was dependent on the activation of NF-κB pathway and was responsible for the enhanced damage of α-irradiated Beas-2B cells. Interestingly, the increased expressions of TNF-α and IL-8 mRNAs in the bystander U937 cells were clearly relayed on the activated ERK and p38 pathways in the irradiated Beas-2B cells, and the upregulation of TNF-α and IL-8 mRNAs in co-cultured Beas-2B cells was also partly due to the activated NF-κB pathway in the bystander U937 cells. With the pretreatment of U0126 (MEK1/2 inhibitor), SB203580 (p38 inhibitor) or BAY 11-7082 (NF-κB inhibitor), the aggravated damage in the α-irradiated Beas-2B cells could be largely alleviated. Our results disclosed novel signaling cascades of macrophage-mediated bilateral

  17. Effects of Size-Fractionated Particulate Matter on Cellular Oxidant Radical Generation in Human Bronchial Epithelial BEAS-2B Cells

    Science.gov (United States)

    Guan, Longfei; Rui, Wei; Bai, Ru; Zhang, Wei; Zhang, Fang; Ding, Wenjun

    2016-01-01

    The aim of the present study was to investigate the effects of size-fractionated (i.e., Metal elements, organic and elemental carbon, and water-soluble inorganic ions in the uPM and sPM were analyzed. The cell viability and ROS generation in PM-exposed BEAS-2B cells were measured by MTS and DCFH-DA. The results showed that both uPM and sPM caused a decrease in the cell viability and an increase in ROS generation. The level of ROS measured in sPM1.0 was approximately triple that in uPM1.0. The results of correlation analysis showed that the ROS activity and cytotoxicity were related to different PM composition. Moreover, deferoxamine (DFO) significantly prevented the increase of ROS generation and the decrease of cell viability. Taken together, our results suggest that the metals absorbed on PM induced oxidant radical generation in BEAS-2B cells that could lead to impairment of pulmonary function. PMID:27171105

  18. Identification of PM10 characteristics involved in cellular responses in human bronchial epithelial cells (Beas-2B)

    International Nuclear Information System (INIS)

    Van Den Heuvel, Rosette; Den Hond, Elly; Govarts, Eva; Colles, Ann; Koppen, Gudrun; Staelens, Jeroen; Mampaey, Maja; Janssen, Nicole; Schoeters, Greet

    2016-01-01

    Notwithstanding evidence is present that physicochemical characteristics of ambient particles attribute to adverse health effects, there is still some lack of understanding in this complex relationship. At this moment it is not clear which properties (such as particle size, chemical composition) or sources of the particles are most relevant for health effects. This study investigates the in vitro toxicity of PM 10 in relation to PM chemical composition, black carbon (BC), endotoxin content and oxidative potential (OP). In 2013–2014 PM 10 was sampled (24 h sampling, 108 sampling days) in ambient air at three sites in Flanders (Belgium) with different pollution characteristics: an urban traffic site (Borgerhout), an industrial area (Zelzate) and a rural background location (Houtem). To characterize the toxic potential of PM 10 , airway epithelial cells (Beas-2B cells) have been exposed to particles in vitro. Different endpoints were studied including cell damage and death (cell viability) using the Neutral red Uptake assay, the production of pro-inflammatory molecules by interleukin 8 (IL-8) induction and DNA-damaging activity using the FPG-modified Comet assay. The endotoxin levels in the collected samples were analysed and the capacity of PM 10 particles to produce reactive oxygen species (OP) was evaluated by electron paramagnetic resonance (EPR) spectroscopy. Chemical characteristics of PM 10 (BC, As, Cd, Cr, Cu, Mn, Ni, Pb, Zn) and meteorological conditions were recorded on the sampling days. PM 10 particles exhibited dose-dependent cytotoxicity in Beas-2B cells and were found to significantly induce the release of IL-8 in samples from the three locations. Oxidatively damaged DNA was observed in exposed Beas-2B cells. Endotoxin levels above the detection limit were detected in half of the samples. OP was measurable in all samples. Associations between PM 10 characteristics and biological effects of PM 10 were assessed by single and multiple regression analyses

  19. Roles of MAPK pathway activation during cytokine induction in BEAS-2B cells exposed to fine World Trade Center (WTC) dust.

    Science.gov (United States)

    Wang, Shang; Prophete, Colette; Soukup, Joleen M; Chen, Lung-Chi; Costa, Max; Ghio, Andrew; Qu, Qingshan; Cohen, Mitchell D; Chen, Haobin

    2010-01-01

    The World Trade Center (WTC) collapse on September 11, 2001 released copious amounts of particulate matter (PM) into the atmosphere of New York City. Follow-up studies on persons exposed to the dusts have revealed a severely increased rate for asthma and other respiratory illnesses. There have only been a few studies that have sought to discern the possible mechanisms underlying these untoward pathologies. In one study, an increased cytokine release was detected in cells exposed to WTC fine dusts (PM₂.₅ fraction or WTC₂.₅). However, the mechanism(s) for these increases has yet to be fully defined. Because activation of the mitogen-activated protein kinase (MAPK) signaling pathways is known to cause cytokine induction, the current study was undertaken to analyze the possible involvement of these pathways in any increased cytokine formation by lung epithelial cells (as BEAS-2B cells) exposed to WTC₂.₅. Our results showed that exposure to WTC₂.₅ for 5 hr increased interleukin-6 (IL-6) mRNA expression in BEAS-2B cells, as well as its protein levels in the culture media, in a dose-dependent manner. Besides IL-6, cytokine multiplex analyses revealed that formation of IL-8 and -10 was also elevated by the exposure. Both extracellular signal-regulated kinase (ERK) and p38, but not c-Jun N-terminal protein kinase, signaling pathways were found to be activated in cells exposed to WTC₂.₅. Inactivation of ERK signaling pathways by PD98059 effectively blocked IL-6, -8, and -10 induction by WTC₂.₅; the p38 kinase inhibitor SB203580 significantly decreased induction of IL-8 and -10. Together, our data demonstrated activation of MAPK signaling pathway(s) likely played an important role in the WTC₂.₅-induced formation of several inflammatory (and, subsequently, anti-inflammatory) cytokines. The results are important in that they help to define one mechanism via which the WTC dusts may have acted to cause the documented increases in asthma and other

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

    Science.gov (United States)

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

    2016-08-01

    Titanium dioxide (TiO2) nanoparticles (NPs) are manufactured worldwide in large quantities for use in a wide range of applications. Evaluating the hazards associated with TiO2 NPs is crucial as it enables risk assessment related to human and environmental exposure. In this study the in vitro human toxicity of a set of TiO2 NPs modified with acetic, oleic and boric acids were studied in order to assess the hazard in view of a future scale-up of the synthesis. The surface reactivity of the powders under simulated solar illumination and in the dark has been evaluated by means of EPR spectroscopy. Human bronchial epithelial cells (BEAS-2B) have been chosen as a model for lung epithelium. Cytotoxicity has been assessed by measuring the cells membrane integrity by lactate dehydrogenase (LDH) assay, and the inflammatory response evaluated as nitric oxide (NO) and TNF-α production, and oxidative stress measured as intracellular reduced glutathione (GSH) levels, and induced lipoperoxidation. Aeroxide P25 was used for comparison. The results demonstrated a low photoreactivity and toxic effects lower than Aeroxide P25 of the nano-TiO2 powders, probably as a consequence of the presence of acidic moieties at the surface. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Prooxidant and proinflammatory potency of air pollution particulate matter (PM₂.₅₋₀.₃) produced in rural, urban, or industrial surroundings in human bronchial epithelial cells (BEAS-2B).

    Science.gov (United States)

    Dergham, Mona; Lepers, Capucine; Verdin, Anthony; Billet, Sylvain; Cazier, Fabrice; Courcot, Dominique; Shirali, Pirouz; Garçon, Guillaume

    2012-04-16

    Compelling evidence indicates that exposure to air pollution particulate matter (PM) affects human health. However, how PM composition interacts with PM-size to cause adverse health effects needs elucidation. In this study, we were also interested in the physicochemical characteristics and toxicological end points of PM₂.₅₋₀.₃ samples produced in rural, urban, or industrial surroundings, thereby expecting to differentiate their respective in vitro adverse health effects in human bronchial epithelial cells (BEAS-2B). Physicochemical characteristics of the three PM₂.₅₋₀.₃ samples, notably their inorganic and organic components, were closely related to their respective emission sources. Referring also to the dose/response relationships of the three PM₂.₅₋₀.₃ samples, the most toxicologically relevant exposure times (i.e., 24, 48, and 72 h) and doses (i.e., 3.75 μg PM/cm² and 15 μg PM/cm²) to use to study the underlying mechanisms of action involved in PM-induced lung toxicity were chosen. Organic chemicals adsorbed on the three PM₂.₅₋₀.₃ samples (i.e., polycyclic aromatic hydrocarbons) were able to induce the gene expression of xenobiotic-metabolizing enzymes (i.e., Cytochrome P4501A1 and 1B1, and, to a lesser extent, NADPH-quinone oxidoreductase-1). Moreover, intracellular reactive oxygen species within BEAS-2B cells exposed to the three PM₂.₅₋₀.₃ samples induced oxidative damage (i.e., 8-hydroxy-2'-deoxyguanosine formation, malondialdehyde production and/or glutathione status alteration). There were also statistically significant increases of the gene expression and/or protein secretion of inflammatory mediators (i.e., notably IL-6 and IL-8) in BEAS-2B cells after their exposure to the three PM₂.₅₋₀.₃ samples. Taken together, the present findings indicated that oxidative damage and inflammatory response preceeded cytotoxicity in air pollution PM₂.₅₋₀.₃-exposed BEAS-2B cells and supported the

  2. Toxicological Impact of Air Pollution Particulate Matter PM 2.5 Collected under Urban Industrial or Rural Influence Occurrence of Oxidative Stress and Inflammatory Reaction in BEAS 2B Human Bronchial Epithelial Cells Corrected Version

    International Nuclear Information System (INIS)

    Dergham, M.; Billet, S; Verdin, A.; Courcot, D.; Cazier, F.; Pirouz, Sh.; Garcon, G.

    2011-01-01

    Exposure to air pollution Particulate Matter (PM) is one of the risk factors involved in the high incidence of respiratory and cardio-vascular diseases. In this work, to integrate inter-seasonal and inter-site variations, fine particle (PM2.5) samples have been collected in spring-summer 2008) and autumn 2008-winter 2009, in Dunkerque (France) under urban or industrial influence, and in Rubrouck (France), under rural influence. Attention was paid to characterize their physico-chemical characteristics, and to determine their ability to induce oxidative stress and inflammatory response in a human bronchial epithelial cell model (BEAS-2B cell line). Physico-chemical characterization of the six PM samples showed their heterogeneities and complexities depending upon their respective natural and/or anthropogenic emission sources. Lung cytotoxicity of these air pollution PM2.5 samples, as shown in BEAS-2B cells, might rely on the induction of oxidative stress conditions and particularly on the excessive inflammatory response. (author)

  3. Impact of ADMA (asymmetric dimethylarginine) on physiology with respect to diabetes mellitus and respiratory system BEAS-2B cells (human bronchial epithelial cells).

    Science.gov (United States)

    Galal, Omneya; Podlogar, Julia; Verspohl, Eugen J

    2013-02-01

    Asymmetric dimethylarginine (ADMA) is a non-selective nitric oxide (NO) synthase inhibitor associated with cardiovascular and metabolic disorders. This study aimed to investigate ADMA with respect to both diabetes and respiratory disease. Glucose was determined by hexokinase method, insulin by a radioimmunoassay. Griess test was used for NO assay and cytokinines were assayed by ELISA. Ciliary beat frequency was determined by high speed video using a microscope. ADMA induced an increase in blood glucose and plasma insulin levels in rats; the ratio of these effects indicates the induction of a diabetic situation (insulin resistance). L-arginine increased blood glucose and initially slightly decreased plasma insulin. A pretreatment with ADMA abolished these effects. ADMA shows similar effects in vitro (insulin-secreting cell line, INS-1 cells). L-arginine increased production of NO, which was reversed by ADMA (INS-1 cells). ADMA also reduced NO production positively modulated by various substances, namely metformin, ciglitazone, losartan and nateglinide, but nevertheless inhibited insulin release induced by these compounds. ADMA stimulated the production of cytokines such as interleukin (IL-6) and macrophage inflammatory protein-2 (MIP-2) (rat IL-8 analogue) from INS-1 cells. 5-Aminoimidazole-4-carboxamide-1-β-4-ribofuranoside (AICAR), a direct adenosine monophosphate protein kinase (AMPK) activator and anti-inflammatory agent, induced NO production and reduced cytokine release. In contrast to diabetes parameters, ADMA had no effect of on the respiratory system (cytokine secretion from BEAS-2B cells (IL-8, regulated on activation, normal T cell expressed and secreted, and tumour necrosis factor-α), ciliary beat frequency and smooth muscle contraction of rat trachea). ADMA has a pathophysiological impact leading to a diabetic situation but has no impact on the respiratory system. © 2012 The Authors. JPP © 2012. Royal Pharmaceutical Society.

  4. Diesel exhaust particles induced release of interleukin 6 and 8 by (primed) human bronchial epithelial cells (BEAS 2B) in vitro.

    Science.gov (United States)

    Steerenberg, P A; Zonnenberg, J A; Dormans, J A; Joon, P N; Wouters, I M; van Bree, L; Scheepers, P T; Van Loveren, H

    1998-01-01

    Several epidemiological studies have recently shown associations of increased premature mortality rates with ambient particulate air pollution. Diesel exhaust particles (DEP) may constitute an important part of (ultra)fine particulate air pollution in urban areas and may therefore contribute to its toxicity. Epithelial lining of the respiratory tract may be the first target of the toxic effects of DEP, that upon exposure may release pro-inflammatory mediators such as interleukin 6 and 8 (IL-6, IL-8), ultimately causing airway tissue damage and immune alterations. In this study the effects of in vitro DEP exposure (0.04-0.33 mg/mL) on IL-6, IL-8 production by a human bronchial epithelial cell line (BEAS-2B) were investigated. For comparison, the production of interleukins during exposure to silica and titanium oxide (TiO2) were also studied, representing relatively toxic and non-toxic particles, respectively. Scanning and transmission electron microscopy showed that the size of the DEP particles ranged between 25 to 35 nm and that DEP was phagocytized by BEAS-2B cells. An increase in IL-6 and IL-8 production (11- and 4-fold, respectively) was found after 24 or 48 h of exposure to DEP compared to the non-exposed cells. This increase was lower compared to silica (17- and 3.3-fold) and higher as compared to TiO2 which showed no increase for IL-6 and IL-8. To study the DEP effect on inflammation-primed cells, BEAS-2B cells were exposed to both tumor necrosis factor-alpha (TNF-alpha) and subsequently to DEP. Exposure to TNF-alpha caused a strong increase in IL-6 and IL-8 production. Additive effects on the IL-6 and IL-8 production by BEAS-2B cells were found after TNF-alpha priming and subsequently exposure to DEP, only at a low dose of DEP and TNF-alpha (0.05-0.2 ng/mL). In conclusion, BEAS-2B phagocytized DEP and produced an increased amount of IL-6 and IL-8. In TNF-alpha primed BEAS-2B cells, DEP increased interleukin production only at low concentrations of DEP and

  5. Poly (I:C, an agonist of toll-like receptor-3, inhibits replication of the Chikungunya virus in BEAS-2B cells

    Directory of Open Access Journals (Sweden)

    Li Yong-Gang

    2012-06-01

    Full Text Available Abstract Background Double-stranded RNA (dsRNA and its mimic, polyinosinic acid: polycytidylic acid [Poly (I:C], are recognized by toll-like receptor 3 (TLR3 and induce interferon (IFN-β in many cell types. Poly (I:C is the most potent IFN inducer. In in vivo mouse studies, intraperitoneal injection of Poly (I:C elicited IFN-α/β production and natural killer (NK cells activation. The TLR3 pathway is suggested to contribute to innate immune responses against many viruses, including influenza virus, respiratory syncytial virus, herpes simplex virus 2, and murine cytomegalovirus. In Chikungunya virus (CHIKV infection, the viruses are cleared within 7–10 days postinfection before adaptive immune responses emerge. The innate immune response is important for CHIKV clearance. Results The effects of Poly (I:C on the replication of CHIKV in human bronchial epithelial cells, BEAS-2B, were studied. Poly (I:C suppressed cytopathic effects (CPE induced by CHIKV infection in BEAS-2B cells in the presence of Poly (I:C and inhibited the replication of CHIKV in the cells. The virus titers of Poly (I:C-treated cells were much lower compared with those of untreated cells. CHIKV infection and Poly (I:C treatment of BEAS-2B cells induced the production of IFN-β and increased the expression of anti-viral genes, including IFN-α, IFN-β, MxA, and OAS. Both Poly (I:C and CHIKV infection upregulate the expression of TLR3 in BEAS-2B cells. Conclusions CHIKV is sensitive to innate immune response induced by Poly (I:C. The inhibition of CHIKV replication by Poly (I:C may be through the induction of TLR3, which triggers the production of IFNs and other anti-viral genes. The innate immune response is important to clear CHIKV in infected cells.

  6. Selective ATP-Binding Cassette Subfamily C Gene Expression and Proinflammatory Mediators Released by BEAS-2B after PM2.5, Budesonide, and Cotreated Exposures

    Directory of Open Access Journals (Sweden)

    Jarline Encarnación-Medina

    2017-01-01

    Full Text Available ATP-binding cassette subfamily C (ABCC genes code for phase III metabolism proteins that translocate xenobiotic (e.g., particulate matter 2.5 (PM2.5 and drug metabolites outside the cells. IL-6 secretion is related with the activation of the ABCC transporters. This study assesses ABCC1–4 gene expression changes and proinflammatory cytokine (IL-6, IL-8 release in human bronchial epithelial cells (BEAS-2B exposed to PM2.5 organic extract, budesonide (BUD, used to control inflammation in asthmatic patients, and a cotreatment (Co-T: PM2.5 and BUD. A real-time PCR assay shows that ABCC1 was upregulated in BEAS-2B exposed after 6 and 7 hr to PM2.5 extract or BUD but downregulated after 6 hr of the Co-T. ABCC3 was downregulated after 6 hr of BUD and upregulated after 6 hr of the Co-T exposures. ABCC4 was upregulated after 5 hr of PM2.5 extract, BUD, and the Co-T exposures. The cytokine assay revealed an increase in IL-6 release by BEAS-2B exposed after 5 hr to PM2.5 extract, BUD, and the Co-T. At 7 hr, the Co-T decreases IL-6 release and IL-8 at 6 hr. In conclusion, the cotreatment showed an opposite effect on exposed BEAS-2B as compared with BUD. The results suggest an interference of the BUD therapeutic potential by PM2.5.

  7. Cadmium induces carcinogenesis in BEAS-2B cells through ROS-dependent activation of PI3K/AKT/GSK-3β/β-catenin signaling

    International Nuclear Information System (INIS)

    Son, Young-Ok; Wang, Lei; Poyil, Pratheeshkumar; Budhraja, Amit; Hitron, J. Andrew; Zhang, Zhuo; Lee, Jeong-Chae; Shi, Xianglin

    2012-01-01

    Cadmium has been widely used in industry and is known to be carcinogenic to humans. Although it is widely accepted that chronic exposure to cadmium increases the incidence of cancer, the mechanisms underlying cadmium-induced carcinogenesis are unclear. The main aim of this study was to investigate the role of reactive oxygen species (ROS) in cadmium-induced carcinogenesis and the signal transduction pathways involved. Chronic exposure of human bronchial epithelial BEAS-2B cells to cadmium induced cell transformation, as evidenced by anchorage-independent growth in soft agar and clonogenic assays. Chronic cadmium treatment also increased the potential of these cells to invade and migrate. Injection of cadmium-stimulated cells into nude mice resulted in the formation of tumors. In contrast, the cadmium-mediated increases in colony formation, cell invasion and migration were prevented by transfection with catalase, superoxide dismutase-1 (SOD1), or SOD2. In particular, chronic cadmium exposure led to activation of signaling cascades involving PI3K, AKT, GSK-3β, and β-catenin and transfection with each of the above antioxidant enzymes markedly inhibited cadmium-mediated activation of these signaling proteins. Inhibitors specific for AKT or β-catenin almost completely suppressed the cadmium-mediated increase in total and active β-catenin proteins and colony formation. Moreover, there was a marked induction of AKT, GSK-3β, β-catenin, and carcinogenic markers in tumor tissues formed in mice after injection with cadmium-stimulated cells. Collectively, our findings suggest a direct involvement of ROS in cadmium-induced carcinogenesis and implicate a role of AKT/GSK-3β/β-catenin signaling in this process. -- Highlights: ► Chronic exposure to cadmium induces carcinogenic properties in BEAS-2B cells. ► ROS involved in cadmium-induced tumorigenicity of BEAS-2B cells. ► Cadmium activates ROS-dependent AKT/GSK-3β/β-catenin-mediated signaling. ► ROS

  8. Proteomic Responses of BEAS-2B Cells to Nontoxic and Toxic Chromium: Protein Indicators of Cytotoxicity Conversion

    Science.gov (United States)

    Hexavalent chromium (Cr (VI)) is an environmental human carcinogen which primarily targets lungs. Among a variety of toxic mechanisms, disruption of biological pathways via translational and post-translational modifications represents a key mechanism through which Cr (VI) induces...

  9. Nicotinamide N-Methyltransferase Suppression Participates in Nickel-Induced Histone H3 Lysine9 Dimethylation in BEAS-2B Cells

    Directory of Open Access Journals (Sweden)

    Qian Li

    2017-04-01

    Full Text Available Background: Nickel compounds are well-established human carcinogens with weak mutagenic activity. Histone methylation has been proposed to play an important role in nickel-induced carcinogenesis. Nicotinamide N-methyltransferase (NNMT decreases histone methylation in several cancer cells by altering the cellular ratio of S-adenosylmethionine (SAM to S-adenosylhomocysteine (SAH. However, the role of NNMT in nickel-induced histone methylation remains unclear. Methods: BEAS-2B cells were exposed to different concentrations of nickel chloride (NiCl2 for 72 h or 200 μM NiCl2 for different time periods. Histone H3 on lysine 9 (H3K9 mono-, di-, and trimethylation and NNMT protein levels were measured by western blot analysis. Expressions of NNMT mRNA and the H3k9me2-associated genes, mitogen-activated protein kinase 3 (MAP2K3 and dickkopf1 (DKK1, were determined by qPCR analysis. The cellular ratio of nicotinamide adenine dinucleotide (NAD+ to reduced NAD (NADH and SAM/SAH ratio were determined. Results: Exposure of BEAS-2B cells to nickel increased H3K9 dimethylation (H3K9me2, suppressed the expressions of H3K9me2-associated genes (MAP2K3 and DKK1, and induced NNMT repression at both the protein and mRNA levels. Furthermore, over-expression of NNMT inhibited nickel-induced H3K9me2 and altered the cellular SAM/SAH ratio. Additionally, the NADH oxidant phenazine methosulfate (PMS not only reversed the nickel-induced reduction in NAD+/NADH but also inhibited the increase in H3K9me2. Conclusions: These findings indicate that the repression of NNMT may underlie nickel-induced H3K9 dimethylation by altering the cellular SAM/SAH ratio.

  10. Nicotine Component of Cigarette Smoke Extract (CSE) Decreases the Cytotoxicity of CSE in BEAS-2B Cells Stably Expressing Human Cytochrome P450 2A13.

    Science.gov (United States)

    Ji, Minghui; Zhang, Yudong; Li, Na; Wang, Chao; Xia, Rong; Zhang, Zhan; Wang, Shou-Lin

    2017-10-13

    Cytochrome P450 2A13 (CYP2A13), an extrahepatic enzyme mainly expressed in the human respiratory system, has been reported to mediate the metabolism and toxicity of cigarette smoke. We previously found that nicotine inhibited 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) metabolism by CYP2A13, but its influence on other components of cigarette smoke remains unclear. The nicotine component of cigarette smoke extract (CSE) was separated, purified, and identified using high-performance liquid chromatography (HPLC) and ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), splitting CSE into a nicotine section (CSE-N) and nicotine-free section (CSE-O). Cell viability and apoptosis by Cell Counting Kit-8 (CCK-8) and flow cytometry assays were conducted on immortalized human bronchial epithelial (BEAS-2B) cells stably expressing CYP2A13 (B-2A13) or vector (B-V), respectively. Interestingly, CSE and CSE-O were toxic to BEAS-2B cells whereas CSE-N showed less cytotoxicity. CSE-O was more toxic to B-2A13 cells than to B-V cells (IC 50 of 2.49% vs. 7.06%), which was flatted by 8-methoxypsoralen (8-MOP), a CYP inhibitor. CSE-O rather than CSE or CSE-N increased apoptosis of B-2A13 cells rather than B-V cells. Accordingly, compared to CSE-N and CSE, CSE-O significantly changed the expression of three pairs of pro- and anti-apoptotic proteins, Bcl-2 Associated X Protein/B cell lymphoma-2 (Bax/Bcl-2), Cleaved Poly (Adenosine Diphosphate-Ribose) Polymerase/Poly (Adenosine Diphosphate-Ribose) Polymerase (C-PARP/PARP), and C-caspase-3/caspase-3, in B-2A13 cells. In addition, recombination of CSE-N and CSE-O (CSE-O/N) showed similar cytotoxicity and apoptosis to the original CSE. These results demonstrate that the nicotine component decreases the metabolic activation of CYP2A13 to CSE and aids in understanding the critical role of CYP2A13 in human respiratory diseases caused by cigarette smoking.

  11. PI3K-delta mediates double-stranded RNA-induced upregulation of B7-H1 in BEAS-2B airway epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Kan-o, Keiko [Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Matsumoto, Koichiro, E-mail: koichi@kokyu.med.kyushu-u.ac.jp [Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Asai-Tajiri, Yukari; Fukuyama, Satoru; Hamano, Saaka; Seki, Nanae; Nakanishi, Yoichi [Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Inoue, Hiromasa [Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520 (Japan)

    2013-05-31

    Highlights: •Double-stranded RNA upregulates B7-H1 on BEAS-2B airway epithelial cells. •The upregulation of B7-H1 is attenuated by inhibition of PI3Kδ isoform. •PI3Kδ-mediated upregulation of B7-H1 is independent of NF-κB activation. •Inhibition of PI3Kδ may prevent persistent viral infection induced by B7-H1. -- Abstract: Airway viral infection disturbs the health-related quality of life. B7-H1 (also known as PD-L1) is a coinhibitory molecule associated with the escape of viruses from the mucosal immunity, leading to persistent infection. Most respiratory viruses generate double-stranded (ds) RNA during replication. The stimulation of cultured airway epithelial cells with an analog of viral dsRNA, polyinosinic-polycytidylic acid (poly IC) upregulates the expression of B7-H1 via activation of the nuclear factor κB(NF-κB). The mechanism of upregulation was investigated in association with phosphatidylinositol 3-kinases (PI3Ks). Poly IC-induced upregulation of B7-H1 was profoundly suppressed by a pan-PI3K inhibitor and partially by an inhibitor or a small interfering (si)RNA for PI3Kδ in BEAS-2B cells. Similar results were observed in the respiratory syncytial virus-infected cells. The expression of p110δ was detected by Western blot and suppressed by pretreatment with PI3Kδ siRNA. The activation of PI3Kδ is typically induced by oxidative stress. The generation of reactive oxygen species was increased by poly IC. Poly IC-induced upregulation of B7-H1 was attenuated by N-acetyl-L-cysteine, an antioxidant, or by oxypurinol, an inhibitor of xanthine oxidase. Poly IC-induced activation of NF-κB was suppressed by a pan-PI3K inhibitor but not by a PI3Kδ inhibitor. These results suggest that PI3Kδ mediates dsRNA-induced upregulation of B7-H1 without affecting the activation of NF-κB.

  12. PI3K-delta mediates double-stranded RNA-induced upregulation of B7-H1 in BEAS-2B airway epithelial cells

    International Nuclear Information System (INIS)

    Kan-o, Keiko; Matsumoto, Koichiro; Asai-Tajiri, Yukari; Fukuyama, Satoru; Hamano, Saaka; Seki, Nanae; Nakanishi, Yoichi; Inoue, Hiromasa

    2013-01-01

    Highlights: •Double-stranded RNA upregulates B7-H1 on BEAS-2B airway epithelial cells. •The upregulation of B7-H1 is attenuated by inhibition of PI3Kδ isoform. •PI3Kδ-mediated upregulation of B7-H1 is independent of NF-κB activation. •Inhibition of PI3Kδ may prevent persistent viral infection induced by B7-H1. -- Abstract: Airway viral infection disturbs the health-related quality of life. B7-H1 (also known as PD-L1) is a coinhibitory molecule associated with the escape of viruses from the mucosal immunity, leading to persistent infection. Most respiratory viruses generate double-stranded (ds) RNA during replication. The stimulation of cultured airway epithelial cells with an analog of viral dsRNA, polyinosinic-polycytidylic acid (poly IC) upregulates the expression of B7-H1 via activation of the nuclear factor κB(NF-κB). The mechanism of upregulation was investigated in association with phosphatidylinositol 3-kinases (PI3Ks). Poly IC-induced upregulation of B7-H1 was profoundly suppressed by a pan-PI3K inhibitor and partially by an inhibitor or a small interfering (si)RNA for PI3Kδ in BEAS-2B cells. Similar results were observed in the respiratory syncytial virus-infected cells. The expression of p110δ was detected by Western blot and suppressed by pretreatment with PI3Kδ siRNA. The activation of PI3Kδ is typically induced by oxidative stress. The generation of reactive oxygen species was increased by poly IC. Poly IC-induced upregulation of B7-H1 was attenuated by N-acetyl-L-cysteine, an antioxidant, or by oxypurinol, an inhibitor of xanthine oxidase. Poly IC-induced activation of NF-κB was suppressed by a pan-PI3K inhibitor but not by a PI3Kδ inhibitor. These results suggest that PI3Kδ mediates dsRNA-induced upregulation of B7-H1 without affecting the activation of NF-κB

  13. Activation of Akt/GSK3β and Akt/Bcl-2 signaling pathways in nickel-transformed BEAS-2B cells.

    Science.gov (United States)

    Pan, Jing-Ju; Chang, Qing-Shan; Wang, Xin; Son, Young-Ok; Liu, Jiankang; Zhang, Zhuo; Bi, Yong-Yi; Shi, Xianglin

    2011-11-01

    The Akt signaling pathway has been implicated in a wide range of cellular functions involving cell survival and proliferation, angiogenesis, metabolism and cell migration. Accumulating evidence suggests that Akt perturbations play an important role in human malignancy. Here, we investigated Akt perturbation in nickel-transformed cells. Chronic treatment of human bronchial epithelial BEAS-2B cells with low doses of nickel chloride resulted in cell transformation demonstrated by anchorage-independent (AI) growth, increased cell growth and alterations of cell growth pattern. Western blot assays show that phosphorylation of Akt at Ser473, but not that of p38, JNK and ERK, was increased in nickel-transformed cells compared with controls. Inhibition of Akt or PI3K by pharmacological or biochemical interference suppressed nickel AI growth and cell growth of transformed cells. Activation of Akt led to inhibition of GSK3β by phosphorylation at Ser9 in nickel-transformed cells. In addition, two major anti-apoptotic proteins of the Bcl family, Bcl-2 and Bcl-XL, were increased in nickel-transformed cells. By employing the small interfering RNA technique (siRNA), our results showed that siRNA Akt attenuated the expression of Bcl-2 and Bcl-XL in nickel-transformed cells, indicating that induction of Bcl-2 and Bcl-XL was likely mediated through Akt. ROS generation was decreased in nickel-transformed cells compared with controls. Moreover, down-regulation of retinoblastoma protein (Rb) was observed in nickel-transformed cells. Taken together, these findings demonstrate that activation of Akt, followed by GSK3β inhibition and Bcl-2, Bcl-XL up-regulation and decrease of ROS generation, along with a synergistic effect of Rb down-regulation may cause apoptosis resistance, contributing to the overall mechanism of nickel carcinogenesis.

  14. DNA damage and DNA damage response in human bronchial epithelial BEAS-2B cells following exposure to 2-nitrobenzanthrone and 3-nitrobenzanthrone: role in apoptosis.

    Science.gov (United States)

    Oya, Elisabeth; Ovrevik, Johan; Arlt, Volker M; Nagy, Eszter; Phillips, David H; Holme, Jørn A

    2011-11-01

    Nitro-polycyclic aromatic hydrocarbons (nitro-PAHs) are mutagenic and carcinogenic environmental pollutants found in diesel exhaust and on urban air pollution particles. In the present study, human bronchial epithelial BEAS-2B cells were exposed to 2-nitrobenzanthrone (2-NBA) and 3-nitrobenzanthrone (3-NBA). DNA damage responses were compared to those observed after exposure to 1-nitropyrene (1-NP) and benzo[a]pyrene (B[a]P). Examination by microscopy revealed that 3-NBA was the most potent toxic compound while weaker responses were observed with 1-NP and B[a]P. Most interestingly, 2-NBA did not induce cell death or any other stress-related responses. 3-NBA induced a typical apoptotic cell death judged by nuclear condensation and little plasma membrane damage as well as cleavage of caspase 3 and poly-(ADP-ribose) polymerase (PARP). Exposure to 3-NBA resulted in an accumulation of cells in S-phase, and further analysis by Western blotting, immunocytochemistry and flow cytometry revealed that 3-NBA induced a DNA damage response characterized by phosphorylation of ATM (ataxia-telangiectasia mutated), checkpoint kinase (Chk) 2/Chk1, H2AX and p53. The p53 inhibitor pifithrin-α inhibited 3-NBA-induced apoptosis while small effects were seen using pifithrin-μ, suggesting that 3-NBA-induced cell death is a result of transcriptional activation of p53. In conclusion, 3-NBA is a potent inducer of apoptosis, which seemed to be triggered by the DNA damage response. Furthermore, a change of the nitro-group to the second position (i.e. 2-NBA) dramatically changed the cellular reactivity of the compound.

  15. Downregulation of B-cell lymphoma/leukemia-2 by overexpressed microRNA 34a enhanced titanium dioxide nanoparticle-induced autophagy in BEAS-2B cells

    Science.gov (United States)

    Bai, Wenlin; Chen, Yujiao; Sun, Pengling; Gao, Ai

    2016-01-01

    Titanium dioxide (TiO2) nanoparticles (TNPs) are manufactured worldwide for a wide range of applications and the toxic effect of TNPs on biological systems is gaining attention. Autophagy is recognized as an emerging toxicity mechanism triggered by nanomaterials. MicroRNA 34a (miR34a) acts as a tumor suppressor gene by targeting many oncogenes, but how it affects autophagy induced by TNPs is not completely understood. Here, we observed the activation of TNP-induced autophagy through monodansylcadaverine staining and LC3-I/LC3-II conversion. Meanwhile, the transmission electron microscope ultrastructural analysis showed typical morphological characteristics in autophagy process. We detected the expression of miR34a and B-cell lymphoma/leukemia-2 (Bcl-2). In addition, the underlying mechanism of TNP-induced autophagy was performed using overexpression of miR34a by lentivirus vector transfection. Results showed that TNPs induced autophagy generation evidently. Typical morphological changes in the process of autophagy were observed by the transmission electron microscope ultrastructural analysis and LC3-I/LC3-II conversion increased significantly in TNP-treated cells. Meanwhile, TNPs induced the downregulation of miR34a and increased the expression of Bcl-2. Furthermore, overexpressed miR34a decreased the expression of Bcl-2 both in messenger RNA and protein level, following which the level of autophagy and cell death rate increased after the transfected cells were incubated with TNPs for 24 hours. These findings provide the first evidence that overexpressed miR34a enhanced TNP-induced autophagy and cell death through targeted downregulation of Bcl-2 in BEAS-2B cells. PMID:27226226

  16. Comparative Analysis of Toxic Responses of Organic Extracts from Diesel and Selected Alternative Fuels Engine Emissions in Human Lung BEAS-2B Cells

    Czech Academy of Sciences Publication Activity Database

    Líbalová, Helena; Rössner ml., Pavel; Vrbová, Kristýna; Brzicová, Táňa; Sikorová, Jitka; Vojtíšek-Lom, M.; Beránek, V.; Kléma, J.; Cigánek, M.; Neča, J.; Pěnčíková, K.; Machala, M.; Topinka, Jan

    2016-01-01

    Roč. 17, č. 11 (2016), s. 1833 E-ISSN 1422-0067 R&D Projects: GA ČR(CZ) GA13-01438S; GA MŠk(CZ) LO1508; GA MŠk(CZ) LM2015073 Institutional support: RVO:68378041 Keywords : diesel * alternative fuels * diesel exhaust particles Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 3.226, year: 2016

  17. Proinflammatory effects of diesel exhaust particles from moderate blend concentrations of 1st and 2nd generation biodiesel in BEAS-2B bronchial epithelial cells-The FuelHealth project.

    Science.gov (United States)

    Skuland, Tonje S; Refsnes, Magne; Magnusson, Pål; Oczkowski, Michał; Gromadzka-Ostrowska, Joanna; Kruszewski, Marcin; Mruk, Remigiusz; Myhre, Oddvar; Lankoff, Anna; Øvrevik, Johan

    2017-06-01

    Biodiesel fuel fuels are introduced at an increasing extent as a more carbon-neutral alternative to reduce CO 2 -emissions, compared to conventional diesel fuel. In the present study we have investigated the impact of increasing the use of 1st generation fatty acid methyl ester (FAME) biodiesel from current 7% blend (B7) to 20% blend (B20), or by increasing the biodiesel content by adding 2nd generation hydrotreated vegetable oil (HVO) based biodiesel (SHB; Synthetic Hydrocarbon Biofuel) on toxicity of diesel exhaust particles (DEP) in an in vitro system. Human bronchial epithelial BEAS-2B cells were exposed for 4 and 20h to DEP from B7, B20 and SHB at different concentrations, and examined for effects on gene expression of interleukin 6 (IL-6), CXCL8 (IL-8), CYP1A1 and heme oxygenase-1 (HO-1). The results show that both B20 and SHB were more potent inducers of IL-6 expression compared to B7. Only B20 induced statistically significant increases in CXCL8 expression. By comparison the rank order of potency to induce CYP1A1 was SHB>B7>B20. No statistically significant difference were observed form HO-1 expression, suggesting that the differences in cytokine responses were not due to oxidative stress. The results show that even moderate increases in biodiesel blends, from 7% to 20%, may increase the proinflammatory potential of emitted DEP in BEAS-2B cells. This effect was observed for both addition of 1st generation FAME and 2nd generation HVO biodiesel. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Cellular Interactions and Biological Responses to Titanium Dioxide Nanoparticles in HepG2 and BEAS-2B Cells: Role of Cell Culture Media

    Science.gov (United States)

    ABSTRACT We have shown previously that the composition of the biological medium used in vitro can affect the cellular interaction and biological response of titanium dioxide nanoparticles (nano-TiO2) in human lung epithelial cells. However, it is unclear if these effects are co...

  19. Adenovirus-mediated delivery and expression of a cAMP-dependent protein kinase inhibitor gene to BEAS-2B epithelial cells abolishes the anti-inflammatory effects of rolipram, salbutamol, and prostaglandin E2: a comparison with H-89.

    Science.gov (United States)

    Meja, Koremu K; Catley, Matthew C; Cambridge, Lisa M; Barnes, Peter J; Lum, Hazel; Newton, Robert; Giembycz, Mark A

    2004-05-01

    cAMP-elevating drugs are thought to mediate their biological effects by activating the cAMP/cAMP-dependent protein kinase (PKA) cascade. However, this hypothesis is difficult to confirm due to a lack of selective inhibitors. Here, we have probed the role of PKA in mediating inhibitory effects of several cAMP-elevating drugs in BEAS-2B epithelial cells using an adenovirus vector encoding a PKA inhibitor protein (PKIalpha) and have compared it to H-89, a commonly used small molecule PKA inhibitor. Initial studies established efficient gene transfer and confirmed functionality of PKIalpha 48 h after virus infection. All cAMP-elevating drugs tested promoted the phosphorylation of cAMP response element-binding protein (CREB), activated a cAMP response element (CRE)-driven luciferase reporter gene, and suppressed both granulocyte/macrophage colony-stimulating factor (GM-CSF) generation and [(3)H]arachidonic acid (AA) release in response to interleukin-1beta and monocyte chemotactic protein (MCP)-1, respectively. These effects were abolished by PKIalpha. In contrast, H-89 behaved unpredictably under the same conditions. Thus, although CREB phosphorylation evoked by a range of cAMP-elevating drugs was abolished by H-89, neither activation of the CRE-dependent luciferase reporter gene construct nor the inhibition of GM-CSF generation was inhibited. Paradoxically, H-89 antagonized MCP-1-induced [(3)H]AA release and enhanced the inhibitory effect of submaximal concentrations of rolipram and 8-bromo-cAMP. We suggest that expression of PKIalpha in susceptible cells provides a simple and unambiguous way to assess the role of PKA in cAMP signaling and to probe the mechanism of action of other drugs and cAMP-dependent responses where the participation of PKA is equivocal. Furthermore, these data suggest that H-89 is not a selective inhibitor of PKA and should be avoided.

  20. Camptosorus sibiricus rupr aqueous extract prevents lung tumorigenesis via dual effects against ROS and DNA damage.

    Science.gov (United States)

    He, Shugui; Ou, Rilan; Wang, Wensheng; Ji, Liyan; Gao, Hui; Zhu, Yuanfeng; Liu, Xiaomin; Zheng, Hongming; Liu, Zhongqiu; Wu, Peng; Lu, Linlin

    2017-12-16

    Camptosorus sibiricus Rupr (CSR) is a widely used herbal medicine with antivasculitis, antitrauma, and antitumor effects. However, the effect of CSR aqueous extract on B[a]P-initiated tumorigenesis and the underlying mechanism remain unclear. Moreover, the compounds in CSR aqueous extract need to be identified and structurally characterized. We aim to investigate the chemopreventive effect of CSR and the underlying molecular mechanism. A B[a]P-stimulated normal cell model (BEAS.2B) and lung adenocarcinoma animal model were established on A/J mice. In B[a]P-treated BEAS.2B cells, the protective effects of CSR aqueous extract on B[a]P-induced DNA damage and ROS production were evaluated through flow cytometry, Western blot, real-time quantitative PCR, single-cell gel electrophoresis, and immunofluorescence. Moreover, a model of B[a]P-initiated lung adenocarcinoma was established on A/J mice to determine the chemopreventive effect of CSR in vivo. The underlying mechanism was analyzed via immunohistochemistry and microscopy. Furthermore, the new compounds in CSR aqueous extract were isolated and structurally characterized using IR, HR-ESI-MS, and 1D and 2D NMR spectroscopy. CSR effectively suppressed ROS production by re-activating Nrf2-mediated reductases HO-1 and NQO-1. Simultaneously, CSR attenuated the DNA damage of BEAS.2B cells in the presence of B[a]P. Moreover, CSR at 1.5 and 3 g/kg significantly suppressed tumorigenesis with tumor inhibition ratios of 36.65% and 65.80%, respectively. The tumor volume, tumor size, and multiplicity of B[a]P-induced lung adenocarcinoma were effectively decreased by CSR in vivo. After extracting and identifying the compounds in CSR aqueous extract, three new triterpene saponins were isolated and characterized structurally. CSR aqueous extract prevents lung tumorigenesis by exerting dual effects against ROS and DNA damage, suggesting that CSR is a novel and effective agent for B[a]P-induced carcinogenesis. Moreover, by isolating

  1. MicroRNA-223 Promotes Tumor Progression in Lung Cancer A549 Cells via Activation of the NF-κB Signaling Pathway.

    Science.gov (United States)

    Huang, Li; Li, Fang; Deng, Pengbo; Hu, Chengping

    2016-10-27

    Our study aimed to investigate the role of microRNA-223 (miR-223) in lung cancer A549 cells and to further elucidate its possible regulatory mechanism. The expression levels of normal human lung epithelial cell line BEAS-2B and human lung cancer cell line A549 were investigated by quantitative real-time PCR. The A549 cells were transfected with miR-223 inhibitor and miR-223 scramble. Afterward, the effects of miR-223 inhibition on cell viability, invasion, and apoptosis, as well as the expression levels of nuclear factor-κB (NF-κB) and its downstream proteins, were detected. In addition, the NF-κB inhibitor JSH-23 was used to detect the relationship between NF-κB and miR-223. miR-223 was upregulated in human lung cancer A549 cells when compared with BEAS-2B cells. In addition, miR-223 expression was successfully inhibited by the miR-223 inhibitor. Suppression of miR-223 significantly decreased cell viability, inhibited invasion, and induced apoptosis of lung cancer A549 cells. Suppression of miR-223 resulted in a significant decrease in the expression levels of NF-κB and its downstream proteins P-IKBα and P-IKKα/β. After treatment with the NF-κB inhibitor, the inhibitory effects of miR-233 inhibitor on cell invasion, as well as the expression levels of NF-κB and p-p65, were enhanced. Our findings indicate that miR-223 may increase proliferation, promote invasion, and inhibit apoptosis of lung cancer A549 cells via activation of the NF-κB signaling pathway. miR-223 may serve as a potential therapeutic target in lung cancer.

  2. Diatom-derived polyunsaturated aldehydes activate cell death in human cancer cell lines but not normal cells.

    Directory of Open Access Journals (Sweden)

    Clementina Sansone

    Full Text Available Diatoms are an important class of unicellular algae that produce bioactive polyunsaturated aldehydes (PUAs that induce abortions or malformations in the offspring of invertebrates exposed to them during gestation. Here we compare the effects of the PUAs 2-trans,4-trans-decadienal (DD, 2-trans,4-trans-octadienal (OD and 2-trans,4-trans-heptadienal (HD on the adenocarcinoma cell lines lung A549 and colon COLO 205, and the normal lung/brunch epithelial BEAS-2B cell line. Using the viability MTT/Trypan blue assays, we show that PUAs have a toxic effect on both A549 and COLO 205 tumor cells but not BEAS-2B normal cells. DD was the strongest of the three PUAs tested, at all time-intervals considered, but HD was as strong as DD after 48 h. OD was the least active of the three PUAs. The effect of the three PUAs was somewhat stronger for A549 cells. We therefore studied the death signaling pathway activated in A549 showing that cells treated with DD activated Tumor Necrosis Factor Receptor 1 (TNFR1 and Fas Associated Death Domain (FADD leading to necroptosis via caspase-3 without activating the survival pathway Receptor-Interacting Protein (RIP. The TNFR1/FADD/caspase pathway was also observed with OD, but only after 48 h. This was the only PUA that activated RIP, consistent with the finding that OD causes less damage to the cell compared to DD and HD. In contrast, cells treated with HD activated the Fas/FADD/caspase pathway. This is the first report that PUAs activate an extrinsic apoptotic machinery in contrast to other anticancer drugs that promote an intrinsic death pathway, without affecting the viability of normal cells from the same tissue type. These findings have interesting implications also from the ecological viewpoint considering that HD is one of the most common PUAs produced by diatoms.

  3. Cellular senescence in normal and premature lung aging.

    Science.gov (United States)

    Bartling, B

    2013-10-01

    The incidence of chronic respiratory diseases (e.g., chronic obstructive pulmonary disease, COPD) and interstitial lung diseases (e.g., pneumonia and lung fibrosis) increases with age. In addition to immune senescence, the accumulation of senescent cells directly in lung tissue might play a critical role in the increased prevalence of these pulmonary diseases. In the last couple of years, detailed studies have identified the presence of senescent cells in the aging lung and in diseased lungs of patients with COPD and lung fibrosis. Cellular senescence has been shown for epithelial cells of bronchi and alveoli as well as mesenchymal and vascular cells. Known risk factors for pulmonary diseases (cigarette smoke, air pollutions, bacterial infections, etc.) were identified in experimental studies as being possible mediators in the development of cellular senescence. The present findings indicate the importance of cellular senescence in normal lung aging and in premature aging of the lung in patients with COPD, lung fibrosis, and probably other respiratory diseases.

  4. Inhibition of lung cancer cells A549 and H460 by curcuminoid extracts and nanoemulsions prepared from Curcuma longa Linnaeus

    Science.gov (United States)

    Chang, Hong-Bin; Chen, Bing-Huei

    2015-01-01

    The objectives of this study were to explore the inhibition mechanism of lung cancer cells A549 and H460 by curcuminoid extracts and nanoemulsions prepared from Curcuma longa Linnaeus. In addition, human bronchus epithelial cell line BEAS-2B (normal cell) was selected for comparison. A high-performance liquid chromatography (HPLC) method was developed to separate and quantify the various curcuminoids in C. longa extract, including curcumin (1,714.5 μg/mL), demethoxycurcumin (1,147.4 μg/mL), and bisdemethoxycurcumin (190.2 μg/mL). A high-stability nanoemulsion composed of Tween 80, water, and curcuminoid extract was prepared, with mean particle size being 12.6 nm. The cell cycle was retarded at G2/M for both the curcuminoid extract and nanoemulsion treatments; however, the inhibition pathway may be different. H460 cells were more susceptible to apoptosis than A549 cells for both curcuminoid extract and nanoemulsion treatments. Growth of BEAS-2B remained unaffected for both the curcuminoid extract and nanoemulsion treatments, with a concentration range from 1 to 4 μg/mL. Also, the activities of caspase-3, caspase-8, and caspase-9 followed a dose-dependent increase for both A549 and H460 cells for both the treatments, accompanied by a dose-dependent increase in cytochrome C expression and a dose-dependent decrease in CDK1 expression. Interestingly, a dose-dependent increase in cyclin B expression was shown for A549 cells for both the treatments, while a reversed trend was found for H460 cells. Both mitochondria and death receptor pathways may be responsible for apoptosis of both A549 and H460 cells. PMID:26345201

  5. Inhibition of lung cancer cells A549 and H460 by curcuminoid extracts and nanoemulsions prepared from Curcuma longa Linnaeus.

    Science.gov (United States)

    Chang, Hong-Bin; Chen, Bing-Huei

    2015-01-01

    The objectives of this study were to explore the inhibition mechanism of lung cancer cells A549 and H460 by curcuminoid extracts and nanoemulsions prepared from Curcuma longa Linnaeus. In addition, human bronchus epithelial cell line BEAS-2B (normal cell) was selected for comparison. A high-performance liquid chromatography (HPLC) method was developed to separate and quantify the various curcuminoids in C. longa extract, including curcumin (1,714.5 μg/mL), demethoxycurcumin (1,147.4 μg/mL), and bisdemethoxycurcumin (190.2 μg/mL). A high-stability nanoemulsion composed of Tween 80, water, and curcuminoid extract was prepared, with mean particle size being 12.6 nm. The cell cycle was retarded at G2/M for both the curcuminoid extract and nanoemulsion treatments; however, the inhibition pathway may be different. H460 cells were more susceptible to apoptosis than A549 cells for both curcuminoid extract and nanoemulsion treatments. Growth of BEAS-2B remained unaffected for both the curcuminoid extract and nanoemulsion treatments, with a concentration range from 1 to 4 μg/mL. Also, the activities of caspase-3, caspase-8, and caspase-9 followed a dose-dependent increase for both A549 and H460 cells for both the treatments, accompanied by a dose-dependent increase in cytochrome C expression and a dose-dependent decrease in CDK1 expression. Interestingly, a dose-dependent increase in cyclin B expression was shown for A549 cells for both the treatments, while a reversed trend was found for H460 cells. Both mitochondria and death receptor pathways may be responsible for apoptosis of both A549 and H460 cells.

  6. MRI of normal and pathological fetal lung development

    Energy Technology Data Exchange (ETDEWEB)

    Kasprian, Gregor [University Clinic of Radiodiagnostics, Medical University of Vienna (Austria)]. E-mail: gregor.kasprian@meduniwien.ac.at; Balassy, Csilla [University Clinic of Radiodiagnostics, Medical University of Vienna (Austria); Brugger, Peter C. [Center of Anatomy and Cell Biology, Medical University of Vienna (Austria); Prayer, Daniela [University Clinic of Radiodiagnostics, Medical University of Vienna (Austria)

    2006-02-15

    Normal fetal lung development is a complex process influenced by mechanical and many biochemical factors. In addition to ultrasound, fetal magnetic resonance imaging (MRI) constitutes a new method to investigate this process in vivo during the second and third trimester. The techniques of MRI volumetry, assessment of signal intensities, and MRI spectroscopy of the fetal lung have been used to analyze this process and have already been applied clinically to identify abnormal fetal lung growth. Particularly in conditions such as oligohydramnios and congenital diaphragmatic hernia (CDH), pulmonary hypoplasia may be the cause of neonatal death. A precise diagnosis and quantification of compromised fetal lung development may improve post- and perinatal management. The main events in fetal lung development are reviewed and MR volumetric data from 106 normal fetuses, as well as different examples of pathological lung growth, are provided.

  7. Luteolin inhibits Cr(VI)-induced malignant cell transformation of human lung epithelial cells by targeting ROS mediated multiple cell signaling pathways

    Energy Technology Data Exchange (ETDEWEB)

    Pratheeshkumar, Poyil; Son, Young-Ok; Divya, Sasidharan Padmaja; Roy, Ram Vinod; Hitron, John Andrew; Wang, Lei [Center for Research on Environmental Disease, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Kim, Donghern; Dai, Jin [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Asha, Padmaja [National Centre for Aquatic Animal Health, Cochin University of Science and Technology, Cochin (India); Zhang, Zhuo [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Wang, Yitao [State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau (China); Shi, Xianglin, E-mail: xshi5@email.uky.edu [Center for Research on Environmental Disease, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States)

    2014-12-01

    Hexavalent chromium [Cr(VI)] is a well-known human carcinogen associated with the incidence of lung cancer. Inhibition of metal induced carcinogenesis by a dietary antioxidant is a novel approach. Luteolin, a natural dietary flavonoid found in fruits and vegetables, possesses potent antioxidant and anti-inflammatory activity. We found that short term exposure of human bronchial epithelial cells (BEAS-2B) to Cr(VI) (5 μM) showed a drastic increase in ROS generation, NADPH oxidase (NOX) activation, lipid peroxidation, and glutathione depletion, which were significantly inhibited by the treatment with luteolin in a dose dependent manner. Treatment with luteolin decreased AP-1, HIF-1α, COX-2, and iNOS promoter activity induced by Cr(VI) in BEAS-2B cells. In addition, luteolin protected BEAS-2B cells from malignant transformation induced by chronic Cr(VI) exposure. Moreover, luteolin also inhibited the production of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α) and VEGF in chronic Cr(VI) exposed BEAS-2B cells. Western blot analysis showed that luteolin inhibited multiple gene products linked to survival (Akt, Fak, Bcl-2, Bcl-xL), inflammation (MAPK, NF-κB, COX-2, STAT-3, iNOS, TNF-α) and angiogenesis (HIF-1α, VEGF, MMP-9) in chronic Cr(VI) exposed BEAS-2B cells. Nude mice injected with BEAS-2B cells chronically exposed to Cr(VI) in the presence of luteolin showed reduced tumor incidence compared to Cr(VI) alone treated group. Overexpression of catalase (CAT) or SOD2, eliminated Cr(VI)-induced malignant transformation. Overall, our results indicate that luteolin protects BEAS-2B cells from Cr(VI)-induced carcinogenesis by scavenging ROS and modulating multiple cell signaling mechanisms that are linked to ROS. Luteolin, therefore, serves as a potential chemopreventive agent against Cr(VI)-induced carcinogenesis. - Highlights: • Luteolin inhibited Cr(VI)-induced oxidative stress. • Luteolin inhibited chronic Cr(VI)-induced malignant transformation.

  8. The component formula of Salvia miltiorrhiza and Panax ginseng induces apoptosis and inhibits cell invasion and migration through targeting PTEN in lung cancer cells.

    Science.gov (United States)

    Bi, Lei; Yan, Xiaojing; Yang, Ye; Qian, Lei; Tian, Yuan; Mao, Jian-Hua; Chen, Weiping

    2017-11-24

    Lung cancer still remains the leading cause of cancer-related death worldwide. It is an urgent need for development of novel therapeutic agents to improve current treatment of this disease. Here we investigate whether the effective component formula of traditional Chinese Medicine could serve as new potential therapeutic drugs to treat lung cancer. We optimize the most effective component formula of Salvia miltiorrhiza and Panax Ginseng (FMG), which is composed of Salvianolic acid A, 20(S)-Ginsenoside and Ginseng polysaccharide. We discovered that FMG selectively inhibited lung cancer cell proliferation and induced apoptosis but had no any cytotoxic effects on normal lung epithelial BEAS-2B cells. Moreover, FMG inhibited lung cancer cell migration and invasion. Mechanistically, we found that FMG significantly promoted p-PTEN expression and subsequently inhibited PI3K/AKT signaling pathway. The phosphatase activity of PTEN protein was increased after FMG bound to PTEN protein, indicating that PTEN is one of the FMG targeted proteins. In addition, FMG regulated expression of some marker proteins relevant to cell apoptosis, migration and invasion. Collectively, these results provide mechanistic insight into the anti-NSCLC of FMG by enhancing the phosphatase activity of PTEN, and suggest that FMG could be as a potential option for lung cancer treatment.

  9. Near-normal values of extravascular lung water in children

    NARCIS (Netherlands)

    Nusmeier, A.; Cecchetti, C.; Blohm, M.; Lehman, R.; Hoeven, J.G. van der; Lemson, J.

    2015-01-01

    OBJECTIVES: To define near-normal values of extravascular lung water indexed to body weight in children. DESIGN: Prospective multicenter observational study. SETTING: Medical/surgical PICUs of 5 multinational hospitals. PATIENTS: Fifty-eight children with a median age of 4 years (range 1 month to 17

  10. Chronic Pseudomonas aeruginosa lung infection in normal and athymic rats

    DEFF Research Database (Denmark)

    Johansen, H K; Espersen, F; Pedersen, S S

    1993-01-01

    We have compared a chronic lung infection with Pseudomonas aeruginosa embedded in alginate beads in normal and athymic rats with an acute infection with free live P. aeruginosa bacteria. The following parameters were observed and described: mortality, macroscopic and microscopic pathologic changes...

  11. Toxicity of aged gasoline exhaust particles to normal and diseased airway epithelia.

    Science.gov (United States)

    Künzi, Lisa; Krapf, Manuel; Daher, Nancy; Dommen, Josef; Jeannet, Natalie; Schneider, Sarah; Platt, Stephen; Slowik, Jay G; Baumlin, Nathalie; Salathe, Matthias; Prévôt, André S H; Kalberer, Markus; Strähl, Christof; Dümbgen, Lutz; Sioutas, Constantinos; Baltensperger, Urs; Geiser, Marianne

    2015-06-29

    Particulate matter (PM) pollution is a leading cause of premature death, particularly in those with pre-existing lung disease. A causative link between particle properties and adverse health effects remains unestablished mainly due to complex and variable physico-chemical PM parameters. Controlled laboratory experiments are required. Generating atmospherically realistic aerosols and performing cell-exposure studies at relevant particle-doses are challenging. Here we examine gasoline-exhaust particle toxicity from a Euro-5 passenger car in a uniquely realistic exposure scenario, combining a smog chamber simulating atmospheric ageing, an aerosol enrichment system varying particle number concentration independent of particle chemistry, and an aerosol deposition chamber physiologically delivering particles on air-liquid interface (ALI) cultures reproducing normal and susceptible health status. Gasoline-exhaust is an important PM source with largely unknown health effects. We investigated acute responses of fully-differentiated normal, distressed (antibiotics-treated) normal, and cystic fibrosis human bronchial epithelia (HBE), and a proliferating, single-cell type bronchial epithelial cell-line (BEAS-2B). We show that a single, short-term exposure to realistic doses of atmospherically-aged gasoline-exhaust particles impairs epithelial key-defence mechanisms, rendering it more vulnerable to subsequent hazards. We establish dose-response curves at realistic particle-concentration levels. Significant differences between cell models suggest the use of fully-differentiated HBE is most appropriate in future toxicity studies.

  12. CT quantification of lung and airways in normal Korean subjects

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Song Soo; Lee, Jeong Eun; Shin, Hye Soo [Dept. of Radiology, Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon (Korea, Republic of); Jin, Gong Yong; Li, Yuan Zhe [Dept. of Radiology, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju (Korea, Republic of)

    2017-08-01

    To measure and compare the quantitative parameters of the lungs and airways in Korean never-smokers and current or former smokers (“ever-smokers”). Never-smokers (n = 119) and ever-smokers (n = 45) who had normal spirometry and visually normal chest computed tomography (CT) results were retrospectively enrolled in this study. For quantitative CT analyses, the low attenuation area (LAA) of LAA{sub I-950}, LAA{sub E-856}, CT attenuation value at the 15th percentile, mean lung attenuation (MLA), bronchial wall thickness of inner perimeter of a 10 mm diameter airway (Pi10), total lung capacity (TLC{sub CT}), and functional residual capacity (FRC{sub CT}) were calculated based on inspiratory and expiratory CT images. To compare the results between groups according to age, sex, and smoking history, independent t test, one way ANOVA, correlation test, and simple and multiple regression analyses were performed. The values of attenuation parameters and volume on inspiratory and expiratory quantitative computed tomography (QCT) were significantly different between males and females (p < 0.001). The MLA and the 15th percentile value on inspiratory QCT were significantly lower in the ever-smoker group than in the never-smoker group (p < 0.05). On expiratory QCT, all lung attenuation parameters were significantly different according to the age range (p < 0.05). Pi10 in ever-smokers was significantly correlated with forced expiratory volume in 1 second/forced vital capacity (r = −0.455, p = 0.003). In simple and multivariate regression analyses, TLC{sub CT}, FRC{sub CT}, and age showed significant associations with lung attenuation (p < 0.05), and only TLC{sub CT} was significantly associated with inspiratory Pi10. In Korean subjects with normal spirometry and visually normal chest CT, there may be significant differences in QCT parameters according to sex, age, and smoking history.

  13. CT quantification of lung and airways in normal Korean subjects

    International Nuclear Information System (INIS)

    Kim, Song Soo; Lee, Jeong Eun; Shin, Hye Soo; Jin, Gong Yong; Li, Yuan Zhe

    2017-01-01

    To measure and compare the quantitative parameters of the lungs and airways in Korean never-smokers and current or former smokers (“ever-smokers”). Never-smokers (n = 119) and ever-smokers (n = 45) who had normal spirometry and visually normal chest computed tomography (CT) results were retrospectively enrolled in this study. For quantitative CT analyses, the low attenuation area (LAA) of LAA I-950 , LAA E-856 , CT attenuation value at the 15th percentile, mean lung attenuation (MLA), bronchial wall thickness of inner perimeter of a 10 mm diameter airway (Pi10), total lung capacity (TLC CT ), and functional residual capacity (FRC CT ) were calculated based on inspiratory and expiratory CT images. To compare the results between groups according to age, sex, and smoking history, independent t test, one way ANOVA, correlation test, and simple and multiple regression analyses were performed. The values of attenuation parameters and volume on inspiratory and expiratory quantitative computed tomography (QCT) were significantly different between males and females (p < 0.001). The MLA and the 15th percentile value on inspiratory QCT were significantly lower in the ever-smoker group than in the never-smoker group (p < 0.05). On expiratory QCT, all lung attenuation parameters were significantly different according to the age range (p < 0.05). Pi10 in ever-smokers was significantly correlated with forced expiratory volume in 1 second/forced vital capacity (r = −0.455, p = 0.003). In simple and multivariate regression analyses, TLC CT , FRC CT , and age showed significant associations with lung attenuation (p < 0.05), and only TLC CT was significantly associated with inspiratory Pi10. In Korean subjects with normal spirometry and visually normal chest CT, there may be significant differences in QCT parameters according to sex, age, and smoking history

  14. Signalling with retinoids in the human lung: validation of new tools for the expression study of retinoid receptors

    International Nuclear Information System (INIS)

    Poulain, Stéphane; Lacomme, Stéphanie; Battaglia-Hsu, Shyue-Fang; Manoir, Stanislas du; Brochin, Lydia; Vignaud, Jean-Michel; Martinet, Nadine

    2009-01-01

    Retinoid Receptors are involved in development and cell homeostasis. Alterations of their expressions have been observed in lung cancer. However, retinoid chemoprevention trials in populations at risk to develop such tumors have failed. Therefore, the pertinence of new clinical trials using second generation retinoid requires prior better understanding of retinoid signalling. This is our aim when validating extensively research tools, focused on Retinoic Acid Receptor beta, whose major role in lung cancer is documented. Biocomputing was used to assess the genomic organization of RAR beta. Its putative RAR-beta1' promoter features were investigated experimentally. Specific measures realized, with qRT-PCR Syber Green assays and a triplex of Taqman probes, were extensively validated to establish Retinoid Receptors mRNAs reference values for in vivo normal human bronchial cells, lung tumors and cell lines. Finally, a pan-RAR-beta antibody was generated and extensively validated by western-blot and immunoprecipitation. No promoter-like activity was found for RAR-beta1'. RAR-beta2 mRNAs increase signs the normal differentiation of the human bronchial epithelium while a decrease is observed in most lung cancer cell lines. Accordingly, it is also, along with RXR beta, down-regulated in lung tumors. When using nuclear extracts of BEAS-2B and normal lung cells, only the RAR-beta2 long protein isoform was recognized by our antibody. Rigorous samples processing and extensive biocomputing, were the key factors for this study. mRNA reference values and validated tools can now be used to advance researches on retinoid signalling in the lung

  15. Wood combustion particles induce adverse effects to normal and diseased airway epithelia.

    Science.gov (United States)

    Krapf, Manuel; Künzi, Lisa; Allenbach, Sandrine; Bruns, Emily A; Gavarini, Ilaria; El-Haddad, Imad; Slowik, Jay G; Prévôt, André S H; Drinovec, Luka; Močnik, Griša; Dümbgen, Lutz; Salathe, Matthias; Baumlin, Nathalie; Sioutas, Constantinos; Baltensperger, Urs; Dommen, Josef; Geiser, Marianne

    2017-04-19

    Residential wood burning is a major source of poorly characterized, deleterious particulate matter, whose composition and toxicity may vary with wood type, burning condition and photochemical age. The causative link between ambient wood particle constituents and observed adverse health effects is currently lacking. Here we investigate the relationship between chemical properties of primary and atmospherically aged wood combustion particles and acute toxicity in human airway epithelial cells. Emissions from a log wood burner were diluted and injected into a smog chamber for photochemical aging. After concentration-enrichment and removal of oxidizing gases, directly emitted and atmospherically aged particles were deposited on cell cultures at the air-liquid interface for 2 hours in an aerosol deposition chamber mimicking physiological conditions in lungs. Cell models were fully differentiated normal and diseased (cystic fibrosis and asthma) human bronchial epithelia (HBE) and the bronchial epithelial cell line BEAS-2B. Cell responses were assessed at 24 hours after aerosol exposure. Atmospherically relevant doses of wood combustion particles significantly increased cell death in all but the asthma cell model. Expression of oxidative stress markers increased in HBE from all donors. Increased cell death and inflammatory responses could not be assigned to a single chemical fraction of the particles. Exposure to primary and aged wood combustion particles caused adverse effects to airway epithelia, apparently induced by several interacting components.

  16. Inhibition of lung cancer cells A549 and H460 by curcuminoid extracts and nanoemulsions prepared from Curcuma longa Linnaeus

    Directory of Open Access Journals (Sweden)

    Chang HB

    2015-08-01

    Full Text Available Hong-Bin Chang,1 Bing-Huei Chen1,21Department of Food Science, 2Graduate Institute of Medicine, Fu Jen Catholic University, Taipei, TaiwanAbstract: The objectives of this study were to explore the inhibition mechanism of lung cancer cells A549 and H460 by curcuminoid extracts and nanoemulsions prepared from Curcuma longa Linnaeus. In addition, human bronchus epithelial cell line BEAS-2B (normal cell was selected for comparison. A high-performance liquid chromatography (HPLC method was developed to separate and quantify the various curcuminoids in C. longa extract, including curcumin (1,714.5 µg/mL, demethoxycurcumin (1,147.4 µg/mL, and bisdemethoxycurcumin (190.2 µg/mL. A high-stability nanoemulsion composed of Tween 80, water, and curcuminoid extract was prepared, with mean particle size being 12.6 nm. The cell cycle was retarded at G2/M for both the curcuminoid extract and nanoemulsion treatments; however, the inhibition pathway may be different. H460 cells were more susceptible to apoptosis than A549 cells for both curcuminoid extract and nanoemulsion treatments. Growth of BEAS-2B remained unaffected for both the curcuminoid extract and nanoemulsion treatments, with a concentration range from 1 to 4 µg/mL. Also, the activities of caspase-3, caspase-8, and caspase-9 followed a dose-dependent increase for both A549 and H460 cells for both the treatments, accompanied by a dose-dependent increase in cytochrome C expression and a dose-dependent decrease in CDK1 expression. Interestingly, a dose-dependent increase in cyclin B expression was shown for A549 cells for both the treatments, while a reversed trend was found for H460 cells. Both mitochondria and death receptor pathways may be responsible for apoptosis of both A549 and H460 cells.Keywords: curcuminoid extract, curcuminoid nanoemulsion, Curcuma longa Linnaeus, lung cancer cell, cell cycle, apoptosis mechanism

  17. Differences in gene expression and cytokine production by crystalline vs. amorphous silica in human lung epithelial cells

    Directory of Open Access Journals (Sweden)

    Perkins Timothy N

    2012-02-01

    Full Text Available Abstract Background Exposure to respirable crystalline silica particles, as opposed to amorphous silica, is associated with lung inflammation, pulmonary fibrosis (silicosis, and potentially with lung cancer. We used Affymetrix/GeneSifter microarray analysis to determine whether gene expression profiles differed in a human bronchial epithelial cell line (BEAS 2B exposed to cristobalite vs. amorphous silica particles at non-toxic and equal surface areas (75 and 150 × 106μm2/cm2. Bio-Plex analysis was also used to determine profiles of secreted cytokines and chemokines in response to both particles. Finally, primary human bronchial epithelial cells (NHBE were used to comparatively assess silica particle-induced alterations in gene expression. Results Microarray analysis at 24 hours in BEAS 2B revealed 333 and 631 significant alterations in gene expression induced by cristobalite at low (75 and high (150 × 106μm2/cm2 amounts, respectively (p 6μm2/cm2 induced 108 significant gene changes. Bio-Plex analysis of 27 human cytokines and chemokines revealed 9 secreted mediators (p FOS, ATF3, IL6 and IL8 early and over time (2, 4, 8, and 24 h. Patterns of gene expression in NHBE cells were similar overall to BEAS 2B cells. At 75 × 106μm2/cm2, there were 339 significant alterations in gene expression induced by cristobalite and 42 by amorphous silica. Comparison of genes in response to cristobalite (75 × 106μm2/cm2 revealed 60 common, significant gene alterations in NHBE and BEAS 2B cells. Conclusions Cristobalite silica, as compared to synthetic amorphous silica particles at equal surface area concentrations, had comparable effects on the viability of human bronchial epithelial cells. However, effects on gene expression, as well as secretion of cytokines and chemokines, drastically differed, as the crystalline silica induced more intense responses. Our studies indicate that toxicological testing of particulates by surveying viability and

  18. Differences in gene expression and cytokine production by crystalline vs. amorphous silica in human lung epithelial cells.

    Science.gov (United States)

    Perkins, Timothy N; Shukla, Arti; Peeters, Paul M; Steinbacher, Jeremy L; Landry, Christopher C; Lathrop, Sherrill A; Steele, Chad; Reynaert, Niki L; Wouters, Emiel F M; Mossman, Brooke T

    2012-02-02

    Exposure to respirable crystalline silica particles, as opposed to amorphous silica, is associated with lung inflammation, pulmonary fibrosis (silicosis), and potentially with lung cancer. We used Affymetrix/GeneSifter microarray analysis to determine whether gene expression profiles differed in a human bronchial epithelial cell line (BEAS 2B) exposed to cristobalite vs. amorphous silica particles at non-toxic and equal surface areas (75 and 150 × 106μm2/cm2). Bio-Plex analysis was also used to determine profiles of secreted cytokines and chemokines in response to both particles. Finally, primary human bronchial epithelial cells (NHBE) were used to comparatively assess silica particle-induced alterations in gene expression. Microarray analysis at 24 hours in BEAS 2B revealed 333 and 631 significant alterations in gene expression induced by cristobalite at low (75) and high (150 × 106μm2/cm2) amounts, respectively (p amorphous silica micro-particles at high amounts (150 × 106μm2/cm2) induced 108 significant gene changes. Bio-Plex analysis of 27 human cytokines and chemokines revealed 9 secreted mediators (p silica, but none were induced by amorphous silica. QRT-PCR revealed that cristobalite selectively up-regulated stress-related genes and cytokines (FOS, ATF3, IL6 and IL8) early and over time (2, 4, 8, and 24 h). Patterns of gene expression in NHBE cells were similar overall to BEAS 2B cells. At 75 × 106μm2/cm2, there were 339 significant alterations in gene expression induced by cristobalite and 42 by amorphous silica. Comparison of genes in response to cristobalite (75 × 106μm2/cm2) revealed 60 common, significant gene alterations in NHBE and BEAS 2B cells. Cristobalite silica, as compared to synthetic amorphous silica particles at equal surface area concentrations, had comparable effects on the viability of human bronchial epithelial cells. However, effects on gene expression, as well as secretion of cytokines and chemokines, drastically differed, as

  19. Del-1 overexpression potentiates lung cancer cell proliferation and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seung-Hwan; Kim, Dong-Young; Jing, Feifeng; Kim, Hyesoon [Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Yun, Chae-Ok [Department of Bioengineering, College of Engineering, Hanyang University, Seoul (Korea, Republic of); Han, Deok-Jong [Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Choi, Eun Young, E-mail: choieun@ulsan.ac.kr [Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2015-12-04

    Developmental endothelial locus-1 (Del-1) is an endogenous anti-inflammatory molecule that is highly expressed in the lung and the brain and limits leukocyte migration to these tissues. We previously reported that the expression of Del-1 is positively regulated by p53 in lung endothelial cells. Although several reports have implicated the altered expression of Del-1 gene in cancer patients, little is known about its role in tumor cells. We here investigated the effect of Del-1 on the features of human lung carcinoma cells. Del-1 mRNA was found to be significantly decreased in the human lung adenocarcinoma cell lines A549 (containing wild type of p53), H1299 (null for p53) and EKVX (mutant p53), compared to in human normal lung epithelial BEAS-2B cells and MRC-5 fibroblasts. The decrease of Del-1 expression was dependent on the p53 activity in the cell lines, but not on the expression of p53. Neither treatment with recombinant human Del-1 protein nor the introduction of adenovirus expressing Del-1 altered the expression of the apoptosis regulators BAX, PUMA and Bcl-2. Unexpectedly, the adenovirus-mediated overexpression of Del-1 gene into the lung carcinoma cell lines promoted proliferation and invasion of the lung carcinoma cells, as revealed by BrdU incorporation and transwell invasion assays, respectively. In addition, overexpression of the Del-1 gene enhanced features of epithelial–mesenchymal transition (EMT), such as increasing vimentin while decreasing E-cadherin in A549 cells, and increases in the level of Slug, an EMT-associated transcription regulator. Our findings demonstrated for the first time that there are deleterious effects of high levels of Del-1 in lung carcinoma cells, and suggest that Del-1 may be used as a diagnostic or prognostic marker for cancer progression, and as a novel therapeutic target for lung carcinoma. - Highlights: • Developmental Endothelial Locus-1 (Del-1) expression is downregulated in human lung cancer cells.

  20. Del-1 overexpression potentiates lung cancer cell proliferation and invasion

    International Nuclear Information System (INIS)

    Lee, Seung-Hwan; Kim, Dong-Young; Jing, Feifeng; Kim, Hyesoon; Yun, Chae-Ok; Han, Deok-Jong; Choi, Eun Young

    2015-01-01

    Developmental endothelial locus-1 (Del-1) is an endogenous anti-inflammatory molecule that is highly expressed in the lung and the brain and limits leukocyte migration to these tissues. We previously reported that the expression of Del-1 is positively regulated by p53 in lung endothelial cells. Although several reports have implicated the altered expression of Del-1 gene in cancer patients, little is known about its role in tumor cells. We here investigated the effect of Del-1 on the features of human lung carcinoma cells. Del-1 mRNA was found to be significantly decreased in the human lung adenocarcinoma cell lines A549 (containing wild type of p53), H1299 (null for p53) and EKVX (mutant p53), compared to in human normal lung epithelial BEAS-2B cells and MRC-5 fibroblasts. The decrease of Del-1 expression was dependent on the p53 activity in the cell lines, but not on the expression of p53. Neither treatment with recombinant human Del-1 protein nor the introduction of adenovirus expressing Del-1 altered the expression of the apoptosis regulators BAX, PUMA and Bcl-2. Unexpectedly, the adenovirus-mediated overexpression of Del-1 gene into the lung carcinoma cell lines promoted proliferation and invasion of the lung carcinoma cells, as revealed by BrdU incorporation and transwell invasion assays, respectively. In addition, overexpression of the Del-1 gene enhanced features of epithelial–mesenchymal transition (EMT), such as increasing vimentin while decreasing E-cadherin in A549 cells, and increases in the level of Slug, an EMT-associated transcription regulator. Our findings demonstrated for the first time that there are deleterious effects of high levels of Del-1 in lung carcinoma cells, and suggest that Del-1 may be used as a diagnostic or prognostic marker for cancer progression, and as a novel therapeutic target for lung carcinoma. - Highlights: • Developmental Endothelial Locus-1 (Del-1) expression is downregulated in human lung cancer cells.

  1. Inhibition of normal human lung fibroblast growth by beryllium.

    Science.gov (United States)

    Lehnert, N M; Gary, R K; Marrone, B L; Lehnert, B E

    2001-03-07

    Inhalation of particulate beryllium (Be) and its compounds causes chronic Be disease (CBD) in a relatively small subset ( approximately 1-6%) of exposed individuals. Hallmarks of this pulmonary disease include increases in several cell types, including lung fibroblasts, that contribute to the fibrotic component of the disorder. In this regard, enhancements in cell proliferation appear to play a fundamental role in CBD development and progression. Paradoxically, however, some existing evidence suggests that Be actually has antiproliferative effects. In order to gain further information about the effects of Be on cell growth, we: (1) assessed cell proliferation and cell cycle effects of low concentrations of Be in normal human diploid fibroblasts, and (2) investigated the molecular pathway(s) by which the cell cycle disturbing effects of Be may be mediated. Treatment of human lung and skin fibroblasts with Be added in the soluble form of BeSO(4) (0.1-100 microM) caused inhibitions of their growth in culture in a concentration-dependent manner. Such growth inhibition was found to persist, even after cells were further cultured in Be(2+)-free medium. Flow cytometric analyses of cellular DNA labeled with the DNA-binding fluorochrome DAPI revealed that Be causes a G(0)-G(1)/pre-S phase arrest. Western blot analyses indicated that the Be-induced G(0)-G(1)/pre-S phase arrest involves elevations in TP53 (p53) and the cyclin-dependent kinase inhibitor CDKN1A (p21(Waf-1,Cip1)). That Be at low concentrations inhibits the growth of normal human fibroblasts suggests the possibility of the existence of abnormal cell cycle inhibitory responses to Be in individuals who are sensitive to the metal and ultimately develop CBD.

  2. Three-Dimensional Engineered High Fidelity Normal Human Lung Tissue-Like Assemblies (TLA) as Targets for Human Respiratory Virus Infections

    Science.gov (United States)

    Goodwin, T. J.; Deatly, A. M.; Suderman, M. T.; Lin, Y.-H.; Chen, W.; Gupta, C. K.; Randolph, V. B.; Udem, S. A.

    2003-01-01

    Unlike traditional two-dimensional (2D) cell cultures, three-dimensional (3D) tissue-like assemblies (TLA) (Goodwin et aI, 1992, 1993, 2000 and Nickerson et aI. , 2001,2002) offer high organ fidelity with the potential to emulate the infective dynamics of viruses and bacteria in vivo. Thus, utilizing NASA micro gravity Rotating Wall Vessel (RWV) technology, in vitro human broncho-epithelial (HBE) TLAs were engineered to mimic in vivo tissue for study of human respiratory viruses. These 3D HBE TLAs were propagated from a human broncho-tracheal cell line with a mesenchymal component (HBTC) as the foundation matrix and either an adult human broncho-epithelial cell (BEAS-2B) or human neonatal epithelial cell (16HBE140-) as the overlying element. Resulting TLAs share several characteristic features with in vivo human respiratory epithelium including tight junctions, desmosomes and cilia (SEM, TEM). The presence of epithelium and specific lung epithelium markers furthers the contention that these HBE cells differentiate into TLAs paralleling in vivo tissues. A time course of infection of these 3D HBE TLAs with human respiratory syncytial virus (hRSV) wild type A2 strain, indicates that virus replication and virus budding are supported and manifested by increasing virus titer and detection of membrane-bound F and G glycoproteins. Infected 3D HBE TLAs remain intact for up to 12 days compared to infected 2D cultures that are destroyed in 2-3 days. Infected cells show an increased vacuolation and cellular destruction (by transmission electron microscopy) by day 9; whereas, uninfected cells remain robust and morphologically intact. Therefore, the 3D HBE TLAs mimic aspects of human respiratory epithelium providing a unique opportunity to analyze, for the first time, simulated in vivo viral infection independent of host immune response.

  3. The protective effect of dexmedetomidine on LPS-induced acute lung injury through the HMGB1-mediated TLR4/NF-κB and PI3K/Akt/mTOR pathways.

    Science.gov (United States)

    Meng, Lu; Li, Longyun; Lu, Shan; Li, Kai; Su, Zhenbo; Wang, Yunyun; Fan, Xiaodi; Li, Xuyang; Zhao, Guoqing

    2018-02-01

    The aim of present study was to evaluate the protective effects of dexmedetomidine (DEX) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and investigate its possible mechanisms mediated by HMGB1. In vivo, pulmonary pathology observation and myeloperoxidase (MPO) activity were also examined to evaluate the protective effect of DEX in the lungs. Tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in bronchoalveolar lavage fluid (BALF), serum and lung tissues LPS-induced rats were detected. The oxidative indices including superoxide dismutase (SOD), Malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) in serum were also determined. Additionally, nitric oxide (NO), TNF-α, IL-6 and IL-1β, MDA, SOD and GSH-Px in the supernatants of LPS-induced BEAS-2B cells were measured. Furthermore, we detected the protein expression of high mobility group box-1 protein (HMGB1), Toll-like receptor 4 (TLR4), myeloid differentiating factor 88 (MyD88), inhibitor of NF-κB (IκBα), p-IκBα, nuclear factor kappa-B (NF-κB), p-NF-κB, phosphatidylinositol 3'-kinase (PI3K), p-PI3K, protein kinase B (Akt), p-Akt, mammalian target of rapamycin (mTOR) and p-mTOR in LPS-induced ALI rats and LPS-induced BEAS-2B cells. Immunohistochemical and immunofluorescence analyses of HMGB1 in lung tissues or BEAS-2B cells were also conducted to evaluate the mechanisms of DEX. DEX effectively attenuated pulmonary pathology, and ameliorated the levels of MPO, SOD, MDA, GSH-Px, TNF-α, IL-6, IL-1β and NO in LPS-stimulated rats and BEAS-2B cells. Additionally, treatment with DEX inhibited the expression of HMGB1, TLR4, MyD88, p-IκB, p-NF-κB, p-PI3K, p-Akt and p-mTOR in vivo and in vitro. Immunohistochemical and immunofluorescence analyses also showed that DEX suppressed HMGB1 levels in lung sections and BEAS-2B cells. Treatment with glycyrrhizin, an inhibitor of HMGB1, confirmed that HMGB1 was involved in the mechanism of DEX on LPS-induced ALI. The

  4. Andrographolide protects against cigarette smoke-induced oxidative lung injury via augmentation of Nrf2 activity

    Science.gov (United States)

    Guan, SP; Tee, W; Ng, DSW; Chan, TK; Peh, HY; Ho, WE; Cheng, C; Mak, JC; Wong, WSF

    2013-01-01

    Background and Purpose Cigarette smoke is a major cause for chronic obstructive pulmonary disease (COPD). Andrographolide is an active biomolecule isolated from the plant Andrographis paniculata. Andrographolide has been shown to activate nuclear factor erythroid-2-related factor 2 (Nrf2), a redox-sensitive antioxidant transcription factor. As Nrf2 activity is reduced in COPD, we hypothesize that andrographolide may have therapeutic value for COPD. Experimental Approach Andrographolide was given i.p. to BALB/c mice daily 2 h before 4% cigarette smoke exposure for 1 h over five consecutive days. Bronchoalveolar lavage fluid and lungs were collected for analyses of cytokines, oxidative damage markers and antioxidant activities. BEAS-2B bronchial epithelial cells were exposed to cigarette smoke extract (CSE) and used to study the antioxidant mechanism of action of andrographolide. Key Results Andrographolide suppressed cigarette smoke-induced increases in lavage fluid cell counts; levels of IL-1β, MCP-1, IP-10 and KC; and levels of oxidative biomarkers 8-isoprostane, 8-OHdG and 3-nitrotyrosine in a dose-dependent manner. Andrographolide promoted inductions of glutathione peroxidase (GPx) and glutathione reductase (GR) activities in lungs from cigarette smoke-exposed mice. In BEAS-2B cells, andrographolide markedly increased nuclear Nrf2 accumulation, promoted binding to antioxidant response element (ARE) and total cellular glutathione level in response to CSE. Andrographolide up-regulated ARE-regulated gene targets including glutamate-cysteine ligase catalytic (GCLC) subunit, GCL modifier (GCLM) subunit, GPx, GR and heme oxygenase-1 in BEAS-2B cells in response to CSE. Conclusions Andrographolide possesses antioxidative properties against cigarette smoke-induced lung injury probably via augmentation of Nrf2 activity and may have therapeutic potential for treating COPD. PMID:23146110

  5. Trace element load in cancer and normal lung tissue

    Energy Technology Data Exchange (ETDEWEB)

    Kubala-Kukus, A. E-mail: akuku@pu.kielce.pl; Braziewicz, J.; Banas, D.; Majewska, U.; Gozdz, S.; Urbaniak, A

    1999-04-02

    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.

  6. 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

  7. Macrophage accumulation of inhaled gallium-67 citrate in normal lungs

    International Nuclear Information System (INIS)

    Kennedy, S.M.; Walker, D.C.; Belzberg, A.S.; Hogg, J.C.

    1985-01-01

    Injected 67 Ga has been used extensively to monitor inflammatory processes in the peripheral lung. The authors hypothesized that inhaled 67 Ga may be useful in marking early airway inflammation in smokers. Eight nonsmokers and eight smokers breathed a 67 Ga aerosol and imaging was performed immediately and 24 and 96 hr later. Approximately two-thirds of the initial dose remained in the lungs at 24 hr in both groups and no difference was seen between the groups. Only a very slight decrease was seen in both groups at 96 hr suggesting the gallium becomes bound to lung tissue or to cells not rapidly removed from the lungs. Autoradiography was performed on tissue from two smoke-exposed guinea pigs and two human patients undergoing resection surgery who breathed the gallium aerosol 24 hr prior to tissue removal. Silver grain accumulations were seen only over macrophages. They conclude that macrophage associated accumulation of 67 Ga occurs in healthy lungs, and that it is not feasible to use aerosolized gallium to assess airway inflammation in smokers

  8. Altered regulation of c-jun and its involvement in anchorage-independent growth of human lung cancers.

    Science.gov (United States)

    Maeno, K; Masuda, A; Yanagisawa, K; Konishi, H; Osada, H; Saito, T; Ueda, R; Takahashi, T

    2006-01-12

    The c-jun oncogene is frequently overexpressed in non-small-cell lung cancers (NSCLC), but its functional involvement in lung cancer development has not been clearly elucidated. In this study, we found that among the immediate-early serum responsible genes, exemplified by c-jun, c-fos and c-myc, induction of c-jun in a human bronchial epithelial cell line, BEAS-2B, was dependent on anchorage, in contrast to clear induction of c-fos and c-myc under both anchorage-dependent and -independent conditions. In fact, forced expression of c-jun in BEAS-2B cells significantly increased cell viability and colony formation in soft agar. Furthermore, we also found that such anchorage-dependent regulation of c-jun was lost in a significant fraction of human lung cancer cell lines. Interestingly, suppressed anchorage-independent but not anchorage-dependent growth was noted by constitutive expression of a dominant-negative c-jun mutant in a lung cancer cell line showing dysregulated and sustained c-jun expression in the absence of anchorage. These findings suggest that dysregulated c-jun expression may be involved in the acquisition of anchorage independence in the process of human lung carcinogenesis.

  9. ADAM28 is expressed by epithelial cells in human normal tissues and protects from C1q-induced cell death.

    Science.gov (United States)

    Miyamae, Yuka; Mochizuki, Satsuki; Shimoda, Masayuki; Ohara, Kentaro; Abe, Hitoshi; Yamashita, Shuji; Kazuno, Saiko; Ohtsuka, Takashi; Ochiai, Hiroki; Kitagawa, Yuko; Okada, Yasunori

    2016-05-01

    ADAM28 (disintegrin and metalloproteinase 28), which was originally reported to be lymphocyte-specific, is over-expressed by carcinoma cells and plays a key role in cell proliferation and progression in human lung and breast carcinomas. We studied ADAM28 expression in human normal tissues and examined its biological function. By using antibodies specific to ADAM28, ADAM28 was immunolocalized mainly to epithelial cells in several tissues, including epididymis, bronchus and stomach, whereas lymphocytes in lymph nodes and spleen were negligibly immunostained. RT-PCR, immunoblotting and ELISA analyses confirmed the expression in these tissues, and low or negligible expression by lymphocytes was found in the lymph node and spleen. C1q was identified as a candidate ADAM28-binding protein from a human lung cDNA library by yeast two-hybrid system, and specific binding was demonstrated by binding assays, immunoprecipitation and surface plasmon resonance. C1q treatment of normal bronchial epithelial BEAS-2B and NHBE cells, both of which showed low-level expression of ADAM28, caused apoptosis through activation of p38 and caspase-3, and cell death with autophagy through accumulation of LC3-II and autophagosomes, respectively. C1q-induced cell death was attenuated by treatment of the cells with antibodies against the C1q receptor gC1qR/p33 or cC1qR/calreticulin. Treatment of C1q with recombinant ADAM28 prior to addition to culture media reduced C1q-induced cell death, and knockdown of ADAM28 using siRNAs increased cell death. These data demonstrate that ADAM28 is expressed by epithelial cells of several normal organs, and suggest that ADAM28 plays a role in cell survival by suppression of C1q-induced cytotoxicity in bronchial epithelial cells. © 2016 Federation of European Biochemical Societies.

  10. I Vivo Characterization of Ultrasonic Backscattering from Normal and Abnormal Lungs.

    Science.gov (United States)

    Jafari, Farhad

    The primary goal of this project has been to characterize the lung tissue in its in vivo ultrasonic backscattering properties in normal human subjects, and study the changes in the lung echo characteristics under various pathological conditions. Such a characterization procedure is used to estimate the potential of ultrasound for providing useful diagnostic information about the superficial region of the lung. The results of this study may be divided into three categories: (1) This work has resulted in the ultrasonic characterization of lung tissue, in vivo, and has investigated the various statistical features of the lung echo properties in normal human subjects. The echo properties of the lungs are characterized with respect to the mean echo amplitude relative to a perfect reflector and the mean autocorrelation of normalized echo signals. (2) A theoretical model is developed to simulate the ultrasonic backscattering properties of the lung under normal and various simulated abnormal conditions. This model has been tested on various phantoms simulating the strong acoustic interactions of the lung. When applied to the lung this model has shown excellent agreement to experimental data gathered on a population of normal human subjects. By varying a few of the model parameters, the effect of changes in the lung structural parameters on the detected ultrasonic echoes is investigated. It is found that alveoli size changes of about 50 percent and concentration changes of 40 percent may produce spectral changes exceeding the variability exhibited by normal lungs. (3) Ultrasonic echoes from the lungs of 4 groups of patients were studied. The groups included patients with edema, emphysema, pneumothorax, and patients undergoing radiation therapy for treatment of lung cancer. Significant deviations from normal lung echo characteristics is observed in more than 80 percent of the patients studied. These deviations are intercompared and some qualitative associations between the

  11. CT Densitometry of the Lung in Healthy Nonsmokers with Normal Pulmonary Function

    International Nuclear Information System (INIS)

    Oh, Tack Sun; Chae, Eun Jin; Seo, Joon Beom; Jung, Young Ju; Oh, Yeon Mok; Lee, Sang Do

    2012-01-01

    To investigate the upper normal limit of low attenuation area in healthy nonsmokers. A total of 36 nonsmokers with normal pulmonary function test underwent a CT scan. Six thresholds (-980 --930 HU) on inspiration CT and two thresholds (-950 and -910 HU) on expiration CT were used for obtaining low attenuation area. The mean lung density was obtained on both inspiration CT and expiration CT. Descriptive statistics of low attenuation area and the mean lung density, evaluation of difference of low attenuation area and the mean lung density in both sex and age groups, analysis of the relationship between demographic information and CT parameters were performed. Upper normal limit for low attenuation area was 12.96% on inspiration CT (-950 HU) and 9.48% on expiration CT (-910 HU). Upper normal limit for the mean lung density was -837.58 HU on inspiration CT and 686.82 HU on expiration CT. Low attenuation area and the mean lung density showed no significant differences in both sex and age groups. Body mass index (BMI) was negatively correlated with low attenuation area on inspiration CT (-950 HU, r = -0.398, p = 0.016) and positively correlated with the mean lung density on inspiration CT (r 0.539, p = 0.001) and expiration CT (r = 0.432, p = 0.009). Age and body surface area were not correlated with low attenuation area or the mean lung density. Low attenuation area on CT densitometry of the lung could be found in healthy nonsmokers with normal pulmonary function, and showed negative association with BMI. Reference values, such as range and upper normal limit for low attenuation area in healthy subjects could be helpful in quantitative analysis and follow up of early emphysema, using CT densitometry of the lung.

  12. CT Densitometry of the Lung in Healthy Nonsmokers with Normal Pulmonary Function

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Tack Sun; Chae, Eun Jin; Seo, Joon Beom; Jung, Young Ju; Oh, Yeon Mok; Lee, Sang Do [University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of)

    2012-09-15

    To investigate the upper normal limit of low attenuation area in healthy nonsmokers. A total of 36 nonsmokers with normal pulmonary function test underwent a CT scan. Six thresholds (-980 --930 HU) on inspiration CT and two thresholds (-950 and -910 HU) on expiration CT were used for obtaining low attenuation area. The mean lung density was obtained on both inspiration CT and expiration CT. Descriptive statistics of low attenuation area and the mean lung density, evaluation of difference of low attenuation area and the mean lung density in both sex and age groups, analysis of the relationship between demographic information and CT parameters were performed. Upper normal limit for low attenuation area was 12.96% on inspiration CT (-950 HU) and 9.48% on expiration CT (-910 HU). Upper normal limit for the mean lung density was -837.58 HU on inspiration CT and 686.82 HU on expiration CT. Low attenuation area and the mean lung density showed no significant differences in both sex and age groups. Body mass index (BMI) was negatively correlated with low attenuation area on inspiration CT (-950 HU, r = -0.398, p = 0.016) and positively correlated with the mean lung density on inspiration CT (r 0.539, p = 0.001) and expiration CT (r = 0.432, p = 0.009). Age and body surface area were not correlated with low attenuation area or the mean lung density. Low attenuation area on CT densitometry of the lung could be found in healthy nonsmokers with normal pulmonary function, and showed negative association with BMI. Reference values, such as range and upper normal limit for low attenuation area in healthy subjects could be helpful in quantitative analysis and follow up of early emphysema, using CT densitometry of the lung.

  13. T2 relaxation time in MR imaging of normal and abnormal lung parenchyma

    International Nuclear Information System (INIS)

    Mayo, J.R.; McKay, A.; Mueller, N.L.

    1990-01-01

    To measure the T2 relaxation times of normal and abnormal lung parenchyma and to evaluate the influence of field strength and lung inflation on T2. Five healthy volunteers and five patients with diffuse lung disease were imaged at 0.15 and 1.5 T. Excised normal pig lung was imaged at 0.15 and 1.5 T and analyzed in a spectrometer at 2.0 T. Single-echo (Hahn) pulse sequences (TR, 2,000 msec; TE, 20, 40, 60, 80, and 100 msec) were compared with multiecho trains (Carr-Purcell-Meiboom-Gill [CPMG] at 0.15 T (TR, 2,000 msec; TE, 20-40-60... 240 msec) and 2.0 T (TR, 2,000 msec; TE, 1, 2, 3,..., 10msec). T2 relaxation times calculated from single-echo sequences showed considerable variation between 0.15 and 2.0 T. T2 also changed with lung inflation. However, the T2 measurements on CPMG sequences did not change significantly (P > .05) with field strength and were only minimally affected by lung inflation. The mean ± SD T2 values for normal lung were 99 ± 8 and for abnormal lung were 84 ± 17. Lung parenchyma T2 measurements obtained with the use of conventional single-echo pulse sequences are variable and inaccurate because of inflation and field strength dependent magnetic susceptibility effects that lead to rapid nonrecoverable dephasing. The results indicate that multiecho sequences with appropriately short echo spacings yield more reproducible determinations of T2, which are independent of field strength and less dependent on lung inflation

  14. Classification of normal and abnormal images of lung cancer

    Science.gov (United States)

    Bhatnagar, Divyesh; Tiwari, Amit Kumar; Vijayarajan, V.; Krishnamoorthy, A.

    2017-11-01

    To find the exact symptoms of lung cancer is difficult, because of the formation of the most cancers tissues, wherein large structure of tissues is intersect in a different way. This problem can be evaluated with the help of digital images. In this strategy images will be examined with basic operation of PCA Algorithm. In this paper, GLCM method is used for pre-processing of the snap shots and function extraction system and to test the level of diseases of a patient in its premature stage get to know it is regular or unusual. With the help of result stage of cancer will be evaluated. With the help of dataset and result survival rate of cancer patient can be estimated. Result is based totally on the precise and wrong arrangement of the patterns of tissues.

  15. Fetal lung development on MRI. Normal course and impairment due to premature rupture of membranes

    International Nuclear Information System (INIS)

    Kasprian, G.; Zentrum fuer Anatomie und Zellbiologie der Medizinischen Universitaet Wien; Brugger, P.C.; Helmer, H.; Langer, M.; Balassy, C.; Prayer, D.

    2006-01-01

    A well-organized interplay between many molecular factors as well as mechanical forces influence fetal lung development. At the end of this complex process a sufficiently sized and structurally mature organ should ensure the postnatal survival of the newborn. Besides prenatal ultrasonography, magnetic resonance imaging (MRI) can now be used to investigate normal and pathological human lung growth in utero. Oligohydramnios, due to premature rupture of membranes (PROM), is an important risk factor for compromised fetal lung growth. In these situations MR volumetry can be used to measure the size of the fetal lung quite accurately. Together with the evaluation of lung signal intensities on T2-weighted sequences, fetuses with pulmonary hypoplasia can be readily detected. (orig.) [de

  16. Lung function not affected by asbestos exposure in workers with normal Computed Tomography scan.

    Science.gov (United States)

    Schikowsky, Christian; Felten, Michael K; Eisenhawer, Christian; Das, Marco; Kraus, Thomas

    2017-05-01

    It has been suggested that asbestos exposure affects lung function, even in the absence of asbestos-related pulmonary interstitial or pleural changes or emphysema. We analyzed associations between well-known asbestos-related risk factors, such as individual cumulative asbestos exposure, and key lung function parameters in formerly asbestos-exposed power industry workers (N = 207) with normal CT scans. For this, we excluded participants with emphysema, fibrosis, pleural changes, or any combination of these. The lung function parameters of FVC, FEV1, DLCO/VA, and airway resistance were significantly associated with the burden of smoking, BMI and years since end of exposure (only DLCO/VA). However, they were not affected by factors directly related to amount (eg, cumulative exposure) or duration of asbestos exposure. Our results confirm the well-known correlation between lung function, smoking habits, and BMI. However, we found no significant association between lung function and asbestos exposure. © 2017 Wiley Periodicals, Inc.

  17. High-resolution computed tomography of the lungs: the borderlands of normality

    International Nuclear Information System (INIS)

    Dalal, P.U.; Hansell, D.M.

    2006-01-01

    High-resolution computed tomography (HRCT) is now widely used in the assessment of airways and diffuse lung disease. Considerable literature on pathologic correlation has increased the understanding of the signs of disease seen on HRCT. However, neither the significance of subtle individual signs nor the spectrum of HRCT appearances in healthy lungs is well documented. HRCT signs that cause diagnostic uncertainty and the spectrum of findings that exist between definite normality and definite abnormality are discussed. (orig.)

  18. Frequency and number of ultrasound lung rockets (B-lines) using a regionally based lung ultrasound examination named vet BLUE (veterinary bedside lung ultrasound exam) in dogs with radiographically normal lung findings.

    Science.gov (United States)

    Lisciandro, Gregory R; Fosgate, Geoffrey T; Fulton, Robert M

    2014-01-01

    Lung ultrasound is superior to lung auscultation and supine chest radiography for many respiratory conditions in human patients. Ultrasound diagnoses are based on easily learned patterns of sonographic findings and artifacts in standardized images. By applying the wet lung (ultrasound lung rockets or B-lines, representing interstitial edema) versus dry lung (A-lines with a glide sign) concept many respiratory conditions can be diagnosed or excluded. The ultrasound probe can be used as a visual stethoscope for the evaluation of human lungs because dry artifacts (A-lines with a glide sign) predominate over wet artifacts (ultrasound lung rockets or B-lines). However, the frequency and number of wet lung ultrasound artifacts in dogs with radiographically normal lungs is unknown. Thus, the primary objective was to determine the baseline frequency and number of ultrasound lung rockets in dogs without clinical signs of respiratory disease and with radiographically normal lung findings using an 8-view novel regionally based lung ultrasound examination called Vet BLUE. Frequency of ultrasound lung rockets were statistically compared based on signalment, body condition score, investigator, and reasons for radiography. Ten left-sided heart failure dogs were similarly enrolled. Overall frequency of ultrasound lung rockets was 11% (95% confidence interval, 6-19%) in dogs without respiratory disease versus 100% (95% confidence interval, 74-100%) in those with left-sided heart failure. The low frequency and number of ultrasound lung rockets observed in dogs without respiratory disease and with radiographically normal lungs suggests that Vet BLUE will be clinically useful for the identification of canine respiratory conditions. © 2014 American College of Veterinary Radiology.

  19. Estimation of respiratory flow by means of normal lung sound.

    Science.gov (United States)

    Schudt, Florian; Gross, Volker; Weissflog, Andreas; Mursina, Ljudmila; Koehler, Ulrich; Sohrabi, Keywan

    2014-01-01

    The respiratory flow is a good indicator of sleep-related breathing disorders. Common praxis is to use a pneumotachograph as the golden standard for flow measurement. However, it does not have to be necessarily the best possible test device for long-term condition, because the device is very uncomfortable and rarely suitable for measurement during sleep. A computer-based method to determine the respiratory flow, called ThorAKUSTIK, yielded a highly positive correlation between the calculated flow out of the tracheal breath sound and a measured flow signal. In order to avoid noise interference due to a breath-mask or a pneumotachograph, in this study we applied the ThorAKUSTIK-method to lung sound which was measured at the back of 18 subjects and investigated the correlation between the calculated flow and the measured flow by a pneumotachograph. The new method showed a highly positive correlation (r = 0.89 and 0.90). Additionally we examined the use of an accelerometer signal to distinguish between inspiration and expiration. In this case we got high correlation coefficients of r = 0.87 and 0.88 between the calculated and measured airflow as well.

  20. Positioning effects on lung ventilation in older normal subjects: a technegas study

    International Nuclear Information System (INIS)

    Krieg, S.; McCarren, B.; Alison, J.; Cowell, S.F.; Leiper, C.; Bankstown-Lidcombe Hospital, Sydney, NSW; El Zein, H.

    2002-01-01

    Full text: While the effects of positioning on the distribution of ventilation in the lungs of younger subjects has been relatively well investigated, this is not so in the older age group. Known age-associated changes in the respiratory system are proposed to alter the distribution of ventilation in the lungs of older people. The aim of the present study was therefore to determine the effects of positioning on the distribution of ventilation in the lungs of older normal subjects. The distribution of ventilation in upright sitting and right side lying was measured in ten subjects using Technegas lung ventilation during tidal breathing. In the upright sitting position ventilation was preferentially distributed to the middle and basal regions (dependent regions). Right side lying ventilation was preferentially distributed to the right lung (dependent region). These results suggest that preferential distribution of ventilation to the dependent lung regions in older subjects is mainly due to the gravity-dependent gradient in pleural pressure. It is proposed that this distribution may partly result from loss of elasticity in the lungs with ageing. Predominantly, the distribution of ventilation in the lungs of older normal subjects in our study is similar to that previously described in younger subjects (Amis et al., 1984, Kaneko et al, 1966, Milic-Emili et al, 1966. This suggests that a similar pleural pressure gradient may exist in the lungs of older and younger subjects. This is an important implication as the majority of patients that physiotherapists treat with cardiopulmonary dysfunction are in the older age group. Further research is required to determine the effects of positioning on the distribution of ventilation in older patients with cardiopulmonary dysfunction to enable direct clinical implications to be made. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc

  1. Automatic Classification of Normal and Cancer Lung CT Images Using Multiscale AM-FM Features

    Directory of Open Access Journals (Sweden)

    Eman Magdy

    2015-01-01

    Full Text Available Computer-aided diagnostic (CAD systems provide fast and reliable diagnosis for medical images. In this paper, CAD system is proposed to analyze and automatically segment the lungs and classify each lung into normal or cancer. Using 70 different patients’ lung CT dataset, Wiener filtering on the original CT images is applied firstly as a preprocessing step. Secondly, we combine histogram analysis with thresholding and morphological operations to segment the lung regions and extract each lung separately. Amplitude-Modulation Frequency-Modulation (AM-FM method thirdly, has been used to extract features for ROIs. Then, the significant AM-FM features have been selected using Partial Least Squares Regression (PLSR for classification step. Finally, K-nearest neighbour (KNN, support vector machine (SVM, naïve Bayes, and linear classifiers have been used with the selected AM-FM features. The performance of each classifier in terms of accuracy, sensitivity, and specificity is evaluated. The results indicate that our proposed CAD system succeeded to differentiate between normal and cancer lungs and achieved 95% accuracy in case of the linear classifier.

  2. Automatic Classification of Normal and Cancer Lung CT Images Using Multiscale AM-FM Features

    Science.gov (United States)

    Zayed, Nourhan; Fakhr, Mahmoud

    2015-01-01

    Computer-aided diagnostic (CAD) systems provide fast and reliable diagnosis for medical images. In this paper, CAD system is proposed to analyze and automatically segment the lungs and classify each lung into normal or cancer. Using 70 different patients' lung CT dataset, Wiener filtering on the original CT images is applied firstly as a preprocessing step. Secondly, we combine histogram analysis with thresholding and morphological operations to segment the lung regions and extract each lung separately. Amplitude-Modulation Frequency-Modulation (AM-FM) method thirdly, has been used to extract features for ROIs. Then, the significant AM-FM features have been selected using Partial Least Squares Regression (PLSR) for classification step. Finally, K-nearest neighbour (KNN), support vector machine (SVM), naïve Bayes, and linear classifiers have been used with the selected AM-FM features. The performance of each classifier in terms of accuracy, sensitivity, and specificity is evaluated. The results indicate that our proposed CAD system succeeded to differentiate between normal and cancer lungs and achieved 95% accuracy in case of the linear classifier. PMID:26451137

  3. Genomic variations in the counterpart normal controls of lung squamous cell carcinomas.

    Science.gov (United States)

    Qu, Liwei; Zhou, Bo; Wang, Guizhen; Zhou, Guangbiao

    2017-11-28

    Lung squamous cell carcinoma (LUSC) causes approximately 400 000 deaths each year worldwide. The occurrence of LUSC is attributed to exposure to cigarette smoke, which induces the development of numerous genomic abnormalities. However, few studies have investigated the genomic variations that occur only in normal tissues that have been similarly exposed to tobacco smoke as tumor tissues. In this study, we sequenced the whole genomes of three normal lung tissue samples and their paired adjacent squamous cell carcinomas.We then called genomic variations specific to the normal lung tissues through filtering the genomic sequence of the normal lung tissues against that of the paired tumors, the reference human genome, the dbSNP138 common germline variants, and the variations derived from sequencing artifacts. To expand these observations, the whole exome sequences of 478 counterpart normal controls (CNCs) and paired LUSCs of The Cancer Genome Atlas (TCGA) dataset were analyzed. Sixteen genomic variations were called in the three normal lung tissues. These variations were confirmed by Sanger capillary sequencing. A mean of 0.5661 exonic variations/Mb and 7.7887 altered genes per sample were identified in the CNC genome sequences of TCGA. In these CNCs, C:G→T:A transitions, which are the genomic signatures of tobacco carcinogen N-methyl-N-nitro-N-nitrosoguanidine, were the predominant nucleotide changes. Twenty five genes in CNCs had a variation rate that exceeded 2%, including ARSD (18.62%), MUC4 (8.79%), and RBMX (7.11%). CNC variations in CTAGE5 and USP17L7 were associated with the poor prognosis of patients with LUSC. Our results uncovered previously unreported genomic variations in CNCs, rather than LUSCs, that may be involved in the development of LUSC.

  4. Estimation of fetal lung development using quantitative analysis of ultrasonographic images in normal canine pregnancy.

    Science.gov (United States)

    Banzato, T; Zovi, G; Milani, C

    2017-07-01

    We investigated the quantitative analysis of sonographic images to predict fetal lung maturity of the canine foetus in normal pregnancy. Twelve bitches were recruited in the present study. Serial ultrasonographic exams were performed at three pre-determined time periods corresponding to the pseudoglandular (40-48 days of pregnancy), canalicular (49-56 days of pregnancy) and saccular phase (57-63 days of pregnancy) of lung development. Mean grey level (MGL) and the standard deviation of the histogram (SDH) of fetal lung and liver sonographic images were measured with dedicated software. The lung-to-liver ratio (LLR) for both parameters was also calculated. Measurements were taken on the two caudal-most foetuses and then averaged. SDH did not show any statistically significant difference between the three time periods in the lungs or in the liver. MGL measured in the lungs significantly increased in the first period and reached a plateau during the last two periods. Liver echogenicity was constant during the first two periods and significantly increased during the last week of gestation. The LLR of MGL significantly decreased during the last week of pregnancy. The LLR was a very good test to detect fetal lung maturity (area under the receiver operator curve (AUROC) = 0.875); using a cut-off value of LLR < 1.541, sensitivity was 83.33% and specificity was 83.33%, positive likelihood ratio = 5. LLR of MGL is an accurate test to estimate lung development in normal canine pregnancies. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. [Basic lung ultrasound. Part 1. Normal lung ultrasound and diseases of the chest wall and the pleura].

    Science.gov (United States)

    de la Quintana Gordon, F B; Nacarino Alcorta, B

    2015-01-01

    Lung ultrasound has become part of the diagnostic armamentarium in Resuscitation and Recovery Units with an enormous potential due to its many advantages: capacity to diagnose more precisely than conventional radiology, earlier diagnosis, convenience due to being able to performed at the bedside, possibility of being performed by one person, absence of ionising radiation, and, due to its dynamic character, is capable of transforming into physiological processes that were once static images. However, lung ultrasound also has its limitations and has a learning curve. The aim of this review is to provide sufficient information that may help the specialist starting in this field to approach the technique with good possibilities of success. To do this, the review is structured into two parts. In the first, the normal ultrasound of the chest wall is presented, as well as the pleura, diaphragm, and lung parenchyma, and the most important pathologies of the chest wall (rib fractures and hematomas), the pleura (pleural effusion and its different types, and pneumothorax), and the diaphragm (hypokinesia and paralysis). In the second part, parenchymal diseases will be approached and will include, atelectasis, pneumonia and abscess, lung oedema, respiratory distress, and pulmonary thromboembolism. Copyright © 2014 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. Cigarette smoke inhibits BAFF expression and mucosal immunoglobulin A responses in the lung during influenza virus infection.

    Science.gov (United States)

    Wang, Jianmiao; Li, Qinghai; Xie, Jungang; Xu, Yongjian

    2015-03-14

    It is incompletely understood how cigarette smoke (CS) exposure affects lung mucosal immune responses during viral respiratory infections. B cell activating factor belonging to the tumor necrosis factor family (BAFF) plays an important role in the induction of secretory immunoglobulin A (S-IgA) which is the main effector of the mucosal immune system. We therefore investigated the effects of CS exposure on BAFF expression and S-IgA responses in the lung during influenza virus infection. Mice were exposed to CS and/or infected with influenza virus. Bronchoalveolar lavage fluid and lung compartments were analyzed for BAFF expression, influenza-specific S-IgA level and histological changes. Lung B cells were isolated and the activation-induced cytidine deaminase (Aicda) expression was determined. BEAS-2B cells were treated with CS extract (CSE), influenza virus, interferon beta or N-acetylcysteine and BAFF expression was measured. CS inhibited BAFF expression in the lung, particularly after long-term exposure. BAFF and S-IgA levels were increased during influenza virus infection. Three-month CS exposure prior to influenza virus infection resulted in reduced BAFF and S-IgA levels in the lung as well as augmented pulmonary inflammation on day 7 after infection. Prior CS exposure also caused decreased Aicda expression in lung B cells during infection. Neutralization of BAFF in the lung resulted in reduced S-IgA levels during influenza virus infection. CSE inhibited virus-mediated BAFF induction in a dose-dependent manner in BEAS-2B cells, while this inhibition of BAFF by CSE was prevented by pretreatment with the antioxidant N-acetylcysteine. Our findings indicate that CS may hinder early mucosal IgA responses in the lung during influenza virus infection through oxidative inhibition of BAFF, which might contribute to the increased incidence and severity of viral infections in smokers.

  7. Imaging and Pathological Features of Percutaneous Cryosurgery on Normal Lung Evaluated in a Porcine Model

    Directory of Open Access Journals (Sweden)

    Lizhi NIU

    2010-07-01

    Full Text Available Background and objective Lung cancer is one of the most commonly occurring malignancies and frequent causes of death in the world. Cryoablation is a safe and alternative treatment for unresectable lung cancer. Due to the lung being gas-containing organ and different from solid organs such as liver and pancreas, it is difficult to achieve the freezing range of beyond the tumor edge 1 cm safety border. The aim of this study is to examine the effect of different numbers of freeze cycles on the effectiveness of cryoablation on normal lung tissue and to create an operation guideline that gives the best effect. Methods Six healthy Tibetan miniature pigs were given a CT scan and histological investigation after percutaneous cryosurgery. Cryoablation was performed as 2 cycles of 10 min of active freezing in the left lung; each freeze followed by a 5 min thaw. In the right lung, we performed the same 2 cycles of 5 min of freezing followed by 5 min of thawing. However, for the right lung, we included a third cycle of consisting of 10 min of freezing followed by 5 min of thawing. Three cryoprobes were inserted into the left lung and three cryoprobes in the right lung per animal, one in the upper and two in the lower lobe, so as to be well away from each other. Comparison under the same experimental condition was necessary. During the experiment, observations were made regarding the imaging change of ice-ball. The lungs were removed postoperatively at 3 intervals: 4 h, 3 d of postoperation and 7 d of postoperation, respectively, to view microscopic and pathological change. Results The ice-ball grew gradually in relation to the increase in time, and the increase in number of cycles. The size of the cryolesion (hypothesis necrotic area in specimens, over time, became larger in size than the size of the ice-ball during operation, regardless of whether 2 or 3 freeze-thaw cycles were performed. The area of necrosis was gradually increased over the course of time

  8. Pulmonary veins in the normal lung and pulmonary hypertension due to left heart disease

    Science.gov (United States)

    Hunt, James M.; Bethea, Brian; Liu, Xiang; Gandjeva, Aneta; Mammen, Pradeep P. A.; Stacher, Elvira; Gandjeva, Marina R.; Parish, Elisabeth; Perez, Mario; Smith, Lynelle; Graham, Brian B.; Kuebler, Wolfgang M.

    2013-01-01

    Despite the importance of pulmonary veins in normal lung physiology and the pathobiology of pulmonary hypertension with left heart disease (PH-LHD), pulmonary veins remain largely understudied. Difficult to identify histologically, lung venous endothelium or smooth muscle cells display no unique characteristic functional and structural markers that distinguish them from pulmonary arteries. To address these challenges, we undertook a search for unique molecular markers in pulmonary veins. In addition, we addressed the expression pattern of a candidate molecular marker and analyzed the structural pattern of vascular remodeling of pulmonary veins in a rodent model of PH-LHD and in lung tissue of patients with PH-LHD obtained at time of placement on a left ventricular assist device. We detected urokinase plasminogen activator receptor (uPAR) expression preferentially in normal pulmonary veins of mice, rats, and human lungs. Expression of uPAR remained elevated in pulmonary veins of rats with PH-LHD; however, we also detected induction of uPAR expression in remodeled pulmonary arteries. These findings were validated in lungs of patients with PH-LHD. In selected patients with sequential lung biopsy at the time of removal of the left ventricular assist device, we present early data suggesting improvement in pulmonary hemodynamics and venous remodeling, indicating potential regression of venous remodeling in response to assist device treatment. Our data indicate that remodeling of pulmonary veins is an integral part of PH-LHD and that pulmonary veins share some key features present in remodeled yet not normotensive pulmonary arteries. PMID:24039255

  9. Pulmonary veins in the normal lung and pulmonary hypertension due to left heart disease.

    Science.gov (United States)

    Hunt, James M; Bethea, Brian; Liu, Xiang; Gandjeva, Aneta; Mammen, Pradeep P A; Stacher, Elvira; Gandjeva, Marina R; Parish, Elisabeth; Perez, Mario; Smith, Lynelle; Graham, Brian B; Kuebler, Wolfgang M; Tuder, Rubin M

    2013-11-15

    Despite the importance of pulmonary veins in normal lung physiology and the pathobiology of pulmonary hypertension with left heart disease (PH-LHD), pulmonary veins remain largely understudied. Difficult to identify histologically, lung venous endothelium or smooth muscle cells display no unique characteristic functional and structural markers that distinguish them from pulmonary arteries. To address these challenges, we undertook a search for unique molecular markers in pulmonary veins. In addition, we addressed the expression pattern of a candidate molecular marker and analyzed the structural pattern of vascular remodeling of pulmonary veins in a rodent model of PH-LHD and in lung tissue of patients with PH-LHD obtained at time of placement on a left ventricular assist device. We detected urokinase plasminogen activator receptor (uPAR) expression preferentially in normal pulmonary veins of mice, rats, and human lungs. Expression of uPAR remained elevated in pulmonary veins of rats with PH-LHD; however, we also detected induction of uPAR expression in remodeled pulmonary arteries. These findings were validated in lungs of patients with PH-LHD. In selected patients with sequential lung biopsy at the time of removal of the left ventricular assist device, we present early data suggesting improvement in pulmonary hemodynamics and venous remodeling, indicating potential regression of venous remodeling in response to assist device treatment. Our data indicate that remodeling of pulmonary veins is an integral part of PH-LHD and that pulmonary veins share some key features present in remodeled yet not normotensive pulmonary arteries.

  10. Cloning and expression of guinea pig TIMP-2. Expression in normal and hyperoxic lung injury.

    Science.gov (United States)

    Meléndez, J; Maldonado, V; Bingle, C D; Selman, M; Pardo, A

    2000-04-01

    Tissue inhibitors of metalloproteinases (TIMPs) play a key regulatory role in extracellular matrix remodeling. By screening a lung library with a human TIMP-2 cDNA probe, we have isolated the cDNA corresponding to guinea pig TIMP-2. The 3.5-kb cDNA presents an open reading frame that predicts a protein of 220 amino acids showing 97.2, 96.8, 97.2, and 77.3% overall identity with human, mouse, rat, and chicken TIMP-2, respectively. Guinea pig TIMP-2 cDNA was expressed in CHO-K1 cells, showing a protein with the expected molecular weight and activity. Northern blot analysis revealed TIMP-2 expression in brain, kidney, intestine, spleen, heart, and lung. Transforming growth factor-beta downregulated TIMP-2 mRNA in guinea pig lung fibroblasts, whereas a variety of other stimuli showed no effect. In normal and hyperoxia-exposed lungs, TIMP-2 mRNA was mainly localized in alveolar macrophages and epithelial cells. No quantitative differences were found by Northern blot. These results confirm that TIMP-2 is highly conserved in mammals and largely expressed in lungs.

  11. [Determination of volatile organic compounds in lung cancer cell lines and lung cancer tissue].

    Science.gov (United States)

    Hu, Yan-jie; Qiu, Yuan-hua; Chen, En-guo; Ying, Ke-jing; Yu, Jin; Wang, Ping

    2010-05-01

    To identify the volatile organic compounds (VOCs) in lung cancer tissue and lung cancer cell lines. The lung cancer tissue samples from 18 patients were cultured and 4 lung cell lines (A549, NCI-H446, SK-MES-1, BEAS-2B) were also included in the study. Air samples in the headspace of culture flasks were analyzed for VOCs with solid-phase micro-extraction and gas chromatography-mass spectroscopy technique (SPME-GC/MS). Two kinds of VOCs 2-pentadecanone and nonadecane were detected in lung cancer cell lines A549, NCI-H446 and SK-MES-1. The concentration of 2-pentadecanone were (1.382 + or -0.171) X 10(-5)mg/L, (1.681 + or - 0.190) X 10(-4)mg/L and (2.835 + or - 0.401) X 10(-6)mg/L, respectively; the concentrations of nonadecane were (8.382 + or - 0.606 ) X 10(-6)mg/L, (1.845 + or - 0.130) X 10(-5)mg/L and (6.220 + or - 0.362) X 10(-6)mg/L), respectively. The eicosane was detected in A549 and NCI-H446 with the concentration of (8.313 + or - 1.130) X 10(-6)mg/L and (1.020 + or - 0.141) X 10(-5)mg/L), respectively. All the 3 VOCs were not detected in cell line BEAS-2B. The concentrations of 12 VOCs including decane, 2- pentadecanone, nonadecane and eicosane were high in 18 lung cancer tissue samples; the concentrations of 2-pentadecanone were 5.421 X 10(-6)mg/L-3.621 X 10(-5)mg/L,those of nonadecane were 5.805 X 10(-6)mg/L-1.830 X 10(-5)mg/L, those of eicosane were 2.730 X 10(-6)mg/L-2.343 X 10(-5)mg/L. There were no differences of VOCs levels among patients with different cancer differentiation (P>0.05). The concentration of eicosane in the non-squamous carcinoma was higher than that in squamous carcinoma, the same results were confirmed in the lung cancer cell lines. This study has identified VOCs produced by lung cancer tissue, which may support to use breath test as a complementary noninvasive diagnostic method for lung cancer.

  12. Effects of acupuncture on the gene expression profile of lung tissue from normal rats.

    Science.gov (United States)

    Yin, Lei-Miao; Wang, Yu; Wang, Yan; Xu, Yu-Dong; Liu, Yan-Yan; Jin, Wei-Rong; Zhang, Qing-Hua; Yang, Yong-Qing

    2012-08-01

    Acupuncture has been demonstrated to be an effective treatment for various diseases. However, little attention has been paid to its physiological influences, especially on the changes in protein and mRNA levels following acupuncture treatment under normal conditions. In this study, we investigated the gene expression profile of lung tissue from acupuncture-treated normal rats and attempted to characterize the underlying mechanisms of the changes in expression. Three common acupoints, Dazhui (GV14), fengmen (BL12) and feishu (BL13) were selected for analysis, and 2 serial analyses of gene expression (SAGE) tag libraries of the lung tissues that were derived from the normal and acupuncture-treated rats were established. Bioinformatic analyses were carried out using the functional annotation tools of the database for annotation, visualization and integrated discovery (DAVID), the gene ontology (GO) Tree Machine and the Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis. In total, 144 tags were differentially expressed (PSAGE libraries. Our results show that the essential effects of acupuncture on normal rats include the regulation of macromolecular biosynthesis, transportation and metabolism. Cellular biosynthesis and cellular lipid metabolism are the common biological processes that occur in response to acupuncture under normal and morbid conditions, which may be the general physiological effects of acupuncture.

  13. A study of radiographic determination of the total lung capacity in the normal Koreans school children

    International Nuclear Information System (INIS)

    Kim, Hyo Leen

    1973-01-01

    Determination of the total lung capacity (TLC) has been widely used in the evaluation of the pulmonary function. The measurements and calculations of the total lung capacity by radiographic method is a relatively simple procedure by which physicians can obtain data regarding the total lung capacity. The total lung capacity was measured and calculated by radiographic method in 270 cases of normal school children, 168 males and 102 females. The following results were obtained. 1. The value of TLC in male was larger than that in female in the same age, height and weight group. The mean value of TLC in female was 86.7% of that in male. 2. TLC tended to increase as height increased, the correlation coefficient (r) being 0.81 with standard deviation of ± 871 ml in male and ± 727 ml in female and it had an approximation to the value of 1 Ht 3 in male and 0.8 Ht 3 in female. 3. The TLC tended to increase slightly as weight increased, the correlation coefficient (r) being 0.84 with standard deviation of ± 871 ml male and ± 727 ml in female. 4. Measurement of roentgenograms as regards TLC determination is relatively simple, rapid and accurate

  14. An experimental randomized study of six different ventilatory modes in a piglet model with normal lungs

    DEFF Research Database (Denmark)

    Nielsen, J B; Sjöstrand, U H; Henneberg, S W

    1991-01-01

    A randomized study of 6 ventilatory modes was made in 7 piglets with normal lungs. Using a Servo HFV 970 (prototype system) and a Servo ventilator 900 C the ventilatory modes examined were as follows: SV-20V, i.e. volume-controlled intermittent positive-pressure ventilation (IPPV); SV-20VIosc, i...... ventilatory modes. Also the mean airway pressures were lower with the HFV modes 8-9 cm H2O compared to 11-14 cm H2O for the other modes. The gas distribution was evaluated by N2 wash-out and a modified lung clearance index. All modes showed N2 wash-out according to a two-compartment model. The SV-20P mode had...

  15. ATP-binding cassette (ABC transporters in normal and pathological lung

    Directory of Open Access Journals (Sweden)

    Timmer-Bosscha Hetty

    2005-06-01

    Full Text Available Abstract ATP-binding cassette (ABC transporters are a family of transmembrane proteins that can transport a wide variety of substrates across biological membranes in an energy-dependent manner. Many ABC transporters such as P-glycoprotein (P-gp, multidrug resistance-associated protein 1 (MRP1 and breast cancer resistance protein (BCRP are highly expressed in bronchial epithelium. This review aims to give new insights in the possible functions of ABC molecules in the lung in view of their expression in different cell types. Furthermore, their role in protection against noxious compounds, e.g. air pollutants and cigarette smoke components, will be discussed as well as the (malfunction in normal and pathological lung. Several pulmonary drugs are substrates for ABC transporters and therefore, the delivery of these drugs to the site of action may be highly dependent on the presence and activity of many ABC transporters in several cell types. Three ABC transporters are known to play an important role in lung functioning. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR gene can cause cystic fibrosis, and mutations in ABCA1 and ABCA3 are responsible for respectively Tangier disease and fatal surfactant deficiency. The role of altered function of ABC transporters in highly prevalent pulmonary diseases such as asthma or chronic obstructive pulmonary disease (COPD have hardly been investigated so far. We especially focused on polymorphisms, knock-out mice models and in vitro results of pulmonary research. Insight in the function of ABC transporters in the lung may open new ways to facilitate treatment of lung diseases.

  16. Physico-chemical properties based differential toxicity of graphene oxide/reduced graphene oxide in human lung cells mediated through oxidative stress

    Science.gov (United States)

    Mittal, Sandeep; Kumar, Veeresh; Dhiman, Nitesh; Chauhan, Lalit Kumar Singh; Pasricha, Renu; Pandey, Alok Kumar

    2016-12-01

    Goraphene derivatives (GD) are currently being evaluated for technological and biomedical applications owing to their unique physico-chemical properties over other carbon allotrope such as carbon nanotubes (CNTs). But, the possible association of their properties with underlying in vitro effects have not fully examined. Here, we assessed the comparative interaction of three GD - graphene oxide (GO), thermally reduced GO (TRGO) and chemically reduced GO (CRGO), which significantly differ in their lateral size and functional groups density, with phenotypically different human lung cells; bronchial epithelial cells (BEAS-2B) and alveolar epithelial cells (A549). The cellular studies demonstrate that GD significantly ineternalize and induce oxidative stress mediated cytotoxicity in both cells. The toxicity intensity was in line with the reduced lateral size and increased functional groups revealed more toxicity potential of TRGO and GO respectively. Further, A549 cells showed more susceptibility than BEAS-2B which reflected cell type dependent differential cellular response. Molecular studies revealed that GD induced differential cell death mechanism which was efficiently prevented by their respective inhibitors. This is prior study to the best of our knowledge involving TRGO for its safety evaluation which provided invaluable information and new opportunities for GD based biomedical applications.

  17. Whole exome sequencing identifies driver mutations in asymptomatic computed tomography-detected lung cancers with normal karyotype.

    Science.gov (United States)

    Belloni, Elena; Veronesi, Giulia; Rotta, Luca; Volorio, Sara; Sardella, Domenico; Bernard, Loris; Pece, Salvatore; Di Fiore, Pier Paolo; Fumagalli, Caterina; Barberis, Massimo; Spaggiari, Lorenzo; Pelicci, Pier Giuseppe; Riva, Laura

    2015-04-01

    The efficacy of curative surgery for lung cancer could be largely improved by non-invasive screening programs, which can detect the disease at early stages. We previously showed that 18% of screening-identified lung cancers demonstrate a normal karyotype and, following high-density genome scanning, can be subdivided into samples with 1) numerous; 2) none; and 3) few copy number alterations. Whole exome sequencing was applied to the two normal karyotype, screening-detected lung cancers, constituting group 2, as well as normal controls. We identified mutations in both tumors, including KEAP1 (commonly mutated in lung cancers) in one, and TP53, PMS1, and MSH3 (well-characterized DNA-repair genes) in the other. The two normal karyotype screening-detected lung tumors displayed a typical lung cancer mutational profile that only next generation sequencing could reveal, which offered an additional contribution to the over-diagnosis bias concept hypothesized within lung cancer screening programs. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Normal overall leakiness of microvasculature for albumin in patients with chronic obstructive lung disease (COLD).

    Science.gov (United States)

    Henriksen, J H; Kok-Jensen, A

    1984-04-01

    The overall extravasation rate of albumin, TER (i.e. the fraction of the intravascular albumin mass (IVM) passing into, and during steady state returning from, the extravascular space per unit time) was determined from the disappearance of i.v. injected radioiodinated serum albumin in seven patients with severe chronic obstructive lung disease (COLD) and in seven normal controls. Arterial oxygen tension in patients with COLD was median 60 mmHg (range 47-80, normal greater than 75 mmHg), vital capacity was on the average 55% of expected normal value (median 1.80 litre, range 1.45-1.95), and forced expired volume in first sec was decreased to 21% of expected normal value (median 0.55 litre, range 0.40-0.70). Right-heart catheterization revealed pulmonary hypertension in all but one patient. TER in patients with COLD was median 6.1% IVM/h (range 3.5-10.1) as compared to that of normal controls 6.0% IVM/h (range 4.3-7.4), indicating that no significant change in microvascular leakiness to albumin could be found in patients with COLD. Thus, the results bring no support to a generally increased microvascular permeability to proteins in patients with COLD.

  19. Normal overall leakiness of microvasculature for albumin in patients with chronic obstructive lung disease (COLD)

    DEFF Research Database (Denmark)

    Kok-Jensen, A; Henriksen, Jens Henrik Sahl

    1984-01-01

    The overall extravasation rate of albumin, TER (i.e. the fraction of the intravascular albumin mass (IVM) passing into, and during steady state returning from, the extravascular space per unit time) was determined from the disappearance of i.v. injected radioiodinated serum albumin in seven...... patients with severe chronic obstructive lung disease (COLD) and in seven normal controls. Arterial oxygen tension in patients with COLD was median 60 mmHg (range 47-80, normal greater than 75 mmHg), vital capacity was on the average 55% of expected normal value (median 1.80 litre, range 1.......45-1.95), and forced expired volume in first sec was decreased to 21% of expected normal value (median 0.55 litre, range 0.40-0.70). Right-heart catheterization revealed pulmonary hypertension in all but one patient. TER in patients with COLD was median 6.1% IVM/h (range 3.5-10.1) as compared to that of normal...

  20. Detection of Apoptosis and Necrosis in Normal Human Lung Cells Using 1H NMR Spectroscopy

    Science.gov (United States)

    Shih, Chwen-Ming; Ko, Wun-Chang; Yang, Liang-Yo; Lin, Chien-Ju; Wu, Jui-Sheng; Lo, Tsui-Yun; Wang, Shwu-Huey; Chen, Chien-Tsu

    2005-05-01

    This study aimed to detect apoptosis and necrosis in MRC-5, a normal human lung cell line, by using noninvasive proton nuclear magnetic resonance (1H NMR). Live MRC-5 cells were processed first for 1H NMR spectroscopy; subsequently their types and the percentage of cell death were assessed on a flow cytometer. Cadmium (Cd) and mercury (Hg) induced apoptosis and necrosis in MRC-5 cells, respectively, as revealed by phosphatidylserine externalization on a flow cytometer. The spectral intensity ratio of methylene (CH2) resonance (at 1.3 ppm) to methyl (CH3) resonance (at 0.9 ppm) was directly proportional to the percentage of apoptosis and strongly and positively correlated with PI staining after Cd treatment (r2 = 0.9868, P In contrast, this ratio only increased slightly within 2-h Hg treatment, and longer Hg exposure failed to produce further increase. Following 2-h Hg exposure, the spectral intensity of choline resonance (at 3.2 ppm) was abolished, but this phenomenon was absent in Cd-induced apoptosis. These findings together demonstrate that 1H NMR is a novel tool with a quantitative potential to distinguish apoptosis from necrosis as early as the onset of cell death in normal human lung cells.

  1. A lung cancer risk classifier comprising genome maintenance genes measured in normal bronchial epithelial cells.

    Science.gov (United States)

    Yeo, Jiyoun; Crawford, Erin L; Zhang, Xiaolu; Khuder, Sadik; Chen, Tian; Levin, Albert; Blomquist, Thomas M; Willey, James C

    2017-05-02

    Annual low dose CT (LDCT) screening of individuals at high demographic risk reduces lung cancer mortality by more than 20%. However, subjects selected for screening based on demographic criteria typically have less than a 10% lifetime risk for lung cancer. Thus, there is need for a biomarker that better stratifies subjects for LDCT screening. Toward this goal, we previously reported a lung cancer risk test (LCRT) biomarker comprising 14 genome-maintenance (GM) pathway genes measured in normal bronchial epithelial cells (NBEC) that accurately classified cancer (CA) from non-cancer (NC) subjects. The primary goal of the studies reported here was to optimize the LCRT biomarker for high specificity and ease of clinical implementation. Targeted competitive multiplex PCR amplicon libraries were prepared for next generation sequencing (NGS) analysis of transcript abundance at 68 sites among 33 GM target genes in NBEC specimens collected from a retrospective cohort of 120 subjects, including 61 CA cases and 59 NC controls. Genes were selected for analysis based on contribution to the previously reported LCRT biomarker and/or prior evidence for association with lung cancer risk. Linear discriminant analysis was used to identify the most accurate classifier suitable to stratify subjects for screening. After cross-validation, a model comprising expression values from 12 genes (CDKN1A, E2F1, ERCC1, ERCC4, ERCC5, GPX1, GSTP1, KEAP1, RB1, TP53, TP63, and XRCC1) and demographic factors age, gender, and pack-years smoking, had Receiver Operator Characteristic area under the curve (ROC AUC) of 0.975 (95% CI: 0.96-0.99). The overall classification accuracy was 93% (95% CI 88%-98%) with sensitivity 93.1%, specificity 92.9%, positive predictive value 93.1% and negative predictive value 93%. The ROC AUC for this classifier was significantly better (p < 0.0001) than the best model comprising demographic features alone. The LCRT biomarker reported here displayed high accuracy and ease

  2. Dynamic Gd-DTPA enhanced breath-hold 1.5 t MRI of normal lungs and patients with interstitial lung disease and pulmonary nodules: preliminary results

    International Nuclear Information System (INIS)

    Semelka, R.C.; Maycher, B.; Shoenut, J.P.; Kroeker, R.; Griffin, P.; Lertzman, M.

    1992-01-01

    A FLASH technique was used, which encompassed the entire thorax in the transverse plane, before and after dynamic intravenous injection of godalinium DTPA (Gd-DTPA) to study 7 patients with normal lungs, 12 patients with interstitial lung disease (ILD), and 11 patients with pulmonary nodules. Comparative CT studies were obtained within 2 weeks of the MRI study in the patients with lung disease. Quantitative signal intensity (SI) measurements were performed. Qualitative evaluation of lung parenchyma was determined in a prospective blinded fashion, and in the normal group comparison was made with the CT images. In normal patients, SI of lung parenchyma increased by 7.7±1.3%. On precontrast images, second-order pulmonary branchings were visible while post-contrast, fifth- to sixth-order branches were apparent. In patients with ILD, interstitial changes enhanced to a variable extent, increases in SI ranging from minimal (49.9%) to substantial (308.4%). Detection of pulmonary nodules improved following contrast injection. The minimum lesion size detectable decreased from 8 mm precontrast to 5 mm post-contrast. Percentage contrast enhancement was greater for malignant nodules (124.2±79.7%) than benign nodules (5.8±4.7%) (p<0.01). (orig.)

  3. Functional and histological assessment of the radiobiology of normal rat lung in BNCT

    International Nuclear Information System (INIS)

    Kiger, J.L.; Riley, K.J.; Binns, P.J.; Harling, O.K.; Coderre, J.A.; Kiger, W.S. III; Patel, H.

    2006-01-01

    This study investigated the radiobiology and sensitivity of the normal rat lung to Boron Neutron Capture Therapy (BNCT) radiation. Rat thorax irradiations were carried out with x-rays or with neutrons in the presence or absence of p-boronophenylalanine (BPA). Lung damage were assessed functionally with breathing rate measurement up to 180 days after irradiation and then histologically. Breathing rates 20% (∼3 σ) above the control group (sham-irradiated rats) mean were considered as positive responses to lung radiation damage. Though most responding animals demonstrated radiation induced pneumonitis (≤110 days) as well as pulmonary fibrosis (>110 days), some animals receiving neutrons plus BPA showed only the latter. The breathing rate dose response data were fit using probit analysis. The ED 50 values measured for x-rays, neutron beam only, and neutrons plus BPA were 11.5±0.4 Gy, 9.2±0.5 Gy, and 6.7±0.4 Gy, respectively. The biological weighting factors for the neutron beam (n+γ), the thermal neutron dose component, and the 10 B dose component were determined to be 1.2±0.1, 2.2±0.4, and 2.3±0.3, respectively. The histological dose response curves were linear. Consistent with the functional assay, the weighting factors measured histologically were 1.2±0.1 for the thermal neutron beam and 1.9±0.2 for the 10 B dose component. (author)

  4. Ulinastatin Protects Against LPS-Induced Acute Lung Injury by Attenuating TLR4/NF-κB Pathway Activation and Reducing Inflammatory Mediators.

    Science.gov (United States)

    Cao, Chao; Yin, Chengfen; Shou, Songtao; Wang, Jun; Yu, Lechang; Li, Xuening; Chai, Yanfen

    2018-01-10

    Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), remain the leading causes of morbidity and mortality in intensive care units. Ulinastatin (UTI), a serine protease inhibitor, possesses anti-inflammatory properties and has been suggested to modulate lipopolysaccharide (LPS)-induced sepsis; thus, it is now widely used in the treatment of pancreatitis, sepsis, and septic shock. Toll-like receptor 4 (TLR4), an essential LPS signaling receptor, plays a critical role in the activation of innate immunity. The aim of this study was to investigate whether UTI alleviates ALI by attenuating TLR4 expression and to explore the underlying molecular mechanisms involved. Male C56BL/6 mice were administered UTI intravenously 1 h before and 6 h after exposure to LPS by intra-tracheal instillation. Human lung epithelial (BEAS-2B) cells were incubated with LPS in the presence or absence of UTI. An enzyme-linked immunosorbent assay was used to detect levels of inflammatory cytokines. Western blot analysis was performed to detect changes in TLR4 expression and nuclear factor-κB (NF-κB) activation. UTI significantly protected animals from LPS-induced ALI, decreasing the lung wet/dry weight ratio, ALI score, total cells, neutrophils, macrophages, myeloperoxidase activity, and malondialdehyde content, factors associated with lung histological damage. UTI treatment also markedly attenuated levels of TLR4 and other pro-inflammatory cytokines. Furthermore, UTI significantly attenuated LPS-induced increases in TLR4 protein expression and NF-κB activation in lung tissues. Similarly, UTI markedly attenuated TLR4 expression and NF-κB activation in LPS-stimulated BEAS-2B cells. These findings indicate that UTI ameliorates LPS-induced ALI by attenuating the TLR4/NF-κB pathway activation.

  5. Characterization and optimization of the RA-3 experimental dosimetry for normal sheep lung radio-tolerance study

    International Nuclear Information System (INIS)

    Soto, M.S.; Gonzalez, S.J.; Thorp, Silvia I.; Pozzi, Emiliano; Gadan, M.; Miller, Marcelo; Farias, R.

    2009-01-01

    In the spirit of the novel technique proposed by the University of Pavia group (Italy) to irradiate an isolated organ using BNCT, the Comision Nacional de Energia Atomica (CNEA) in collaboration with the Fundacion Favaloro has initiated a project that aims to investigate the feasibility of BNCT for ex-situ treatment of diffuse metastatic disease in the lungs. The present work was carried out in the framework of the undergoing experimental study of the radio tolerance of normal sheep lung. With the purpose of characterizing and optimizing the resulting experimental dosimetry in normal lung subjected to neutron irradiation in the BNCT facility of the RA-3 reactor (CNEA), we have performed a series of experiments to find the optimum configuration of the container-lung system deriving a dose distribution preferentially uniform throughout the organ. Once the optimal set-up was established, we measured the total gamma dose rate and estimated the irradiation time compatible with the maximum tolerable dose of normal lung resulting from previous studies in rats. This estimation was performed using RBE, CBE and tolerance dose values derived from radiobiological studies with BNCT. In parallel with the experimental characterization, we built two different computational models of the container-lung system to perform Monte Carlo simulation with MCNP and Treatment Planning System NCTPlan. (author)

  6. Normal organ weights in men: part II-the brain, lungs, liver, spleen, and kidneys.

    Science.gov (United States)

    Molina, D Kimberley; DiMaio, Vincent J M

    2012-12-01

    Organomegaly can be a sign of disease and pathologic abnormality, although standard tables defining organomegaly have yet to be established and universally accepted. This study was designed to address the issue and to determine a normal weight for the major organs in adult human males. A prospective study of healthy men aged 18 to 35 years who died of sudden, traumatic deaths was undertaken. Cases were excluded if there was a history of medical illness including illicit drug use, if prolonged medical treatment was performed, if there was a prolonged period between the time of injury and death, if body length and weight could not be accurately assessed, or if any illness or intoxication was identified after gross and microscopic analysis including evidence of systemic disease. Individual organs were excluded if there was significant injury to the organ, which could have affected the weight. A total of 232 cases met criteria for inclusion in the study during the approximately 6-year period of data collection from 2005 to 2011. The decedents had a mean age of 23.9 years and ranged in length from 146 to 193 cm, with a mean length of 173 cm. The weight ranged from 48.5 to 153 kg, with a mean weight of 76.4 kg. Most decedents (87%) died of either ballistic or blunt force (including craniocerebral) injuries. The mean weight of the brain was 1407 g (range, 1070-1767 g), that of the liver was 1561 g (range, 838-2584 g), that of the spleen was 139 g (range, 43-344 g), that of the right lung was 445 g (range, 185-967 g), that of the left lung was 395 g (range, 186-885 g), that of the right kidney was 129 g (range, 79-223 g), and that of the left kidney was 137 g (range, 74-235 g). Regression analysis was performed and showed that there were insufficient associations between organ weight and body length, body weight, and body mass index to allow for predictability. The authors, therefore, propose establishing a reference range for organ weights in men, much like those in use

  7. A computational framework to detect normal and tuberculosis infected lung from H and E-stained whole slide images

    Science.gov (United States)

    Niazi, M. Khalid Khan; Beamer, Gillian; Gurcan, Metin N.

    2017-03-01

    Accurate detection and quantification of normal lung tissue in the context of Mycobacterium tuberculosis infection is of interest from a biological perspective. The automatic detection and quantification of normal lung will allow the biologists to focus more intensely on regions of interest within normal and infected tissues. We present a computational framework to extract individual tissue sections from whole slide images having multiple tissue sections. It automatically detects the background, red blood cells and handwritten digits to bring efficiency as well as accuracy in quantification of tissue sections. For efficiency, we model our framework with logical and morphological operations as they can be performed in linear time. We further divide these individual tissue sections into normal and infected areas using deep neural network. The computational framework was trained on 60 whole slide images. The proposed computational framework resulted in an overall accuracy of 99.2% when extracting individual tissue sections from 120 whole slide images in the test dataset. The framework resulted in a relatively higher accuracy (99.7%) while classifying individual lung sections into normal and infected areas. Our preliminary findings suggest that the proposed framework has good agreement with biologists on how define normal and infected lung areas.

  8. SU-F-T-600: Influence of Acuros XB and AAA Dose Calculation Algorithms On Plan Quality Metrics and Normal Lung Doses in Lung SBRT

    Energy Technology Data Exchange (ETDEWEB)

    Yaparpalvi, R; Mynampati, D; Kuo, H; Garg, M; Tome, W; Kalnicki, S [Montefiore Medical Center, Bronx, NY (United States)

    2016-06-15

    Purpose: To study the influence of superposition-beam model (AAA) and determinant-photon transport-solver (Acuros XB) dose calculation algorithms on the treatment plan quality metrics and on normal lung dose in Lung SBRT. Methods: Treatment plans of 10 Lung SBRT patients were randomly selected. Patients were prescribed to a total dose of 50-54Gy in 3–5 fractions (10?5 or 18?3). Doses were optimized accomplished with 6-MV using 2-arcs (VMAT). Doses were calculated using AAA algorithm with heterogeneity correction. For each plan, plan quality metrics in the categories- coverage, homogeneity, conformity and gradient were quantified. Repeat dosimetry for these AAA treatment plans was performed using AXB algorithm with heterogeneity correction for same beam and MU parameters. Plan quality metrics were again evaluated and compared with AAA plan metrics. For normal lung dose, V{sub 20} and V{sub 5} to (Total lung- GTV) were evaluated. Results: The results are summarized in Supplemental Table 1. PTV volume was mean 11.4 (±3.3) cm{sup 3}. Comparing RTOG 0813 protocol criteria for conformality, AXB plans yielded on average, similar PITV ratio (individual PITV ratio differences varied from −9 to +15%), reduced target coverage (−1.6%) and increased R50% (+2.6%). Comparing normal lung doses, the lung V{sub 20} (+3.1%) and V{sub 5} (+1.5%) were slightly higher for AXB plans compared to AAA plans. High-dose spillage ((V105%PD - PTV)/ PTV) was slightly lower for AXB plans but the % low dose spillage (D2cm) was similar between the two calculation algorithms. Conclusion: AAA algorithm overestimates lung target dose. Routinely adapting to AXB for dose calculations in Lung SBRT planning may improve dose calculation accuracy, as AXB based calculations have been shown to be closer to Monte Carlo based dose predictions in accuracy and with relatively faster computational time. For clinical practice, revisiting dose-fractionation in Lung SBRT to correct for dose overestimates

  9. Normal spectrum of pulmonary parametric response map to differentiate lung collapsibility: distribution of densitometric classifications in healthy adult volunteers

    International Nuclear Information System (INIS)

    Silva, Mario; Nemec, Stefan F.; Dufresne, Valerie; Occhipinti, Mariaelena; Heidinger, Benedikt H.; Bankier, Alexander A.; Chamberlain, Ryan

    2016-01-01

    Pulmonary parametric response map (PRM) was proposed for quantitative densitometric phenotypization of chronic obstructive pulmonary disease. However, little is known about this technique in healthy subjects. The purpose of this study was to describe the normal spectrum of densitometric classification of pulmonary PRM in a group of healthy adults. 15 healthy volunteers underwent spirometrically monitored chest CT at total lung capacity (TLC) and functional residual capacity (FRC). The paired CT scans were analyzed by PRM for voxel-by-voxel characterization of lung parenchyma according to 4 densitometric classifications: normal lung (TLC ≥ -950 HU, FRC ≥ -856 HU); expiratory low attenuation area (LAA) (TLC ≥ -950 HU, FRC < -856 HU); dual LAA (TLC<-950 HU, FRC < -856 HU); uncharacterized (TLC < -950 HU, FRC ≥ -856 HU). PRM spectrum was 78 % ± 10 % normal lung, 20 % ± 8 % expiratory LAA, and 1 % ± 1 % dual LAA. PRM was similar between genders, there was moderate correlation between dual LAA and spirometrically assessed TLC (R = 0.531; p = 0.042), and between expiratory LAA and Vol Exp/Insp ratio (R = -0.572; p = 0.026). PRM reflects the predominance of normal lung parenchyma in a group of healthy volunteers. However, PRM also confirms the presence of physiological expiratory LAA seemingly related to air trapping and a minimal amount of dual LAA likely reflecting emphysema. (orig.)

  10. Volume-controlled histographic analysis of pulmonary parenchyma in normal and diffuse parenchymal lung disease: a pilot study

    International Nuclear Information System (INIS)

    Park, Hyo Yong; Lee, Jongmin; Kim, Jong Seob; Won, Chyl Ho; Kang, Duk Sik; Kim, Myoung Nam

    2000-01-01

    To evaluate the clinical usefulness of a home-made histographic analysis system using a lung volume controller. Our study involved ten healthy volunteers, ten emphysema patients, and two idiopathic pulmonary fibrosis (IPF) patients. Using a home-made lung volume controller, images were obtained in the upper, middle, and lower lung zones at 70%, 50%, and 20% of vital capacity. Electron beam tomography was used and scanning parameters were single slice mode, 10-mm slice thickness, 0.4-second scan time, and 35-cm field of view. Usinga home-made semi-automated program, pulmonary parenchyma was isolated and a histogrm then obtained. Seven histographic parameters, namely mean density (MD), density at maximal frequency (DMF), maximal ascending gradient (MAG),maximal ascending gradient density (MAGD), maximal sescending gradient (MDG), maximal descending gradient density (MDGD), and full width at half maximum (FWHM) were derived from the histogram. We compared normal controls with abnormal groups including emphysema and IPF patients at the same respiration levels. A normal histographic zone with ± 1 standard deviation was obtained. Histographic curves of normal controls shifted toward the high density level, and the width of the normal zone increased as the level of inspiration decreased. In ten normal controls, MD, DMF, MAG, MAGD, MDG, MDGD, and FWHM readings at a 70% inspiration level were lower than those at 20% (p less than0.05). At the same level of inspiration, histograms of emphysema patients were locatedat a lower density area than those of normal controls. As inspiration status decreased, histograms of emphysema patients showed diminished shift compared with those of normal controls. At 50% and 20% inspiration levels, the MD, DMF, and MAGD readings of emphysema patients were significantly lower than those of normal controls (p less than 0.05). Compared with those of normal controls, histogrms of the two IPF patients obtained at three inspiration levels were

  11. 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

  12. Volúmenes pulmonares normales en pacientes con fibrosis pulmonar idiopática y enfisema Normal lung volumes in patients with idiopathic pulmonary fibrosis and emphysema

    Directory of Open Access Journals (Sweden)

    Juan Pablo Casas

    2008-08-01

    pattern with hyperinflation results in emphysema by loss of elastic recoil, expiratory collapse of the peripheral airways and air trapping. Previous reports suggest that when both diseases coexist, pulmonary volumes are compensated and a smaller than expected reduction or even normal lung volumes can be found. We report 4 male patients of 64, 60, 73 and 70 years, all with heavy cigarette smoking history and progressive breathlessness. Three of them had severe limitation in their quality of life. All four showed advanced lung interstitial involvement, at high resolution CT scan, fibrotic changes predominantly in the subpleural areas of lower lung fields and concomitant emphysema in the upper lobes. Emphysema and pulmonary fibrosis was confirmed by open lung biopsy in one patient. The four patients showed normal spirometry and lung volumes with severe compromise of gas exchange and poor exercise tolerance evaluated by 6 minute walk test. Severe pulmonary arterial hypertension was also confirmed in three patients. Normal lung volumes does not exclude diagnosis of idiopathic pulmonary fibrosis in patients with concomitant emphysema. The relatively preserved lung volumes may underestimate the severity of idiopathic pulmonary fibrosis and attenuate its effects on lung function parameters.

  13. Normalization.

    Science.gov (United States)

    Cuevas, Eduardo J.

    1997-01-01

    Discusses cornerstone of Montessori theory, normalization, which asserts that if a child is placed in an optimum prepared environment where inner impulses match external opportunities, the undeviated self emerges, a being totally in harmony with its surroundings. Makes distinctions regarding normalization, normalized, and normality, indicating how…

  14. Transforming growth factor-β impairs glucocorticoid activity in the A549 lung adenocarcinoma cell line.

    Science.gov (United States)

    Salem, S; Harris, T; Mok, J S L; Li, M Y S; Keenan, C R; Schuliga, M J; Stewart, A G

    2012-08-01

    The lung adenocarcinoma cell line, A549, undergoes epithelial-mesenchymal cell transition (EMT) in response to TGF-β. Glucocorticoids do not prevent the EMT response, but TGF-β induced resistance to the cytokine-regulatory action of glucocorticoids. We sought to characterize the impairment of glucocorticoid response in A549 cells. A549 cells were exposed to TGF-β for up to 96 h before glucocorticoid treatment and challenge with IL-1α to assess glucocorticoid regulation of IL-6 and CXCL8 production. Nuclear localization of the glucocorticoid receptor α (GRα) was ascertained by immunofluorescence and Western blotting. Transactivation of the glucocorticoid response element (GRE) was measured with a transfected GRE-secreted human placental alkaline phosphatase reporter. TGF-β (40-400 pM) reduced the maximum inhibitory effect of dexamethasone on IL-1α-induced IL-6 and CXCL8 production. The impaired glucocorticoid response was detected with 4 h of TGF-β (40 pM) exposure (and 4 h IL-1α to induce CXCL8 expression) and therefore was not secondary to EMT, a process that requires longer incubation periods and higher concentrations of TGF-β. TGF-β also impaired dexamethasone regulation of granulocyte-macrophage colony-stimulating factor in thrombin-stimulated BEAS-2B epithelial cells. Impaired regulation of CXCL8 was associated with markedly reduced GRE transactivation and reduced induction of mRNA for IκBα, the glucocorticoid-inducible leucine zipper and the epithelial sodium channel (SCNN1A). The expression, cellular levels and nuclear localization of GRα were reduced by TGF-β. We have identified mechanisms underlying the impairment of responses to glucocorticoids by TGF-β in the A549 and BEAS-2B cell lines. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  15. Evaluation of oxidative stress in caprine bronchoalveolar lavage fluid of pneumonic and normal lungs

    Directory of Open Access Journals (Sweden)

    T.A. Jarikre

    2017-12-01

    Full Text Available Research in the area of oxidative stress in pneumonic pathology still requires attention in small ruminants especially with the use of bronchoalveolar lavage (BAL which may be a more sensitive indicator of respiratory diseases than blood. This investigation evaluates the role of oxidative stress in the pathogenesis of caprine pneumonia using BAL fluid (BALf from healthy and pneumonic goats. A BALf from 192 goats (whose pneumonic histopathology had been characterized using standard techniques was biochemically assayed for anti-oxidants and pro-oxidants. Malondialdehyde (MDA, hydrogen peroxide generation (H2O2, myeloperoxidase (MPO and reduced glutathione (GSH contents were measured to assess free radical activity in the BALf. Superoxide dismutase (SOD, Glutathione transferase (GST and Glutathione peroxidase (GPx activity were also determined colourimetrically. There were significant increases in the BALf supernatant of MDA, H2O2 and MPO with decreases in GSH level and SOD activity in the pneumonic goats (P < 0.05. There was also significant correlation of BALf oxidative assay to the type and severity of pneumonia. The levels of MDA, H2O2, and MPO increased significantly (P < 0.05 in bronchopneumonia and bronchointerstitial pneumonia than other pneumonic conditions and normal lungs. The management of caprine pneumonia should often incorporate antioxidant supplementation to correct the imbalance in pro-oxidant and anti-oxidant levels. Keywords: Anti-oxidants, Pro-oxidants, Pneumonia, Myeloperoxidase, Malondialdehyde, Glutathione transferase

  16. A study on the radiographic determination of total lung capacity in normal Korean Adults

    International Nuclear Information System (INIS)

    Park, Soo Soung; Choo, Dong Woon

    1970-01-01

    The measurements and calculations of total lung capacity (TLC) by radiographic method were carried out in 231 cases of normal Korean adults, 125 males and 106 females, and correlation with the conventional physiologic method was investigated simultaneous in 8 cases. The following results were obtained: 1. The calculated value of TLC in male was far larger than that in females, even in same age, height and weight group. The mean value of TLC in female was 67.3% of the male. 2. The TLC tended to show a gradual increase as height increased, and it had an approximation to the value of 1 X Ht 3 in male and 0.9 X Ht 3 in female. 3. There was no significant correlation between the value of TLC and age, and body weight either. 4. Each mean value of TLC in the radiographic and physiologic method was 5410 ± 546 and 5655 ± 567, and there was no significant different between the two mean values

  17. Lung sound intensity in patients with emphysema and in normal subjects at standardised airflows

    NARCIS (Netherlands)

    Schreur, H. J.; Sterk, P. J.; Vanderschoot, J.; van Klink, H. C.; van Vollenhoven, E.; Dijkman, J. H.

    1992-01-01

    A common auscultatory finding in pulmonary emphysema is a reduction of lung sounds. This might be due to a reduction in the generation of sounds due to the accompanying airflow limitation or to poor transmission of sounds due to destruction of parenchyma. Lung sound intensity was investigated in

  18. Distinctive Regulatory T Cells and Altered Cytokine Profile Locally in the Airways of Young Smokers with Normal Lung Function.

    Science.gov (United States)

    Ostadkarampour, Mahyar; Müller, Malin; Öckinger, Johan; Kullberg, Susanna; Lindén, Anders; Eklund, Anders; Grunewald, Johan; Wahlström, Jan

    2016-01-01

    Smoking influences the immune system in different ways and, hypothetically, effects on pulmonary effector and regulatory T cells emerge as potentially detrimental. Therefore, we characterized the frequencies and characteristics of CD4+ and CD8+ T cell subsets in the blood and lungs of young tobacco smokers. Bronchoalveolar lavage (BAL) and peripheral blood were obtained from healthy moderate smokers (n = 18; 2-24 pack-years) and never-smokers (n = 15), all with normal lung function. Cells were stimulated ex vivo and key intracellular cytokines (IFNγ, IL-17, IL-10 and TNFα) and transcription factors (Foxp3, T-bet and Helios) were analyzed using flow cytometry. Our results indicate that smoking is associated with a decline in lung IL-17+ CD4+ T cells, increased IFNγ+ CD8+ T cells and these alterations relate to the history of daily cigarette consumption. There is an increased fraction of Foxp3+ regulatory T cells being Helios- in the lungs of smokers. Cytokine production is mainly confined to the Helios- T cells, both in regulatory and effector subsets. Moreover, we detected a decline of Helios+Foxp3- postulated regulatory CD8+ T cells in smokers. These alterations in the immune system are likely to increase risk for infection and may have implications for autoimmune processes initiated in the lungs among tobacco smokers.

  19. 4-Methoxyestradiol-induced oxidative injuries in human lung epithelial cells

    International Nuclear Information System (INIS)

    Cheng Yahsin; Chang, Louis W.; Cheng Lichuan; Tsai, M.-H.; Lin Pinpin

    2007-01-01

    Epidemiological studies indicated that people exposed to dioxins were prone to the development of lung diseases including lung cancer. Animal studies demonstrated that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increased liver tumors and promoted lung metaplasia in females. Metabolic changes in 17β-estradiol (E 2 ) resulted from an interaction between TCDD and E 2 could be associated with gender difference. Previously, we reported that methoxylestradiols (MeOE 2 ), especially 4-MeOE 2 , accumulated in human lung cells (BEAS-2B) co-treated with TCDD and E 2 . In the present study, we demonstrate unique accumulation of 4-MeOE 2 , as a result of TCDD/E 2 interaction and revealed its bioactivity in human lung epithelial cell line (H1355). 4-Methoxyestradiol treatment significantly decreased cell growth and increased mitotic index. Elevation of ROS and SOD activity, with a concomitant decrease in the intracellular GSH/GSSG ratio, was also detected in 4-MeOE 2 -treated cells. Quantitative comet assay showed increased oxidative DNA damage in the 4-MeOE 2 -treated H1355 cells, which could be significantly reduced by the anti-oxidant N-acetylcysteine (NAC). However, inhibition of cell growth and increase in mitotic arrest induced by 4-MeOE 2 were unaffected by NAC. We concluded that 4-MeOE 2 accumulation resulting from TCDD and E 2 interaction would contribute to the higher vulnerability on lung pathogenesis in females when exposed to TCDD

  20. Transarterial embolization treatment for aberrant systemic arterial supply to the normal lung: A case report and literature review

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Bo Ra; Jo, Jeong Hyun; Park, Byeong Ho [Dept. of Radiology, Dong A University Hospital, Dong A University College of Medicine, Busan (Korea, Republic of)

    2017-06-15

    A 24-year-old man presented with dyspnea on exertion and intermittent blood-tinged sputum. He was diagnosed with aberrant systemic arterial supply to the normal lung (ASANL) based on the results of imaging studies. The patient was successfully treated with transarterial embolization using coils and a vascular plug and his symptoms disappeared during the follow-up. Herein, we reported the imaging findings of ASANL, differential diagnoses, and its treatment options. In addition, we reviewed the relevant literature.

  1. Time evolution of regional CT density changes in normal lung after IMRT for NSCLC

    International Nuclear Information System (INIS)

    Bernchou, Uffe; Schytte, Tine; Bertelsen, Anders; Bentzen, Søren M.; Hansen, Olfred; Brink, Carsten

    2013-01-01

    Purpose: This study investigates the clinical radiobiology of radiation induced lung disease in terms of regional computed tomography (CT) density changes following intensity modulated radiotherapy (IMRT) for non-small-cell lung cancer (NSCLC). Methods: A total of 387 follow-up CT scans in 131 NSCLC patients receiving IMRT to a prescribed dose of 60 or 66 Gy in 2 Gy fractions were analyzed. The dose-dependent temporal evolution of the density change was analyzed using a two-component model, a superposition of an early, transient component and a late, persistent component. Results: The CT density of healthy lung tissue was observed to increase significantly (p 12 months. Conclusions: The radiobiology of lung injury may be analyzed in terms of CT density change. The initial transient change in density is consistent with radiation pneumonitis, while the subsequent stabilization of the density is consistent with pulmonary fibrosis

  2. Prediction of the gene expression in normal lung tissue by the gene expression in blood.

    Science.gov (United States)

    Halloran, Justin W; Zhu, Dakai; Qian, David C; Byun, Jinyoung; Gorlova, Olga Y; Amos, Christopher I; Gorlov, Ivan P

    2015-11-17

    Comparative analysis of gene expression in human tissues is important for understanding the molecular mechanisms underlying tissue-specific control of gene expression. It can also open an avenue for using gene expression in blood (which is the most easily accessible human tissue) to predict gene expression in other (less accessible) tissues, which would facilitate the development of novel gene expression based models for assessing disease risk and progression. Until recently, direct comparative analysis across different tissues was not possible due to the scarcity of paired tissue samples from the same individuals. In this study we used paired whole blood/lung gene expression data from the Genotype-Tissue Expression (GTEx) project. We built a generalized linear regression model for each gene using gene expression in lung as the outcome and gene expression in blood, age and gender as predictors. For ~18 % of the genes, gene expression in blood was a significant predictor of gene expression in lung. We found that the number of single nucleotide polymorphisms (SNPs) influencing expression of a given gene in either blood or lung, also known as the number of quantitative trait loci (eQTLs), was positively associated with efficacy of blood-based prediction of that gene's expression in lung. This association was strongest for shared eQTLs: those influencing gene expression in both blood and lung. In conclusion, for a considerable number of human genes, their expression levels in lung can be predicted using observable gene expression in blood. An abundance of shared eQTLs may explain the strong blood/lung correlations in the gene expression.

  3. RELEASE OF IL-8 AND IL-6 BY BEAS-2B CELLS FOLLOWING IN VITRO EXPOSURE TO BIODIESEL PM EXTRACTS

    Science.gov (United States)

    Abstract Body: Biodiesel, an alkyl ester of plant oils that can be used in an unmodified diesel engine, is a renewable fuel alternative which show signs of becoming a commercially accepted part of our nation¿s energy infrastructure. Biodiesel exhaust has been physicochemically ch...

  4. Proteome Profiling of BEAS-2B Cells Treated with Titanium Dioxide Reveals Potential Toxicity of and Detoxification Pathways for Nanomaterial

    Science.gov (United States)

    Oxidative stress is known to play important roles in nanomaterial-induced toxicities. However, the proteins and signaling pathways associated with nanomaterial-mediated oxidative stress and toxicity are largely unknown. To identify oxidative stress-responding toxicity pathways an...

  5. Proteome Profiling Reveals Potential Toxicity and Detoxification Pathways Following Exposure of BEAS-2B Cells to Engineered Nanoparticle Titanium Dioxide

    Science.gov (United States)

    Identification of toxicity pathways linked to chemical -exposure is critical for a better understanding of biological effects of the exposure, toxic mechanisms, and for enhancement of the prediction of chemical toxicity and adverse health outcomes. To identify toxicity pathways a...

  6. Proteome Profiling Reveals Potential Toxicity and Detoxification Pathways Following Exposure of BEAS-2B Cells to Engineered Titanium Dioxide Nanoparticles

    Science.gov (United States)

    Oxidative stress is known to play important roles in engineered nanomaterial induced cellular toxicity. However, the proteins and signaling pathways associated with the engineered nanomaterial mediated oxidative stress and toxicity are largely unknown. To identify these toxicity ...

  7. A study of radiographic determination of the total lung capacity in the normal Korean pre-school children

    International Nuclear Information System (INIS)

    Lee, Do Haeng

    1974-01-01

    Determination of the total lung capacity (TLC) has been widely used in the evaluation of the pulmonary function. A roentgenographic method for the determination of total lung capacity of pre-school children has been studied. This method requires posteroanterior and lateral views of the chest and consists principally of the summation of a series of elliptical cylindroids into which the lungs are divided. The measurements and calculations of the total lung capacity by radiographic method were carried out in 96 cases of normal Korean pre-school children, 51 males and 45 females. The results were obtained as follows; 1. As a whole the calculation value of TLC in male was larger than that in female in the same age group in height and weight. The mean value of TLC in female was 68.4% of that in male. 2. The standard deviation of height and body weight are ± 337 ml in male and ±284 ml in female. 3. The TLC tended to show a gradual increase as height increased. A linear relationship found between the variables of height and TLC was 0.74 in terms of coefficient of correlation. The confidence interval for the coefficient of correlation was from +0.65 to +0.84 at 95 percent confidence level. 4. There was no significant correlation between the value of TLC and the body weight

  8. Quantitative assessment of thallium myocardial washout rate: Importance of peak heart rate and lung thallium uptake in defining normal values

    International Nuclear Information System (INIS)

    Nishimura, Tsunehiko; Uehara, Toshiisa; Hayashida, Kohei; Kozuka, Takahiro; Saito, Muneyasu; Sumiyoshi, Tetsuya; National Cardiovascular Center, Suita, Osaka

    1987-01-01

    Traditionally, the results of exercise thallium scintigraphy were interpreted by transient defect analysis using initial and delayed images. Recently, washout rate analysis has been used for the relative quantification of exercise thallium scintigraphy. A diffuse slow washout from all myocardial regions has been defined as the indicator of extensive coronary artery disease. However, slow washout has occasionally been observed in normal cases and in healthy myocardial segments which are not supplied by a stenosed artery in patients with single or double vessel disease. We evaluate the factors influencing washout rate in 100 normal patients and 63 patients with angina pectoris (33 cases of single vessel disease and 30 cases of double vessel disease). The washout rates were calculated using circumferential profile analysis. In normal patients, washout rate was closely related to peak heart rate (r=0.72) and inversely related to lung thallium uptake (r=-0.56). A diffuse slow washout was observed in seven (7%) of 100 normal patients, six (18%) of 33 cases of single vessel disease and eight (24%) of 30 cases of double vessel disease. The patients with diffuse slow washout showed significantly higher lung thallium uptake values and lower peak heart rates than those without diffuse slow washout (P<0.01). Thus, this false positive slow washout should be considered in the interpretation of quantitative exercise thallium scintigraphy. (orig.)

  9. Roles of microRNA-15 family in normal and pathological late lung development

    OpenAIRE

    Sakkas, Elpidoforos

    2016-01-01

    MicroRNAs are key regulators of organogenesis and during the last years many studies focused on microRNA expression during embryonic development. To date, there is no study to report possible roles of microRNAs in late lung development and especially during the alveolarization process. The objective of this study was to identify microRNAs that are deregulated under hyperoxic conditions and to assess whether microRNA expression can be modulated in vivo. Lung microRNA expression screening wa...

  10. Correlation of lung collapse and gas exchange - a computer tomographic study in sheep and pigs with atelectasis in otherwise normal lungs.

    Science.gov (United States)

    Wolf, Samuel J; Reske, Alexander P; Hammermüller, Sören; Costa, Eduardo L V; Spieth, Peter M; Hepp, Pierre; Carvalho, Alysson R; Kraßler, Jens; Wrigge, Hermann; Amato, Marcelo B P; Reske, Andreas W

    2015-01-01

    Atelectasis can provoke pulmonary and non-pulmonary complications after general anaesthesia. Unfortunately, there is no instrument to estimate atelectasis and prompt changes of mechanical ventilation during general anaesthesia. Although arterial partial pressure of oxygen (PaO2) and intrapulmonary shunt have both been suggested to correlate with atelectasis, studies yielded inconsistent results. Therefore, we investigated these correlations. Shunt, PaO2 and atelectasis were measured in 11 sheep and 23 pigs with otherwise normal lungs. In pigs, contrasting measurements were available 12 hours after induction of acute respiratory distress syndrome (ARDS). Atelectasis was calculated by computed tomography relative to total lung mass (Mtotal). We logarithmically transformed PaO2 (lnPaO2) to linearize its relationships with shunt and atelectasis. Data are given as median (interquartile range). Mtotal was 768 (715-884) g in sheep and 543 (503-583) g in pigs. Atelectasis was 26 (16-47) % in sheep and 18 (13-23) % in pigs. PaO2 (FiO2 = 1.0) was 242 (106-414) mmHg in sheep and 480 (437-514) mmHg in pigs. Shunt was 39 (29-51) % in sheep and 15 (11-20) % in pigs. Atelectasis correlated closely with lnPaO2 (R2 = 0.78) and shunt (R2 = 0.79) in sheep (P-valuessheep and pigs, changes in atelectasis correlated strongly with corresponding changes in lnPaO2 and shunt. In lung-healthy sheep, atelectasis correlates closely with lnPaO2 and shunt, when blood gases are measured during ventilation with pure oxygen. In lung-healthy pigs, these correlations were significantly weaker, likely because pigs have stronger hypoxic pulmonary vasoconstriction (HPV) than sheep and humans. Nevertheless, correlations improved also in pigs after blunting of HPV during ARDS. In humans, the observed relationships may aid in assessing anaesthesia-related atelectasis.

  11. Prenatal exposure to thyroid hormone is necessary for normal postnatal development of murine heart and lungs

    NARCIS (Netherlands)

    van Tuyl, Minke; Blommaart, Pietjan E.; de Boer, Piet A. J.; Wert, Susan E.; Ruijter, Jan M.; Islam, Saleem; Schnitzer, Jay; Ellison, Aaron R.; Tibboel, Dick; Moorman, Antoon F. M.; Lamers, Wouter H.

    2004-01-01

    Maternal hypothyroxinemia during early pregnancy poses an increased risk for poor neuropsychological development of the fetus. We tested the hypothesis that maternal hypothyroidism before the onset of fetal thyroid function also affects postnatal development of heart and lungs. This question was

  12. Abnormal intracellular localization of Bax with a normal membrane anchor domain in human lung cancer cell lines.

    Science.gov (United States)

    Salah-eldin, A; Inoue, S; Tsuda, M; Matsuura, A

    2000-12-01

    Proapoptotic Bax is a member of the Bcl-2 family proteins, which have a key role in regulating programmed cell death. The intracellular localization and redistribution of Bax are important in promoting apoptosis. Bax contains a BH3 domain heterodimerizing with Bcl-2 and a hydrophobic transmembrane segment to be inserted in specified organelle membranes. In this study, Bcl-2 showed cytoplasmic localization in all of ten human lung cancer cell lines tested. Interestingly, Bax was localized in the nucleus in 7 cell lines, although Bax lacks nuclear import signals. This may allow cancer cells to escape from apoptosis. Why Bax is able to exist in the nucleus is still unclear. We hypothesized that mutation in the BH3 domain and / or transmembrane segment of Bax possibly causes intracellular Bax distribution. We analyzed the sequence of the bax gene in these cell lines and found only a silent point mutation at codon 184 (TCG-->TCA) in the transmembrane segment in all cell lines. This finding indicates that changes in cellular localization of Bax in lung cancer cell lines do not depend on bax mutation and that Bax is possibly translocated into the nucleus without any mutation. This is the first report showing that Bax with the normal amino acid sequence can be localized in the nucleus in established lung cancer cell lines without any treatment of the cells.

  13. Increased Rho-kinase expression and activity and pulmonary endothelial dysfunction in smokers with normal lung function.

    Science.gov (United States)

    Duong-Quy, S; Dao, P; Hua-Huy, T; Guilluy, C; Pacaud, P; Dinh-Xuan, A T

    2011-02-01

    Endothelial dysfunction is one of the main consequences of the toxic effects of cigarette smoke on the vascular system. Increasing evidence suggests that the small G-protein RhoA and its downstream effectors, the Rho-kinases (ROCKs), are involved in systemic endothelial dysfunction induced by cigarette smoke. This study aimed to evaluate the role of the RhoA/ROCKs pathway in pulmonary artery endothelial function in current smokers with normal lung function. Lung tissues were obtained from nonsmokers and smokers who underwent lobectomy for lung carcinoma. Arterial relaxation in response to acetylcholine (ACh) was assessed in isolated pulmonary arterial rings. Protein expressions and activities of endothelial nitric oxide synthase (eNOS), ROCKs and the myosin phosphatase subunit 1 (MYPT-1) were sought. Relaxation in response to ACh was significantly lower in smokers as compared with nonsmokers (n = 8 in each group), consistent with reduced eNOS activity in the former compared with the latter. eNOS protein expression remained, however, the same in both groups. Expression of ROCKs, guanosine triphosphate-RhoA and phosphorylated MYPT-1 were significantly increased in smokers compared with controls. Pulmonary endothelial dysfunction is present in smokers whose lung function has not yet been impaired. Reduced activity of eNOS accounts at least in part for this endothelial dysfunction. Increased expression and activity of ROCKs accounts for another part through direct or indirect inhibition of the Rho-A/ROCKs pathway on nitric oxide synthesis and sustained pulmonary vasoconstriction through inhibition of myosin phosphatase.

  14. An experimental randomized study of six different ventilatory modes in a piglet model with normal lungs

    DEFF Research Database (Denmark)

    Nielsen, J B; Sjöstrand, U H; Henneberg, S W

    1991-01-01

    ventilatory modes. Also the mean airway pressures were lower with the HFV modes 8-9 cm H2O compared to 11-14 cm H2O for the other modes. The gas distribution was evaluated by N2 wash-out and a modified lung clearance index. All modes showed N2 wash-out according to a two-compartment model. The SV-20P mode had...... the fastest wash-out, but the HFV-60 and HFV-20 ventilatory modes also showed a faster N2 wash-out than the others.(ABSTRACT TRUNCATED AT 250 WORDS)...

  15. Base excision repair activities differ in human lung cancer cells and corresponding normal controls

    DEFF Research Database (Denmark)

    Karahalil, Bensu; Bohr, Vilhelm A; De Souza-Pinto, Nadja C

    2010-01-01

    for the repair of oxidized modifications both in nuclear and mitochondrial DNA. In order to ascertain whether diminished BER capacity might account for increased levels of oxidative DNA damage in cancer cells, the activities of BER enzymes in three different lung cancer cell lines and their non...... cell lines used. However, the specific activities and cancer versus control comparison differed significantly between the nuclear and mitochondrial compartments. OGG1 activity, as measured by 8-oxodA incision, was up-regulated in cancer cell mitochondria but down-regulated in the nucleus when compared...

  16. Correlation of lung collapse and gas exchange - a computer tomographic study in sheep and pigs with atelectasis in otherwise normal lungs.

    Directory of Open Access Journals (Sweden)

    Samuel J Wolf

    Full Text Available Atelectasis can provoke pulmonary and non-pulmonary complications after general anaesthesia. Unfortunately, there is no instrument to estimate atelectasis and prompt changes of mechanical ventilation during general anaesthesia. Although arterial partial pressure of oxygen (PaO2 and intrapulmonary shunt have both been suggested to correlate with atelectasis, studies yielded inconsistent results. Therefore, we investigated these correlations.Shunt, PaO2 and atelectasis were measured in 11 sheep and 23 pigs with otherwise normal lungs. In pigs, contrasting measurements were available 12 hours after induction of acute respiratory distress syndrome (ARDS. Atelectasis was calculated by computed tomography relative to total lung mass (Mtotal. We logarithmically transformed PaO2 (lnPaO2 to linearize its relationships with shunt and atelectasis. Data are given as median (interquartile range.Mtotal was 768 (715-884 g in sheep and 543 (503-583 g in pigs. Atelectasis was 26 (16-47 % in sheep and 18 (13-23 % in pigs. PaO2 (FiO2 = 1.0 was 242 (106-414 mmHg in sheep and 480 (437-514 mmHg in pigs. Shunt was 39 (29-51 % in sheep and 15 (11-20 % in pigs. Atelectasis correlated closely with lnPaO2 (R2 = 0.78 and shunt (R2 = 0.79 in sheep (P-values<0.0001. The correlation of atelectasis with lnPaO2 (R2 = 0.63 and shunt (R2 = 0.34 was weaker in pigs, but R2 increased to 0.71 for lnPaO2 and 0.72 for shunt 12 hours after induction of ARDS. In both, sheep and pigs, changes in atelectasis correlated strongly with corresponding changes in lnPaO2 and shunt.In lung-healthy sheep, atelectasis correlates closely with lnPaO2 and shunt, when blood gases are measured during ventilation with pure oxygen. In lung-healthy pigs, these correlations were significantly weaker, likely because pigs have stronger hypoxic pulmonary vasoconstriction (HPV than sheep and humans. Nevertheless, correlations improved also in pigs after blunting of HPV during ARDS. In humans, the observed

  17. Normal overall leakiness of microvasculature for albumin in patients with chronic obstructive lung disease (COLD)

    DEFF Research Database (Denmark)

    Kok-Jensen, A; Henriksen, Jens Henrik Sahl

    1984-01-01

    .45-1.95), and forced expired volume in first sec was decreased to 21% of expected normal value (median 0.55 litre, range 0.40-0.70). Right-heart catheterization revealed pulmonary hypertension in all but one patient. TER in patients with COLD was median 6.1% IVM/h (range 3.5-10.1) as compared to that of normal...

  18. Prenatal exposure to thyroid hormone is necessary for normal postnatal development of murine heart and lungs.

    Science.gov (United States)

    van Tuyl, Minke; Blommaart, Pietjan E; de Boer, Piet A J; Wert, Susan E; Ruijter, Jan M; Islam, Saleem; Schnitzer, Jay; Ellison, Aaron R; Tibboel, Dick; Moorman, Antoon F M; Lamers, Wouter H

    2004-08-01

    Maternal hypothyroxinemia during early pregnancy poses an increased risk for poor neuropsychological development of the fetus. We tested the hypothesis that maternal hypothyroidism before the onset of fetal thyroid function also affects postnatal development of heart and lungs. This question was addressed in transgenic mice that express herpes simplex virus thymidine kinase in their thyroidal follicle cells. Treatment with ganciclovir rendered these mice severely hypothyroid because viral thymidine kinase converts ganciclovir into a cytotoxic nucleoside analog. Since ganciclovir crosses the placenta, it also destroyed the thyroid of transgenic embryos while leaving the thyroids of nontransgenic littermates unaffected. Hypothyroidism of both mother and fetus did not affect prenatal heart and lung development. However, the postnatal switch from beta- to alpha-myosin heavy chain (beta- and alpha-MHC, respectively) gene expression and the increase of SERCA-2a mRNA expression did not occur in the ventricular myocardium of either the transgenic (thyroid destroyed) or nontransgenic (intact thyroid) offspring of hypothyroid mothers. Similarly, postnatal animals of the latter two groups retained elevated surfactant protein (SP) A, B, and C mRNA levels in their alveolar epithelium. In hypothyroid pups from hypothyroid mothers, these changes were accompanied by decreased alveolar septation. Our study shows that these effects of maternal hypothyroidism become manifest after birth and are aggravated by the concomitant existence of neonatal hypothyroidism.

  19. 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 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.

  20. Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells

    International Nuclear Information System (INIS)

    Stueckle, Todd A.; Lu, Yongju; Davis, Mary E.; Wang, Liying; Jiang, Bing-Hua; Holaskova, Ida; Schafer, Rosana; Barnett, John B.; Rojanasakul, Yon

    2012-01-01

    Chronic arsenic exposure remains a human health risk; however a clear mode of action to understand gene signaling-driven arsenic carcinogenesis is currently lacking. This study chronically exposed human lung epithelial BEAS-2B cells to low-dose arsenic trioxide to elucidate cancer promoting gene signaling networks associated with arsenic-transformed (B-As) cells. Following a 6 month exposure, exposed cells were assessed for enhanced cell proliferation, colony formation, invasion ability and in vivo tumor formation compared to control cell lines. Collected mRNA was subjected to whole genome expression microarray profiling followed by in silico Ingenuity Pathway Analysis (IPA) to identify lung carcinogenesis modes of action. B-As cells displayed significant increases in proliferation, colony formation and invasion ability compared to BEAS-2B cells. B-As injections into nude mice resulted in development of primary and secondary metastatic tumors. Arsenic exposure resulted in widespread up-regulation of genes associated with mitochondrial metabolism and increased reactive oxygen species protection suggesting mitochondrial dysfunction. Carcinogenic initiation via reactive oxygen species and epigenetic mechanisms was further supported by altered DNA repair, histone, and ROS-sensitive signaling. NF-κB, MAPK and NCOR1 signaling disrupted PPARα/δ-mediated lipid homeostasis. A ‘pro-cancer’ gene signaling network identified increased survival, proliferation, inflammation, metabolism, anti-apoptosis and mobility signaling. IPA-ranked signaling networks identified altered p21, EF1α, Akt, MAPK, and NF-κB signaling networks promoting genetic disorder, altered cell cycle, cancer and changes in nucleic acid and energy metabolism. In conclusion, transformed B-As cells with their whole genome expression profile provide an in vitro arsenic model for future lung cancer signaling research and data for chronic arsenic exposure risk assessment. Highlights: ► Chronic As 2 O 3

  1. Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Stueckle, Todd A., E-mail: tstueckle@hsc.wvu.edu [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States); Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States); Lu, Yongju, E-mail: yongju6@hotmail.com [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States); Davis, Mary E., E-mail: mdavis@wvu.edu [Department of Physiology, West Virginia University, Morgantown, WV 26506 (United States); Wang, Liying, E-mail: lmw6@cdc.gov [Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States); Jiang, Bing-Hua, E-mail: bhjiang@jefferson.edu [Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Holaskova, Ida, E-mail: iholaskova@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Schafer, Rosana, E-mail: rschafer@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Barnett, John B., E-mail: jbarnett@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Rojanasakul, Yon, E-mail: yrojan@hsc.wvu.edu [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States)

    2012-06-01

    Chronic arsenic exposure remains a human health risk; however a clear mode of action to understand gene signaling-driven arsenic carcinogenesis is currently lacking. This study chronically exposed human lung epithelial BEAS-2B cells to low-dose arsenic trioxide to elucidate cancer promoting gene signaling networks associated with arsenic-transformed (B-As) cells. Following a 6 month exposure, exposed cells were assessed for enhanced cell proliferation, colony formation, invasion ability and in vivo tumor formation compared to control cell lines. Collected mRNA was subjected to whole genome expression microarray profiling followed by in silico Ingenuity Pathway Analysis (IPA) to identify lung carcinogenesis modes of action. B-As cells displayed significant increases in proliferation, colony formation and invasion ability compared to BEAS-2B cells. B-As injections into nude mice resulted in development of primary and secondary metastatic tumors. Arsenic exposure resulted in widespread up-regulation of genes associated with mitochondrial metabolism and increased reactive oxygen species protection suggesting mitochondrial dysfunction. Carcinogenic initiation via reactive oxygen species and epigenetic mechanisms was further supported by altered DNA repair, histone, and ROS-sensitive signaling. NF-κB, MAPK and NCOR1 signaling disrupted PPARα/δ-mediated lipid homeostasis. A ‘pro-cancer’ gene signaling network identified increased survival, proliferation, inflammation, metabolism, anti-apoptosis and mobility signaling. IPA-ranked signaling networks identified altered p21, EF1α, Akt, MAPK, and NF-κB signaling networks promoting genetic disorder, altered cell cycle, cancer and changes in nucleic acid and energy metabolism. In conclusion, transformed B-As cells with their whole genome expression profile provide an in vitro arsenic model for future lung cancer signaling research and data for chronic arsenic exposure risk assessment. Highlights: ► Chronic As{sub 2}O

  2. Graphene-induced apoptosis in lung epithelial cells through EGFR

    Science.gov (United States)

    Tsai, Shih-Ming; Bangalore, Preeti; Chen, Eric Y.; Lu, David; Chiu, Meng-Hsuen; Suh, Andrew; Gehring, Matthew; Cangco, John P.; Garcia, Santiago G.; Chin, Wei-Chun

    2017-07-01

    Expanding interest in nanotechnology applied to electronic and biomedical fields has led to fast-growing development of various nanomaterials. Graphene is a single-atom thick, two-dimensional sheet of hexagonally arranged carbon atoms with unique physical and chemical properties. Recently, graphene has been used in many studies on electronics, photonics, composite materials, energy generation and storage, sensors, and biomedicine. However, the current health risk assessment for graphene has been relatively limited and inconclusive. This study evaluated the toxicity effects of graphene on the airway epithelial cell line BEAS-2B, which represents the first barrier of the human body to interact with airborne graphene particles. Our result showed that graphene can induce the cellular Ca2+ by phospholipase C (PLC) associated pathway by activating epidermal growth factor receptor (EGFR). Subsequently, inositol 1,4,5-triphosphate (IP3) receptors activate the release of Ca2+ from the endoplasmic reticulum (ER) Ca2+ stores. Those Ca2+ signals further trigger the calcium-regulated apoptosis in the cell. Furthermore, the stimulation can cause EGFR upregulation, which have been demonstrated to associate with diseases such as lung cancer, chronic obstructive pulmonary disease (COPD), and cardiovascular diseases. This study highlights the additional health risk considering that it can function as a contributing factor for other respiratory diseases.

  3. Chest wall mechanics and abdominal pressure during general anaesthesia in normal and obese individuals and in acute lung injury.

    Science.gov (United States)

    Pelosi, Paolo; Luecke, Thomas; Rocco, Patricia R M

    2011-02-01

    This article discusses the methods available to evaluate chest wall mechanics and the relationship between intraabdominal pressure (IAP) and chest wall mechanics during general anaesthesia in normal and obese individuals, as well as in acute lung injury/acute respiratory distress syndrome. The interactions between the abdominal and thoracic compartments pose a specific challenge for intensive care physicians. IAP affects respiratory system, lung and chest wall elastance in an unpredictable way. Thus, transpulmonary pressure should be measured if IAP is more than 12 mmHg or if chest wall elastance is compromised for other reasons, even though the absolute values of pleural and transpulmonary pressures are not easily obtained at bedside. We suggest defining intraabdominal hypertension (IAH) as IAP at least 20 mmHg and abdominal compartment syndrome (ACS) as IAP at least 20 mmHg associated with failure of one or more organs, although further studies are required to confirm this hypothesis. Additionally, in the presence of IAH, controlled mechanical ventilation should be applied and positive end-expiratory pressure individually titrated. Prophylactic open abdomen should be considered in the presence of ACS. Increased IAP markedly affects respiratory function and complicates patient management. Frequent assessment of IAP is recommended.

  4. Spirometry and volumetric capnography in lung function assessment of obese and normal-weight individuals without asthma.

    Science.gov (United States)

    Ferreira, Mariana S; Mendes, Roberto T; Marson, Fernando A L; Zambon, Mariana P; Antonio, Maria A R G M; Paschoal, Ilma A; Toro, Adyléia A D C; Severino, Silvana D; Ribeiro, Maria A G O; Ribeiro, José D

    To analyze and compare lung function of obese and healthy, normal-weight children and adolescents, without asthma, through spirometry and volumetric capnography. Cross-sectional study including 77 subjects (38 obese) aged 5-17 years. All subjects underwent spirometry and volumetric capnography. The evaluations were repeated in obese subjects after the use of a bronchodilator. At the spirometry assessment, obese individuals, when compared with the control group, showed lower values of forced expiratory volume in the first second by forced vital capacity (FEV 1 /FVC) and expiratory flows at 75% and between 25 and 75% of the FVC (p11 years (p<0.05). Even without the diagnosis of asthma by clinical criteria and without response to bronchodilator use, obese individuals showed lower FEV 1 /FVC values and forced expiratory flow, indicating the presence of an obstructive process. Volumetric capnography showed that obese individuals had higher alveolar tidal volume, with no alterations in ventilation homogeneity, suggesting flow alterations, without affecting lung volumes. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  5. Dose-modifying factor for captopril for mitigation of radiation injury to normal lung

    Science.gov (United States)

    Medhora, Meetha; Gao, Feng; Fish, Brian L.; Jacobs, Elizabeth R.; Moulder, John E.; Szabo, Aniko

    2012-01-01

    Our goal is to develop countermeasures for pulmonary injury following unpredictable events such as radiological terrorism or nuclear accidents. We have previously demonstrated that captopril, an angiotensin converting enzyme (ACE) inhibitor, is more effective than losartan, an angiotensin type-1 receptor blocker, in mitigating radiation-pneumopathy in a relevant rodent model. In the current study we determined the dose modifying factors (DMFs) of captopril for mitigation of parameters of radiation pneumonitis. We used a whole animal model, irradiating 9–10-week-old female rats derived from a Wistar strain (WAG/RijCmcr) with a single dose of irradiation to the thorax of 11, 12, 13, 14 or 15 Gy. Our study develops methodology to measure DMFs for morbidity (survival) as well as physiological endpoints such as lung function, taking into account attrition due to lethal radiation-induced pneumonitis. Captopril delivered in drinking water (140–180 mg/m2/day, comparable with that given clinically) and started one week after irradiation has a DMF of 1.07–1.17 for morbidity up to 80 days (survival) and 1.21–1.35 for tachypnea at 42 days (at the peak of pneumonitis) after a single dose of ionizing radiation (X-rays). These encouraging results advance our goals, since DMF measurements are essential for drug labeling and comparison with other mitigators. PMID:22843631

  6. Enhanced DNA double-strand break repair of microbeam targeted A549 lung carcinoma cells by adjacent WI38 normal lung fibroblast cells via bi-directional signaling.

    Science.gov (United States)

    Kobayashi, Alisa; Tengku Ahmad, Tengku Ahbrizal Farizal; Autsavapromporn, Narongchai; Oikawa, Masakazu; Homma-Takeda, Shino; Furusawa, Yoshiya; Wang, Jun; Konishi, Teruaki

    2017-10-01

    Understanding the mechanisms underlying the radiation-induced bystander effect (RIBE) and bi-directional signaling between irradiated carcinoma cells and their surrounding non-irradiated normal cells is relevant to cancer radiotherapy. The present study investigated propagation of RIBE signals between human lung carcinoma A549 cells and normal lung fibroblast WI38 cells in bystander cells, either directly or indirectly contacting irradiated A549 cells. We prepared A549-GFP/WI38 co-cultures and A549-GFP/A549 co-cultures, in which A549-GFP cells stably expressing H2BGFP were co-cultured with either A549 cells or WI38 cells, respectively. Using the SPICE-NIRS microbeam, only the A549-GFP cells were irradiated with 500 protons per cell. The level of γ-H2AX, a marker for DNA double-strand breaks (DSB), was subsequently measured for up to 24h post-irradiation in three categories of cells: (1) "targeted"/irradiated A549-GFP cells; (2) "neighboring"/non-irradiated cells directly contacting the "targeted" cells; and (3) "distant"/non-irradiated cells, which were not in direct contact with the "targeted" cells. We found that DSB repair in targeted A549-GFP cells was enhanced by co-cultured WI38 cells. The bystander response in A549-GFP/A549 cell co-cultures, as marked by γ-H2AX levels at 8h post-irradiation, showed a decrease to non-irradiated control level when approaching 24h, while the neighboring/distant bystander WI38 cells in A549-GFP/WI38 co-cultures was maintained at a similar level until 24h post-irradiation. Surprisingly, distant A549-GFP cells in A549-GFP/WI38 co-cultures showed time dependency similar to bystander WI38 cells, but not to distant cells in A549-GFP/A549 co-cultures. These observations indicate that γ-H2AX was induced in WI38 cells as a result of RIBE. WI38 cells were not only involved in rescue of targeted A549, but also in the modification of RIBE against distant A549-GFP cells. The present results demonstrate that radiation-induced bi

  7. Transthoracic lung ultrasound in normal dogs and dogs with cardiogenic pulmonary edema: a pilot study.

    Science.gov (United States)

    Rademacher, Nathalie; Pariaut, Romain; Pate, Julie; Saelinger, Carley; Kearney, Michael T; Gaschen, Lorrie

    2014-01-01

    Pulmonary edema is the most common complication of left-sided heart failure in dogs and early detection is important for effective clinical management. In people, pulmonary edema is commonly diagnosed based on transthoracic ultrasonography and detection of B line artifacts (vertical, narrow-based, well-defined hyperechoic rays arising from the pleural surface). The purpose of this study was to determine whether B line artifacts could also be useful diagnostic predictors for cardiogenic pulmonary edema in dogs. Thirty-one normal dogs and nine dogs with cardiogenic pulmonary edema were prospectively recruited. For each dog, presence or absence of cardiogenic pulmonary edema was based on physical examination, heartworm testing, thoracic radiographs, and echocardiography. A single observer performed transthoracic ultrasonography in all dogs and recorded video clips and still images for each of four quadrants in each hemithorax. Distribution, sonographic characteristics, and number of B lines per thoracic quadrant were determined and compared between groups. B lines were detected in 31% of normal dogs (mean 0.9 ± 0.3 SD per dog) and 100% of dogs with cardiogenic pulmonary edema (mean 6.2 ± 3.8 SD per dog). Artifacts were more numerous and widely distributed in dogs with congestive heart failure (P edema on radiographs. Findings from the current study supported the use of thoracic ultrasonography and detection of B lines as techniques for diagnosing cardiogenic pulmonary edema in dogs. © 2014 American College of Veterinary Radiology.

  8. Damaging and protective bystander cross-talk between human lung cancer and normal cells after proton microbeam irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Desai, Sejal [Radiation Signalling and Cancer Biology Section, Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India); Kobayashi, Alisa; Konishi, Teruaki; Oikawa, Masakazu [Radiation System and Engineering Section, Department of Technical Support and Development, Research, Development and Support Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Pandey, Badri N., E-mail: badrinarain@yahoo.co.in [Radiation Signalling and Cancer Biology Section, Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India)

    2014-05-15

    Graphical abstract: - Highlights: • Proton-microbeam irradiated A549 cells send damaging signals to bystander A549 cells. • Irradiated A549–A549 bystander response is through gap junctional communication. • Bystander WI38 cells exert protective signalling in irradiated A549 cells. • Rescue of irradiated A549 cells by WI38 cells is independent of gap junctions. - Abstract: Most of the studies of radiation-induced bystander effects (RIBE) have been focused on understanding the radiobiological changes observed in bystander cells in response to the signals from irradiated cells in a normal cell population with implications to radiation risk assessment. However, reports on RIBE with relevance to cancer radiotherapy especially investigating the bidirectional and criss-cross bystander communications between cancer and normal cells are limited. Hence, in present study employing co-culture approach, we have investigated the bystander cross-talk between lung cancer (A549) and normal (WI38) cells after proton-microbeam irradiation using γ-H2AX foci fluorescence as a measure of DNA double-strand breaks (DSBs). We observed that in A549–A549 co-cultures, irradiated A549 cells exert damaging effects in bystander A549 cells, which were found to be mediated through gap junctional intercellular communication (GJIC). However, in A549–WI38 co-cultures, irradiated A549 did not affect bystander WI38 cells. Rather, bystander WI38 cells induced inverse protective signalling (rescue effect) in irradiated A549 cells, which was independent of GJIC. On the other hand, in response to irradiated WI38 cells neither of the bystander cells (A549 or WI38) showed significant increase in γ-H2AX foci. The observed bystander signalling between tumour and normal cells may have potential implications in therapeutic outcome of cancer radiotherapy.

  9. Damaging and protective bystander cross-talk between human lung cancer and normal cells after proton microbeam irradiation

    International Nuclear Information System (INIS)

    Desai, Sejal; Kobayashi, Alisa; Konishi, Teruaki; Oikawa, Masakazu; Pandey, Badri N.

    2014-01-01

    Graphical abstract: - Highlights: • Proton-microbeam irradiated A549 cells send damaging signals to bystander A549 cells. • Irradiated A549–A549 bystander response is through gap junctional communication. • Bystander WI38 cells exert protective signalling in irradiated A549 cells. • Rescue of irradiated A549 cells by WI38 cells is independent of gap junctions. - Abstract: Most of the studies of radiation-induced bystander effects (RIBE) have been focused on understanding the radiobiological changes observed in bystander cells in response to the signals from irradiated cells in a normal cell population with implications to radiation risk assessment. However, reports on RIBE with relevance to cancer radiotherapy especially investigating the bidirectional and criss-cross bystander communications between cancer and normal cells are limited. Hence, in present study employing co-culture approach, we have investigated the bystander cross-talk between lung cancer (A549) and normal (WI38) cells after proton-microbeam irradiation using γ-H2AX foci fluorescence as a measure of DNA double-strand breaks (DSBs). We observed that in A549–A549 co-cultures, irradiated A549 cells exert damaging effects in bystander A549 cells, which were found to be mediated through gap junctional intercellular communication (GJIC). However, in A549–WI38 co-cultures, irradiated A549 did not affect bystander WI38 cells. Rather, bystander WI38 cells induced inverse protective signalling (rescue effect) in irradiated A549 cells, which was independent of GJIC. On the other hand, in response to irradiated WI38 cells neither of the bystander cells (A549 or WI38) showed significant increase in γ-H2AX foci. The observed bystander signalling between tumour and normal cells may have potential implications in therapeutic outcome of cancer radiotherapy

  10. Lung density

    DEFF Research Database (Denmark)

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

    1977-01-01

    The density of a defined volume of the human lung can be measured in vivo by a new noninvasive technique. A beam of gamma-rays is directed at the lung and, by measuring the scattered gamma-rays, lung density is calculated. The density in the lower lobe of the right lung in normal man during quiet...

  11. Beta-cryptoxanthin restores nicotine-reduced lung SIRT1 to normal levels and inhibits nicotine-promoted lung tumorigenesis and emphysema in A/J mice

    Science.gov (United States)

    Nicotine, a large constituent of cigarette smoke, is associated with an increased risk of lung cancer, but the data supporting this relationship are inconsistent. Here, we found that nicotine treatment not only induced emphysema but also increased both lung tumor multiplicity and volume in 4-nitrosa...

  12. Extracting the normal lung dose–response curve from clinical DVH data: a possible role for low dose hyper-radiosensitivity, increased radioresistance

    International Nuclear Information System (INIS)

    Gordon, J J; Snyder, K; Zhong, H; Barton, K; Sun, Z; Chetty, I J; Matuszak, M; Ten Haken, R K

    2015-01-01

    In conventionally fractionated radiation therapy for lung cancer, radiation pneumonitis’ (RP) dependence on the normal lung dose-volume histogram (DVH) is not well understood. Complication models alternatively make RP a function of a summary statistic, such as mean lung dose (MLD). This work searches over damage profiles, which quantify sub-volume damage as a function of dose. Profiles that achieve best RP predictive accuracy on a clinical dataset are hypothesized to approximate DVH dependence.Step function damage rate profiles R(D) are generated, having discrete steps at several dose points. A range of profiles is sampled by varying the step heights and dose point locations. Normal lung damage is the integral of R(D) with the cumulative DVH. Each profile is used in conjunction with a damage cutoff to predict grade 2 plus (G2+) RP for DVHs from a University of Michigan clinical trial dataset consisting of 89 CFRT patients, of which 17 were diagnosed with G2+ RP.Optimal profiles achieve a modest increase in predictive accuracy—erroneous RP predictions are reduced from 11 (using MLD) to 8. A novel result is that optimal profiles have a similar distinctive shape: enhanced damage contribution from low doses (<20 Gy), a flat contribution from doses in the range ∼20–40 Gy, then a further enhanced contribution from doses above 40 Gy. These features resemble the hyper-radiosensitivity / increased radioresistance (HRS/IRR) observed in some cell survival curves, which can be modeled using Joiner’s induced repair model.A novel search strategy is employed, which has the potential to estimate RP dependence on the normal lung DVH. When applied to a clinical dataset, identified profiles share a characteristic shape, which resembles HRS/IRR. This suggests that normal lung may have enhanced sensitivity to low doses, and that this sensitivity can affect RP risk. (paper)

  13. Functional interaction between human papillomavirus type 16 E6 and E7 oncoproteins and cigarette smoke components in lung epithelial cells.

    Directory of Open Access Journals (Sweden)

    Juan Pablo Muñoz

    Full Text Available The smoking habit is the most important, but not a sufficient cause for lung cancer development. Several studies have reported the human papillomavirus type 16 (HPV16 presence and E6 and E7 transcripts expression in lung carcinoma cases from different geographical regions. The possible interaction between HPV infection and smoke carcinogens, however, remains unclear. In this study we address a potential cooperation between tobacco smoke and HPV16 E6 and E7 oncoproteins for alterations in proliferative and tumorigenic properties of lung epithelial cells. A549 (alveolar, tumoral and BEAS-2B (bronchial, non-tumoral cell lines were stably transfected with recombinant pLXSN vectors expressing HPV16 E6 and E7 oncoproteins and exposed to cigarette smoke condensate (CSC at different concentrations. HPV16 E6 and E7 expression was associated with loss of p53 stability, telomerase (hTERT and p16(INK4A overexpression in BEAS-2B cells as demonstrated by quantitative real-time polymerase chain reaction (qRT-PCR and western blotting (WB. In A549 cells we observed downregulation of p53 but not a significant increase of hTERT transcripts. In addition, the HPV16 E6/E7 transfected cell lines showed an increased proliferation rate and anchorage-independent growth in a HPV16 E6 and E7 expression-dependent manner. Moreover, both HPV16 E6/E7 and mock transfected cells showed an increased proliferation rate and anchorage-independent growth in the presence of 0.1 and 10 µg/mL CSC. However, this increase was significantly greater in HPV16 E6/E7 transfected cells (p<0.001. Data were confirmed by FCSE proliferation assay. The results obtained in this study are suggestive of a functional interaction between tobacco smoke and HPV16 E6/E7 oncoproteins for malignant transformation and tumorigenesis of lung epithelial cells. More studies are warranted in order to dissect the molecular mechanisms involved in this cooperation.

  14. Acrolein-exposed normal human lung fibroblasts in vitro: cellular senescence, enhanced telomere erosion, and degradation of Werner's syndrome protein.

    Science.gov (United States)

    Jang, Jun-Ho; Bruse, Shannon; Huneidi, Salam; Schrader, Ronald M; Monick, Martha M; Lin, Yong; Carter, A Brent; Klingelhutz, Aloysius J; Nyunoya, Toru

    2014-09-01

    Acrolein is a ubiquitous environmental hazard to human health. Acrolein has been reported to activate the DNA damage response and induce apoptosis. However, little is known about the effects of acrolein on cellular senescence. We examined whether acrolein induces cellular senescence in cultured normal human lung fibroblasts (NHLF). We cultured NHLF in the presence or absence of acrolein and determined the effects of acrolein on cell proliferative capacity, senescence-associated β-galactosidase activity, the known senescence-inducing pathways (e.g., p53, p21), and telomere length. We found that acrolein induced cellular senescence by increasing both p53 and p21. The knockdown of p53 mediated by small interfering RNA (siRNA) attenuated acrolein-induced cellular senescence. Acrolein decreased Werner's syndrome protein (WRN), a member of the RecQ helicase family involved in DNA repair and telomere maintenance. Acrolein-induced down-regulation of WRN protein was rescued by p53 knockdown or proteasome inhibition. Finally, we found that acrolein accelerated p53-mediated telomere shortening. These results suggest that acrolein induces p53-mediated cellular senescence accompanied by enhanced telomere attrition and WRN protein down-regulation.

  15. Radiation dose response of normal lung assessed by Cone Beam CT - a potential tool for biologically adaptive radiation therapy

    DEFF Research Database (Denmark)

    Bertelsen, Anders; Schytte, Tine; Bentzen, Søren M

    2011-01-01

    Density changes of healthy lung tissue during radiotherapy as observed by Cone Beam CT (CBCT) might be an early indicator of patient specific lung toxicity. This study investigates the time course of CBCT density changes and tests for a possible correlation with locally delivered dose....

  16. Influence of air pollution on the lung of adult normal, hyperreactive and asthmatic non smokers. Einfluss der Luftverschmutzung auf die Lunge von Erwachsenen

    Energy Technology Data Exchange (ETDEWEB)

    Matthys, H.; Eltschka, R.; Herceg, R. (Freiburg Univ. (Germany, F.R.). Abt. Pneumologie)

    1990-04-01

    The lung function data, gas (NO{sub 2}, SO{sub 2}) and concentration of dust particles of organic and mineral origine are reported from our longterm study (Freiburg, 1987-1990). Three monthly punctual lung function data measured with whole body plethysmography reflect the changes due to seasonal clima and pollution variations less reliable than continuous peak flow (PEF) measurements. On the other hand PEF-measurements over years suffer from compliance problems. Our SO{sub 2} data are to low to be measured reliable with Palmes diffusion tubes. Therefore they don't correlate with the measured lung function data. Similar results we found for the NO{sub 2} measurements which were with a mean concentration of 40 ng/m{sup 3} relativly low. Multivariant analysis of the measured meteorological and medial data, are in preparation. (orig.).

  17. Transcriptional response to organic compounds from diverse gasoline and biogasoline fuel emissions in human lung cells.

    Science.gov (United States)

    Libalova, Helena; Rossner, Pavel; Vrbova, Kristyna; Brzicova, Tana; Sikorova, Jitka; Vojtisek-Lom, Michal; Beranek, Vit; Klema, Jiri; Ciganek, Miroslav; Neca, Jiri; Machala, Miroslav; Topinka, Jan

    2018-04-01

    Modern vehicles equipped with Gasoline Direct Injection (GDI) engine have emerged as an important source of particulate emissions potentially harmful to human health. We collected and characterized gasoline exhaust particles (GEPs) produced by neat gasoline fuel (E0) and its blends with 15% ethanol (E15), 25% n-butanol (n-But25) and 25% isobutanol (i-But25). To study the toxic effects of organic compounds extracted from GEPs, we analyzed gene expression profiles in human lung BEAS-2B cells. Despite the lowest GEP mass, n-But25 extract contained the highest concentration of polycyclic aromatic hydrocarbons (PAHs), while i-But25 extract the lowest. Gene expression analysis identified activation of the DNA damage response and other subsequent events (cell cycle arrest, modulation of extracellular matrix, cell adhesion, inhibition of cholesterol biosynthesis) following 4 h exposure to all GEP extracts. The i-But25 extract induced the most distinctive gene expression pattern particularly after 24 h exposure. Whereas E0, E15 and n-But25 extract treatments resulted in persistent stress signaling including DNA damage response, MAPK signaling, oxidative stress, metabolism of PAHs or pro-inflammatory response, i-But25 induced changes related to the metabolism of the cellular nutrients required for cell recovery. Our results indicate that i-But25 extract possessed the weakest genotoxic potency possibly due to the low PAH content. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

  19. The expression of Foxp3 and ROR gamma t in lung tissues from normal smokers and chronic obstructive pulmonary disease patients.

    Science.gov (United States)

    Chu, Shuyuan; Zhong, Xiaoning; Zhang, Jianquan; Lao, Qifang; He, Zhiyi; Bai, Jing

    2011-11-01

    Foxp3- and ROR gamma t-expressing cells are involved in acquired immune responses. The change in Foxp3 and ROR gamma t expression in lung tissue and their role in emphysema has not been studied for COPD patients and normal smokers. In the present study, Foxp3 and ROR gamma t were assessed using real-time quantitative polymerase chain reaction and western blotting, and the expression and distribution of Foxp3, IL-17, IL-23R and CCR6 were measured by immunohistochemistry in peripheral lung tissue (10 smokers with COPD, 10 smokers and 10 nonsmokers with normal lung function). Foxp3 expression was lower and ROR gamma t expression was higher in COPD patients when compared with smokers and nonsmokers (all P values were less than 0.001). The ratios of Foxp3/ROR gamma t mRNA and protein were positively correlated to FEV1%pred and negatively correlated to the mean alveoli area. Foxp3(+) cell numbers were decreased, while the number of IL-17(+) cells, IL-23R(+) cells and CCR6(+) cells were increased in the lung alveolar walls of COPD patients compared with normal smokers and nonsmokers (all P values were less than 0.001). The IL-17(+) cell numbers were positively correlated to both CCR6(+) and IL-23R(+) cells. Our data show a decreased Foxp3 expression and an increased ROR gamma t expression in COPD patients and normal smokers that parallels the aggravation of the disease. The IL-17(+)-cell-related cytokines receptors CCR6 and IL-23R had an association with the mechanism of IL-17(+) cell number increasing, which will provide a new immuno-therapeutic target for COPD. Copyright © 2011 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2006-01-01

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

  1. Molecular Mechanisms of Malignant Transformation by Low Dose Cadmium in Normal Human Bronchial Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Laura Cartularo

    Full Text Available Cadmium is a carcinogenic metal, the mechanisms of which are not fully understood. In this study, human bronchial epithelial cells were transformed with sub-toxic doses of cadmium (0.01, 0.05, and 0.1 μM and transformed clones were characterized for gene expression changes using RNA-seq, as well as other molecular measurements. 440 genes were upregulated and 47 genes were downregulated in cadmium clones relative to control clones over 1.25-fold. Upregulated genes were associated mostly with gene ontology terms related to embryonic development, immune response, and cell movement, while downregulated genes were associated with RNA metabolism and regulation of transcription. Several embryonic genes were upregulated, including the transcription regulator SATB2. SATB2 is critical for normal skeletal development and has roles in gene expression regulation and chromatin remodeling. Small hairpin RNA knockdown of SATB2 significantly inhibited growth in soft agar, indicating its potential as a driver of metal-induced carcinogenesis. An increase in oxidative stress and autophagy was observed in cadmium clones. In addition, the DNA repair protein O6-methylguanine-DNA-methyltransferase was depleted by transformation with cadmium. MGMT loss caused significant decrease in cell viability after treatment with the alkylating agent temozolomide, demonstrating diminished capacity to repair such damage. Results reveal various mechanisms of cadmium-induced malignant transformation in BEAS-2B cells including upregulation of SATB2, downregulation of MGMT, and increased oxidative stress.

  2. Radiation dose response of normal lung assessed by Cone Beam CT - A potential tool for biologically adaptive radiation therapy

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    Bertelsen, Anders; Schytte, Tine; Bentzen, Soren M.; Hansen, Olfred; Nielsen, Morten; Brink, Carsten

    2011-01-01

    Background: Density changes of healthy lung tissue during radiotherapy as observed by Cone Beam CT (CBCT) might be an early indicator of patient specific lung toxicity. This study investigates the time course of CBCT density changes and tests for a possible correlation with locally delivered dose. Methods: A total of 665 CBCTs in 65 lung cancer patients treated with IMRT/VMAT to 60 or 66 Gy in 2 Gy fractions were analyzed. For each patient, CBCT lung density changes during the treatment course were related to the locally delivered dose. Results: A dose response is observed for the patient population at the end of the treatment course. However, the observed dose response is highly variable among patients. Density changes at 10th and 20th fraction are clearly correlated to those observed at the end of the treatment course. Conclusions: CBCT density changes in healthy lung tissue during radiotherapy correlate with the locally delivered dose and can be detected relatively early during the treatment. If these density changes are correlated to subsequent clinical toxicity this assay could form the basis for biological adaptive radiotherapy.

  3. Exposure of Human Lung Cells to Tobacco Smoke Condensate Inhibits the Nucleotide Excision Repair Pathway.

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    Nathaniel Holcomb

    Full Text Available Exposure to tobacco smoke is the number one risk factor for lung cancer. Although the DNA damaging properties of tobacco smoke have been well documented, relatively few studies have examined its effect on DNA repair pathways. This is especially true for the nucleotide excision repair (NER pathway which recognizes and removes many structurally diverse DNA lesions, including those introduced by chemical carcinogens present in tobacco smoke. The aim of the present study was to investigate the effect of tobacco smoke on NER in human lung cells. We studied the effect of cigarette smoke condensate (CSC, a surrogate for tobacco smoke, on the NER pathway in two different human lung cell lines; IMR-90 lung fibroblasts and BEAS-2B bronchial epithelial cells. To measure NER, we employed a slot-blot assay to quantify the introduction and removal of UV light-induced 6-4 photoproducts and cyclobutane pyrimidine dimers. We find a dose-dependent inhibition of 6-4 photoproduct repair in both cell lines treated with CSC. Additionally, the impact of CSC on the abundance of various NER proteins and their respective RNAs was investigated. The abundance of XPC protein, which is required for functional NER, is significantly reduced by treatment with CSC while the abundance of XPA protein, also required for NER, is unaffected. Both XPC and XPA RNA levels are modestly reduced by CSC treatment. Finally, treatment of cells with MG-132 abrogates the reduction in the abundance of XPC protein produced by treatment with CSC, suggesting that CSC enhances proteasome-dependent turnover of the protein that is mediated by ubiquitination. Together, these findings indicate that tobacco smoke can inhibit the same DNA repair pathway that is also essential for the removal of some of the carcinogenic DNA damage introduced by smoke itself, increasing the DNA damage burden of cells exposed to tobacco smoke.

  4. Low-solubility particles and a Trojan-horse type mechanism of toxicity: the case of cobalt oxide on human lung cells

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    2014-01-01

    Background The mechanisms of toxicity of metal oxide particles towards lung cells are far from being understood. In particular, the relative contribution of intracellular particulate versus solubilized fractions is rarely considered as it is very challenging to assess, especially for low-solubility particles such as cobalt oxide (Co3O4). Methods This study was possible owing to two highly sensitive, independent, analytical techniques, based on single-cell analysis, using ion beam microanalysis, and on bulk analysis of cell lysates, using mass spectrometry. Results Our study shows that cobalt oxide particles, of very low solubility in the culture medium, are readily incorporated by BEAS-2B human lung cells through endocytosis via the clathrin-dependent pathway. They are partially solubilized at low pH within lysosomes, leading to cobalt ions release. Solubilized cobalt was detected within the cytoplasm and the nucleus. As expected from these low-solubility particles, the intracellular solubilized cobalt content is small compared with the intracellular particulate cobalt content, in the parts-per-thousand range or below. However, we were able to demonstrate that this minute fraction of intracellular solubilized cobalt is responsible for the overall toxicity. Conclusions Cobalt oxide particles are readily internalized by pulmonary cells via the endo-lysosomal pathway and can lead, through a Trojan-horse mechanism, to intracellular release of toxic metal ions over long periods of time, involving specific toxicity. PMID:24669904

  5. Low-solubility particles and a Trojan-horse type mechanism of toxicity: the case of cobalt oxide on human lung cells.

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    Ortega, Richard; Bresson, Carole; Darolles, Carine; Gautier, Céline; Roudeau, Stéphane; Perrin, Laura; Janin, Myriam; Floriani, Magali; Aloin, Valérie; Carmona, Asuncion; Malard, Véronique

    2014-03-27

    The mechanisms of toxicity of metal oxide particles towards lung cells are far from being understood. In particular, the relative contribution of intracellular particulate versus solubilized fractions is rarely considered as it is very challenging to assess, especially for low-solubility particles such as cobalt oxide (Co3O4). This study was possible owing to two highly sensitive, independent, analytical techniques, based on single-cell analysis, using ion beam microanalysis, and on bulk analysis of cell lysates, using mass spectrometry. Our study shows that cobalt oxide particles, of very low solubility in the culture medium, are readily incorporated by BEAS-2B human lung cells through endocytosis via the clathrin-dependent pathway. They are partially solubilized at low pH within lysosomes, leading to cobalt ions release. Solubilized cobalt was detected within the cytoplasm and the nucleus. As expected from these low-solubility particles, the intracellular solubilized cobalt content is small compared with the intracellular particulate cobalt content, in the parts-per-thousand range or below. However, we were able to demonstrate that this minute fraction of intracellular solubilized cobalt is responsible for the overall toxicity. Cobalt oxide particles are readily internalized by pulmonary cells via the endo-lysosomal pathway and can lead, through a Trojan-horse mechanism, to intracellular release of toxic metal ions over long periods of time, involving specific toxicity.

  6. Optimization of automated segmentation of monkeypox virus-induced lung lesions from normal lung CT images using hard C-means algorithm

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    Castro, Marcelo A.; Thomasson, David; Avila, Nilo A.; Hufton, Jennifer; Senseney, Justin; Johnson, Reed F.; Dyall, Julie

    2013-03-01

    Monkeypox virus is an emerging zoonotic pathogen that results in up to 10% mortality in humans. Knowledge of clinical manifestations and temporal progression of monkeypox disease is limited to data collected from rare outbreaks in remote regions of Central and West Africa. Clinical observations show that monkeypox infection resembles variola infection. Given the limited capability to study monkeypox disease in humans, characterization of the disease in animal models is required. A previous work focused on the identification of inflammatory patterns using PET/CT image modality in two non-human primates previously inoculated with the virus. In this work we extended techniques used in computer-aided detection of lung tumors to identify inflammatory lesions from monkeypox virus infection and their progression using CT images. Accurate estimation of partial volumes of lung lesions via segmentation is difficult because of poor discrimination between blood vessels, diseased regions, and outer structures. We used hard C-means algorithm in conjunction with landmark based registration to estimate the extent of monkeypox virus induced disease before inoculation and after disease progression. Automated estimation is in close agreement with manual segmentation.

  7. Nrf2/p62 Signaling in Apoptosis Resistance and Its Role in Cadmium-induced Carcinogenesis*

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    Son, Young-Ok; Pratheeshkumar, Poyil; Roy, Ram Vinod; Hitron, John Andrew; Wang, Lei; Zhang, Zhuo; Shi, Xianglin

    2014-01-01

    The cadmium-transformed human lung bronchial epithelial BEAS-2B cells exhibit a property of apoptosis resistance as compared with normal non-transformed BEAS-2B cells. The level of basal reactive oxygen species (ROS) is extremely low in transformed cells in correlation with elevated expressions of both antioxidant enzymes (catalase, SOD1, and SOD2) and antiapoptotic proteins (Bcl-2/Bcl-xL). Moreover, Nrf2 and p62 are highly expressed in these transformed cells. The knockdown of Nrf2 or p62 by siRNA enhances ROS levels and cadmium-induced apoptosis. The binding activities of Nrf2 on the antioxidant response element promoter regions of p62/Bcl-2/Bcl-xL were dramatically increased in the cadmium-exposed transformed cells. Cadmium exposure increased the formation of LC3-II and the frequency of GFP-LC3 punctal cells in non-transformed BEAS-2B cells, whereas these increases are not shown in transformed cells, an indication of autophagy deficiency of transformed cells. Furthermore, the expression levels of Nrf2 and p62 are dramatically increased during chronic long term exposure to cadmium in the BEAS-2B cells as well as antiapoptotic proteins and antioxidant enzymes. These proteins are overexpressed in the tumor tissues derived from xenograft mouse models. Moreover, the colony growth is significantly attenuated in the transformed cells by siRNA transfection specific for Nrf2 or p62. Taken together, this study demonstrates that cadmium-transformed cells have acquired autophagy deficiency, leading to constitutive p62 and Nrf2 overexpression. These overexpressions up-regulate the antioxidant proteins catalase and SOD and the antiapoptotic proteins Bcl-2 and Bcl-xL. The final consequences are decrease in ROS generation, apoptotic resistance, and increased cell survival, proliferation, and tumorigenesis. PMID:25157103

  8. Expression of human MutT homologue (hMTH1) protein in primary non-small-cell lung carcinomas and histologically normal surrounding tissue.

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    Kennedy, Christopher H; Pass, Harvey I; Mitchell, James B

    2003-06-01

    In situ, oxidation of deoxyguanosine yields 8-hydroxy-2'-deoxyguanosine (8-oxo-dG), which is mutation prone and results in a G:C --> T:A transversion following DNA replication. Another pathway to the formation of DNA containing 8-oxo-dG is by the misincorporation of 8-oxo-dGTP via DNA polymerase. Human MutT homologue (hMTH1), an 8-oxo-dGTPase, prevents misincorporation of this oxidized nucleotide by hydrolyzing 8-oxo-dGTP to 8-oxo-dGMP. Previous studies have shown that hMTH1 mRNA is overexpressed in human renal cell carcinomas and breast tumors. Elevated levels of hMTH1 protein have also been detected in brain tumors. In the current study, we determined whether hMTH1 protein is overexpressed in primary non-small-cell lung carcinomas as compared to adjacent histologically normal lung tissue. Twenty matched human lung tumor/normal pairs were examined by Western analysis for expression of hMTH1 protein. Overexpression in the tumors was detected in 4/8 (50%) adenocarcinomas, 4/4 (100%) adenocarcinomas with bronchioalveolar (BAC) features, 2/2 (100%) BACs, and 3/6 (50%) squamous cell carcinomas. The data from Western analysis were validated by immunohistochemical staining for hMTH1 protein. The results of this study indicate that hMTH1 protein may be a potential marker for the detection of persistent oxidative stress in lung cancer.

  9. Cigarette smoke induces endoplasmic reticulum stress and the unfolded protein response in normal and malignant human lung cells

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    Yang Jin

    2008-08-01

    Full Text Available Abstract Background Although lung cancer is among the few malignancies for which we know the primary etiological agent (i.e., cigarette smoke, a precise understanding of the temporal sequence of events that drive tumor progression remains elusive. In addition to finding that cigarette smoke (CS impacts the functioning of key pathways with significant roles in redox homeostasis, xenobiotic detoxification, cell cycle control, and endoplasmic reticulum (ER functioning, our data highlighted a defensive role for the unfolded protein response (UPR program. The UPR promotes cell survival by reducing the accumulation of aberrantly folded proteins through translation arrest, production of chaperone proteins, and increased degradation. Importance of the UPR in maintaining tissue health is evidenced by the fact that a chronic increase in defective protein structures plays a pathogenic role in diabetes, cardiovascular disease, Alzheimer's and Parkinson's syndromes, and cancer. Methods Gene and protein expression changes in CS exposed human cell cultures were monitored by high-density microarrays and Western blot analysis. Tissue arrays containing samples from 110 lung cancers were probed with antibodies to proteins of interest using immunohistochemistry. Results We show that: 1 CS induces ER stress and activates components of the UPR; 2 reactive species in CS that promote oxidative stress are primarily responsible for UPR activation; 3 CS exposure results in increased expression of several genes with significant roles in attenuating oxidative stress; and 4 several major UPR regulators are increased either in expression (i.e., BiP and eIF2α or phosphorylation (i.e., phospho-eIF2α in a majority of human lung cancers. Conclusion These data indicate that chronic ER stress and recruitment of one or more UPR effector arms upon exposure to CS may play a pivotal role in the etiology or progression of lung cancers, and that phospho-eIF2α and BiP may have

  10. Evaluations of thyme extract effects in human normal bronchial and tracheal epithelial cell lines and in human lung cancer cell line.

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    Oliviero, Marinelli; Romilde, Iannarelli; Beatrice, Morelli Maria; Matteo, Valisi; Giovanna, Nicotra; Consuelo, Amantini; Claudio, Cardinali; Giorgio, Santoni; Filippo, Maggi; Massimo, Nabissi

    2016-08-25

    Thyme (Thymus vulgaris) is used traditionally to prepare herbal remedies possessing expectorant, mucolytic, antitussive and antispasmodic properties. The aim of the present study was to investigate the effects of a standardized hydroalcoholic extract of thyme on primary human airway (bronchial/tracheal) epithelial cell lines in a model of lung inflammation induced by LPS. In addition, the effects of thyme extract on human lung cancer cell line (H460) were analysed. Thyme extract showed significant anti-inflammatory properties by reducing the NF-κB p65 and NF-κB p52 transcription factors protein levels followed by the decrease of pro-inflammatory cytokines (IL-1 beta and IL-8), and Muc5ac secretion in human normal bronchial and tracheal epithelial cells. Moreover, the extract showed cytotoxic effects on H460 cancer cells, modulated the release of IL-1 beta, IL-8 and down-regulated NF-κB p65 and NF-κB p52 proteins. Taken together, these results substantiated the traditional uses of thyme in the treatment of respiratory diseases. Thyme extract might be an effective treatment of chronic diseases based on inflammatory processes when hypersecretion of mucus overwhelms the ciliary clearance and obstructs airways, causing morbidity and mortality. Moreover thyme extract, evaluated in H460 lung cancer cell line, demonstrated to induce cell cytotoxicity in addition to reduce inflammatory cell signals. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Normal Lung Quantification in Usual Interstitial Pneumonia Pattern: The Impact of Threshold-based Volumetric CT Analysis for the Staging of Idiopathic Pulmonary Fibrosis.

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    Hirotsugu Ohkubo

    Full Text Available Although several computer-aided computed tomography (CT analysis methods have been reported to objectively assess the disease severity and progression of idiopathic pulmonary fibrosis (IPF, it is unclear which method is most practical. A universal severity classification system has not yet been adopted for IPF.The purpose of this study was to test the correlation between quantitative-CT indices and lung physiology variables and to determine the ability of such indices to predict disease severity in IPF.A total of 27 IPF patients showing radiological UIP pattern on high-resolution (HR CT were retrospectively enrolled. Staging of IPF was performed according to two classification systems: the Japanese and GAP (gender, age, and physiology staging systems. CT images were assessed using a commercially available CT imaging analysis workstation, and the whole-lung mean CT value (MCT, the normally attenuated lung volume as defined from -950 HU to -701 Hounsfield unit (NL, the volume of the whole lung (WL, and the percentage of NL to WL (NL%, were calculated.CT indices (MCT, WL, and NL closely correlated with lung physiology variables. Among them, NL strongly correlated with forced vital capacity (FVC (r = 0.92, P <0.0001. NL% showed a large area under the receiver operating characteristic curve for detecting patients in the moderate or advanced stages of IPF. Multivariable logistic regression analyses showed that NL% is significantly more useful than the percentages of predicted FVC and predicted diffusing capacity of the lungs for carbon monoxide (Japanese stage II/III/IV [odds ratio, 0.73; 95% confidence intervals (CI, 0.48 to 0.92; P < 0.01]; III/IV [odds ratio. 0.80; 95% CI 0.59 to 0.96; P < 0.01]; GAP stage II/III [odds ratio, 0.79; 95% CI, 0.56 to 0.97; P < 0.05].The measurement of NL% by threshold-based volumetric CT analysis may help improve IPF staging.

  12. Overexpression of microRNA-155 suppresses chemokine expression induced by Interleukin-13 in BEAS-2B human bronchial epithelial cells

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    Satoshi Matsukura

    2016-09-01

    Conclusions: miR-155 specifically inhibits IL-13-induced expression of eosinophilic chemokines CCL11 and CCL26 in bronchial epithelial cells, even though the 3'-untranslated region of these genes do not contain a consensus binding site for miR-155.

  13. SU-E-T-630: Predictive Modeling of Mortality, Tumor Control, and Normal Tissue Complications After Stereotactic Body Radiotherapy for Stage I Non-Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Lindsay, WD; Berlind, CG; Gee, JC; Simone, CB

    2015-01-01

    Purpose: While rates of local control have been well characterized after stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC), less data are available characterizing survival and normal tissue toxicities, and no validated models exist assessing these parameters after SBRT. We evaluate the reliability of various machine learning techniques when applied to radiation oncology datasets to create predictive models of mortality, tumor control, and normal tissue complications. Methods: A dataset of 204 consecutive patients with stage I non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT) at the University of Pennsylvania between 2009 and 2013 was used to create predictive models of tumor control, normal tissue complications, and mortality in this IRB-approved study. Nearly 200 data fields of detailed patient- and tumor-specific information, radiotherapy dosimetric measurements, and clinical outcomes data were collected. Predictive models were created for local tumor control, 1- and 3-year overall survival, and nodal failure using 60% of the data (leaving the remainder as a test set). After applying feature selection and dimensionality reduction, nonlinear support vector classification was applied to the resulting features. Models were evaluated for accuracy and area under ROC curve on the 81-patient test set. Results: Models for common events in the dataset (such as mortality at one year) had the highest predictive power (AUC = .67, p < 0.05). For rare occurrences such as radiation pneumonitis and local failure (each occurring in less than 10% of patients), too few events were present to create reliable models. Conclusion: Although this study demonstrates the validity of predictive analytics using information extracted from patient medical records and can most reliably predict for survival after SBRT, larger sample sizes are needed to develop predictive models for normal tissue toxicities and more advanced

  14. Epithelium-Specific Ets-Like Transcription Factor 1, ESE-1, Regulates ICAM-1 Expression in Cultured Lung Epithelial Cell Lines

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    Zhiqi Yu

    2015-01-01

    Full Text Available Cystic fibrosis (CF patients suffer from chronic airway inflammation with excessive neutrophil infiltration. Migration of neutrophils to the lung requires chemokine and cytokine signaling as well as cell adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1, which plays an important role in mediating adhesive interactions between effector and target cells in the immune system. In this study, we investigated the relationship between ICAM-1 and epithelium-specific ETS-like transcription factor 1 (ESE-1 and found that ICAM-1 expression is upregulated in cell lines of CF (IB3-1 as well as non-CF (BEAS-2B and A549 epithelial origin in response to inflammatory cytokine stimulation. Since ESE-1 is highly expressed in A549 cells without stimulation, we examined the effect of ESE-1 knockdown on ICAM-1 expression in these cells. We found that ICAM-1 expression was downregulated when ESE-1 was knocked down in A549 cells. We also tested the effect of ESE-1 knockdown on cell-cell interactions and demonstrate that the knocking down ESE-1 in A549 cells reduce their interactions with HL-60 cells (human promyelocytic leukemia cell line. These results suggest that ESE-1 may play a role in regulating airway inflammation by regulating ICAM-1 expression.

  15. Gene expression profiles in asbestos-exposed epithelial and mesothelial lung cell lines

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    Kaski Samuel

    2007-03-01

    Full Text Available Abstract Background Asbestos has been shown to cause chromosomal damage and DNA aberrations. Exposure to asbestos causes many lung diseases e.g. asbestosis, malignant mesothelioma, and lung cancer, but the disease-related processes are still largely unknown. We exposed the human cell lines A549, Beas-2B and Met5A to crocidolite asbestos and determined time-dependent gene expression profiles by using Affymetrix arrays. The hybridization data was analyzed by using an algorithm specifically designed for clustering of short time series expression data. A canonical correlation analysis was applied to identify correlations between the cell lines, and a Gene Ontology analysis method for the identification of enriched, differentially expressed biological processes. Results We recognized a large number of previously known as well as new potential asbestos-associated genes and biological processes, and identified chromosomal regions enriched with genes potentially contributing to common responses to asbestos in these cell lines. These include genes such as the thioredoxin domain containing gene (TXNDC and the potential tumor suppressor, BCL2/adenovirus E1B 19kD-interacting protein gene (BNIP3L, GO-terms such as "positive regulation of I-kappaB kinase/NF-kappaB cascade" and "positive regulation of transcription, DNA-dependent", and chromosomal regions such as 2p22, 9p13, and 14q21. We present the complete data sets as Additional files. Conclusion This study identifies several interesting targets for further investigation in relation to asbestos-associated diseases.

  16. Modulation of the ρ/rock pathway in heart and lung after thorax irradiation reveals targets to improve normal tissue toxicity

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    Monceau, V.; Pasinetti, N.; Schupp, C.; Pouzoulet, F.; Opolon, P.; Vozenin, M.C.

    2010-01-01

    The medical options available to prevent or treat radiation-induced injury are scarce and developing effective countermeasures is still an open research field. In addition, more than half of cancer patients are treated with radiation therapy, which displays a high antitumor efficacy but can cause, albeit rarely, disabling long-term toxicities including radiation fibrosis. Progress has been made in the definition of molecular pathways associated with normal tissue toxicity that suggest potentially effective therapeutic targets. Targeting the Rho/ROCK pathway seems a promising anti-fibrotic approach, at least in the gut; the current study was performed to assess whether this target was relevant to the prevention and/or treatment of injury to the main thoracic organs, namely heart and lungs. First, we showed activation of two important fibro-genic pathways (Smad and Rho/ROCK) in response to radiation-exposure to adult cardio-myocytes; we extended these observations in vivo to the heart and lungs of mice, 15 and 30 weeks post-irradiation. We correlated this fibro-genic molecular imprint with alteration of heart physiology and long-term remodelling of pulmonary and cardiac histological structures. Lastly, cardiac and pulmonary radiation injury and bleomycin-induced pulmonary fibrosis were successfully modulated using Rho/ROCK inhibitors (statins and Y-27632) and this was associated with a normalization of fibro-genic markers. In conclusion, the present paper shows for the first time, activation of Rho/ROCK and Smad pathways in pulmonary and cardiac radiation-induced delayed injury. Our findings thereby reveal a safe and efficient therapeutic opportunity for the abrogation of late thoracic radiation injury, potentially usable either before or after radiation exposure; this approach is especially attractive in (1) the radiation oncology setting, as it does not interfere with prior anti-cancer treatment and in (2) radioprotection, as applicable to the treatment of

  17. Modulation of the Rho/ROCK pathway in heart and lung after thorax irradiation reveals targets to improve normal tissue toxicity.

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    Monceau, Virginie; Pasinetti, Nadia; Schupp, Charlotte; Pouzoulet, Fred; Opolon, Paule; Vozenin, Marie-Catherine

    2010-11-01

    The medical options available to prevent or treat radiation-induced injury are scarce and developing effective countermeasures is still an open research field. In addition, more than half of cancer patients are treated with radiation therapy, which displays a high antitumor efficacy but can cause, albeit rarely, disabling long-term toxicities including radiation fibrosis. Progress has been made in the definition of molecular pathways associated with normal tissue toxicity that suggest potentially effective therapeutic targets. Targeting the Rho/ROCK pathway seems a promising anti-fibrotic approach, at least in the gut; the current study was performed to assess whether this target was relevant to the prevention and/or treatment of injury to the main thoracic organs, namely heart and lungs. First, we showed activation of two important fibrogenic pathways (Smad and Rho/ROCK) in response to radiation-exposure to adult cardiomyocytes; we extended these observations in vivo to the heart and lungs of mice, 15 and 30 weeks post-irradiation. We correlated this fibrogenic molecular imprint with alteration of heart physiology and long-term remodelling of pulmonary and cardiac histological structures. Lastly, cardiac and pulmonary radiation injury and bleomycin-induced pulmonary fibrosis were successfully modulated using Rho/ROCK inhibitors (statins and Y-27632) and this was associated with a normalization of fibrogenic markers. In conclusion, the present paper shows for the first time, activation of Rho/ROCK and Smad pathways in pulmonary and cardiac radiation-induced delayed injury. Our findings thereby reveal a safe and efficient therapeutic opportunity for the abrogation of late thoracic radiation injury, potentially usable either before or after radiation exposure; this approach is especially attractive in (1) the radiation oncology setting, as it does not interfere with prior anti-cancer treatment and in (2) radioprotection, as applicable to the treatment of established

  18. Effect of mixing scanner types and reconstruction kernels on the characterization of lung parenchymal pathologies: emphysema, interstitial pulmonary fibrosis and normal non-smokers

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    Xu, Ye; van Beek, Edwin J.; McLennan, Geoffrey; Guo, Junfeng; Sonka, Milan; Hoffman, Eric

    2006-03-01

    In this study we utilize our texture characterization software (3-D AMFM) to characterize interstitial lung diseases (including emphysema) based on MDCT generated volumetric data using 3-dimensional texture features. We have sought to test whether the scanner and reconstruction filter (kernel) type affect the classification of lung diseases using the 3-D AMFM. We collected MDCT images in three subject groups: emphysema (n=9), interstitial pulmonary fibrosis (IPF) (n=10), and normal non-smokers (n=9). In each group, images were scanned either on a Siemens Sensation 16 or 64-slice scanner, (B50f or B30 recon. kernel) or a Philips 4-slice scanner (B recon. kernel). A total of 1516 volumes of interest (VOIs; 21x21 pixels in plane) were marked by two chest imaging experts using the Iowa Pulmonary Analysis Software Suite (PASS). We calculated 24 volumetric features. Bayesian methods were used for classification. Images from different scanners/kernels were combined in all possible combinations to test how robust the tissue classification was relative to the differences in image characteristics. We used 10-fold cross validation for testing the result. Sensitivity, specificity and accuracy were calculated. One-way Analysis of Variances (ANOVA) was used to compare the classification result between the various combinations of scanner and reconstruction kernel types. This study yielded a sensitivity of 94%, 91%, 97%, and 93% for emphysema, ground-glass, honeycombing, and normal non-smoker patterns respectively using a mixture of all three subject groups. The specificity for these characterizations was 97%, 99%, 99%, and 98%, respectively. The F test result of ANOVA shows there is no significant difference (p <0.05) between different combinations of data with respect to scanner and convolution kernel type. Since different MDCT and reconstruction kernel types did not show significant differences in regards to the classification result, this study suggests that the 3-D AMFM can

  19. Acrolein-Exposed Normal Human Lung Fibroblasts in Vitro: Cellular Senescence, Enhanced Telomere Erosion, and Degradation of Werner’s Syndrome Protein

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    Jang, Jun-Ho; Bruse, Shannon; Huneidi, Salam; Schrader, Ronald M.; Monick, Martha M.; Lin, Yong; Carter, A. Brent; Klingelhutz, Aloysius J.

    2014-01-01

    Background: Acrolein is a ubiquitous environmental hazard to human health. Acrolein has been reported to activate the DNA damage response and induce apoptosis. However, little is known about the effects of acrolein on cellular senescence. Objectives: We examined whether acrolein induces cellular senescence in cultured normal human lung fibroblasts (NHLF). Methods: We cultured NHLF in the presence or absence of acrolein and determined the effects of acrolein on cell proliferative capacity, senescence-associated β-galactosidase activity, the known senescence-inducing pathways (e.g., p53, p21), and telomere length. Results: We found that acrolein induced cellular senescence by increasing both p53 and p21. The knockdown of p53 mediated by small interfering RNA (siRNA) attenuated acrolein-induced cellular senescence. Acrolein decreased Werner’s syndrome protein (WRN), a member of the RecQ helicase family involved in DNA repair and telomere maintenance. Acrolein-induced down-regulation of WRN protein was rescued by p53 knockdown or proteasome inhibition. Finally, we found that acrolein accelerated p53-mediated telomere shortening. Conclusions: These results suggest that acrolein induces p53-mediated cellular senescence accompanied by enhanced telomere attrition and WRN protein down-regulation. Citation: Jang JH, Bruse S, Huneidi S, Schrader RM, Monick MM, Lin Y, Carter AB, Klingelhutz AJ, Nyunoya T. 2014. Acrolein-exposed normal human lung fibroblasts in vitro: cellular senescence, enhanced telomere erosion, and degradation of Werner’s syndrome protein. Environ Health Perspect 122:955–962; http://dx.doi.org/10.1289/ehp.1306911 PMID:24747221

  20. Bone Morphogenetic Protein (BMP-4 and BMP-7 regulate differentially Transforming Growth Factor (TGF-β1 in normal human lung fibroblasts (NHLF

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    Lloyd Clare M

    2010-06-01

    Full Text Available Abstract Background Airway remodelling is thought to be under the control of a complex group of molecules belonging to the Transforming Growth Factor (TGF-superfamily. The Bone Morphogenetic Proteins (BMPs belong to this family and have been shown to regulate fibrosis in kidney and liver diseases. However, the role of BMPs in lung remodelling remains unclear. BMPs may regulate tissue remodelling in asthma by controlling TGF-β-induced profibrotic functions in lung fibroblasts. Methods Cell cultures were exposed to TGF-β1 alone or in the presence of BMP-4 or BMP-7; control cultures were exposed to medium only. Cell proliferation was assessed by quantification of the incorporation of [3H]-thymidine. The expression of the mRNA encoding collagen type I and IV, tenascin C and fibronectin in normal human lung fibroblasts (NHLF was determined by real-time quantitative PCR and the main results were confirmed by ELISA. Cell differentiation was determined by the analysis of the expression of α-smooth muscle actin (α-SMA by western blot and immunohistochemistry. The effect on matrix metalloproteinase (MMP activity was assessed by zymography. Results We have demonstrated TGF-β1 induced upregulation of mRNAs encoding the extracellular matrix proteins, tenascin C, fibronectin and collagen type I and IV when compared to unstimulated NHLF, and confirmed these results at the protein level. BMP-4, but not BMP-7, reduced TGF-β1-induced extracellular matrix protein production. TGF-β1 induced an increase in the activity of the pro-form of MMP-2 which was inhibited by BMP-7 but not BMP-4. Both BMP-4 and BMP-7 downregulated TGF-β1-induced MMP-13 release compared to untreated and TGF-β1-treated cells. TGF-β1 also induced a myofibroblast-like transformation which was partially inhibited by BMP-7 but not BMP-4. Conclusions Our study suggests that some regulatory properties of BMP-7 may be tissue or cell type specific and unveil a potential regulatory role for

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

    Science.gov (United States)

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

    2015-10-10

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

  2. [Study on the Relationship Between Normalization of Tumor Microvessels and CA9 for Rh-Endostatin to Inhibit Lewis Lung Cancer].

    Science.gov (United States)

    He, Lang; Sun, Yong-Hong; Liu, Kang; Xu, Xing-Xing; Yang, Mi; Wu, Xun; Jiang, Li

    2017-05-01

    To explore the relationship between normalization of tumor microvessels and CA9 for rh-Endostatin to inhibit Lewis lung cancer (LLC) and the expression level of CA9 in LLC. Lewis cells of logarithmic growth phase were collected and made into 1×10 6 mL -1 cell suspensions were prepared. The transplanted tumor model of LLC was established on C57/BL6 mice by injected 0.2 mL cell suspensions/mice into 40 C57/BL6 mice. 40 LLC mice were randomly divided into control group and rh-ES group (20 mice per group). Control group experienced treatment of intraperitoneal injection (ip) for 0.2 mL NS/d, while rh-ES group was treated for 5 mg rh-ES/(kg·d) from the first to the ninth day. The samples of 5 mice were obtained from day 2, day 4, day 6 and day 9 after treatment in control group or rh-ES group, respectively. CA9 was tested by IHC in LLC and paracancerous tissues and estimated by RT-PCR and ELISA in the each time point of both rh-ES group and control group,respectively. The transplanted tumor model of LLC on C57/BL6 mice was established successfully. The expression of CA9 decreased on day 4 and day 6 in rh-ES group estimated by RT-PCR and ELISA, which indicated some great significance when compared with day 2, day 9 in rh-ES group and day 4, day 6 in control group ( P Rh-ES could have positive effect on LLC model of C57/BL6 mice, in day 4-6 (a brief normalized time course) decreased the expression of CA9 and reversed the tumor hypoxia.

  3. [The clinical characteristics of intra-acinar pulmonary artery inflammation and its effect on clinical parameters in smokers with normal lung function and patients with chronic obstructive pulmonary disease].

    Science.gov (United States)

    Lao, Qi-fang; Zhong, Xiao-ning; He, Zhi-yi; Liu, Guang-nan; Lü, Zi-li; Wan, Peng

    2011-10-01

    To study the pathological characteristics of intra-acinar pulmonary artery inflammation and its correlation with smoking index and disease progression in smokers with normal lung function and smokers with chronic obstructive pulmonary disease (COPD). Patients requiring lung resection for peripheral lung cancer were divided into group A (nonsmokers with normal lung function, n = 10), group B (smokers with normal lung function, n = 13), and group C (smokers with stable COPD, n = 10). The lung tissue far away from tumor were resected to compare the pathological changes of intra-acinar pulmonary arteries and infiltration level of inflammatory cell in pulmonary non-muscularized arteries (NMA), pulmonary partially muscularized arteries (PMA) and muscularized arteries (MA) among the three groups. The correlation analysis was made among infiltration level, smoking index, percentage of predicted value of forced expiratory volume in one second (FEV(1)%Pred), six-minute-walk distance (6MWD) and BODE index. (1) Both group B and group C showed the intima and media thickness of MA was significantly higher, the lumen area of MA was narrower and the proportion of MA was higher, and collagenous fiber of MA adventitial proliferated and area increased in group C (P arteries that contained leukocytes, T lymphocytes, CD(8)(+)T lymphocytes and the number of these positive cells infiltrating the intra-acinar pulmonary arteries were increased, especially an increased number of CD(8)(+)T lymphocytes infiltrating in the arterial adventitia as compared with group A, moreover there were significant difference between group C and group B (P 0.05). (3) The number of leukocytes, T lymphocytes, CD(8)(+)T lymphocytes infiltrating MA showed a positive correlation with the thickness of MA (r = 0.563, 0.627, 0.589, P arterial inflammation appears in smokers with normal lung function and smokers with COPD patients. It involves in all types of intra-acinar pulmonary arteries especially NMA and

  4. Comparative study on cytotoxicity effect of biological and commercial synthesized nanosilver on human gastric carcinoma and normal lung fibroblast cell lines

    Directory of Open Access Journals (Sweden)

    Mohammad Ali Rashmezad

    2015-03-01

    Full Text Available Background: Biosynthesis of nanoparticles has attracted the attention of the scientific community in nanotechnology and biotechnology due to their extensive application in the area of material sciences and medicine. Nowadays, despite a various application of nanomaterial’s, there is a little information about their impact on human health. In this study, we investigated the comparative study on cytotoxicity effect of biological and commercial synthesized nanosilver on human gastric carcinoma (AGS and normal lung fibroblast (MRC-5 cell lines. Methods: The current experimental study was carried out in Islamic Azad University, East Tehran Branch, from April to November 2014. The biological synthesis of nanosilver was obtained from Eucalyptus plant extract as a reducing agent. Further to more analysis, morphological study on size and shape of developed biological nanosilver was characterized by performing scanning electron microscopy and dynamic light scattering. AGS and MCR-5 cell lines were treated with various concentration of nanosilver for 24, 48 and 72 hours. Finally, the cell viability was evaluated by using MTT assay. Results: The results show that the nanosilver exerts a dose-dependent inhibitory effect on viability of cells. At 100µg/mL of commercial and biological synthesized nanosilver, the viability of AGS was reduced to 7.47±0.002% (P=0.002 and 3.65±0.01% (P=0.003 after 72 hours, respectively. In addition, the viability of MRC-5 at the same condition was reduced to 10.27±0.19% (P=0.001 and 9.16±1.53% (P=0.002, respectively. Conclusion: Based on a thorough literature surveys, the present study is the first research about biosynthesis of nanosilver using Eucalyptus plant extract. This eco-friendly and cost effective method can be used for large scale production of silver nanoparticle. In addition, based on the current obtained data, commercial and biological synthesized nanosilver can more inhibitory effect on cancer cells compared

  5. Cytotoxic and genotoxic responses of human lung cells to combustion smoke particles of Miscanthus straw, softwood and beech wood chips

    Science.gov (United States)

    Arif, Ali Talib; Maschowski, Christoph; Garra, Patxi; Garcia-Käufer, Manuel; Petithory, Tatiana; Trouvé, Gwenaëlle; Dieterlen, Alain; Mersch-Sundermann, Volker; Khanaqa, Polla; Nazarenko, Irina; Gminski, Richard; Gieré, Reto

    2017-08-01

    Inhalation of particulate matter (PM) from residential biomass combustion is epidemiologically associated with cardiovascular and pulmonary diseases. This study investigates PM0.4-1 emissions from combustion of commercial Miscanthus straw (MS), softwood chips (SWC) and beech wood chips (BWC) in a domestic-scale boiler (40 kW). The PM0.4-1 emitted during combustion of the MS, SWC and BWC were characterized by ICP-MS/OES, XRD, SEM, TEM, and DLS. Cytotoxicity and genotoxicity in human alveolar epithelial A549 and human bronchial epithelial BEAS-2B cells were assessed by the WST-1 assay and the DNA-Alkaline Unwinding Assay (DAUA). PM0.4-1 uptake/translocation in cells was investigated with a new method developed using a confocal reflection microscope. SWC and BWC had a inherently higher residual water content than MS. The PM0.4-1 emitted during combustion of SWC and BWC exhibited higher levels of Polycyclic Aromatic Hydrocarbons (PAHs), a greater variety of mineral species and a higher heavy metal content than PM0.4-1 from MS combustion. Exposure to PM0.4-1 from combustion of SWC and BWC induced cytotoxic and genotoxic effects in human alveolar and bronchial cells, whereby the strongest effect was observed for BWC and was comparable to that caused by diesel PM (SRM 2 975), In contrast, PM0.4-1 from MS combustion did not induce cellular responses in the studied lung cells. A high PAH content in PM emissions seems to be a reliable chemical marker of both combustion efficiency and particle toxicity. Residual biomass water content strongly affects particulate emissions and their toxic potential. Therefore, to minimize the harmful effects of fine PM on health, improvement of combustion efficiency (aiming to reduce the presence of incomplete combustion products bound to PM) and application of fly ash capture technology, as well as use of novel biomass fuels like Miscanthus straw is recommended.

  6. Anti-oxidative and inflammatory responses induced by fly ash particles and carbon black in lung epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Diabate, Silvia; Plaumann, Diana; Uebel, Caroline; Weiss, Carsten [Karlsruhe Institute of Technology, Institute of Toxicology and Genetics, Eggenstein-Leopoldshafen (Germany); Bergfeldt, Britta [Karlsruhe Institute of Technology, Institute of Technical Chemistry, Eggenstein-Leopoldshafen (Germany)

    2011-12-15

    Combustion-derived nanoparticles as constituents of ambient particulate matter have been shown to induce adverse health effects due to inhalation. However, the components inducing these effects as well as the biological mechanisms are still not fully understood. The fine fraction of fly ash particles collected from the electrostatic precipitator of a municipal solid waste incinerator was taken as an example for real particles with complex composition released into the atmosphere to study the mechanism of early biological responses of BEAS-2B human lung epithelial cells. The studies include the effects of the water-soluble and -insoluble fractions of the fly ash and the well-studied carbon black nanoparticles were used as a reference. Fly ash induced reactive oxygen species (ROS) and increased the total cellular glutathione (tGSH) content. Carbon black also induced ROS generation; however, in contrast to the fly ash, it decreased the intracellular tGSH. The fly ash-induced oxidative stress was correlated with induction of the anti-oxidant enzyme heme oxygenase-1 and increase of the redox-sensitive transcription factor Nrf2. Carbon black was not able to induce HO-1. ROS generation, tGSH increase and HO-1 induction were only induced by the insoluble fraction of the fly ash, not by the water-soluble fraction. ROS generation and HO-1 induction were markedly inhibited by pre-incubation of the cells with the anti-oxidant N-acetyl cysteine which confirmed the involvement of oxidative stress. Both effects were also reduced by the metal chelator deferoxamine indicating a contribution of bioavailable transition metals. In summary, both fly ash and carbon black induce ROS but only fly ash induced an increase of intracellular tGSH and HO-1 production. Bioavailable transition metals in the solid water-insoluble matrix of the fly ash mostly contribute to the effects. (orig.)

  7. Diagnosis of disorders of oxygenation and thoracopulmonary restriction during mechanical ventilation of lungs from the point of view of normal and pathological physiology

    Directory of Open Access Journals (Sweden)

    М. Г. Чеченин

    2015-10-01

    Full Text Available The goal of the study was to develop methods for diagnosing oxygenation disorders and thoracopulmonary restriction during respiratory support and to evaluate their efficacy. 206 patients receiving prolonged respiratory support were included in the study. The developed method of diagnosing oxygenation disorders during respiratory support is 1.4 times faster than the Murrays lung ingury score. Sensitivity and specificity oftheauthorsmethod fordiagnosing thoracopulmonaryrestrictionamounted to0.897and 0.838 respectively as compared to 0.47 and 0.189 achieved by using the Murrays lung injury score. A new modification of the acute lung injury score including a respiratory function calculator was also developed.

  8. A novel synthetic analog of militarin, MA-1 induces mitochondrial dependent apoptosis by ROS generation in human lung cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Deok Hyo; Lim, Mi-Hee [Department of Biochemistry, Kangwon National University, Chuncheon 200-701 (Korea, Republic of); Lee, Yu Ran [Department of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747 (Korea, Republic of); Sung, Gi-Ho [Mushroom Research Division, National Institute of Horticultural and Herbal Science, Rural Development Administration, Suwon 404-707 (Korea, Republic of); Lee, Tae-Ho [R and D Center, Dong-A Pharmaceutical Co, Ltd, Yongin 446-905 (Korea, Republic of); Jeon, Byeong Hwa [Department of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747 (Korea, Republic of); Cho, Jae Youl [Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Song, Won O. [Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824 (United States); Park, Haeil [College of Pharmacy, Kangwon National University, Chuncheon 200-701 (Korea, Republic of); Choi, Sunga, E-mail: sachoi@cnu.ac.kr [Department of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747 (Korea, Republic of); Kim, Tae Woong, E-mail: tawkim@kangwon.ac.kr [Department of Biochemistry, Kangwon National University, Chuncheon 200-701 (Korea, Republic of)

    2013-12-15

    A synthetic Militarin analog-1[(2R,3R,4R,5R)-1,6-bis(4-(2,4,4-trimethylpentan-2-yl)phenoxy) hexane-2,3,4,5-tetraol] is a novel derivative of constituents from Cordyceps militaris, which has been used to treat a variety of chronic diseases including inflammation, diabetes, hyperglycemia and cancers. Here, we report for the first time the synthesis of Militarin analog-1 (MA-1) and the apoptotic mechanism of MA-1 against human lung cancer cell lines. Treatment with MA-1 significantly inhibited the viability of 3 human lung cancer cell lines. The inhibition of viability and growth in MA-1-treated A549 cells with an IC{sub 50} of 5 μM were mediated through apoptosis induction, as demonstrated by an increase in DNA fragmentation, sub-G{sub 0}/G{sub 1}-DNA fraction, nuclear condensation, and phosphatidylserine exposure. The apoptotic cell death caused mitochondrial membrane permeabilization through regulation of expression of the Bcl-2 family proteins, leading to cytochrome c release in a time-dependent manner. Subsequently, the final stage of apoptosis, activation of caspase-9/-3 and cleavage of poly (ADP ribose) polymerase, was induced. Furthermore, A549 lung cancer cells were more responsive to MA-1 than a bronchial epithelial cell line (BEAS-2B), involving the rapid generation of reactive oxygen species (ROS), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) activation. The pharmacological inhibition of ROS generation and JNK/p38 MAPK exhibited attenuated DNA fragmentation in MA-1-induced apoptosis. Oral administration of MA-1 also retarded growth of A549 orthotopic xenografts. In conclusion, the present study indicates that the new synthetic derivative MA-1 triggers mitochondrial apoptosis through ROS generation and regulation of MAPKs and may be a potent therapeutic agent against human lung cancer. - Highlights: • We report a novel synthesized derivative, militarin analog-1 (MA-1). • MA-1-induced cancer cell death was triggered by

  9. A novel synthetic analog of militarin, MA-1 induces mitochondrial dependent apoptosis by ROS generation in human lung cancer cells

    International Nuclear Information System (INIS)

    Yoon, Deok Hyo; Lim, Mi-Hee; Lee, Yu Ran; Sung, Gi-Ho; Lee, Tae-Ho; Jeon, Byeong Hwa; Cho, Jae Youl; Song, Won O.; Park, Haeil; Choi, Sunga; Kim, Tae Woong

    2013-01-01

    A synthetic Militarin analog-1[(2R,3R,4R,5R)-1,6-bis(4-(2,4,4-trimethylpentan-2-yl)phenoxy) hexane-2,3,4,5-tetraol] is a novel derivative of constituents from Cordyceps militaris, which has been used to treat a variety of chronic diseases including inflammation, diabetes, hyperglycemia and cancers. Here, we report for the first time the synthesis of Militarin analog-1 (MA-1) and the apoptotic mechanism of MA-1 against human lung cancer cell lines. Treatment with MA-1 significantly inhibited the viability of 3 human lung cancer cell lines. The inhibition of viability and growth in MA-1-treated A549 cells with an IC 50 of 5 μM were mediated through apoptosis induction, as demonstrated by an increase in DNA fragmentation, sub-G 0 /G 1 -DNA fraction, nuclear condensation, and phosphatidylserine exposure. The apoptotic cell death caused mitochondrial membrane permeabilization through regulation of expression of the Bcl-2 family proteins, leading to cytochrome c release in a time-dependent manner. Subsequently, the final stage of apoptosis, activation of caspase-9/-3 and cleavage of poly (ADP ribose) polymerase, was induced. Furthermore, A549 lung cancer cells were more responsive to MA-1 than a bronchial epithelial cell line (BEAS-2B), involving the rapid generation of reactive oxygen species (ROS), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) activation. The pharmacological inhibition of ROS generation and JNK/p38 MAPK exhibited attenuated DNA fragmentation in MA-1-induced apoptosis. Oral administration of MA-1 also retarded growth of A549 orthotopic xenografts. In conclusion, the present study indicates that the new synthetic derivative MA-1 triggers mitochondrial apoptosis through ROS generation and regulation of MAPKs and may be a potent therapeutic agent against human lung cancer. - Highlights: • We report a novel synthesized derivative, militarin analog-1 (MA-1). • MA-1-induced cancer cell death was triggered by the ROS

  10. Streptococcus pneumoniae-Induced Oxidative Stress in Lung Epithelial Cells Depends on Pneumococcal Autolysis and Is Reversible by Resveratrol.

    Science.gov (United States)

    Zahlten, Janine; Kim, Ye-Ji; Doehn, Jan-Moritz; Pribyl, Thomas; Hocke, Andreas C; García, Pedro; Hammerschmidt, Sven; Suttorp, Norbert; Hippenstiel, Stefan; Hübner, Ralf-Harto

    2015-06-01

    Streptococcus pneumoniae is the most common cause of community-acquired pneumonia worldwide. During pneumococcal pneumonia, the human airway epithelium is exposed to large amounts of H2O2 as a product of host and pathogen oxidative metabolism. Airway cells are known to be highly vulnerable to oxidant damage, but the pathophysiology of oxidative stress induced by S. pneumoniae and the role of nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant systems of the host are not well characterized. For gluthation/gluthathion disulfide analysis BEAS-2B cells, primary broncho-epithelial cells (pBEC), explanted human lung tissue and mouse lungs were infected with different S. pneumoniae strains (D39, A66, R6x, H2O2/pneumolysin/LytA- deficient mutants of R6x). Cell death was proven by LDH assay and cell viability by IL-8 ELISA. The translocation of Nrf2 and the expression of catalase were shown via Western blot. The binding of Nrf2 at the catalase promoter was analyzed by ChIP. We observed a significant induction of oxidative stress induced by S. pneumoniae in vivo, ex vivo, and in vitro. Upon stimulation, the oxidant-responsive transcription factor Nrf2 was activated, and catalase was upregulated via Nrf2. The pneumococci-induced oxidative stress was independent of S. pneumoniae-derived H2O2 and pneumolysin but depended on the pneumococcal autolysin LytA. The Nrf2 inducer resveratrol, as opposed to catalase, reversed oxidative stress in lung epithelial cells. These observations indicate a H2O2-independent induction of oxidative stress in lung epithelial cells via the release of bacterial factors of S. pneumoniae. Resveratrol might be an option for prevention of acute lung injury and inflammatory responses observed in pneumococcal pneumonia. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. SATB2 expression increased anchorage-independent growth and cell migration in human bronchial epithelial cells

    International Nuclear Information System (INIS)

    Wu, Feng; Jordan, Ashley; Kluz, Thomas; Shen, Steven; Sun, Hong; Cartularo, Laura A.; Costa, Max

    2016-01-01

    The special AT-rich sequence-binding protein 2 (SATB2) is a protein that binds to the nuclear matrix attachment region of the cell and regulates gene expression by altering chromatin structure. In our previous study, we reported that SATB2 gene expression was induced in human bronchial epithelial BEAS-2B cells transformed by arsenic, chromium, nickel and vanadium. In this study, we show that ectopic expression of SATB2 in the normal human bronchial epithelial cell-line BEAS-2B increased anchorage-independent growth and cell migration, meanwhile, shRNA-mediated knockdown of SATB2 significantly decreased anchorage-independent growth in Ni transformed BEAS-2B cells. RNA sequencing analyses of SATB2 regulated genes revealed the enrichment of those involved in cytoskeleton, cell adhesion and cell-movement pathways. Our evidence supports the hypothesis that SATB2 plays an important role in BEAS-2B cell transformation. - Highlights: • We performed SATB2 overexpression in the BEAS-2B cell line. • We performed SATB2 knockdown in a Ni transformed BEAS-2B cell line. • SATB2 induced anchorage-independent growth and increased cell migration. • SATB2 knockdown significantly decreased anchorage-independent growth. • We identified alterations in gene involved in cytoskeleton, cell adhesion.

  12. Fixed ratio or lower limit of normal for the FEV1/VC ratio: relation to symptoms and extended lung function tests.

    Science.gov (United States)

    Wollmer, Per; Frantz, Sophia; Engström, Gunnar; Dencker, Magnus; Löfdahl, Claes-Göran; Nihlén, Ulf

    2017-05-01

    There is no general agreement on the spirometric definition of chronic obstructive pulmonary disease (COPD). The global initiative for obstructive lung disease recommends a fixed ratio between forced expiratory volume in one-second (FEV 1 ) and forced vital capacity (FVC) of System (IOS) and answered a questionnaire on respiratory symptoms and diseases. Seventy subjects fulfilled both spirometric COPD criteria (FR+LLN+), 62 subjects the fixed ratio criterion (FR+) only. Of the remaining 318 subjects, 236 were ever smokers (N-ES). Significant differences between all groups were seen for FEV 1 and D L,CO . Significant differences between groups were also seen for residual volume (RV) and RV/total lung capacity. For IOS, variables and symptoms increasingly abnormal values were seen from never smokers to FR+LLN+. This study shows that subjects meeting both spirometric COPD criteria frequently have symptoms and findings at extended lung function tests compatible with the diagnosis. Also subjects meeting the fixed ratio criterion only tend to have more symptoms and lung function findings compatible with COPD than ever-smoking subjects with FEV 1 /VC > 0·7. © 2015 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

  13. Lung cysts in chronic paracoccidioidomycosis*

    OpenAIRE

    Costa, André Nathan; Marchiori, Edson; Benard, Gil; Araújo, Mariana Sponholz; Baldi, Bruno Guedes; Kairalla, Ronaldo Adib; Carvalho, Carlos Roberto Ribeiro

    2013-01-01

    On HRCT scans, lung cysts are characterized by rounded areas of low attenuation in the lung parenchyma and a well-defined interface with the normal adjacent lung. The most common cystic lung diseases are lymphangioleiomyomatosis, Langerhans cell histiocytosis, and lymphocytic interstitial pneumonia. In a retrospective analysis of the HRCT findings in 50 patients diagnosed with chronic paracoccidioidomycosis, we found lung cysts in 5 cases (10%), indicating that patients with paracoccidioidomy...

  14. TH-E-BRF-04: Characterizing the Response of Texture-Based CT Image Features for Quantification of Radiation-Induced Normal Lung Damage

    International Nuclear Information System (INIS)

    Krafft, S; Court, L; Briere, T; Martel, M

    2014-01-01

    Purpose: Radiation induced lung damage (RILD) is an important dose-limiting toxicity for patients treated with radiation therapy. Scoring systems for RILD are subjective and limit our ability to find robust predictors of toxicity. We investigate the dose and time-related response for texture-based lung CT image features that serve as potential quantitative measures of RILD. Methods: Pre- and post-RT diagnostic imaging studies were collected for retrospective analysis of 21 patients treated with photon or proton radiotherapy for NSCLC. Total lung and selected isodose contours (0–5, 5–15, 15–25Gy, etc.) were deformably registered from the treatment planning scan to the pre-RT and available follow-up CT studies for each patient. A CT image analysis framework was utilized to extract 3698 unique texture-based features (including co-occurrence and run length matrices) for each region of interest defined by the isodose contours and the total lung volume. Linear mixed models were fit to determine the relationship between feature change (relative to pre-RT), planned dose and time post-RT. Results: Seventy-three follow-up CT scans from 21 patients (median: 3 scans/patient) were analyzed to describe CT image feature change. At the p=0.05 level, dose affected feature change in 2706 (73.1%) of the available features. Similarly, time affected feature change in 408 (11.0%) of the available features. Both dose and time were significant predictors of feature change in a total of 231 (6.2%) of the extracted image features. Conclusion: Characterizing the dose and time-related response of a large number of texture-based CT image features is the first step toward identifying objective measures of lung toxicity necessary for assessment and prediction of RILD. There is evidence that numerous features are sensitive to both the radiation dose and time after RT. Beyond characterizing feature response, further investigation is warranted to determine the utility of these features as

  15. Lung cysts in chronic paracoccidioidomycosis.

    Science.gov (United States)

    Costa, André Nathan; Marchiori, Edson; Benard, Gil; Araújo, Mariana Sponholz; Baldi, Bruno Guedes; Kairalla, Ronaldo Adib; Carvalho, Carlos Roberto Ribeiro

    2013-01-01

    On HRCT scans, lung cysts are characterized by rounded areas of low attenuation in the lung parenchyma and a well-defined interface with the normal adjacent lung. The most common cystic lung diseases are lymphangioleiomyomatosis, Langerhans cell histiocytosis, and lymphocytic interstitial pneumonia. In a retrospective analysis of the HRCT findings in 50 patients diagnosed with chronic paracoccidioidomycosis, we found lung cysts in 5 cases (10%), indicating that patients with paracoccidioidomycosis can present with lung cysts on HRCT scans. Therefore, paracoccidioidomycosis should be included in the differential diagnosis of cystic lung diseases.

  16. Lung cysts in chronic paracoccidioidomycosis*

    Science.gov (United States)

    Costa, André Nathan; Marchiori, Edson; Benard, Gil; Araújo, Mariana Sponholz; Baldi, Bruno Guedes; Kairalla, Ronaldo Adib; Carvalho, Carlos Roberto Ribeiro

    2013-01-01

    On HRCT scans, lung cysts are characterized by rounded areas of low attenuation in the lung parenchyma and a well-defined interface with the normal adjacent lung. The most common cystic lung diseases are lymphangioleiomyomatosis, Langerhans cell histiocytosis, and lymphocytic interstitial pneumonia. In a retrospective analysis of the HRCT findings in 50 patients diagnosed with chronic paracoccidioidomycosis, we found lung cysts in 5 cases (10%), indicating that patients with paracoccidioidomycosis can present with lung cysts on HRCT scans. Therefore, paracoccidioidomycosis should be included in the differential diagnosis of cystic lung diseases. PMID:23857700

  17. Lung cysts in chronic paracoccidioidomycosis

    Directory of Open Access Journals (Sweden)

    Andre Nathan Costa

    2013-06-01

    Full Text Available On HRCT scans, lung cysts are characterized by rounded areas of low attenuation in the lung parenchyma and a well-defined interface with the normal adjacent lung. The most common cystic lung diseases are lymphangioleiomyomatosis, Langerhans cell histiocytosis, and lymphocytic interstitial pneumonia. In a retrospective analysis of the HRCT findings in 50 patients diagnosed with chronic paracoccidioidomycosis, we found lung cysts in 5 cases (10%, indicating that patients with paracoccidioidomycosis can present with lung cysts on HRCT scans. Therefore, paracoccidioidomycosis should be included in the differential diagnosis of cystic lung diseases.

  18. Antenatal steroids and the IUGR fetus: are exposure and physiological effects on the lung and cardiovascular system the same as in normally grown fetuses?

    Science.gov (United States)

    Morrison, Janna L; Botting, Kimberley J; Soo, Poh Seng; McGillick, Erin V; Hiscock, Jennifer; Zhang, Song; McMillen, I Caroline; Orgeig, Sandra

    2012-01-01

    Glucocorticoids are administered to pregnant women at risk of preterm labour to promote fetal lung surfactant maturation. Intrauterine growth restriction (IUGR) is associated with an increased risk of preterm labour. Hence, IUGR babies may be exposed to antenatal glucocorticoids. The ability of the placenta or blood brain barrier to remove glucocorticoids from the fetal compartment or the brain is compromised in the IUGR fetus, which may have implications for lung, brain, and heart development. There is conflicting evidence on the effect of exogenous glucocorticoids on surfactant protein expression in different animal models of IUGR. Furthermore, the IUGR fetus undergoes significant cardiovascular adaptations, including altered blood pressure regulation, which is in conflict with glucocorticoid-induced alterations in blood pressure and flow. Hence, antenatal glucocorticoid therapy in the IUGR fetus may compromise regulation of cardiovascular development. The role of cortisol in cardiomyocyte development is not clear with conflicting evidence in different species and models of IUGR. Further studies are required to study the effects of antenatal glucocorticoids on lung, brain, and heart development in the IUGR fetus. Of specific interest are the aetiology of IUGR and the resultant degree, duration, and severity of hypoxemia.

  19. Antenatal Steroids and the IUGR Fetus: Are Exposure and Physiological Effects on the Lung and Cardiovascular System the Same as in Normally Grown Fetuses?

    Directory of Open Access Journals (Sweden)

    Janna L. Morrison

    2012-01-01

    Full Text Available Glucocorticoids are administered to pregnant women at risk of preterm labour to promote fetal lung surfactant maturation. Intrauterine growth restriction (IUGR is associated with an increased risk of preterm labour. Hence, IUGR babies may be exposed to antenatal glucocorticoids. The ability of the placenta or blood brain barrier to remove glucocorticoids from the fetal compartment or the brain is compromised in the IUGR fetus, which may have implications for lung, brain, and heart development. There is conflicting evidence on the effect of exogenous glucocorticoids on surfactant protein expression in different animal models of IUGR. Furthermore, the IUGR fetus undergoes significant cardiovascular adaptations, including altered blood pressure regulation, which is in conflict with glucocorticoid-induced alterations in blood pressure and flow. Hence, antenatal glucocorticoid therapy in the IUGR fetus may compromise regulation of cardiovascular development. The role of cortisol in cardiomyocyte development is not clear with conflicting evidence in different species and models of IUGR. Further studies are required to study the effects of antenatal glucocorticoids on lung, brain, and heart development in the IUGR fetus. Of specific interest are the aetiology of IUGR and the resultant degree, duration, and severity of hypoxemia.

  20. Cadmium Induces Histone H3 Lysine Methylation by Inhibiting Histone Demethylase Activity

    Science.gov (United States)

    Xiao, Chunlian; Liu, Yin; Xie, Chengfeng; Tu, Wei; Xia, Yujie; Costa, Max; Zhou, Xue

    2015-01-01

    Cadmium is an established human lung carcinogen with weak mutagenicity. However, the mechanisms underlying cadmium-induced carcinogenesis remain obscure. It has been suggested that epigenetic mechanisms may play a role in cadmium-induced carcinogenesis. In this study, we investigated the effects of cadmium on histone methylation and histone demethylases, and the role of histone methylation in transformation of immortalized normal human bronchial epithelial (BEAS-2B) cells. Exposure to 0.625, 1.25, 2.5, and 5.0 μM of cadmium for 6, 24, and 48 h increased global trimethylated histone H3 on lysine 4 (H3K4me3) and dimethylated histone H3 on lysine 9 (H3K9me2) in BEAS-2B cells compared with untreated cells, and most of these changes remained after the removal of cadmium (P cadmium inhibited the activities of histone H3 on lysine 4 (H3K4) and histone H3 on lysine 9 (H3K9) demethylases which were detected by histone demethylation assay. However, there was no significant change in the protein levels of the H3K4 demethylase lysine-specific demethylase 5A (KDM5A) and the H3K9 demethylase lysine-specific demethylase 3A (KDM3A). Interestingly, during transformation of BEAS-2B cells by 20 weeks of exposure to 2.0 μM cadmium as assessed by anchorage-independent growth in soft agar, global H3K4me3, and H3K9me2 were significantly increased at 4 weeks (P cadmium increases global H3K4me3 and H3K9me2 by inhibiting the activities of histone demethylases, and aberrant histone methylation that occurs early (48 h) and at 4 weeks is associated with cadmium-induced transformation of BEAS-2B cells at the early stage. PMID:25673502

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-02-28

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

  2. Circumferential or sectored beam arrangements for stereotactic body radiation therapy (SBRT) of primary lung tumors: Effect on target and normal-structure dose-volume metrics

    International Nuclear Information System (INIS)

    Rosenberg, Mara W.; Kato, Catherine M.; Carson, Kelly M.P.; Matsunaga, Nathan M.; Arao, Robert F.; Doss, Emily J.; McCracken, Charles L.; Meng, Lu Z.; Chen, Yiyi; Laub, Wolfram U.; Fuss, Martin; Tanyi, James A.

    2013-01-01

    To compare 2 beam arrangements, sectored (beam entry over ipsilateral hemithorax) vs circumferential (beam entry over both ipsilateral and contralateral lungs), for static-gantry intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) delivery techniques with respect to target and organs-at-risk (OAR) dose-volume metrics, as well as treatment delivery efficiency. Data from 60 consecutive patients treated using stereotactic body radiation therapy (SBRT) for primary non–small-cell lung cancer (NSCLC) formed the basis of this study. Four treatment plans were generated per data set: IMRT/VMAT plans using sectored (-s) and circumferential (-c) configurations. The prescribed dose (PD) was 60 Gy in 5 fractions to 95% of the planning target volume (PTV) (maximum PTV dose ∼ 150% PD) for a 6-MV photon beam. Plan conformality, R 50 (ratio of volume circumscribed by the 50% isodose line and the PTV), and D 2 cm (D max at a distance ≥2 cm beyond the PTV) were evaluated. For lungs, mean doses (mean lung dose [MLD]) and percent V 30 /V 20 /V 10 /V 5 Gy were assessed. Spinal cord and esophagus D max and D 5 /D 50 were computed. Chest wall (CW) D max and absolute V 30 /V 20 /V 10 /V 5 Gy were reported. Sectored SBRT planning resulted in significant decrease in contralateral MLD and V 10 /V 5 Gy , as well as contralateral CW D max and V 10 /V 5 Gy (all p max and D 5 /D 50 for the spinal cord with sectored planning did not reach statistical significance for static-gantry IMRT, although VMAT metrics did show a statistically significant decrease (all p 50 significantly improved with IMRT-s/VMAT-c (p 2 cm significantly improved with VMAT-c (p < 0.001). Plan delivery efficiency improved with sectored technique (p < 0.001); mean monitor unit (MU)/cGy of PD decreased from 5.8 ± 1.9 vs 5.3 ± 1.7 (IMRT) and 2.7 ± 0.4 vs 2.4 ± 0.3 (VMAT). The sectored configuration achieves unambiguous dosimetric advantages over circumferential arrangement in terms

  3. Differentiating inflamed and normal lungs by the apparent reaction rate constants of lactate dehydrogenase probed by hyperpolarized (13)C labeled pyruvate.

    Science.gov (United States)

    Xu, He N; Kadlececk, Stephen; Shaghaghi, Hoora; Zhao, Huaqing; Profka, Harilla; Pourfathi, Mehrdad; Rizi, Rahim; Li, Lin Z

    2016-02-01

    Clinically translatable hyperpolarized (HP) (13)C-NMR can probe in vivo enzymatic reactions, e.g., lactate dehydrogenase (LDH)-catalyzed reaction by injecting HP (13)C-pyruvate into the subject, which is converted to (13)C labeled lactate by the enzyme. Parameters such as (13)C-lactate signals and lactate-to-pyruvate signal ratio are commonly used for analyzing the HP (13)C-NMR data. However, the biochemical/biological meaning of these parameters remains either unclear or dependent on experimental settings. It is preferable to quantify the reaction rate constants with a clearer physical meaning. Here we report the extraction of the kinetic parameters of the LDH reaction from HP (13)C-NMR data and investigate if they can be potential predictors of lung inflammation. Male Sprague-Dawley rats (12 controls, 14 treated) were used. One dose of bleomycin (2.5 U/kg) was administered intratracheally to the treatment group. The lungs were removed, perfused, and observed by the HP-NMR technique, where a HyperSense dynamic nuclear polarization system was used to generate the HP (13)C-pyruvate for injecting into the lungs. A 20 mm (1)H/(13)C dual-tuned coil in a 9.4-T Varian vertical bore NMR spectrometer was employed to acquire the (13)C spectral data every 1 s over a time period of 300 s using a non-selective, 15-degree radiofrequency pulse. The apparent rate constants of the LDH reaction and their ratio were quantified by applying ratiometric fitting analysis to the time series data of (13)C labeled pyruvate and lactate. The apparent forward rate constant kp =(3.67±3.31)×10(-4) s(-1), reverse rate constant kl =(4.95±2.90)×10(-2) s(-1), rate constant ratio kp /kl =(7.53±5.75)×10(-3) for the control lungs; kp =(11.71±4.35)×10(-4) s(-1), kl =(9.89±3.89)×10(-2) s(-1), and kp /kl =(12.39±4.18)×10(-3) for the inflamed lungs at the 7(th) day post treatment. Wilcoxon rank-sum test showed that the medians of these kinetic parameters of the 7-day cohort were significantly

  4. Overexpression of miR-30a in lung adenocarcinoma A549 cell line inhibits migration and invasion via targeting EYA2

    Science.gov (United States)

    Yuan, Yuncang; Zheng, Shangyong; Li, Qian; Xiang, Xudong; Gao, Tangxin; Ran, Pengzhan; Sun, Lijuan; Huang, Qionglin; Xie, Fei; Du, Jing; Xiao, Chunjie

    2016-01-01

    MicroRNAs (miRNAs) are a class of small non-coding RNAs and closely related to the pathogenesis of cancers. Increasing evidence indicates that miR-30a plays a profound role during the development of cancers. However, the functions of miR-30a in non-small-cell lung cancer (NSCLC) are still ambiguous. Here we found that miR-30a was decreased in lung adenocarcinoma A549 cells and in tissue samples from 14 patients by qRT-PCR, and also found that overexpression of miR-30a in A549 cells inhibited migration and invasion but not cell proliferation and cell cycle progression by wound-healing assay, matrigel invasion assay, MTS-based cell proliferation assay, and flow cytometry-based cell cycle analysis, respectively. We further explored the potential mechanism of miR-30a-mediated gene regulation in lung adenocarcinoma cell lines. EYA2 is a predicted target of miR-30a, and it has been found that EYA2 expression is inhibited by miR-30a in breast cancer cells. We demonstrated that EYA2 is a direct target of miR-30a by using the dual-luciferase reporter assay in A549 cells and showed that EYA2 protein levels are inversely correlated with miR-30a expression in A549 and BEAS-2B cells. In addition, we also confirmed the rescue effects of EYA2 overexpression in A549 cells by cotransfection with EYA2 expression vector and miR-30a mimics. Taken together, our results demonstrate that overexpression of miR-30a in lung adenocarcinoma A549 cells can inhibit cell migration and invasion, which is partially attributed to the decrease of EYA2 expression. Our findings suggest that miR-30a may be used as a new potential target for the treatment of lung adenocarcinoma in the future. PMID:26837415

  5. Circumferential or sectored beam arrangements for stereotactic body radiation therapy (SBRT) of primary lung tumors: Effect on target and normal-structure dose-volume metrics

    Energy Technology Data Exchange (ETDEWEB)

    Rosenberg, Mara W. [Broad Institute of MIT and Harvard, Cambridge, MA (United States); Department of Physics, Brandeis University, Waltham, MA (United States); Kato, Catherine M. [Macalester College, St. Paul, MN (United States); Carson, Kelly M.P. [The University of North Carolina, Chapel Hill, NC (United States); Matsunaga, Nathan M. [Santa Clara University, Santa Clara, CA (United States); Arao, Robert F. [Department of Public Health and Preventive Medicine, Oregon Health and Science University, Portland, OR (United States); Doss, Emily J. [Department of Internal Medicine, Providence St. Vincent Medical Center, Portland, OR (United States); McCracken, Charles L. [Department of Radiation Medicine, Oregon Health and Science University, Portland, OR (United States); Meng, Lu Z. [Department of Radiation Oncology, University of California Davis Comprehensive Cancer Center, Sacramento, CA (United States); Chen, Yiyi [Department of Public Health and Preventive Medicine, Oregon Health and Science University, Portland, OR (United States); Laub, Wolfram U.; Fuss, Martin [Department of Radiation Medicine, Oregon Health and Science University, Portland, OR (United States); Department of Nuclear Engineering and Radiation Health Physics, Oregon State University, Corvallis, OR (United States); Tanyi, James A., E-mail: tanyij@ohsu.edu [Department of Radiation Medicine, Oregon Health and Science University, Portland, OR (United States); Department of Nuclear Engineering and Radiation Health Physics, Oregon State University, Corvallis, OR (United States)

    2013-01-01

    To compare 2 beam arrangements, sectored (beam entry over ipsilateral hemithorax) vs circumferential (beam entry over both ipsilateral and contralateral lungs), for static-gantry intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) delivery techniques with respect to target and organs-at-risk (OAR) dose-volume metrics, as well as treatment delivery efficiency. Data from 60 consecutive patients treated using stereotactic body radiation therapy (SBRT) for primary non–small-cell lung cancer (NSCLC) formed the basis of this study. Four treatment plans were generated per data set: IMRT/VMAT plans using sectored (-s) and circumferential (-c) configurations. The prescribed dose (PD) was 60 Gy in 5 fractions to 95% of the planning target volume (PTV) (maximum PTV dose ∼ 150% PD) for a 6-MV photon beam. Plan conformality, R{sub 50} (ratio of volume circumscribed by the 50% isodose line and the PTV), and D{sub 2} {sub cm} (D{sub max} at a distance ≥2 cm beyond the PTV) were evaluated. For lungs, mean doses (mean lung dose [MLD]) and percent V{sub 30}/V{sub 20}/V{sub 10}/V{sub 5} Gy were assessed. Spinal cord and esophagus D{sub max} and D{sub 5}/D{sub 50} were computed. Chest wall (CW) D{sub max} and absolute V{sub 30}/V{sub 20}/V{sub 10}/V{sub 5} {sub Gy} were reported. Sectored SBRT planning resulted in significant decrease in contralateral MLD and V{sub 10}/V{sub 5} {sub Gy}, as well as contralateral CW D{sub max} and V{sub 10}/V{sub 5} {sub Gy} (all p < 0.001). Nominal reductions of D{sub max} and D{sub 5}/D{sub 50} for the spinal cord with sectored planning did not reach statistical significance for static-gantry IMRT, although VMAT metrics did show a statistically significant decrease (all p < 0.001). The respective measures for esophageal doses were significantly lower with sectored planning (p < 0.001). Despite comparable dose conformality, irrespective of planning configuration, R{sub 50} significantly improved with IMRT

  6. Identification of biomarkers of radioresponse and subsequent progression towards lung cancer in normal human bronchial epithelial cells after HZE particle irradiation

    Science.gov (United States)

    Story, Michael; Ding, Liang-Hao; Park, Seongmi; Minna, John

    mice. Tumors that develop will be examined for radiosensitivity and aggres-siveness and will be also be examined for genomic, epigenomic and proteomic changes. Com-parisons of unirradiated cells, transformed cells, and tumor cells will allow the development of biomarkers of radiation-induced lung cancer, in particular HZE-induced lung tumors, and help to generate risk factors for lung cancer as a result of travel through deep space environments.

  7. The gravitational distribution of ventilation-perfusion ratio is more uniform in prone than supine posture in the normal human lung

    Science.gov (United States)

    Sá, Rui Carlos; Theilmann, Rebecca J.; Buxton, Richard B.; Prisk, G. Kim; Hopkins, Susan R.

    2013-01-01

    The gravitational gradient of intrapleural pressure is suggested to be less in prone posture than supine. Thus the gravitational distribution of ventilation is expected to be more uniform prone, potentially affecting regional ventilation-perfusion (V̇a/Q̇) ratio. Using a novel functional lung magnetic resonance imaging technique to measure regional V̇a/Q̇ ratio, the gravitational gradients in proton density, ventilation, perfusion, and V̇a/Q̇ ratio were measured in prone and supine posture. Data were acquired in seven healthy subjects in a single sagittal slice of the right lung at functional residual capacity. Regional specific ventilation images quantified using specific ventilation imaging and proton density images obtained using a fast gradient-echo sequence were registered and smoothed to calculate regional alveolar ventilation. Perfusion was measured using arterial spin labeling. Ventilation (ml·min−1·ml−1) images were combined on a voxel-by-voxel basis with smoothed perfusion (ml·min−1·ml−1) images to obtain regional V̇a/Q̇ ratio. Data were averaged for voxels within 1-cm gravitational planes, starting from the most gravitationally dependent lung. The slope of the relationship between alveolar ventilation and vertical height was less prone than supine (−0.17 ± 0.10 ml·min−1·ml−1·cm−1 supine, −0.040 ± 0.03 prone ml·min−1·ml−1·cm−1, P = 0.02) as was the slope of the perfusion-height relationship (−0.14 ± 0.05 ml·min−1·ml−1·cm−1 supine, −0.08 ± 0.09 prone ml·min−1·ml−1·cm−1, P = 0.02). There was a significant gravitational gradient in V̇a/Q̇ ratio in both postures (P < 0.05) that was less in prone (0.09 ± 0.08 cm−1 supine, 0.04 ± 0.03 cm−1 prone, P = 0.04). The gravitational gradients in ventilation, perfusion, and regional V̇a/Q̇ ratio were greater supine than prone, suggesting an interplay between thoracic cavity configuration, airway and vascular tree anatomy, and the effects of

  8. Signaling networks associated with AKT activation in non-small cell lung cancer (NSCLC: new insights on the role of phosphatydil-inositol-3 kinase.

    Directory of Open Access Journals (Sweden)

    Marianna Scrima

    Full Text Available Aberrant activation of PI3K/AKT signalling represents one of the most common molecular alterations in lung cancer, though the relative contribution of the single components of the cascade to the NSCLC development is still poorly defined. In this manuscript we have investigated the relationship between expression and genetic alterations of the components of the PI3K/AKT pathway [KRAS, the catalytic subunit of PI3K (p110α, PTEN, AKT1 and AKT2] and the activation of AKT in 107 surgically resected NSCLCs and have analyzed the existing relationships with clinico-pathologic features. Expression analysis was performed by immunohistochemistry on Tissue Micro Arrays (TMA; mutation analysis was performed by DNA sequencing; copy number variation was determined by FISH. We report that activation of PI3K/AKT pathway in Italian NSCLC patients is associated with high grade (G3-G4 compared with G1-G2; n = 83; p<0.05 and more advanced disease (TNM stage III vs. stages I and II; n = 26; p<0.05. In addition, we found that PTEN loss (41/104, 39% and the overexpression of p110α (27/92, 29% represent the most frequent aberration observed in NSCLCs. Less frequent molecular lesions comprised the overexpression of AKT2 (18/83, 22% or AKT1 (17/96, 18%, and KRAS mutation (7/63, 11%. Our results indicate that, among all genes, only p110α overexpression was significantly associated to AKT activation in NSCLCs (p = 0.02. Manipulation of p110α expression in lung cancer cells carrying an active PI3K allele (NCI-H460 efficiently reduced proliferation of NSCLC cells in vitro and tumour growth in vivo. Finally, RNA profiling of lung epithelial cells (BEAS-2B expressing a mutant allele of PIK3 (E545K identified a network of transcription factors such as MYC, FOS and HMGA1, not previously recognised to be associated with aberrant PI3K signalling in lung cancer.

  9. Darkfield-Confocal Microscopy detection of nanoscale particle internalization by human lung cells

    Directory of Open Access Journals (Sweden)

    Samet James M

    2011-01-01

    Full Text Available Abstract Background Concerns over the health effects of nanomaterials in the environment have created a need for microscopy methods capable of examining the biological interactions of nanoparticles (NP. Unfortunately, NP are beyond the diffraction limit of resolution for conventional light microscopy (~200 nm. Fluorescence and electron microscopy techniques commonly used to examine NP interactions with biological substrates have drawbacks that limit their usefulness in toxicological investigation of NP. EM is labor intensive and slow, while fluorescence carries the risk of photobleaching the sample and has size resolution limits. In addition, many relevant particles lack intrinsic fluorescence and therefore can not be detected in this manner. To surmount these limitations, we evaluated the potential of a novel combination of darkfield and confocal laser scanning microscopy (DF-CLSM for the efficient 3D detection of NP in human lung cells. The DF-CLSM approach utilizes the contrast enhancements of darkfield microscopy to detect objects below the diffraction limit of 200 nm based on their light scattering properties and interfaces it with the power of confocal microscopy to resolve objects in the z-plane. Results Validation of the DF-CLSM method using fluorescent polystyrene beads demonstrated spatial colocalization of particle fluorescence (Confocal and scattered transmitted light (Darkfield along the X, Y, and Z axes. DF-CLSM imaging was able to detect and provide reasonable spatial locations of 27 nm TiO2 particles in relation to the stained nuclei of exposed BEAS 2B cells. Statistical analysis of particle proximity to cellular nuclei determined a significant difference between 5 min and 2 hr particle exposures suggesting a time-dependant internalization process. Conclusions DF-CLSM microscopy is an alternative to current conventional light and electron microscopy methods that does not rely on particle fluorescence or contrast in electron

  10. Cytotoxicity and Genotoxicity of Panel of Single- and Multiwalled Carbon Nanotubes: In Vitro Effects on Normal Syrian Hamster Embryo and Immortalized V79 Hamster Lung Cells

    Directory of Open Access Journals (Sweden)

    C. Darne

    2014-01-01

    Full Text Available Carbon nanotubes (CNTs belong to a specific class of nanomaterials with unique properties. Because of their anticipated use in a wide range of industrial applications, their toxicity is of increasing concern. In order to determine whether specific physicochemical characteristics of CNTs are responsible for their toxicological effects, we investigated the cytotoxic and genotoxic effects of eight CNTs representative of each of the commonly encountered classes: single- SW-, double- DW-, and multiwalled (MW CNTs, purified and raw. In addition, because most previous studies of CNT toxicity were conducted on immortalized cell lines, we decided to compare results obtained from V79 cells, an established cell line, with results from SHE (Syrian hamster embryo cells, an easy-to-handle normal cell model. After 24 hours of treatment, MWCNTs were generally found to be more cytotoxic than SW- or DWCNTs. MWCNTs also provoked more genotoxic effects. No correlation could be found between CNT genotoxicity and metal impurities, length, surface area, or induction of cellular oxidative stress, but genotoxicity was seen to increase with CNT width. The toxicity observed for some CNTs leads us to suggest that they might also act by interfering with the cell cycle, but no significant differences were observed between normal and immortalized cells.

  11. The Phosphodiesterase 4 Inhibitor Roflumilast Protects against Cigarette Smoke Extract-Induced Mitophagy-Dependent Cell Death in Epithelial Cells.

    Science.gov (United States)

    Kyung, Sun Young; Kim, Yu Jin; Son, Eun Suk; Jeong, Sung Hwan; Park, Jeong Woong

    2018-04-01

    Recent studies show that mitophagy, the autophagy-dependent turnover of mitochondria, mediates pulmonary epithelial cell death in response to cigarette smoke extract (CSE) exposure and contributes to the development of emphysema in vivo during chronic cigarette smoke (CS) exposure, although the underlying mechanisms remain unclear. In this study, we investigated the role of mitophagy in the regulation of CSE-exposed lung bronchial epithelial cell (Beas-2B) death. We also investigated the role of a phosphodiesterase 4 inhibitor, roflumilast, in CSE-induced mitophagy-dependent cell death. Our results demonstrated that CSE induces mitophagy in Beas-2B cells through mitochondrial dysfunction and increased the expression levels of the mitophagy regulator protein, PTEN-induced putative kinase-1 (PINK1), and the mitochondrial fission protein, dynamin-1-like protein (DRP1). CSE-induced epithelial cell death was significantly increased in Beas-2B cells exposed to CSE but was decreased by small interfering RNA-dependent knockdown of DRP1. Treatment with roflumilast in Beas-2B cells inhibited CSE-induced mitochondrial dysfunction and mitophagy by inhibiting the expression of phospho-DRP1 and -PINK1. Roflumilast protected against cell death and increased cell viability, as determined by the lactate dehydrogenase release test and the MTT assay, respectively, in Beas-2B cells exposed to CSE. These findings suggest that roflumilast plays a protective role in CS-induced mitophagy-dependent cell death. Copyright©2018. The Korean Academy of Tuberculosis and Respiratory Diseases.

  12. Proliferative activity of a blend of Echinacea angustifolia and Echinacea purpurea root extracts in human vein epithelial, HeLa, and QBC-939 cell lines, but not in Beas-2b cell lines

    Directory of Open Access Journals (Sweden)

    Simon Angelo Cichello

    2016-04-01

    Full Text Available Echinacea is used for its immunostimulating properties and may have a role in modulating adverse immune effects of chemotherapy (i.e., use of 5-fluorouracil (5-FU; fluorouracil and its immunosuppressive effect. Patients may seek herbal remedies such as Echinacea (Echinacea angustifolia and Echinacea purpurea for immune stimulation. Echinacea extracts have been prescribed to supplement cancer chemotherapy for their immune-supportive effects; however, the extracts may also influence tumourgenesis. Our study aimed to determine the proliferative effect of the ethanolic blend of E. angustifolia and E. purpurea on various cancer cervical and bile duct cell lines, including HELA and QBC-939. Various cancer cells (HeLa and QBC-939 and human vein epithelial cells (HUVEC were treated with the Echinacea blend sample that was evaporated and reconstituted in Dimethyl sulfoxide (DMSO. As the extract concentration of Echinacea was increased from 12.5 μg/mL to 25 μg/mL, there was an increase in cell inhibition up to 100%, which then reduced to 90% over the next three concentrations, 50 μg/mL, 100 μg/mL, and 200 μg/mL, in HeLa cells; further inhibitory effects were observed in QBC-939 cells, from 9% inhibition at a concentration of 25 μg/mL up to 37.96% inhibition at 100 μg/mL concentration. Moreover, this is the first study to report the growth-promoting effects of this Echinacea blend in HUVEC, up to 800% at a dose concentration of 200 μg/mL. Previous studies have suggested that chicoric acid of Echinacea spp. is responsible for the increased cell growth. The results of this study show that the hydroethanolic extract of Echinacea herbal medicine promotes the growth of HeLa cells and QBC-939 cancer cell proliferation, and may interfere with cancer treatment (i.e., chemotherapy drugs such as 5-fluorouracil and Cisplatin (DDP. However, the Echinacea blend shows potential in neurodegenerative diseases with growth-promoting effects in HUVEC. Further animal trials (in vivo effect measuring dose toxicology are necessary to demonstrate the interaction of this blend with body and tumor growth, and also any positive synergistic or adverse interaction with chemotherapeutic drugs listed, so as to confirm the current observation and epithelial tissue growth or regeneration in a neurodegenerative disease model.

  13. Proliferative activity of a blend of Echinacea angustifolia and Echinacea purpurea root extracts in human vein epithelial, HeLa, and QBC-939 cell lines, but not in Beas-2b cell lines.

    Science.gov (United States)

    Cichello, Simon Angelo; Yao, Qian; He, Xiao Qiong

    2016-04-01

    Echinacea is used for its immunostimulating properties and may have a role in modulating adverse immune effects of chemotherapy (i.e., use of 5-fluorouracil (5-FU); fluorouracil and its immunosuppressive effect). Patients may seek herbal remedies such as Echinacea (Echinacea angustifolia and Echinacea purpurea) for immune stimulation. Echinacea extracts have been prescribed to supplement cancer chemotherapy for their immune-supportive effects; however, the extracts may also influence tumourgenesis. Our study aimed to determine the proliferative effect of the ethanolic blend of E. angustifolia and E. purpurea on various cancer cervical and bile duct cell lines, including HELA and QBC-939. Various cancer cells (HeLa and QBC-939) and human vein epithelial cells (HUVEC) were treated with the Echinacea blend sample that was evaporated and reconstituted in Dimethyl sulfoxide (DMSO). As the extract concentration of Echinacea was increased from 12.5 μg/mL to 25 μg/mL, there was an increase in cell inhibition up to 100%, which then reduced to 90% over the next three concentrations, 50 μg/mL, 100 μg/mL, and 200 μg/mL, in HeLa cells; further inhibitory effects were observed in QBC-939 cells, from 9% inhibition at a concentration of 25 μg/mL up to 37.96% inhibition at 100 μg/mL concentration. Moreover, this is the first study to report the growth-promoting effects of this Echinacea blend in HUVEC, up to 800% at a dose concentration of 200 μg/mL. Previous studies have suggested that chicoric acid of Echinacea spp. is responsible for the increased cell growth. The results of this study show that the hydroethanolic extract of Echinacea herbal medicine promotes the growth of HeLa cells and QBC-939 cancer cell proliferation, and may interfere with cancer treatment (i.e., chemotherapy drugs such as 5-fluorouracil and Cisplatin (DDP)). However, the Echinacea blend shows potential in neurodegenerative diseases with growth-promoting effects in HUVEC. Further animal trials (in vivo effect) measuring dose toxicology are necessary to demonstrate the interaction of this blend with body and tumor growth, and also any positive synergistic or adverse interaction with chemotherapeutic drugs listed, so as to confirm the current observation and epithelial tissue growth or regeneration in a neurodegenerative disease model.

  14. Lung Emergencies

    Science.gov (United States)

    ... The Marfan Foundation Marfan & Related Disorders What is Marfan Syndrome? What are Related Disorders? What are the Signs? ... Emergencies Lung Emergencies Surgeries Lung Emergencies People with Marfan syndrome can be at increased risk of sudden lung ...

  15. Luteoloside induces G0/G1 arrest and pro-death autophagy through the ROS-mediated AKT/mTOR/p70S6K signalling pathway in human non-small cell lung cancer cell lines.

    Science.gov (United States)

    Zhou, Menglu; Shen, Shuying; Zhao, Xin; Gong, Xingguo

    2017-12-09

    Autophagy has attracted a great deal of interest in tumour therapy research in recent years. However, the anticancer effect of luteoloside, a naturally occurring flavonoid isolated from the medicinal plant Gentiana macrophylla, on autophagy remains poorly understood in human lung cells. In the present study, we have investigated the anticancer effects of luteoloside on non-small cell lung cancer (NSCLC) cells and demonstrated that luteoloside effectively inhibited cancer cell proliferation, inducing G 0 /G 1 phase arrest associated with reduced expression of CyclinE, CyclinD1 and CDK4; we further found that treatment with luteoloside did not strongly result in apoptotic cell death in NSCLC (A549 and H292) cells. Interestingly, luteoloside induced autophagy in lung cancer cells, which was correlated with the formation of autophagic vacuoles, breakdown of p62, and the overexpression of Beclin-1 and LC3-II, but not in a human bronchial epithelial cell line (BEAS-2B). Notably, pretreatment of cancer cells with 3-MA, an autophagy inhibitor, protected against autophagy and promoted cell viability but not apoptosis. To further clarify whether luteoloside-induced autophagy depended on the PI3K/AKT/mTOR/p70S6K signalling pathway, a major autophagy-suppressive cascade, cells were treated with a combination of AKT inhibitor (LY294002) and mTOR inhibitor (Rap). These results demonstrated that luteoloside induced autophagy in lung cancer cell lines by inhibiting the pathway at p-Akt (Ser473), p-mTOR and p-p70S6K (Thr389). Moreover, we observed that luteoloside-induced cell autophagy was correlated with production of reactive oxygen species (ROS). NAC-mediated protection against ROS clearly implicated ROS in the activation of autophagy and cell death. In addition, the results showed that ROS served as an upstream effector of the PI3K/AKT/mTOR/p70S6K pathway. Taken together, the present study provides new insights into the molecular mechanisms underlying luteoloside-mediated cell

  16. The R213G polymorphism in SOD3 protects against allergic airway inflammation

    DEFF Research Database (Denmark)

    Gaurav, Rohit; Varasteh, Jason T; Weaver, Michael R

    2017-01-01

    ) in bronchoalveolar lavage fluid and reduced type II innate lymphoid cells (ILC2s) in lungs. SOD mimetic (Mn (III) tetrakis (N-ethylpyridinium-2-yl) porphyrin) attenuated Alternaria-induced expression of IL-33 and IL-8 release in BEAS-2B cells. These results suggest that R213G SNP potentially benefits its carriers...

  17. Lung scintigraphy

    International Nuclear Information System (INIS)

    Dalenz, Roberto.

    1994-01-01

    A review of lung scintigraphy, perfusion scintigraphy with SPECT, lung ventilation SPECT, blood pool SPECT. The procedure of lung perfusion studies, radiopharmaceutical, administration and clinical applications, imaging processing .Results encountered and evaluation criteria after Biello and Pioped. Recommendations and general considerations have been studied about relation of this radiopharmaceutical with other pathologies

  18. Lung transplant

    Science.gov (United States)

    ... transplant surgery include: You are placed on the heart-lung machine. One or both of your lungs are removed. For people who are having a double lung transplant, most or all of the steps from the first side are completed before the second side is ...

  19. Industrial PM2.5cause pulmonary adverse effect through RhoA/ROCK pathway.

    Science.gov (United States)

    Yan, Junyan; Lai, Chia-Hsiang; Lung, Shih-Chun Candice; Chen, Chongjun; Wang, Wen-Cheng; Huang, Pin-I; Lin, Chia-Hua

    2017-12-01

    According to the Chinese Ministry of Health, industrial pollution-induced health impacts have been the leading cause of death in China. While industrial fine particulate matter (PM 2.5 ) is associated with adverse health effects, the major action mechanisms of different compositions of PM 2.5 are currently unclear. In this study, we treated normal human lung epithelial BEAS-2B cells with industrial organic and water-soluble PM 2.5 extracts under daily alveolar deposition dose to elucidate the molecular mechanisms underlying adverse pulmonary effects induced by PM 2.5 , including oxidative damage, inflammatory response, lung epithelial barrier dysfunction, and the recruitment of macrophages. We found that water-soluble PM 2.5 extracts caused more severe cytotoxic effects on BEAS-2B cells compared with that of organic extracts. Both organic and water-soluble PM 2.5 extracts induced activation of the RhoA/ROCK pathway. Inflammatory response, epithelial barrier dysfunction, and the activation of NF-кB caused by both PM 2.5 extracts were attenuated by ROCK inhibitor Y-27632. This indicated that both PM 2.5 extracts could cause damage to epithelial cells through RhoA/ROCK-dependent NF-кB activation. Furthermore, the upregulation of macrophage adhesion induced by both PM 2.5 extracts was also attenuated by Y-27632 in a co-culture model of macrophages and the epithelial cells. Therefore, our results support that industrial PM 2.5 extracts-induced activation of the RhoA/ROCK-dependent NF-кB pathway induces pulmonary adverse effect. Thus, pharmacological inhibition of ROCK activation might have therapeutic potential in preventing lung disease associated with PM 2.5 . Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Carcinogenic risk of chromium, copper and arsenic in CCA-treated wood

    International Nuclear Information System (INIS)

    Ohgami, Nobutaka; Yamanoshita, Osamu; Thang, Nguyen Dinh; Yajima, Ichiro; Nakano, Chihiro; Wenting, Wu; Ohnuma, Shoko

    2015-01-01

    We showed that 2.1% of 233 pieces of lumber debris after the Great East Japan Earthquake was chromated copper arsenate (CCA)-treated wood. Since hexavalent chromium (Cr), copper (Cu) and pentavalent arsenic (As) in the debris may be diffused in the air via incineration, we exposed human lung normal (BEAS-2B) and carcinoma (A549) cells to Cr, Cu and As at the molar ratio in a representative CCA-treated wood. Co-exposure to 0.10 μM Cr and 0.06 μM As, which solely had no effect on colony formation, synergistically promoted colony formation in BEAS-2B cells, but not A549 cells, with activation of the PI3K/AKT pathway. Sole exposure and co-exposure to Cu showed limited effects. Since previous reports showed Cr and As concentrations to which human lungs might be exposed, our results suggest the importance to avoid diffusion of Cr and As in the air via incineration of debris including CCA-treated wood after the disaster. - Highlights: • CCA-treated wood was found in debris after the Great East Japan Earthquake in 2011. • Carcinogenic risk of CCA-treated woods was evaluated with human lung cell lines. • Co-exposure to Cr and As synergistically promoted colony formation. • Co-exposure to Cr and As synergistically activated the PI3/AKT pathway. • Effects of sole exposure and co-exposure to Cu on colony formation were limited. - Co-exposure to Cr and As, but not Cu, in CCA-treated wood debris from the Great East Japan Earthquake showed carcinogenicity in vitro.

  1. Neonatal opaque right lung: delayed fluid resorption

    International Nuclear Information System (INIS)

    Swischuk, L.E.; Hayden, K.; Richardson, J.

    1981-01-01

    Eight newborn infants with opaque right lungs were examined. Clinically, the main problem associated with the opaque right lung is mild respiratory distress, and radiographyically, the findings consist of (a) a totally opaque right lung, (b) a semiopaque right lung, or (c) an opaque right upper lobe only. These findings are usually interpreted as representing pneumonia, empyema, or hydrochlothorax, but the fact that they clear within 24 to 48 hours indicates that none of these diseases is the cause. It is thought that neonatal opaque right lung results from the transient retention of normal fetal fluid in the right lung

  2. Estimation of lung growth using computed tomography

    NARCIS (Netherlands)

    P.A. de Jong (Pim); Y. Nakano (Yasutaka); M.H. Lequin (Maarten); P.J.F.M. Merkus (Peter); H.A.W.M. Tiddens (Harm); J.C. Hogg (James); H.O. Coxson (Harvey)

    2003-01-01

    textabstractAnatomical studies suggest that normal lungs grow by rapid alveolar addition until about 2 yrs of age followed by a gradual increase in alveolar dimensions. The aim of this study was to examine the hypothesis that normal lung growth can be monitored by computed

  3. Staging of lung cancer.

    Science.gov (United States)

    de Groot, Patricia M; Carter, Brett W; Betancourt Cuellar, Sonia L; Erasmus, Jeremy J

    2015-06-01

    Primary lung cancer is the leading cause of cancer mortality in the world. Thorough clinical staging of patients with lung cancer is important, because therapeutic options and management are to a considerable degree dependent on stage at presentation. Radiologic imaging is an essential component of clinical staging, including chest radiography in some cases, computed tomography, MRI, and PET. Multiplanar imaging modalities allow assessment of features that are important for surgical, oncologic, and radiation therapy planning, including size of the primary tumor, location and relationship to normal anatomic structures in the thorax, and existence of nodal and/or metastatic disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Specific gene expression signatures induced by the multiple oncogenic alterations that occur within the PTEN/PI3K/AKT pathway in lung cancer.

    Directory of Open Access Journals (Sweden)

    Carmela De Marco

    Full Text Available Hyperactivation of the phosphatydil-inositol-3' phosphate kinase (PI3K/AKT pathway is observed in most NSCLCs, promoting proliferation, migration, invasion and resistance to therapy. AKT can be activated through several mechanisms that include loss of the negative regulator PTEN, activating mutations of the catalytic subunit of PI3K (PIK3CA and/or mutations of AKT1 itself. However, number and identity of downstream targets of activated PI3K/AKT pathway are poorly defined. To identify the genes that are targets of constitutive PI3K/AKT signalling in lung cancer cells, we performed a comparative transcriptomic analysis of human lung epithelial cells (BEAS-2B expressing active mutant AKT1 (AKT1-E17K, active mutant PIK3CA (PIK3CA-E545K or that are silenced for PTEN. We found that, altogether, aberrant PI3K/AKT signalling in lung epithelial cells regulated the expression of 1,960/20,436 genes (9%, though only 30 differentially expressed genes (DEGs (15 up-regulated, 12 down-regulated and 3 discordant out of 20,436 that were common among BEAS-AKT1-E17K, BEAS-PIK3CA-E545K and BEAS-shPTEN cells (0.1%. Conversely, DEGs specific for mutant AKT1 were 133 (85 up-regulated; 48 down-regulated, DEGs specific for mutant PIK3CA were 502 (280 up-regulated; 222 down-regulated and DEGs specific for PTEN loss were 1549 (799 up-regulated, 750 down-regulated. The results obtained from array analysis were confirmed by quantitative RT-PCR on selected up- and down-regulated genes (n = 10. Treatment of BEAS-C cells and the corresponding derivatives with pharmacological inhibitors of AKT (MK2206 or PI3K (LY294002 further validated the significance of our findings. Moreover, mRNA expression of selected DEGs (SGK1, IGFBP3, PEG10, GDF15, PTGES, S100P, respectively correlated with the activation status of the PI3K/AKT pathway assessed by S473 phosphorylation in NSCLC cell lines (n = 6. Finally, we made use of Ingenuity Pathway Analysis (IPA to investigate the relevant Bio

  5. Advances in lung ultrasound

    International Nuclear Information System (INIS)

    Francisco Neto, Miguel Jose; Rahal Junior, Antonio; Vieira, Fabio Augusto Cardillo; Silva, Paulo Savoia Dias da; Funari, Marcelo Buarque de Gusmao

    2016-01-01

    Ultrasound examination of the chest has advanced in recent decades. This imaging modality is currently used to diagnose several pathological conditions and provides qualitative and quantitative information. Acoustic barriers represented by the aerated lungs and the bony framework of the chest generate well-described sonographic artifacts that can be used as diagnostic aids. The normal pleural line and A, B, C, E and Z lines (also known as false B lines) are artifacts with specific characteristics. Lung consolidation and pneumothorax sonographic patterns are also well established. Some scanning protocols have been used in patient management. The Blue, FALLS and C.A.U.S.E. protocols are examples of algorithms using artifact combinations to achieve accurate diagnoses. Combined chest ultrasonography and radiography are often sufficient to diagnose and manage lung and chest wall conditions. Chest ultrasonography is a highly valuable diagnostic tool for radiologists, emergency and intensive care physicians. (author)

  6. Lung Cancer

    Science.gov (United States)

    Lung cancer is one of the most common cancers in the world. It is a leading cause of cancer death in men and women in the United States. Cigarette smoking causes most lung cancers. The more cigarettes you smoke per day and ...

  7. Lung Development and Aging.

    Science.gov (United States)

    Bush, Andrew

    2016-12-01

    The onset of chronic obstructive pulmonary disease (COPD) can arise either from failure to attain the normal spirometric plateau or from an accelerated decline in lung function. Despite reports from numerous big cohorts, no single adult life factor, including smoking, accounts for this accelerated decline. By contrast, five childhood risk factors (maternal and paternal asthma, maternal smoking, childhood asthma and respiratory infections) are strongly associated with an accelerated rate of lung function decline and COPD. Among adverse effects on lung development are transgenerational (grandmaternal smoking), antenatal (exposure to tobacco and pollution), and early childhood (exposure to tobacco and pollution including pesticides) factors. Antenatal adverse events can operate by causing structural changes in the developing lung, causing low birth weight and prematurity and altered immunological responses. Also important are mode of delivery, early microbiological exposures, and multiple early atopic sensitizations. Early bronchial hyperresponsiveness, before any evidence of airway inflammation, is associated with adverse respiratory outcomes. Overlapping cohort studies established that spirometry tracks from the preschool years to late middle age, and those with COPD in the sixth decade already had the worst spirometry at age 10 years. Alveolar development is now believed to continue throughout somatic growth and is adversely impacted by early tobacco smoke exposure. Genetic factors are also important, with genes important in lung development and early wheezing also being implicated in COPD. The inescapable conclusion is that the roots of COPD are in early life, and COPD is a disease of childhood adverse factors interacting with genetic factors.

  8. Lung scintigraphy in differential diagnosis of peripheral lung cancer and community-acquired pneumonia

    Science.gov (United States)

    Krivonogov, Nikolay G.; Efimova, Nataliya Y.; Zavadovsky, Konstantin W.; Lishmanov, Yuri B.

    2016-08-01

    Ventilation/perfusion lung scintigraphy was performed in 39 patients with verified diagnosis of community-acquired pneumonia (CAP) and in 14 patients with peripheral lung cancer. Ventilation/perfusion ratio, apical-basal gradients of ventilation (U/L(V)) and lung perfusion (U/L(P)), and alveolar capillary permeability of radionuclide aerosol were determined based on scintigraphy data. The study demonstrated that main signs of CAP were increases in ventilation/perfusion ratio, perfusion and ventilation gradient on a side of the diseased lung, and two-side increase in alveolar capillary permeability rate for radionuclide aerosol. Unlike this, scintigraphic signs of peripheral lung cancer comprise an increase in ventilation/perfusion ratio over 1.0 on a side of the diseased lung with its simultaneous decrease on a contralateral side, normal values of perfusion and ventilation gradients of both lungs, and delayed alveolar capillary clearance in the diseased lung compared with the intact lung.

  9. Lung scintigraphy in differential diagnosis of peripheral lung cancer and community-acquired pneumonia

    Energy Technology Data Exchange (ETDEWEB)

    Krivonogov, Nikolay G., E-mail: kng@cardio-tomsk.ru [Research Institute of Cardiology, Kievskaya Street 111a, Tomsk, 634012 (Russian Federation); Efimova, Nataliya Y., E-mail: efimova@cardio-tomsk.ru; Zavadovsky, Konstantin W.; Lishmanov, Yuri B. [Research Institute of Cardiology, Kievskaya Street 111a, Tomsk, 634012 (Russian Federation); Tomsk Polytechnic University, Lenin Avenue 30, Tomsk, 634050 (Russian Federation)

    2016-08-02

    Ventilation/perfusion lung scintigraphy was performed in 39 patients with verified diagnosis of community-acquired pneumonia (CAP) and in 14 patients with peripheral lung cancer. Ventilation/perfusion ratio, apical-basal gradients of ventilation (U/L(V)) and lung perfusion (U/L(P)), and alveolar capillary permeability of radionuclide aerosol were determined based on scintigraphy data. The study demonstrated that main signs of CAP were increases in ventilation/perfusion ratio, perfusion and ventilation gradient on a side of the diseased lung, and two-side increase in alveolar capillary permeability rate for radionuclide aerosol. Unlike this, scintigraphic signs of peripheral lung cancer comprise an increase in ventilation/perfusion ratio over 1.0 on a side of the diseased lung with its simultaneous decrease on a contralateral side, normal values of perfusion and ventilation gradients of both lungs, and delayed alveolar capillary clearance in the diseased lung compared with the intact lung.

  10. Lung Cancer Screening

    Science.gov (United States)

    ... Treatment Lung Cancer Prevention Lung Cancer Screening Research Lung Cancer Screening (PDQ®)–Patient Version What is screening? Go ... These are called diagnostic tests . General Information About Lung Cancer Key Points Lung cancer is a disease in ...

  11. Microbiome overview in swine lungs.

    Science.gov (United States)

    Siqueira, Franciele Maboni; Pérez-Wohlfeil, Esteban; Carvalho, Fabíola Marques; Trelles, Oswaldo; Schrank, Irene Silveira; Vasconcelos, Ana Tereza Ribeiro; Zaha, Arnaldo

    2017-01-01

    Mycoplasma hyopneumoniae is the etiologic agent of swine enzootic pneumonia. However other mycoplasma species and secondary bacteria are found as inhabitants of the swine respiratory tract, which can be also related to disease. In the present study we have performed a total DNA metagenomic analysis from the lungs of pigs kept in a field condition, with suggestive signals of enzootic pneumonia and without any infection signals to evaluate the bacteria variability of the lungs microbiota. Libraries from metagenomic DNA were prepared and sequenced using total DNA shotgun metagenomic pyrosequencing. The metagenomic distribution showed a great abundance of bacteria. The most common microbial families identified from pneumonic swine's lungs were Mycoplasmataceae, Flavobacteriaceae and Pasteurellaceae, whereas in the carrier swine's lungs the most common families were Mycoplasmataceae, Bradyrhizobiaceae and Flavobacteriaceae. Analysis of community composition in both samples confirmed the high prevalence of M. hyopneumoniae. Moreover, the carrier lungs had more diverse family population, which should be related to the lungs normal flora. In summary, we provide a wide view of the bacterial population from lungs with signals of enzootic pneumonia and lungs without signals of enzootic pneumonia in a field situation. These bacteria patterns provide information that may be important for the establishment of disease control measures and to give insights for further studies.

  12. Microbiome overview in swine lungs.

    Directory of Open Access Journals (Sweden)

    Franciele Maboni Siqueira

    Full Text Available Mycoplasma hyopneumoniae is the etiologic agent of swine enzootic pneumonia. However other mycoplasma species and secondary bacteria are found as inhabitants of the swine respiratory tract, which can be also related to disease. In the present study we have performed a total DNA metagenomic analysis from the lungs of pigs kept in a field condition, with suggestive signals of enzootic pneumonia and without any infection signals to evaluate the bacteria variability of the lungs microbiota. Libraries from metagenomic DNA were prepared and sequenced using total DNA shotgun metagenomic pyrosequencing. The metagenomic distribution showed a great abundance of bacteria. The most common microbial families identified from pneumonic swine's lungs were Mycoplasmataceae, Flavobacteriaceae and Pasteurellaceae, whereas in the carrier swine's lungs the most common families were Mycoplasmataceae, Bradyrhizobiaceae and Flavobacteriaceae. Analysis of community composition in both samples confirmed the high prevalence of M. hyopneumoniae. Moreover, the carrier lungs had more diverse family population, which should be related to the lungs normal flora. In summary, we provide a wide view of the bacterial population from lungs with signals of enzootic pneumonia and lungs without signals of enzootic pneumonia in a field situation. These bacteria patterns provide information that may be important for the establishment of disease control measures and to give insights for further studies.

  13. Lung cancer

    Science.gov (United States)

    ... causing chemicals such as uranium, beryllium, vinyl chloride, nickel chromates, coal products, mustard gas, chloromethyl ethers, gasoline, and diesel exhaust Exposure to radon gas Family history of lung cancer ...

  14. Lung function

    International Nuclear Information System (INIS)

    Sorichter, S.

    2009-01-01

    The term lung function is often restricted to the assessment of volume time curves measured at the mouth. Spirometry includes the assessment of lung volumes which can be mobilised with the corresponding flow-volume curves. In addition, lung volumes that can not be mobilised, such as the residual volume, or only partially as FRC and TLC can be measured by body plethysmography combined with the determination of the airway resistance. Body plethysmography allows the correct positioning of forced breathing manoeuvres on the volume-axis, e.g. before and after pharmacotherapy. Adding the CO single breath transfer factor (T LCO ), which includes the measurement of the ventilated lung volume using He, enables a clear diagnosis of different obstructive, restrictive or mixed ventilatory defects with and without trapped air. Tests of reversibility and provocation, as well as the assessment of inspiratory mouth pressures (PI max , P 0.1 ) help to classify the underlying disorder and to clarify treatment strategies. For further information and to complete the diagnostic of disturbances of the ventilation, diffusion and/or perfusion (capillar-)arterial bloodgases at rest and under physical strain sometimes amended by ergospirometry are recommended. Ideally, lung function measurements are amended by radiological and nuclear medicine techniques. (orig.) [de

  15. Lung cancer - small cell

    Science.gov (United States)

    Cancer - lung - small cell; Small cell lung cancer; SCLC ... About 15% of all lung cancer cases are SCLC. Small cell lung cancer is slightly more common in men than women. Almost all cases of SCLC are ...

  16. Interstitial Lung Diseases

    Science.gov (United States)

    Interstitial lung disease is the name for a large group of diseases that inflame or scar the lungs. The inflammation and ... is responsible for some types of interstitial lung diseases. Specific types include Black lung disease among coal ...

  17. Lung radiopharmaceuticals

    International Nuclear Information System (INIS)

    Gonzalez, B.M.

    1994-01-01

    Indication or main clinical use of Lung radiopharmaceuticals is presented and clasification of radiopharmaceuticals as ventilation and perfusion studies. Perfusion radiopharmaceuticals, main controls for administration quality acceptance. Clearence after blood administration and main clinical applications. Ventilation radiopharmaceuticals, gases and aerosols, characteristics of a ideal radioaerosol, techniques of good inhalation procedure, clinical applications. Comparison of several radiopharmaceuticals reflering to retention time as 50% administered dose, percent administered dose at 6 hours post inhalation, blood activity at 30 and 60 minutes post inhalation, initial lung absorbed dose, cumulated activity.Kinetic description of two radiopharmaceuticals, 99mTcDTPA and 99mTc-PYP

  18. Pursuing Normality

    DEFF Research Database (Denmark)

    Madsen, Louise Sofia; Handberg, Charlotte

    2018-01-01

    BACKGROUND: The present study explored the reflections on cancer survivorship care of lymphoma survivors in active treatment. Lymphoma survivors have survivorship care needs, yet their participation in cancer survivorship care programs is still reported as low. OBJECTIVE: The aim of this study...... implying an influence on whether to participate in cancer survivorship care programs. Because of "pursuing normality," 8 of 9 participants opted out of cancer survivorship care programming due to prospects of "being cured" and perceptions of cancer survivorship care as "a continuation of the disease...

  19. Hedgehog signaling in neonatal and adult lung.

    Science.gov (United States)

    Liu, Li; Kugler, Matthias C; Loomis, Cynthia A; Samdani, Rashmi; Zhao, Zhicheng; Chen, Gregory J; Brandt, Julia P; Brownell, Isaac; Joyner, Alexandra L; Rom, William N; Munger, John S

    2013-06-01

    Sonic Hedgehog (Shh) signaling is essential during embryonic lung development, but its role in postnatal lung development and adult lung are not known. Using Gli1(nlacZ) reporter mice to identify cells with active Hh signaling, we found that Gli1(nlacZ)-positive mesenchymal cells are densely and diffusely present up to 2 weeks after birth and decline in number thereafter. In adult mice, Gli1(nlacZ)-positive cells are present around large airways and vessels and are sparse in alveolar septa. Hh-stimulated cells are mostly fibroblasts; only 10% of Gli1(nlacZ)-positive cells are smooth muscle cells, and most smooth muscle cells do not have activation of Hh signaling. To assess its functional relevance, we influenced Hh signaling in the developing postnatal lung and adult injured lung. Inhibition of Hh signaling during early postnatal lung development causes airspace enlargement without diminished alveolar septation. After bleomycin injury in the adult lung, there are abundant Gli1(nlacZ)-positive mesenchymal cells in fibrotic lesions and increased numbers of Gli1(nlacZ)-positive cells in preserved alveolar septa. Inhibition of Hh signaling with an antibody against all Hedgehog isoforms does not reduce bleomycin-induced fibrosis, but adenovirus-mediated overexpression of Shh increases collagen production in this model. Our data provide strong evidence that Hh signaling can regulate lung stromal cell function in two critical scenarios: normal development in postnatal lung and lung fibrosis in adult lung.

  20. Pleuroparenchymal fibroelastosis: a rare interstitial lung disease

    Science.gov (United States)

    English, John C; Mayo, John R; Levy, Robert; Yee, John; Leslie, Kevin O

    2015-01-01

    Pleuroparenchymal fibroelastosis (PPFE) is a newly described form of interstitial lung disease that originates in the upper lung zones and typically progresses to involve the entire lung. The disease may be idiopathic but is often associated with other pre- or coexisting conditions. Pneumothorax is a common complication and can occur at presentation or at other times during the course of the disease. Pathologically, interstitial fibrosis takes the form of a dense consolidation with some preservation of alveolar septal outlines and demonstrates a distinctly abrupt interface with residual normal lung. Unrecognized cases of PPFE may be incorrectly diagnosed as sarcoidosis, atypical idiopathic pulmonary fibrosis, or other unclassifiable interstitial pneumonias. PMID:26090119

  1. Welders’ lung

    Directory of Open Access Journals (Sweden)

    Izidor Kern

    2010-02-01

    Conclusions: h is study coni rms that longterm welders may have symptoms with no functional disorders, but with prominent morphological changes. h e key to correct diagnosis is an occupational history of the patient. Diagnostic work-up includes funda-mental procedures in suspected interstitial lung disease. h e best therapy is cessation of exposure.

  2. Lung cancer

    DEFF Research Database (Denmark)

    Hansen, H H; Rørth, M

    1999-01-01

    The results of the many clinical trials published in 1997 had only modest impact on the treatment results using either cytostatic agents alone or combined with radiotherapy in lung cancer. In SCLC, combination chemotherapy including platin-compounds (cisplatin, carboplatin) and the podophyllotoxins...

  3. 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...

  4. 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)

  5. Lung function changes in wildland firefighters working at prescribed burns.

    Energy Technology Data Exchange (ETDEWEB)

    Adetona, Olorunfemi; Hall, Daniel, B.; Naeher, L,P.

    2011-10-01

    Although decline in lung function across workshift has been observed in wildland firefighters, measurements have been restricted to days when they worked at fires. Consequently, such results could have been confounded by normal circadian variation associated with lung function. We investigated the across-shift changes in lung function of wildland firefighters, and the effect of cumulative exposure on lung function during the burn season.

  6. Estimation of lung tissue incompressibility variation throughout respiration for tumor targeting in lung radiotherapy

    Science.gov (United States)

    Shirzadi, Zahra; Samani, Abbas

    2013-03-01

    A novel technique is proposed to characterize lung tissue incompressibility variation during respiration. Lung tissue incompressibility variation stems from significant air content variation in the tissue throughout respiration. Estimating lung tissue incompressibility and its variation is critical for computer assisted tumor motion tracking. Continuous tumor motion during respiration is a major challenge in lung cancer treatment by external beam radiotherapy. If not accounted for, this motion leads to areas of radiation over dosage for the lung normal tissues. Since no effective imaging modality is available for real-time lung tumor tracking, computer based modeling which has the capability for accurate tissue deformation estimation can be a good alternative. Lung tissue deformation estimation can be made using the lung Finite Element (FE) model where its accuracy depends on input tissue biomechanical properties including incompressibility parameter. In this research, an optimization algorithm is proposed to estimate the incompressibility parameter function in terms of respiration cycle time. In this algorithm, the incompressibility parameter and lung pressure values are varied systematically until optimal values, which result in maximum similarity between acquired and simulated 4D CT images of the lung, are achieved for each respiration time point. The simulated images are constructed using a reference image in conjunction with the deformation field obtained from the lung's FE model in each respiration time increment. We demonstrated that utilizing the calculated function along with respiratory system FE modeling leads to accurate tumor targeting, hence potentially improving lung radiotherapy outcome.

  7. Early detection of acute lung injury uncoupled to hypoxemia in pigs using ultrasound lung comets.

    Science.gov (United States)

    Gargani, Luna; Lionetti, Vincenzo; Di Cristofano, Claudio; Bevilacqua, Generoso; Recchia, Fabio A; Picano, Eugenio

    2007-12-01

    Oleic acid-induced lung injury is an established experimental model of acute lung injury in pigs and is considered to reproduce the early exudative phase of acute respiratory distress syndrome. Ultrasound lung comets are an echographic sign of extravascular lung water, originating from thickened interlobular septa. The objective of this study was to evaluate the timing and relationship between the number of ultrasound lung comets, the Pao2/Fio2 ratio, and the static respiratory compliance in an experimental model of oleic acid-induced lung injury in pigs. Laboratory experiment. Research institute. Ten anesthetized pigs. Acute lung injury was induced by injection of oleic acid (0.1 mL/kg, intravenously). Ultrasound lung comets, Pao2/Fio2, and static respiratory compliance were measured at baseline and at 15, 30, 60, and 90 mins after the injection of oleic acid. We evaluated ultrasound lung comets by transthoracic echography (7.5-MHz vascular probe), scanning on right and left hemithoraxes at 12 predefined scanning sites. Acute lung injury/acute respiratory distress syndrome was present in all pigs at 90 mins. The number of ultrasound lung comets increased over time and was consistently earlier than the decrease in Pao2/Fio2. At 15 mins, ultrasound lung comets were markedly increased, but no significant changes in Pao2/Fio2 were observed. Accordingly, static respiratory compliance was dramatically reduced at 15 mins compared with baseline (17.04 +/- 1.82 vs. 34.84 +/- 2.62 mL/cm H2O, p comets, assessed by transthoracic echography, detected extravascular lung water accumulation very early in the course of the oleic acid lung injury in pigs, in the presence of a normal Pao2/Fio2. These results suggest that ultrasound lung comets could be a very early, noninvasive, and simple method to detect and quantify pulmonary edema in acute lung injury.

  8. Glycocalyx of lung epithelial cells.

    Science.gov (United States)

    Martins, Maria de Fátima; Bairos, Vasco A

    2002-01-01

    Due to their diversity and external location on cell membranes, glycans, as glycocalyx components, are key elements in eukaryotic cell, tissue, and organ homeostasis. Although information on the lung glycocalyx is scarce, this article aims to review, discuss, and summarize what is known about bronchoalveolar glycocalyx composition, mainly the sialic acids. It was deemed relevant, however, to make a brief introductory overview of the cell glycocalyx and its particular development in epithelial cells. After that, follows a summary of the evolution of the knowledge regarding the bronchoalveolar glycocalyx composition throughout the years, particularly its morphological features. Since sialic acids are located terminally on the bronchoalveolar lining cells' glycocalyx and play crucial roles, we focused mainly on the existing lung histochemical and biochemical data of these sugar residues, as well as their evolution throughout lung development. The functions of the lung glycocalyx sialic acids are discussed and interpretations of their roles analyzed, including those related to the negative overall superficial shield provided by these molecules. The increasing presence of these sugar residues throughout postnatal lung development should be regarded as pivotal in the development and maintenance of a dynamic bronchoalveolar architecture, supporting the normal histophysiology of the respiratory system. The case for a profound knowledge of lung glycocalyx--given its potential to provide answers to serious clinical problems--is made with particular reference to cystic fibrosis. Finally, concluding remarks and perspectives for future research in this field are put forth.

  9. Magnetic resonance imaging in children: common problems and possible solutions for lung and airways imaging

    NARCIS (Netherlands)

    P. Ciet (Pierluigi); H.A.W.M. Tiddens (Harm); P.A. Wielopolski (Piotr); J.M. Wild (Jim); E.Y. Lee (Edward); G. Morana (Giovanni); M. Leguin (Maarten)

    2015-01-01

    textabstractPediatric chest MRI is challenging. High-resolution scans of the lungs and airways are compromised by long imaging times, low lung proton density and motion. Low signal is a problem of normal lung. Lung abnormalities commonly cause increased signal intenstities. Among the most important

  10. Lung cancer

    DEFF Research Database (Denmark)

    Hansen, H H; Rørth, M

    1999-01-01

    The results of the many clinical trials published in 1997 had only modest impact on the treatment results using either cytostatic agents alone or combined with radiotherapy in lung cancer. In SCLC, combination chemotherapy including platin-compounds (cisplatin, carboplatin) and the podophyllotoxi...... II trials, but results from large phase III trials are necessary in order to measure the impact of these new agents in the management of NSCLC. Major improvements of therapy for mesothelioma have not occurred within the last year....

  11. Hyperlucent lung

    International Nuclear Information System (INIS)

    Jimenez-Gutierrez, Florana; Soto-Quiros, Manuel E.

    2007-01-01

    Unilateral hyperlucent lung is also known as Swyer-James Syndrome, Macleod Syndrome or lobular or unilateral emphysema. It is an uncommon disease characterized by lung or unilateral lobe hiperlucency associated to an air trapping upon expiration. As regards to etiology, this syndrome is considered to be an acquired disease that appears secondary to respiratory infections during the early years of life, probably bronchiolitis and/ or viral pneumonia. The clinical presentation varies among patients. Some of them are asymptomatic, others present a history of recurrent episodes of pulmonary infections from early years of life or present effort dyspnea. The diagnosis is usually made accidentally by a chest radiograph in a child with history of respiratory infections or in an adult during a routine chest x- ray in an asymptomatic person. It is important to differentiate this syndrome from other causes of unilateral pulmonary hiperlucency on conventional chest x-rays. Few cases of Swyer-James Syndrome in children have been reported, it is presented the clinical case of a patient who had a parainfluenza 3 bronchopneumonia when he was a month and eighteen days of age. The differential diagnosis of this syndrome should be done with other thoracic entities that diminish the radiological pulmonary unilateral density. A case of a child who is the bearer of hyperlucent lung is described. (author) [es

  12. Sliding thin slab, minimum intensity projection of the lung in asymptomatic subjects: lower limits of lung attenuation, without airways

    International Nuclear Information System (INIS)

    Ishihara, Katsutoshi; Satoh, Shiro; Ohdama, Shinichi; Shibuya, Hitoshi

    2006-01-01

    A sliding thin slab, minimum intensity projection (STS-MinIP) is considered to be useful for detecting diseases that decrease lung attenuation. For evaluating these diseases, it would be useful to ascertain the lower limits of normal lung attenuation, allowing a division between normal and subnormal attenuation. However, normal lung attenuation may vary depending on respiratory status, anatomical position, and patient background factors. Our aim was to determine whether the lower limits of lung attenuation, without airways, in asymptomatic subjects using STS-MinIP varies under different conditions. The study subjects were 43 volunteers without pulmonary symptoms. STS-MinIP was performed at full inspiration and full expiration at three levels of the lung. The lower limits of lung attenuation were compared among the three lung levels and between full inspiration and full expiration, the sexes, age groups, smokers and nonsmokers, and the right and left lungs. The lower limits of lung attenuation had significantly different Hounsfield unit values among lung levels, between the sexes at full inspiration, and between age groups at full expiration. This study shows that the lower limits of lung attenuation are influenced by lung fields, sex, and, on expiration, age. (author)

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

    International Nuclear Information System (INIS)

    Carter, Charleata A.; Hamm, Jonathan T.

    2009-01-01

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

  14. Planimetric determination of lung volume

    International Nuclear Information System (INIS)

    Bieber, M.; Maurer, H.J.

    1984-01-01

    The total volume of the lungs was determined by digital planimetry in 102 patients with emphysema and 33 normal controls aged between 30 and 79 years. The results were compared with the findings obtained from spirometric measurements. Mean values showed a significant relationship to age, body size and body surface. Planimetrically determined lung volume did not show a linear relationship with age, but increased after 60 years. Beyong 60 years, spirometric findings were lower because of an increase in the number of patients with emphysema. The results have shown that digital planimetry is a useful addition to spirometry. (orig.) [de

  15. Bioengineered Lungs: A Challenge and An Opportunity.

    Science.gov (United States)

    Farré, Ramon; Otero, Jordi; Almendros, Isaac; Navajas, Daniel

    2018-01-01

    Lung biofabrication is a new tissue engineering and regenerative development aimed at providing organs for potential use in transplantation. Lung biofabrication is based on seeding cells into an acellular organ scaffold and on culturing them in an especial purpose bioreactor. The acellular lung scaffold is obtained by decellularizing a non-transplantable donor lung by means of conventional procedures based on application of physical, enzymatic and detergent agents. To avoid immune recipient's rejection of the transplanted bioengineered lung, autologous bone marrow/adipose tissue-derived mesenchymal stem cells, lung progenitor cells or induced pluripotent stem cells are used for biofabricating the bioengineered lung. The bioreactor applies circulatory perfusion and mechanical ventilation with physiological parameters to the lung during biofabrication. These physical stimuli to the organ are translated into the stem cell local microenvironment - e.g. shear stress and cyclic stretch - so that cells sense the physiological conditions in normally functioning mature lungs. After seminal proof of concept in a rodent model was published in 2010, the hypothesis that lungs can be biofabricated is accepted and intense research efforts are being devoted to the topic. The current experimental evidence obtained so far in animal tests and in ex vivo human bioengineered lungs suggests that the date of first clinical tests, although not immediate, is coming. Lung bioengineering is a disrupting concept that poses a challenge for improving our basic science knowledge and is also an opportunity for facilitating lung transplantation in future clinical translation. Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. Molecular Profiles for Lung Cancer Pathogenesis and Detection in U.S. Veterans

    Science.gov (United States)

    2013-10-01

    matched lung tumors, controlled normal and uninvolved normal lung tissues were obtained from 20 resected early-stage (I-IIIA) NSCLC specimens. Gene...matched tumors, multiple cytologically controlled normal airways with varying distances from tumors and uninvolved normal lung tissues (n=194 samples... parent vector as a negative control (n=10). Overexpression of miR-4423 in four of the cell lines tested decreases the number of colonies formed in

  17. New estimates for human lung dimensions

    International Nuclear Information System (INIS)

    Kennedy, Christine; Sidavasan, Sivalal; Kramer, Gary

    2008-01-01

    Full text: The currently used lung dimensions in dosimetry were originally estimated in the 1940s from Army recruits. This study provides new estimates of lung dimensions based on images acquired from a sample from the general population (varying age and sex). Building accurate models, called phantoms, of the human lung requires that the spatial dimensions (length, width, and depth) be quantified, in addition to volume. Errors in dose estimates may result from improperly sized lungs as the counting efficiency of externally mounted detectors (e.g., in a lung counter) is dependent on the position of internally deposited radioactive material (i.e., the size of the lung). This study investigates the spatial dimensions of human lungs. Lung phantoms have previously been made in one of two sizes. The Lawrence Livermore National Laboratory Torso Phantom (LLNL) has deep, short lungs whose dimensions do not comply well with the data published in Report 23 (Reference Man) issued by the International Commission on Radiological Protection (ICRP). The Japanese Atomic Energy Research Institute Torso Phantom(JAERI), has longer, shallower lungs that also deviate from the ICRP values. However, careful examination of the ICRP recommended values shows that they are soft. In fact, they have been dropped from the ICRP's Report 89 which updates Report 23. Literature surveys have revealed a wealth of information on lung volume, but very little data on the spatial dimensions of human lungs. Better lung phantoms need to be constructed to more accurately represent a person so that dose estimates may be quantified more accurately in view of the new, lower, dose limits for occupationally exposed workers and the general public. Retrospective chest images of 60 patients who underwent imaging of the chest- lungs as part of their healthy persons occupational screening for lung disease were chosen. The chosen normal lung images represent the general population). Ages, gender and weight of the

  18. Lung perfusion scintigraphy by SPECT

    International Nuclear Information System (INIS)

    Hirayama, Takanobu

    1990-01-01

    The initial study reports the characteristic performance using lung segmental phantom filled in Tc-99m pertechnetate. To evaluate the segmental defect in lung perfusion scintigraphy, we applied Bull's-eye analysis in addition to planar image set. Bull's-eye analysis especially facilitated the interpretation in both middle and lower lobes. Subsequently, to evolute the clinical application of Bull's-eye analysis, pulmonary scintigraphy was performed on 10 normal subjects and 60 patients with several pulmonary diseases. Of interest, Bull's-eye analysis, however, encouraged the interpretation in both lower lobes. To calculate the extention and severity of perfusion defect, the present study describes Bull's-eye analysis. Quantitative scoring showed higher in patients with lung cancer than those with pulmonary tuberculosis. The present study focus that Bull's-eye analysis can be useful for evaluating perfusion in patients with a couple of pulmonary diseases. (author)

  19. PET in lung cancer staging

    Energy Technology Data Exchange (ETDEWEB)

    Coleman, R. E. [Duke University Medical Center, Dept. of Radiology, Durham, NC (United States)

    2001-09-01

    The primary clinical application of FDG-PET is in the evaluation of patients with lung cancer and includes diagnosis, staging and restaging of non-small cell lung cancer. PET has a very high accuracy (sensitivity=97%, specificity=78%) for characterizing nodules that are indeterminate by chest radiograph and computed tomography. The major utility of PET in the evaluation of patients with lung cancer is the staging of the entire body. PET is more accurate than the conventional imaging modalities of CT and bone scans in the detection of metastatic disease. PET is accurate in the staging of the mediastinum, adrenal glands, and the skeletal system. PET is not as accurate in the detection of brain metastases because of their small size and the normal cortical accumulation.

  20. How Lungs Work

    Science.gov (United States)

    ... Health and Diseases > How Lungs Work How Lungs Work The Respiratory System Your lungs are part of ... Parts of the Respiratory System and How They Work Airways SINUSES are hollow spaces in the bones ...

  1. Lung diffusion testing

    Science.gov (United States)

    ... medlineplus.gov/ency/article/003854.htm Lung diffusion testing To use the sharing features on this page, please enable JavaScript. Lung diffusion testing measures how well the lungs exchange gases. This ...

  2. 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)

  3. Extravascular Lung Water and Acute Lung Injury

    Directory of Open Access Journals (Sweden)

    Ritesh Maharaj

    2012-01-01

    Full Text Available Acute lung injury carries a high burden of morbidity and mortality and is characterised by nonhydrostatic pulmonary oedema. The aim of this paper is to highlight the role of accurate quantification of extravascular lung water in diagnosis, management, and prognosis in “acute lung injury” and “acute respiratory distress syndrome”. Several studies have verified the accuracy of both the single and the double transpulmonary thermal indicator techniques. Both experimental and clinical studies were searched in PUBMED using the term “extravascular lung water” and “acute lung injury”. Extravascular lung water measurement offers information not otherwise available by other methods such as chest radiography, arterial blood gas, and chest auscultation at the bedside. Recent data have highlighted the role of extravascular lung water in response to treatment to guide fluid therapy and ventilator strategies. The quantification of extravascular lung water may predict mortality and multiorgan dysfunction. The limitations of the dilution method are also discussed.

  4. Stem cells and repair of lung injuries

    Directory of Open Access Journals (Sweden)

    Randell Scott H

    2004-07-01

    Full Text Available Abstract Fueled by the promise of regenerative medicine, currently there is unprecedented interest in stem cells. Furthermore, there have been revolutionary, but somewhat controversial, advances in our understanding of stem cell biology. Stem cells likely play key roles in the repair of diverse lung injuries. However, due to very low rates of cellular proliferation in vivo in the normal steady state, cellular and architectural complexity of the respiratory tract, and the lack of an intensive research effort, lung stem cells remain poorly understood compared to those in other major organ systems. In the present review, we concisely explore the conceptual framework of stem cell biology and recent advances pertinent to the lungs. We illustrate lung diseases in which manipulation of stem cells may be physiologically significant and highlight the challenges facing stem cell-related therapy in the lung.

  5. Pathophysiology of Pulmonary Hypertension in Chronic Parenchymal Lung Disease.

    Science.gov (United States)

    Singh, Inderjit; Ma, Kevin Cong; Berlin, David Adam

    2016-04-01

    Pulmonary hypertension commonly complicates chronic obstructive pulmonary disease and interstitial lung disease. The association of chronic lung disease and pulmonary hypertension portends a worse prognosis. The pathophysiology of pulmonary hypertension differs in the presence or absence of lung disease. We describe the physiological determinants of the normal pulmonary circulation to better understand the pathophysiological factors implicated in chronic parenchymal lung disease-associated pulmonary hypertension. This review will focus on the pathophysiology of 3 forms of chronic lung disease-associated pulmonary hypertension: idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, and sarcoidosis. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Total lung capacity estimation: comparison of radiologic and helium dilution methods

    International Nuclear Information System (INIS)

    Prasad, J.P.; Katariya, S.; Behera, D.; Malik, S.K.; Bansal, S.C.

    1990-01-01

    The accuracy of radiologic method in determining total lung capacity (TLC) was assessed by correlating radiologic TLC values with those obtained by helium dlution method. Total lung capacity was estimated by both the methods in 60 normal healthy adult subjects and 30 patients of obstructive and restrictive lung diseases. Excellent correlation was found between these two methods in case of normal subjects and interstitial lung disease patients. No correlation however, was found in chronic obstructive airways disease patients. (author). 17 refs

  7. Intersections of lung progenitor cells, lung disease and lung cancer

    Directory of Open Access Journals (Sweden)

    Carla F. Kim

    2017-06-01

    Full Text Available The use of stem cell biology approaches to study adult lung progenitor cells and lung cancer has brought a variety of new techniques to the field of lung biology and has elucidated new pathways that may be therapeutic targets in lung cancer. Recent results have begun to identify the ways in which different cell populations interact to regulate progenitor activity, and this has implications for the interventions that are possible in cancer and in a variety of lung diseases. Today's better understanding of the mechanisms that regulate lung progenitor cell self-renewal and differentiation, including understanding how multiple epigenetic factors affect lung injury repair, holds the promise for future better treatments for lung cancer and for optimising the response to therapy in lung cancer. Working between platforms in sophisticated organoid culture techniques, genetically engineered mouse models of injury and cancer, and human cell lines and specimens, lung progenitor cell studies can begin with basic biology, progress to translational research and finally lead to the beginnings of clinical trials.

  8. CCAAT/enhancer binding protein β is dispensable for development of lung adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Yi Cai

    Full Text Available Lung cancer is the leading cause of cancer death worldwide. Although disruption of normal proliferation and differentiation is a vital component of tumorigenesis, the mechanisms of this process in lung cancer are still unclear. A transcription factor, C/EBPβ is a critical regulator of proliferation and/or differentiation in multiple tissues. In lung, C/EBPβ is expressed in alveolar pneumocytes and bronchial epithelial cells; however, its roles on normal lung homeostasis and lung cancer development have not been well described. Here we investigated whether C/EBPβ is required for normal lung development and whether its aberrant expression and/or activity contribute to lung tumorigenesis. We showed that C/EBPβ was expressed in both human normal pneumocytes and lung adenocarcinoma cell lines. We found that overall lung architecture was maintained in Cebpb knockout mice. Neither overexpression of nuclear C/EBPβ nor suppression of CEBPB expression had significant effects on cell proliferation. C/EBPβ expression and activity remained unchanged upon EGF stimulation. Furthermore, deletion of Cebpb had no impact on lung tumor burden in a lung specific, conditional mutant EGFR lung cancer mouse model. Analyses of data from The Cancer Genome Atlas (TCGA revealed that expression, promoter methylation, or copy number of CEBPB was not significantly altered in human lung adenocarcinoma. Taken together, our data suggest that C/EBPβ is dispensable for development of lung adenocarcinoma.

  9. Surfactant gene polymorphisms and interstitial lung diseases

    Directory of Open Access Journals (Sweden)

    Pantelidis Panagiotis

    2001-11-01

    Full Text Available Abstract Pulmonary surfactant is a complex mixture of phospholipids and proteins, which is present in the alveolar lining fluid and is essential for normal lung function. Alterations in surfactant composition have been reported in several interstitial lung diseases (ILDs. Furthermore, a mutation in the surfactant protein C gene that results in complete absence of the protein has been shown to be associated with familial ILD. The role of surfactant in lung disease is therefore drawing increasing attention following the elucidation of the genetic basis underlying its surface expression and the proof of surfactant abnormalities in ILD.

  10. Lung needle biopsy

    Science.gov (United States)

    ... if you have certain lung diseases such as emphysema. Usually, a collapsed lung after a biopsy does not need treatment. But ... any type Bullae (enlarged alveoli that occur with emphysema) Cor pulmonale (condition ... of the lung High blood pressure in the lung arteries Severe ...

  11. Lung Cancer Screening

    Science.gov (United States)

    ... experience complications from follow-up tests. For this reason, lung cancer screening is offered to people who are in ... is more likely to be cancerous. For that reason, you might be referred to a lung ... problems. Your lung cancer screening test may detect other lung and heart ...

  12. Quantitative CT characterization of pediatric lung development using routine clinical imaging

    Energy Technology Data Exchange (ETDEWEB)

    Stein, Jill M.; Brody, Alan S.; Fleck, Robert J. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Walkup, Laura L. [Cincinnati Children' s Hospital Medical Center, Center for Pulmonary Imaging Research, Pulmonary Medicine and Radiology, Cincinnati, OH (United States); Woods, Jason C. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Cincinnati Children' s Hospital Medical Center, Center for Pulmonary Imaging Research, Pulmonary Medicine and Radiology, Cincinnati, OH (United States)

    2016-12-15

    The use of quantitative CT analysis in children is limited by lack of normal values of lung parenchymal attenuation. These characteristics are important because normal lung development yields significant parenchymal attenuation changes as children age. To perform quantitative characterization of normal pediatric lung parenchymal X-ray CT attenuation under routine clinical conditions in order to establish a baseline comparison to that seen in pathological lung conditions. We conducted a retrospective query of normal CT chest examinations in children ages 0-7 years from 2004 to 2014 using standard clinical protocol. During these examinations semi-automated lung parenchymal segmentation was performed to measure lung volume and mean lung attenuation. We analyzed 42 CT examinations in 39 children, ages 3 days to 83 months (mean ± standard deviation [SD] = 42 ± 27 months). Lung volume ranged 0.10-1.72 liters (L). Mean lung attenuation was much higher in children younger than 12 months, with values as high as -380 Hounsfield units (HU) in neonates (lung volume 0.10 L). Lung volume decreased to approximately -650 HU by age 2 years (lung volume 0.47 L), with subsequently slower exponential decrease toward a relatively constant value of -860 HU as age and lung volume increased. Normal lung parenchymal X-ray CT attenuation decreases with increasing lung volume and age; lung attenuation decreases rapidly in the first 2 years of age and more slowly thereafter. This change in normal lung attenuation should be taken into account as quantitative CT methods are translated to pediatric pulmonary imaging. (orig.)

  13. Micromechanical model of lung parenchyma hyperelasticity

    Science.gov (United States)

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

    2018-03-01

    Mechanics plays a key role in respiratory physiology, as lung tissue cyclically deforms to bring air in and out the lung, a life-long process necessary for respiration. The study of regional mechanisms of deformation in lung parenchyma has received great attention to date due to its clinical relevance, as local overstretching and stress concentration in lung tissue is currently associated to pathological conditions such as lung injury during mechanical ventilation therapy. This mechanical approach to lung physiology has motivated the development of constitutive models to better understand the relation between stress and deformation in the lung. While material models proposed to date have been key in the development of whole-lung simulations, either they do not directly relate microstructural properties of alveolar tissue with coarse-scale behavior, or they require a high computational effort when based on real alveolar geometries. Furthermore, most models proposed to date have not been thoroughly validated for anisotropic deformation states, which are commonly found in normal lungs in-vivo. In this work, we develop a novel micromechanical model of lung parenchyma hyperelasticity using the framework of finite-deformation homogenization. To this end, we consider a tetrakaidecahedron unit cell with incompressible Neo-Hookean structural elements that account for the alveolar wall tissue responsible for the elastic response, and derive expressions for its effective coarse-scale behavior that directly depend on the alveolar wall elasticity, reference porosity, and two other geometrical coefficients. To validate the proposed model, we simulate the non-linear elastic response of twelve representative volume elements (RVEs) of lung parenchyma with micrometric dimensions, whose geometry is obtained from micrometric computed-tomography reconstructions of murine lungs. We show that the proposed micromechanical model accurately captures the RVEs response not only for isotropic

  14. Computed Tomography Measure of Lung at Risk and Lung Function Decline in Chronic Obstructive Pulmonary Disease.

    Science.gov (United States)

    Bhatt, Surya P; Bodduluri, Sandeep; Hoffman, Eric A; Newell, John D; Sieren, Jessica C; Dransfield, Mark T; Reinhardt, Joseph M

    2017-09-01

    The rate of decline of lung function is greater than age-related change in a substantial proportion of patients with chronic obstructive pulmonary disease, even after smoking cessation. Regions of the lung adjacent to emphysematous areas are subject to abnormal stretch during respiration, and this biomechanical stress likely influences emphysema initiation and progression. To assess whether quantifying this penumbra of lung at risk would predict FEV 1 decline. We analyzed paired inspiratory-expiratory computed tomography images at baseline of 680 subjects participating in a large multicenter study (COPDGene) over approximately 5 years. By matching inspiratory and expiratory images voxel by voxel using image registration, we calculated the Jacobian determinant, a measure of local lung expansion and contraction with respiration. We measured the distance between each normal voxel to the nearest emphysematous voxel, and quantified the percentage of normal voxels within each millimeter distance from emphysematous voxels as mechanically affected lung (MAL). Multivariable regression analyses were performed to assess the relationship between the Jacobian determinant, MAL, and FEV 1 decline. The mean (SD) rate of decline in FEV 1 was 39.0 (58.6) ml/yr. There was a progressive decrease in the mean Jacobian determinant of both emphysematous and normal voxels with increasing disease stage (P < 0.001). On multivariable analyses, the mean Jacobian determinant of normal voxels within 2 mm of emphysematous voxels (MAL 2 ) was significantly associated with FEV 1 decline. In mild-moderate disease, for participants at or above the median MAL 2 (threshold, 36.9%), the mean decline in FEV 1 was 56.4 (68.0) ml/yr versus 43.2 (59.9) ml/yr for those below the median (P = 0.044). Areas of normal-appearing lung are mechanically influenced by emphysematous areas and this lung at risk is associated with lung function decline. Clinical trial registered with www.clinicaltrials.gov (NCT

  15. Normal Pressure Hydrocephalus (NPH)

    Science.gov (United States)

    ... local chapter Join our online community Normal Pressure Hydrocephalus (NPH) Normal pressure hydrocephalus is a brain disorder ... Symptoms Diagnosis Causes & risks Treatments About Normal Pressure Hydrocephalus Normal pressure hydrocephalus occurs when excess cerebrospinal fluid ...

  16. Advances in lung ultrasound.

    Science.gov (United States)

    Francisco, Miguel José; Rahal, Antonio; Vieira, Fabio Augusto Cardillo; Silva, Paulo Savoia Dias da; Funari, Marcelo Buarque de Gusmão

    2016-01-01

    Ultrasound examination of the chest has advanced in recent decades. This imaging modality is currently used to diagnose several pathological conditions and provides qualitative and quantitative information. Acoustic barriers represented by the aerated lungs and the bony framework of the chest generate well-described sonographic artifacts that can be used as diagnostic aids. The normal pleural line and A, B, C, E and Z lines (also known as false B lines) are artifacts with specific characteristics. Lung consolidation and pneumothorax sonographic patterns are also well established. Some scanning protocols have been used in patient management. The Blue, FALLS and C.A.U.S.E. protocols are examples of algorithms using artifact combinations to achieve accurate diagnoses. Combined chest ultrasonography and radiography are often sufficient to diagnose and manage lung and chest wall conditions. Chest ultrasonography is a highly valuable diagnostic tool for radiologists, emergency and intensive care physicians. RESUMO O exame ultrassonográfico do tórax avançou nas últimas décadas, sendo utilizado para o diagnóstico de inúmeras condições patológicas, e fornecendo informações qualitativas e quantitativas. Os pulmões aerados e o arcabouço ósseo do tórax representam barreira sonora para o estudo ultrassonográfico, gerando artefatos que, bem conhecidos, são utilizados como ferramentas diagnósticas. Eco pleural normal, linhas A, linhas B, linhas C, linhas E e Z (conhecidas como falsas linhas B) são artefatos com características peculiares. Os padrões de consolidação e de pneumotórax também são bem estabelecidos. Alguns protocolos têm sido utilizados no manuseio dos pacientes: Blue Protocol, Protocolo FALLS e Protocolo C.A.U.S.E são exemplos de três propostas que, por meio da associação entre os artefatos, permitem sugerir diagnósticos precisos. A ultrassonografia de tórax, aliada à radiografia de tórax, muitas vezes é suficiente para o diagn

  17. Lung Lavage and Surfactant Replacement During Ex Vivo Lung Perfusion for Treatment of Gastric Acid Aspiration-Induced Donor Lung Injury.

    Science.gov (United States)

    Nakajima, Daisuke; Liu, Mingyao; Ohsumi, Akihiro; Kalaf, Ricardo; Iskender, Ilker; Hsin, Michael; Kanou, Takashi; Chen, Manyin; Baer, Brandon; Coutinho, Rafael; Maahs, Lucas; Behrens, Paula; Azad, Sassan; Martinu, Tereza; Waddell, Thomas K; Lewis, James F; Post, Martin; Veldhuizen, Ruud A W; Cypel, Marcelo; Keshavjee, Shaf

    2017-05-01

    Ex vivo lung perfusion (EVLP) provides opportunities to treat injured donor lungs before transplantation. We investigated whether lung lavage, to eliminate inflammatory inhibitory components, followed by exogenous surfactant replacement, could aid lung recovery and improve post-transplant lung function after gastric aspiration injury. Gastric acid aspiration was induced in donor pigs, which were ventilated for 6 hours to develop lung injury. After retrieval and 10 hours of cold preservation, EVLP was performed for 6 hours. The lungs were randomly divided into 4 groups (n = 5, each): (1) no treatment (control), (2) lung lavage, (3) surfactant administration, and (4) lung lavage, followed by surfactant administration. After another 2-hour period of cold preservation, the left lung was transplanted and reperfused for 4 hours. Physiologic lung function significantly improved after surfactant administration during EVLP. The EVLP perfusate from the lavage + surfactant group showed significantly lower levels of interleukin (IL)-1β, IL-6, IL-8, and secretory phospholipase A 2 . Total phosphatidylcholine was increased, and minimum surface tension was recovered to normal levels (≤5 mN/m) in the bronchioalveolar fluid after surfactant administration. Lysophosphatidylcholine in bronchioalveolar fluid was significantly lower in the lavage + surfactant group than in the surfactant group. Post-transplant lung function was significantly better in the lavage + surfactant group compared with all other groups. Lung lavage, followed by surfactant replacement during EVLP, reduced inflammatory mediators and prevented hydrolysis of phosphatidylcholine, which contributed to the superior post-transplant function in donor lungs with aspiration injury. Copyright © 2017 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  18. Lung growth and development.

    Science.gov (United States)

    Joshi, Suchita; Kotecha, Sailesh

    2007-12-01

    Human lung growth starts as a primitive lung bud in early embryonic life and undergoes several morphological stages which continue into postnatal life. Each stage of lung growth is a result of complex and tightly regulated events governed by physical, environmental, hormonal and genetic factors. Fetal lung liquid and fetal breathing movements are by far the most important determinants of lung growth. Although timing of the stages of lung growth in animals do not mimic that of human, numerous animal studies, mainly on sheep and rat, have given us a better understanding of the regulators of lung growth. Insight into the genetic basis of lung growth has helped us understand and improve management of complex life threatening congenital abnormalities such as congenital diaphragmatic hernia and pulmonary hypoplasia. Although advances in perinatal medicine have improved survival of preterm infants, premature birth is perhaps still the most important factor for adverse lung growth.

  19. Epidemiology of Lung Cancer

    Science.gov (United States)

    Brock, Malcolm V.; Ford, Jean G.; Samet, Jonathan M.; Spivack, Simon D.

    2013-01-01

    Background: Ever since a lung cancer epidemic emerged in the mid-1900s, the epidemiology of lung cancer has been intensively investigated to characterize its causes and patterns of occurrence. This report summarizes the key findings of this research. Methods: A detailed literature search provided the basis for a narrative review, identifying and summarizing key reports on population patterns and factors that affect lung cancer risk. Results: Established environmental risk factors for lung cancer include smoking cigarettes and other tobacco products and exposure to secondhand tobacco smoke, occupational lung carcinogens, radiation, and indoor and outdoor air pollution. Cigarette smoking is the predominant cause of lung cancer and the leading worldwide cause of cancer death. Smoking prevalence in developing nations has increased, starting new lung cancer epidemics in these nations. A positive family history and acquired lung disease are examples of host factors that are clinically useful risk indicators. Risk prediction models based on lung cancer risk factors have been developed, but further refinement is needed to provide clinically useful risk stratification. Promising biomarkers of lung cancer risk and early detection have been identified, but none are ready for broad clinical application. Conclusions: Almost all lung cancer deaths are caused by cigarette smoking, underscoring the need for ongoing efforts at tobacco control throughout the world. Further research is needed into the reasons underlying lung cancer disparities, the causes of lung cancer in never smokers, the potential role of HIV in lung carcinogenesis, and the development of biomarkers. PMID:23649439

  20. Lung and Heart Dose Variability During Radiation Therapy of Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Jan, Nuzhat; Guy, Christopher; Reshko, Leonid B; Hugo, Geoffrey D; Weiss, Elisabeth

    2017-07-01

    To investigate the hypothesis that positional and anatomic variations during radiation therapy induce changes in lung and heart volumes and associated radiation doses. In this longitudinal investigation, variations in lung and heart volumes and standard dose parameters of mean lung dose, lung V 20Gy , mean heart dose, and heart V 40Gy were analyzed on weekly 4-dimensional CT scans of 15 lung cancer patients during conventionally fractionated radiochemotherapy. Tumor, individual lung lobes, and heart were delineated on the mid-ventilation phase of weekly 4-dimensional CT scans. Lung lobes and heart were also contoured on individual breathing phases of pre-, mid-, and end-of-treatment scans. Planning dose was transferred to consecutive scans via rigid registration. Volume and dose variations were assessed relative to the initial planning scan. Interfraction lung volume variability relative to week 0 was twice as large as tidal volume variability (8.0% ± 5.3% vs 4.0% ± 3.3%, P=.003). Interfraction lung volume variation ranged between 0.8% and 17.1% for individual patient means. Lower lung lobes had larger volume variability compared with upper lobes (13.5% ± 8.1% vs 7.0% ± 5.0%, Pheart volume variation was 7.2% (range, 3.4%-12.6%). Average mean heart dose variation was 1.2 Gy (range, 0.1-3.0 Gy) and average heart V 40Gy variation 1.4% (range, 0%-4.2%). Anatomic and positional variations during radiation therapy induce changes in radiation doses to lung and heart. Repeated lung and heart dose assessment will provide a better estimate of the actual delivered dose and will improve prediction models for normal tissue toxicity, if assessed in larger cohorts. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. β2-Microglobulin participates in development of lung emphysema by inducing lung epithelial cell senescence.

    Science.gov (United States)

    Gao, Na; Wang, Ying; Zheng, Chun-Ming; Gao, Yan-Li; Li, Hui; Li, Yan; Fu, Ting-Ting; Xu, Li-Li; Wang, Wei; Ying, Sun; Huang, Kewu

    2017-05-01

    β 2 -Microglobulin (β 2 M), the light chain of the major histocompatibility complex class I (MHC I), has been identified as a proaging factor and is involved in the pathogenesis of neurodegenerative disorders by driving cognitive and regenerative impairments. However, little attention has focused on the effect of β 2 M in the development of lung emphysema. Here, we found that concentrations of β 2 M in plasma were significantly elevated in patients with lung emphysema than those in normal control subjects (1.89 ± 0.12 vs. 1.42 ± 0.06 mg/l, P lung tissue of emphysema (39.90 ± 1.97 vs. 23.94 ± 2.11%, P lung emphysema through induction of lung epithelial cell senescence and inhibition. Copyright © 2017 the American Physiological Society.

  2. The adaptive response of the rat lung after bilobectomy.

    Science.gov (United States)

    Burri, P H; Sehovic, S

    1979-05-01

    Rats 23 days of age were subjected to resection of the upper and middle lobes of the right lung. After 45 days of recovery, their lungs were fixed and the tissue was processed for quantitative light and electron microscopic analysis. Normal and sham-operated animals of identical age served as control animals. At death, the lobectomized rats had normal body weights and lung volumes; both the left lung and the remainder of the right lung participated proportionally in the restoration of the original lung volume. Air space, tissue and capillary volumes, and alveolar and capillary surface areas were as large as those of the control lungs. Tissue composition was slightly altered: the volume proportion of the interstitium was increased at the cost of the epithelium; endothelial volume density and air-blood barrier thicknesses were normal. Nonparenchymal structures had a smaller potential to adapt than the gas-exchanging parenchyma: the volume of conducting airways was smaller than expected for a normal lung. An analogous trend was observed for the larger blood vessels. Based on the recreated dimensions of the gas-exchange apparatus in operated animals, one can assume that the organ fully restores the conditions for adequate gas diffusion.

  3. Haemophilia, AIDS and lung epithelial permeability

    Energy Technology Data Exchange (ETDEWEB)

    O' Doherty, M.J.; Page, C.J.; Harrington, C.; Nunan, T.; Savidge, G. (Haemophilia Centre and Coagulation Research Unit, Department of Nuclear Medicine, Rayne Institute, St. Thomas' Hospital, London (United Kingdom))

    1990-01-01

    Lung {sup 99m}Tc DTPA transfer was measured in HIV antibodypositive haemophiliacs (11 smokers, 26 nonsmokers, 5 patients with Pneumocystis carinii pneumonia (PCP)). Lung {sup 99m}Tc DTPA transfer as a marker of lung epithelial permeability was measured as the half time of transfer (from airspace into blood). This half time was faster in smokers compred to nonsmokers and the transfer curve was monoexponential. In nonsmokers no difference was observed between asymptomatic HIV-positive haemophiliacs and normal subjects, with the exception of the lung bases. At the lung basis in HIV-positive haemophiliac nonsmokers the transfer was faster than in normal individuals, implying increased alveolar permeability. Pneumocystis carinii pneumonia resulted in a rapid transfer of {sup 99m}Tc DTPA (mean T50 of 2 minutes) and the transfer curve was biphasic, confirming previous observations in homosexual HIV antibody-positive patients with PCP. These changes returned to a monoexponential profile by 6 weeks following successful treatment. The DTPA lung transfer study may enable clinicians to instigate therapy for PCP without the need for initial bronchoscopy and provide a noninvasive method for the reassessment of patients should further respiratory signs or symptoms develop. This method is considered to be highly cost-effective in that it obviates the use of factor VIII concentrates required to cover bronchoscopic procedures and, with its early application and ease of use as a follow-up investigation, permits the evaluation of patients on an outpatient basis, thus reducing hospital costs. (au).

  4. Haemophilia, AIDS and lung epithelial permeability

    International Nuclear Information System (INIS)

    O'Doherty, M.J.; Page, C.J.; Harrington, C.; Nunan, T.; Savidge, G.

    1990-01-01

    Lung 99m Tc DTPA transfer was measured in HIV antibodypositive haemophiliacs (11 smokers, 26 nonsmokers, 5 patients with Pneumocystis carinii pneumonia (PCP)). Lung 99m Tc DTPA transfer as a marker of lung epithelial permeability was measured as the half time of transfer (from airspace into blood). This half time was faster in smokers compred to nonsmokers and the transfer curve was monoexponential. In nonsmokers no difference was observed between asymptomatic HIV-positive haemophiliacs and normal subjects, with the exception of the lung bases. At the lung basis in HIV-positive haemophiliac nonsmokers the transfer was faster than in normal individuals, implying increased alveolar permeability. Pneumocystis carinii pneumonia resulted in a rapid transfer of 99m Tc DTPA (mean T50 of 2 minutes) and the transfer curve was biphasic, confirming previous observations in homosexual HIV antibody-positive patients with PCP. These changes returned to a monoexponential profile by 6 weeks following successful treatment. The DTPA lung transfer study may enable clinicians to instigate therapy for PCP without the need for initial bronchoscopy and provide a noninvasive method for the reassessment of patients should further respiratory signs or symptoms develop. This method is considered to be highly cost-effective in that it obviates the use of factor VIII concentrates required to cover bronchoscopic procedures and, with its early application and ease of use as a follow-up investigation, permits the evaluation of patients on an outpatient basis, thus reducing hospital costs. (au)

  5. Placental Transmogrification of the lung

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Woo; Park, Il Hwan; Kwon, Woo Cheol; Eom, Min Seob; Kim, Young Ju; Hwan, Joong Hwan [Yonsei University Wonju College of Medicine, Wonju (Korea, Republic of)

    2013-12-15

    Placental transmogrification is a very rare lung disease, where the alveoli resemble the chorionic villi of placenta, and this change is a characteristic finding. A 31-year-old female patient presented with cough and dyspnea that had begun 2 weeks prior to admission. Along with giant bulla found in the left upper lung field, subsegmental consolidation was also identified in the lingular segment on plain chest radiograph and CT scan. Wedge resection was performed to remove the bulla. Pathologic examination of the resected bulla revealed destruction of the normal structures and characteristic villous and papillary changes. These changes led to a diagnosis of placental transmogrification. We made an encounter of an unusual placental transmogrification which had different image findings from other reported transmogrification cases. Thus, we report an atypical placental transmogrification case where both consolidation and giant bulla coexist.

  6. IKKβ Activation in the Fetal Lung Mesenchyme Alters Lung Vascular Development but Not Airway Morphogenesis.

    Science.gov (United States)

    McCoy, Alyssa M; Herington, Jennifer L; Stouch, Ashley N; Mukherjee, Anamika B; Lakhdari, Omar; Blackwell, Timothy S; Prince, Lawrence S

    2017-12-01

    In the immature lung, inflammation and injury disrupt the epithelial-mesenchymal interactions required for normal development. Innate immune signaling and NF-κB activation disrupt the normal expression of multiple mesenchymal genes that play a key role in airway branching and alveolar formation. To test the role of the NF-κB pathway specifically in lung mesenchyme, we utilized the mesenchymal Twist2-Cre to drive expression of a constitutively active inhibitor of NF-κB kinase subunit β (IKKβca) mutant in developing mice. Embryonic Twist2-IKKβca mice were generated in expected numbers and appeared grossly normal. Airway branching also appeared normal in Twist2-IKKβca embryos, with airway morphometry, elastin staining, and saccular branching similar to those in control littermates. While Twist2-IKKβca lungs did not contain increased levels of Il1b, we did measure an increased expression of the chemokine-encoding gene Ccl2. Twist2-IKKβca lungs had increased staining for the vascular marker platelet endothelial cell adhesion molecule 1. In addition, type I alveolar epithelial differentiation appeared to be diminished in Twist2-IKKβca lungs. The normal airway branching and lack of Il1b expression may have been due to the inability of the Twist2-IKKβca transgene to induce inflammasome activity. While Twist2-IKKβca lungs had an increased number of macrophages, inflammasome expression remained restricted to macrophages without evidence of spontaneous inflammasome activity. These results emphasize the importance of cellular niche in considering how inflammatory signaling influences fetal lung development. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  7. Lungs and Respiratory System

    Science.gov (United States)

    ... even smaller tubes called bronchioles. Bronchioles end in tiny air sacs called alveoli, where the exchange of oxygen and carbon dioxide actually takes place. Each lung houses about 300-400 million alveoli. The lungs also ...

  8. Nutrition for Lung Cancer

    Science.gov (United States)

    ... to help prepare meals or do the grocery shopping for you. Most people you know want to ... Better Breathers Clubs Asthma Basics LUNG FORCE Expos Online Support Communities FUNDRAISERS Fight For Air Climb LUNG ...

  9. Lung Cancer Trends

    Science.gov (United States)

    ... Cervical Colorectal (Colon) Ovarian Prostate Skin Cancer Home Lung Cancer Trends Language: English Español (Spanish) Recommend on Facebook ... in the United States, the incidence rate of lung cancer— Men Decreased significantly by 2.5% per year ...

  10. Immunological risk stratification of the bronchiolitis obliterans syndrome after lung transplantation

    NARCIS (Netherlands)

    Kwakkel - van Erp, J.M.

    2011-01-01

    The development of chronic allograft rejection after lung transplantation (LTx) is the most common cause of poor long-term survival in lung transplant recipients. This rejection leads to obliteration of the bronchioli. Since this obliteration has a patchy distribution and normal lung tissue obtained

  11. 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

  12. PPARGC1A is upregulated and facilitates lung cancer metastasis.

    Science.gov (United States)

    Li, Jin-Dong; Feng, Qing-Chuan; Qi, Yu; Cui, Guanghui; Zhao, Song

    2017-10-15

    Lung cancer remains a leading cause of cancer-related mortality, with metastatic progression remaining the single largest cause of lung cancer mortality. Hence it is imperative to determine reliable biomarkers for lung cancer prognosis. We performed quantitative real-time PCR (qRT-PCR) analysis to explore epithelial-mesenchymal transition (EMT) inducers that regulate EMT process in three patients with advanced lung cancer disease. Peroxisome proliferator-activated receptor gamma (PPARGC1A) was uniformly the topmost overexpressed gene in all three human non-small cell lung cancer (NSCLC) patient samples. Further evaluation in human normal lung and metastatic lung cancer cell lines revealed that the expression of PPARGC1A was upregulated in metastatic lung cancer cell lines. Metagenomic analysis revealed direct correlation among PPARGC1A, zinc-finger transcription factor snail homolog 1 (SNAI1), and metastatic lung disease. Upregulation of PPARGC1A transcript expression was independent of a differential upregulation of the upstream AMP-dependent protein kinase (AMPK) activation or steady state expression of the silent mating type information regulation 2 homolog 1 (SIRT1). Xenograft tail vein colonization assays proved that the high expression of PPARGC1A was a prerequisite for metastatic progression of lung cancer to brain. Our results indicate that PPARGC1A might be a potential biomarker for lung cancer prognosis. Copyright © 2017. Published by Elsevier Inc.

  13. Testing for normality

    CERN Document Server

    Thode, Henry C

    2002-01-01

    Describes the selection, design, theory, and application of tests for normality. Covers robust estimation, test power, and univariate and multivariate normality. Contains tests ofr multivariate normality and coordinate-dependent and invariant approaches.

  14. SU-E-J-87: Ventilation Weighting Effect On Mean Doses of Both Side Lungs for Patients with Advanced Stage Lung Cancer

    International Nuclear Information System (INIS)

    Qu, H; Xia, P; Yu, N

    2015-01-01

    Purpose: To study ventilation weighting effect on radiation doses to both side lungs for patients with advanced stage lung cancer. Methods: Fourteen patients with advanced stage lung cancer were included in this retrospective study. Proprietary software was developed to calculate the lung ventilation map based on 4DCT images acquired for radiation therapy. Two phases of inhale (0%) and exhale (50%) were used for the lung ventilation calculations. For each patient, the CT images were resampled to the same dose calculation resolution of 3mmx3mmx3mm. The ventilation distribution was then normalized by the mean value of the ventilation. The ventilation weighted dose was calculated by applying linearly weighted ventilation to the dose of each pixel. The lung contours were automatically delineated from patient CT image with lung window, excluding the tumor and high density tissues. For contralateral and ipsilateral lungs, the mean lung doses from the original plan and ventilation weighted mean lung doses were compared using two tail t-Test. Results: The average of mean dose was 6.1 ±3.8Gy for the contralateral lungs, and 26.2 ± 14.0Gy for the ipsilateral lungs. The average of ventilation weighted dose was 6.3± 3.8Gy for the contralateral lungs and 24.6 ± 13.1Gy for the ipsilateral lungs. The statistics analysis shows the significance of the mean dose increase (p<0.015) for the contralateral lungs and decrease (p<0.005) for the ipsilateral lungs. Conclusion: Ventilation weighted doses were greater than the un-weighted doses for contralateral lungs and smaller for ipsilateral lungs. This Result may be helpful to understand the radiation dosimetric effect on the lung function and provide planning guidance for patients with advance stage lung cancer

  15. Relationship between radiation dose and lung function in patients with lung cancer receiving radiotherapy

    International Nuclear Information System (INIS)

    Harsaker, V.; Dale, E.; Bruland, O.S.; Olsen, D.R.

    2003-01-01

    In patients with inoperable non-small cell lung cancer (NSCLC), radical radiotherapy is the treatment of choice. The dose is limited by consequential pneumonitis and lung fibrosis. Hence, a better understanding of the relationship between the dose-volume distributions and normal tissue side effects is needed. CT is a non-invasive method to monitor the development of fibrosis and pneumonitis, and spirometry is an established tool to measure lung function. NSCLC patients were included in a multicenter trial and treated with megavoltage conformal radiotherapy. In a subgroup comprising 16 patients, a total dose of 59-63 Gy with 1.8-1.9 Gy per fraction was given. Dose-volume histograms were calculated and corrected according to the linear-quadratic formula using alpha/beta=3 Gy. The patients underwent repetitive CT examinations (mean follow-up, 133 days) following radiotherapy, and pre and post treatment spirometry (mean follow-up, 240 days). A significant correlation was demonstrated between local lung dose and changes in CT numbers >30 days after treatment (p 40 Gy Gy there was a sudden increase in CT numbers at 70-90 days. Somewhat unexpectedly, the highest mean lung doses were found in patients with the least reductions in lung function (peak expiratory flow; p<0.001). The correlation between CT numbers, radiation dose and time after treatment show that CT may be used to monitor development of lung fibrosis/pneumonitis after radiotherapy for lung cancer. Paradoxically, the patients with the highest mean lung doses experienced the minimum deterioration of lung function. This may be explained by reduction in the volume of existing tumour masses obstructing the airways, leading to relief of symptoms. This finding stresses the role of radiotherapy for lung cancer, especially where the treatment aim is palliative

  16. VERTICAL GRADIENTS IN REGIONAL LUNG DENSITY AND PERFUSION IN THE SUPINE HUMAN LUNG: THE SLINKY® EFFECT

    Science.gov (United States)

    Hopkins, Susan R.; Henderson, A. Cortney; Levin, David L.; Yamada, Kei; Arai, Tatsuya; Buxton, Richard B.; Prisk., G. Kim

    2008-01-01

    In-vivo radioactive tracer and microsphere studies have differing conclusions as to the magnitude of the gravitational effect on the distribution of pulmonary blood flow. We hypothesized that some of the apparent vertical perfusion gradient in-vivo is due to compression of dependent lung increasing local lung density and therefore perfusion/volume. To test this, 6 normal subjects underwent functional MRI with arterial spin labeling during a breath-hold at functional residual capacity, and perfusion quantified in non-overlapping 15mm sagittal slices covering most of the right lung. Lung proton density was measured in the same slices using a short echo 2D-FLASH sequence. Mean perfusion was 1.7 ± 0.6 ml/min/cm3 and was related to vertical height above the dependent lung (slope = −3%/cm, p Slinky®, a deformable spring distorting under its own weight. The greater density of lung tissue in the dependent regions of the lung is analogous to a greater number of coils in the dependent portion of the vertically oriented spring. This implies that measurements of perfusion in-vivo will be influenced by density distributions and will differ from excised lungs where density gradients are reduced by processing. PMID:17395757

  17. Vertical gradients in regional lung density and perfusion in the supine human lung: the Slinky effect.

    Science.gov (United States)

    Hopkins, Susan R; Henderson, A Cortney; Levin, David L; Yamada, Kei; Arai, Tatsuya; Buxton, Richard B; Prisk, G Kim

    2007-07-01

    In vivo radioactive tracer and microsphere studies have differing conclusions as to the magnitude of the gravitational effect on the distribution of pulmonary blood flow. We hypothesized that some of the apparent vertical perfusion gradient in vivo is due to compression of dependent lung increasing local lung density and therefore perfusion/volume. To test this, six normal subjects underwent functional magnetic resonance imaging with arterial spin labeling during breath holding at functional residual capacity, and perfusion quantified in nonoverlapping 15 mm sagittal slices covering most of the right lung. Lung proton density was measured in the same slices using a short echo 2D-Fast Low-Angle SHot (FLASH) sequence. Mean perfusion was 1.7 +/- 0.6 ml x min(-1) x cm(-3) and was related to vertical height above the dependent lung (slope = -3%/cm, P Slinky (Slinky is a registered trademark of Poof-Slinky Incorporated), a deformable spring distorting under its own weight. The greater density of lung tissue in the dependent regions of the lung is analogous to a greater number of coils in the dependent portion of the vertically oriented spring. This implies that measurements of perfusion in vivo will be influenced by density distributions and will differ from excised lungs where density gradients are reduced by processing.

  18. Difference of regional lung density in inspiration and expiration CT

    International Nuclear Information System (INIS)

    Kim, Young Min; Kwak, Byung Kook; Yang, Sang Kyu; Park, Hyun Sun; Yoon, Hye Ran; Jung, In Ju; Lee, Chang Joon

    1997-01-01

    To evaluate differences in regional density of normal lung, as seen on CT, according to respiration and gravity. The subjects were 15 healthy volunteers, all non-smokers and without previous pulmonary disease. CT scans were obtained at three selected levels through the apex, middle and basal lung at the aortic arch, carina and just above the diaphragm, respectively at both full inspiration (FVC) and full expiration (RV). Within these regions of interest and at the three scanning levels, lung density was measured in the anterior, lateral, and posterior portions of the peripheral lung field. Attenuation of the anterior portion of the lung was lower than that of the posterior portion (p<0.005);average lung attenuation increase from the anterior to the posterior portion was significantly greater during full expiration than full inspiration (p<0.005), and was significantly greater at the base of the lung than at the apex (p<0.005 on expiration, p=0.006 on inspiration). Lung density during inspiration was lower than during expiration (p<0.005);average lung density increase from full inspiration to full expiration was significantly greater in the posterior portion than in the anterior (p<0.005). In the former, the average increase at the base of the lung was greater than at the apex (p=0.007), but in the latter, the average increase at the apex was greater than at the base (p<0.005). In normal lung, respiration and gravity cause regional density changes, as seen on CT, and result in difference of lung attenuation between dependent and nondependent portions and between the apex, middle and base of the lung, according to inspiration and expiration

  19. Ventilation-perfusion lung imaging in diaphragmatic paralysis

    International Nuclear Information System (INIS)

    Chopra, S.K.; Taplin, G.V.

    1977-01-01

    Clinical, radiological, physiological, and lung imaging findings from a patient with paralysis of the diaphragm are described. Dyspnea, hypoxemia and hypercapnia increased when the patient changed from the upright to the supine positions. Ventilation (V) and perfusion (P) images of the right lung appeared to be relatively normal and remained nearly the same in the upright and supine positions. In contrast, V/P images of the left lung were smaller than those of the right lung in the upright position and decreased further in the supine position. In addition, the size of the ventilation image was much smaller than that of the perfusion

  20. Production and assessment of decellularized pig and human lung scaffolds.

    Science.gov (United States)

    Nichols, Joan E; Niles, Jean; Riddle, Michael; Vargas, Gracie; Schilagard, Tuya; Ma, Liang; Edward, Kert; La Francesca, Saverio; Sakamoto, Jason; Vega, Stephanie; Ogadegbe, Marie; Mlcak, Ronald; Deyo, Donald; Woodson, Lee; McQuitty, Christopher; Lick, Scott; Beckles, Daniel; Melo, Esther; Cortiella, Joaquin

    2013-09-01

    The authors have previously shown that acellular (AC) trachea-lung scaffolds can (1) be produced from natural rat lungs, (2) retain critical components of the extracellular matrix (ECM) such as collagen-1 and elastin, and (3) be used to produce lung tissue after recellularization with murine embryonic stem cells. The aim of this study was to produce large (porcine or human) AC lung scaffolds to determine the feasibility of producing scaffolds with potential clinical applicability. We report here the first attempt to produce AC pig or human trachea-lung scaffold. Using a combination of freezing and sodium dodecyl sulfate washes, pig trachea-lungs and human trachea-lungs were decellularized. Once decellularization was complete we evaluated the structural integrity of the AC lung scaffolds using bronchoscopy, multiphoton microscopy (MPM), assessment of the ECM utilizing immunocytochemistry and evaluation of mechanics through the use of pulmonary function tests (PFTs). Immunocytochemistry indicated that there was loss of collagen type IV and laminin in the AC lung scaffold, but retention of collagen-1, elastin, and fibronectin in some regions. MPM scoring was also used to examine the AC lung scaffold ECM structure and to evaluate the amount of collagen I in normal and AC lung. MPM was used to examine the physical arrangement of collagen-1 and elastin in the pleura, distal lung, lung borders, and trachea or bronchi. MPM and bronchoscopy of trachea and lung tissues showed that no cells or cell debris remained in the AC scaffolds. PFT measurements of the trachea-lungs showed no relevant differences in peak pressure, dynamic or static compliance, and a nonrestricted flow pattern in AC compared to normal lungs. Although there were changes in content of collagen I and elastin this did not affect the mechanics of lung function as evidenced by normal PFT values. When repopulated with a variety of stem or adult cells including human adult primary alveolar epithelial type II

  1. The Normal Distribution From Binomial to Normal

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 2; Issue 6. The Normal Distribution From Binomial to Normal. S Ramasubramanian. Series Article Volume 2 Issue 6 June 1997 pp 15-24. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/002/06/0015-0024 ...

  2. Estimation of pulmonary hypertension in lung and valvular heart diseases by perfusion lung scintigraphy

    International Nuclear Information System (INIS)

    Fujii, Tadashige; Tanaka, Masao; Yazaki, Yoshikazu; Kitabayashi, Hirosi; Koizumi, Tomonori; Kubo, Keisi; Sekiguchi, Morie; Yano, Kesato

    1999-01-01

    To estimate pulmonary hypertension, we measured postural differences in pulmonary blood flow for the lateral decubitus positions on perfusion lung scintigrams with Tc-99 m macro-aggregated albumin, applying the method devised by Tanaka et al (Eur J Nucl Med 17: 320-326, 1990). Utilizing a scintillation camera coupled to a minicomputer system, changes in the distribution of pulmonary blood flow caused by gravitational effects, namely, changes in the total count ratios for the right lung versus the left lung in the right and left lateral decubitus positions (R/L), were obtained for 44 patients with lung disease, 95 patients with valvular heart disease, and 23 normal subjects. Mean standard deviation in the R/L ratios was 3.09±1.28 for the normal subjects, 1.97±0.89 for the patients with lung disease, and 1.59±0.59 for the patients with valvular heart disease. The R/L ratios correlated with mean pulmonary arterial pressure and cardio-thoracic ratios in the lung disease and valvular heart disease groups, with pulmonary arteriolar resistance in the former, and with pulmonary capillary wedge pressure in the latter. Defining pulmonary hypertension (>20 mmHg) as an R/L ratio of less than 1.81, which is the mean-1 standard deviation for normal subjects, the sensitivity and the specificity of the R/L ratio for the diagnosis of pulmonary hypertension were 62.9% and 76.2%, respectively, for the lung disease patients, and 80.3% and 61.8%, respectively, for the valvular heart disease patients. This method seems to be useful for the pathophysiologic evaluation of pulmonary perfusion in cases of lung disease and valvular heart disease. (author)

  3. Diet and lung cancer

    DEFF Research Database (Denmark)

    Fabricius, P; Lange, Peter

    2003-01-01

    with vitamins A, C and E and beta-carotene offers no protection against the development of lung cancer. On the contrary, beta-carotene supplementation has, in two major randomised intervention trials, resulted in an increased mortality. Smoking remains the leading cause of lung cancer. The adverse effects......Lung cancer is the leading cause of cancer-related deaths worldwide. While cigarette smoking is of key importance, factors such as diet also play a role in the development of lung cancer. MedLine and Embase were searched with diet and lung cancer as the key words. Recently published reviews...

  4. Statistical Analysis of Haralick Texture Features to Discriminate Lung Abnormalities

    Science.gov (United States)

    Zayed, Nourhan; Elnemr, Heba A.

    2015-01-01

    The Haralick texture features are a well-known mathematical method to detect the lung abnormalities and give the opportunity to the physician to localize the abnormality tissue type, either lung tumor or pulmonary edema. In this paper, statistical evaluation of the different features will represent the reported performance of the proposed method. Thirty-seven patients CT datasets with either lung tumor or pulmonary edema were included in this study. The CT images are first preprocessed for noise reduction and image enhancement, followed by segmentation techniques to segment the lungs, and finally Haralick texture features to detect the type of the abnormality within the lungs. In spite of the presence of low contrast and high noise in images, the proposed algorithms introduce promising results in detecting the abnormality of lungs in most of the patients in comparison with the normal and suggest that some of the features are significantly recommended than others. PMID:26557845

  5. Statistical Analysis of Haralick Texture Features to Discriminate Lung Abnormalities

    Directory of Open Access Journals (Sweden)

    Nourhan Zayed

    2015-01-01

    Full Text Available The Haralick texture features are a well-known mathematical method to detect the lung abnormalities and give the opportunity to the physician to localize the abnormality tissue type, either lung tumor or pulmonary edema. In this paper, statistical evaluation of the different features will represent the reported performance of the proposed method. Thirty-seven patients CT datasets with either lung tumor or pulmonary edema were included in this study. The CT images are first preprocessed for noise reduction and image enhancement, followed by segmentation techniques to segment the lungs, and finally Haralick texture features to detect the type of the abnormality within the lungs. In spite of the presence of low contrast and high noise in images, the proposed algorithms introduce promising results in detecting the abnormality of lungs in most of the patients in comparison with the normal and suggest that some of the features are significantly recommended than others.

  6. Multigene deletions in lung adenocarcinomas from irradiated and control mice

    International Nuclear Information System (INIS)

    Zhang, Y.; Woloschak, G.E.

    1996-01-01

    K-ras codon 12 point mutations mRb and p53 gene deletions were examined in tissues from 120 normal lungs and lung adenocarcinomas that were Formalin-treated and paraffin-embedded 25 years ago. The results showed that 12 of 60 (20%) lung adenocarcinomas had mRb deletions. All lung adenocarcinomas that were initially found bearing deleted mRb had p53 deletions (15 of 15; 100%). A significantly higher mutation frequency for K-ras codon 12 point mutations was also found in the lung adenocarcinomas from mice exposed to 24 once-weekly neutron irradiation (10 of 10; 100%) compared with those exposed to 24 or 60 once-weekly γ-ray doses (5 of 10; 50%). The data suggested that p53 and K-ras gene alterations were two contributory factors responsible for the increased incidence of lung adenocarcinoma in B6CF 1 male mice exposed to protracted neutron radiation

  7. 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.

  8. The differential role of human macrophage in triggering secondary bystander effects after either gamma-ray or carbon beam irradiation.

    Science.gov (United States)

    Dong, Chen; He, Mingyuan; Tu, Wenzhi; Konishi, Teruaki; Liu, Weili; Xie, Yuexia; Dang, Bingrong; Li, Wenjian; Uchihori, Yukio; Hei, Tom K; Shao, Chunlin

    2015-07-10

    The abscopal effect could be an underlying factor in evaluating prognosis of radiotherapy. This study established an in vitro system to examine whether tumor-generated bystander signals could be transmitted by macrophages to further trigger secondary cellular responses after different irradiations, where human lung cancer NCI-H446 cells were irradiated with either γ-rays or carbon ions and co-cultured with human macrophage U937 cells, then these U937 cells were used as a bystander signal transmitter and co-cultured with human bronchial epithelial cells BEAS-2B. Results showed that U937 cells were only activated by γ-irradiated NCI-H446 cells so that the secondary injuries in BEAS-2B cells under carbon ion irradiation were weaker than γ-rays. Both TNF-α and IL-1α were involved in the γ-irradiation induced secondary bystander effect but only TNF-α contributed to the carbon ion induced response. Further assay disclosed that IL-1α but not TNF-α was largely responsible for the activation of macrophages and the formation of micronucleus in BEAS-2B cells. These data suggest that macrophages could transfer secondary bystander signals and play a key role in the secondary bystander effect of photon irradiation, while carbon ion irradiation has conspicuous advantage due to its reduced secondary injury. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. Modification of radiation injury to normal tissues by chemotherapeutic agents

    International Nuclear Information System (INIS)

    Phillips, T.L.; Wharam, M.D.; Margolis, L.W.

    1975-01-01

    The effects of several cancer chemotherapeutic agents on radiation damage to normal intestine, esophagus, and lung tissue were evaluated in LAF 1 mice using quantitative endpoints. In all tissues tested, actinomycin D increased injury and BCNU did not. In the intestine, adriamycin enhanced radiation damage more than any other agent. Bleomycin increased damage in the esophagus but not in the lung or intestine. Cyclophosphamide increased injury only in the lung, where vincristine caused minimal injury, and hyroxyurea, none. Only prednisolone caused significant radioprotection when given at the time of irradiation or at the time of expected death from pulmonary injury. (U.S.)

  10. Connexins as therapeutic targets in lung disease.

    Science.gov (United States)

    Losa, Davide; Chanson, Marc; Crespin, Sophie

    2011-08-01

    The lung is a mechanically active system exposed to the external environment and is particularly sensitive to injury and inflammation. Studies have identified intercellular communication pathways that promote proper lung function in response to injury and disease. These pathways involve connexins (Cxs) and gap junctional intercellular communication (GJIC). The functional expression of Cxs in airway epithelium and vasculature, under normal and pathological conditions, is reviewed. Inhibition of GJIC and/or silencing of Cxs have been shown to modulate the course of disease development. Cx-based channels: i) coordinate ciliary beating and fluid transport to promote clearance of particulates, ii) regulate secretion of pulmonary surfactant, in response to deep inhalation by interconnecting type I and type II alveolar epithelial cells, and iii) are key mediators of pro- and anti-inflammatory signalling by the pulmonary endothelium, in order to modulate leukocyte recruitment from the circulation. Cx-based channels play several central roles in promoting a regulated inflammatory response and facilitating lung repair, thus enabling the pulmonary epithelium and vasculature to behave as integrated systems. Several pathologies can disrupt the normal communication pathways required for proper lung function, including acute lung injury, asthma, cystic fibrosis, pulmonary fibrosis and cancer.

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

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jia-lei [Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032 (China); Lu, Fan-zhen [Department of Thoracic Surgery, The Huadong Hospital, Fudan University, Shanghai 200040 (China); Shen, Xiao-Yong, E-mail: shengxiaoyong_sh@163.com [Department of Thoracic Surgery, The Huadong Hospital, Fudan University, Shanghai 200040 (China); Wu, Yun, E-mail: WuYun_hd@163.com [Department of Thoracic Surgery, The Huadong Hospital, Fudan University, Shanghai 200040 (China); Zhao, Li-ting [Department of Thoracic Surgery, The Huadong Hospital, Fudan University, Shanghai 200040 (China)

    2014-12-12

    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.

  12. Scintigraphy at 3 months after single lung transplantation and observations of primary graft dysfunction and lung function

    DEFF Research Database (Denmark)

    Belmaati, Esther Okeke; Iversen, Martin; Kofoed, Klaus F

    2012-01-01

    Scintigraphy has been used as a tool to detect dysfunction of the lung before and after transplantation. The aims of this study were to evaluate the development of the ventilation-perfusion relationships in single lung transplant recipients in the first year, at 3 months after transplantation......, and to investigate whether scintigraphic findings at 3 months were predictive for the outcome at 12 months in relation to primary graft dysfunction (PGD) and lung function. A retrospective study was carried out on all patients who prospectively and consecutively were referred for a routine lung scintigraphy...... abnormal. There was a significant difference in the normal versus abnormal perfusion and ventilation scintigraphic images evaluated from the same patients. Ventilation was distributed more homogenously in the transplanted lung than perfusion in the same lung. The relative distribution of perfusion...

  13. Quantitative pulmonary gallium scanning in interstitial lung disease

    International Nuclear Information System (INIS)

    Ramsay, S.C.; Yeates, M.G.; Burke, W.M.J.; Morgan, G.W.; Breit, S.N.; Bryant, D.H.

    1992-01-01

    The mechanisms responsible for gallium uptake in chronic, non-infective, diffuse lung disease are not completely understood. This study attempted to clarify some of them. A lung/liver gallium index was calculated in 113 subjects, some normal and some with various interstitial lung diseases, predominantly those associated with connective tissue disease. The mean gallium index was significantly higher in the groups with active interstitial lung disease (5.7) and non-infective bronchiolitis (4.1) compared with non-smoking normals (3.0; P<0.05). To investigate the mechanisms responsible for gallium uptake, the gallium index was correlated with bronchoalveolar lavage findings, respiratory function tests and clinical features. Significant correlations (P<0.05) were found with age in non-smoking normals; lavage macrophages in smoking normals; age but no other parameter in bronchiolitis; lavage lymphocytes, lavage albumin and improvement in diffusion capacity for carbon monoxide in those with active interstitial lung disease. It is concluded that in normal smokers gallium uptake may be due to a macrophage-mediated process. Gallium uptake in active interstitial lung disease associated with connective tissue disease appears to be an immunological process in which transport and retention of gallium is associated with that of albumin. (orig.)

  14. Bronchoscopic cryobiopsy for the diagnosis of diffuse parenchymal lung disease.

    Directory of Open Access Journals (Sweden)

    Jonathan A Kropski

    Full Text Available Although in some cases clinical and radiographic features may be sufficient to establish a diagnosis of diffuse parenchymal lung disease (DPLD, surgical lung biopsy is frequently required. Recently a new technique for bronchoscopic lung biopsy has been developed using flexible cryo-probes. In this study we describe our clinical experience using bronchoscopic cryobiopsy for diagnosis of diffuse lung disease.A retrospective study of subjects who had undergone bronchoscopic cryobiopsy for evaluation of DPLD at an academic tertiary care center from January 1, 2012 through January 15, 2013 was performed. The procedure was performed using a flexible bronchoscope to acquire biopsies of lung parenchyma. H&E stained biopsies were reviewed by an expert lung pathologist.Twenty-five eligible subjects were identified. With a mean area of 64.2 mm(2, cryobiopsies were larger than that typically encountered with traditional transbronchial forceps biopsy. In 19 of the 25 subjects, a specific diagnosis was obtained. In one additional subject, biopsies demonstrating normal parenchyma were felt sufficient to exclude diffuse lung disease as a cause of dyspnea. The overall diagnostic yield of bronchoscopic cryobiopsy was 80% (20/25. The most frequent diagnosis was usual interstitial pneumonia (UIP (n = 7. Three of the 25 subjects ultimately required surgical lung biopsy. There were no significant complications.In patients with suspected diffuse parenchymal lung disease, bronchoscopic cryobiopsy is a promising and minimally invasive approach to obtain lung tissue with high diagnostic yield.

  15. 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.

  16. Normalized modes at selected points without normalization

    Science.gov (United States)

    Kausel, Eduardo

    2018-04-01

    As every textbook on linear algebra demonstrates, the eigenvectors for the general eigenvalue problem | K - λM | = 0 involving two real, symmetric, positive definite matrices K , M satisfy some well-defined orthogonality conditions. Equally well-known is the fact that those eigenvectors can be normalized so that their modal mass μ =ϕT Mϕ is unity: it suffices to divide each unscaled mode by the square root of the modal mass. Thus, the normalization is the result of an explicit calculation applied to the modes after they were obtained by some means. However, we show herein that the normalized modes are not merely convenient forms of scaling, but that they are actually intrinsic properties of the pair of matrices K , M, that is, the matrices already "know" about normalization even before the modes have been obtained. This means that we can obtain individual components of the normalized modes directly from the eigenvalue problem, and without needing to obtain either all of the modes or for that matter, any one complete mode. These results are achieved by means of the residue theorem of operational calculus, a finding that is rather remarkable inasmuch as the residues themselves do not make use of any orthogonality conditions or normalization in the first place. It appears that this obscure property connecting the general eigenvalue problem of modal analysis with the residue theorem of operational calculus may have been overlooked up until now, but which has in turn interesting theoretical implications.Á

  17. The pulmonary mesenchyme directs lung development.

    Science.gov (United States)

    McCulley, David; Wienhold, Mark; Sun, Xin

    2015-06-01

    Each of the steps of respiratory system development relies on intricate interactions and coordinated development of the lung epithelium and mesenchyme. In the past, more attention has been paid to the epithelium than the mesenchyme. The mesenchyme is a source of specification and morphogenetic signals as well as a host of surprisingly complex cell lineages that are crucial for normal lung development and function. This review highlights recent research focusing on the mesenchyme that has revealed genetic and epigenetic mechanisms of its development in the context of other cell layers during respiratory lineage specification, branching morphogenesis, epithelial differentiation, lineage distinction, vascular development, and alveolar maturation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. 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.

  19. Diet and lung cancer

    DEFF Research Database (Denmark)

    Fabricius, P; Lange, Peter

    2003-01-01

    Lung cancer is the leading cause of cancer-related deaths worldwide. While cigarette smoking is of key importance, factors such as diet also play a role in the development of lung cancer. MedLine and Embase were searched with diet and lung cancer as the key words. Recently published reviews...... and large well designed original articles were preferred to form the basis for the present article. A diet rich in fruit and vegetables reduces the incidence of lung cancer by approximately 25%. The reduction is of the same magnitude in current smokers, ex-smokers and never smokers. Supplementation...... with vitamins A, C and E and beta-carotene offers no protection against the development of lung cancer. On the contrary, beta-carotene supplementation has, in two major randomised intervention trials, resulted in an increased mortality. Smoking remains the leading cause of lung cancer. The adverse effects...

  20. Effects of various modes of mechanical ventilation in normal rats.

    Science.gov (United States)

    Pecchiari, Matteo; Monaco, Ario; Koutsoukou, Antonia; Della Valle, Patrizia; Gentile, Guendalina; D'Angelo, Edgardo

    2014-04-01

    Recent studies in healthy mice and rats have reported that positive pressure ventilation delivered with physiological tidal volumes at normal end-expiratory volume worsens lung mechanics and induces cytokine release, thus suggesting that detrimental effects are due to positive pressure ventilation per se. The aim of this study in healthy animals is to assess whether these adverse outcomes depend on the mode of mechanical ventilation. Rats were subjected to 4 h of spontaneous, positive pressure, and whole-body or thorax-only negative pressure ventilation (N = 8 per group). In all instances the ventilatory pattern was that of spontaneous breathing. Lung mechanics, cytokines concentration in serum and broncho-alveolar lavage fluid, lung wet-to-dry ratio, and histology were assessed. Values from eight animals euthanized shortly after anesthesia served as control. No evidence of mechanical ventilation-dependent lung injury was found in terms of lung mechanics, histology, or wet-to-dry ratio. Relative to control, cytokine levels and recruitment of polymorphonuclear leucocytes increased slightly, and to the same extent with spontaneous, positive pressure, and whole-body negative pressure ventilation. Thorax-only negative pressure ventilation caused marked chest and lung distortion, reversible increase of lung elastance, and higher polymorphonuclear leucocyte count and cytokine levels. Both positive and negative pressure ventilation performed with tidal volumes and timing of spontaneous, quiet breathing neither elicit an inflammatory response nor cause morpho-functional alterations in normal animals, thus supporting the notion of the presence of a critical volume threshold above which acute lung injury ensues. Distortion of lung parenchyma can induce an inflammatory response, even in the absence of volotrauma.

  1. Computed tomography of the lungs in acquired immunodeficiency syndrome

    International Nuclear Information System (INIS)

    Hartelius, H.; Gaub, J.; Jensen, L.I.; Jensen, J.; Faber, V.; Rigshospitalet, Copenhagen

    1988-01-01

    Computed tomography of the chest was performed on 42 occasions as part of the diagnostic work-up in 26 homosexual men with, or suspected of the acquired immunodeficiency syndrome (AIDS). In 17 cases both the chest radiographs and the lung scans were abnormal, and bronchoscopy and/or lung biopsy established an etiologic diagnosis in the majority of these cases. In 9 cases CT of the lungs revealed unequivocal interstitial infiltration in the presence of a normal chest radiography, and subsequently and etiologic agent was demonstrated in all these cases. In 9 cases, patients with symptoms indicative of pulmonary infection had both a normal chest radiograph and a normal lung scan, and in none of these cases did the clinical course or additional diagnostic procedures indicate the presence of current opportunistic lung infection. CT of the lungs seems to identify accurately those patients with severe HIV-related diseases in whom invasive diagnostic procedures such as bronchoalveolar lavage and/or lung biopsy should be done. (orig.)

  2. Nonrespiratory lung function

    International Nuclear Information System (INIS)

    Isawa, Toyoharu

    1994-01-01

    The function of the lungs is primarily the function as a gas exchanger: the venous blood returning to the lungs is arterialized with oxygen in the lungs and the arterialized blood is sent back again to the peripheral tissues of the whole body to be utilized for metabolic oxygenation. Besides the gas exchanging function which we call ''respiratory lung function'' the lungs have functions that have little to do with gas exchange itself. We categorically call the latter function of the lungs as ''nonrespiratory lung function''. The lungs consist of the conductive airways, the gas exchanging units like the alveoli, and the interstitial space that surrounds the former two compartments. The interstitial space contains the blood and lymphatic capillaries, collagen and elastic fibers and cement substances. The conductive airways and the gas exchanging units are directly exposed to the atmosphere that contains various toxic and nontoxic gases, fume and biological or nonbiological particles. Because the conductive airways are equipped with defense mechanisms like mucociliary clearance or coughs to get rid of these toxic gases, particles or locally produced biological debris, we are usually free from being succumbed to ill effects of inhaled materials. By use of nuclear medicine techniques, we can now evaluate mucociliary clearance function, and other nonrespiratory lung functions as well in vivo

  3. Diet and lung cancer

    DEFF Research Database (Denmark)

    Fabricius, P; Lange, Peter

    2003-01-01

    Lung cancer is the leading cause of cancer-related deaths worldwide. While cigarette smoking is of key importance, factors such as diet also play a role in the development of lung cancer. MedLine and Embase were searched with diet and lung cancer as the key words. Recently published reviews...... and large well designed original articles were preferred to form the basis for the present article. A diet rich in fruit and vegetables reduces the incidence of lung cancer by approximately 25%. The reduction is of the same magnitude in current smokers, ex-smokers and never smokers. Supplementation...... are only ameliorated to a minor degree by a healthy diet....

  4. Lung disease - resources

    Science.gov (United States)

    ... Pulmonary Disease): COPD Foundation -- www.copdfoundation.org National Emphysema Foundation -- www.emphysemafoundation.org National Heart, Lung, and Blood Institute -- www.nhlbi.nih.gov/health/ ...

  5. Parasitic diseases of lungs

    International Nuclear Information System (INIS)

    Rozenshtraukh, L.C.; Rybakova, N.I.; Vinner, M.G.

    1987-01-01

    Roentgenologic semiotics of the main parasitic diseases of lungs is described: echinococcosis, paragonimiasis, cysticercosis, toxoplasmosis, ascariasis, amebiosis and some rarely met parasitic diseases

  6. Lung cancer: atypical brain metastases mimicking neurocysticercosis.

    Science.gov (United States)

    Mota, Patrícia Caetano; Reis, Carina; Pires, Nuno Filipe; Sousa, Graça; Chamadoira, Clara; Guimarães, Marcos; Castro, Lígia; Marques, Margarida; Gomes, Isabel

    2011-12-01

    The authors describe a case of a 47-year-old male smoker with a 3-month history of hearing loss, tinnitus and dizziness. Physical examination revealed neurosensory hearing loss. Small rounded hypodensities without mass effect were evident in a computed tomography scan of the head, confirmed by brain magnetic resonance imaging as multiple cystic lesions in both cerebral and cerebellar hemispheres, without perilesional edema or gadolinium enhancement, suggestive of neurocysticercosis. Extraparenchymal involvement was also noted. Albendazole and dexamethasone were started. As a chest radiograph showed a bilateral reticulonodular pattern, a bronchoscopy was performed showing normal results. However, transbronchial biopsy revealed lung adenocarcinoma. Thoracoabdominopelvic computed tomography scan showed secondary lung and bone lesions. Since brain lesions were not suggestive of secondary tumor lesions, a brain biopsy was performed confirming metastatic disease. This case illustrates some peculiar imagiological features of brain metastases in lung cancer, indicating that sometimes invasive procedures are required to establish a definitive diagnosis.

  7. Dissimilarity Representations in Lung Parenchyma Classification

    DEFF Research Database (Denmark)

    Sørensen, Lauge Emil Borch Laurs; de Bruijne, Marleen

    2009-01-01

    as distance in a emph{k} nearest neighbor classifier, which achieves a classification accuracy of $92.9%$, the best dissimilarity representation based classifier is significantly better with a classification accuracy of 97.0% ($text{emph{p" border="0" class="imgtopleft"> = 0.046$)....... are built in this representation. This is also the general trend in lung parenchyma classification in computed tomography (CT) images, where the features often are measures on feature histograms. Instead, we propose to build normal density based classifiers in dissimilarity representations for lung...... parenchyma classification. This allows for the classifiers to work on dissimilarities between objects, which might be a more natural way of representing lung parenchyma. In this context, dissimilarity is defined between CT regions of interest (ROI)s. ROIs are represented by their CT attenuation histogram...

  8. 18FDG uptake associated with CT density on PET/CT in lungs with and without chronic interstitial lung diseases

    International Nuclear Information System (INIS)

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

    2009-01-01

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

  9. Prenatal and Perinatal Determinants of Lung Health and Disease in Early Life: A National Heart, Lung, and Blood Institute Workshop Report.

    Science.gov (United States)

    Manuck, Tracy A; Levy, Philip T; Gyamfi-Bannerman, Cynthia; Jobe, Alan H; Blaisdell, Carol J

    2016-05-02

    Human lung growth and development begins with preconception exposures and continues through conception and childhood into early adulthood. Numerous environmental exposures (both positive and negative) can affect lung health and disease throughout life. Infant lung health correlates with adult lung function, but significant knowledge gaps exist regarding the influence of preconception, perinatal, and postnatal exposures on general lung health throughout life. On October 1 and 2, 2015, the National Heart, Lung, and Blood Institute convened a group of extramural investigators to develop their recommendations for the direction(s) for future research in prenatal and perinatal determinants of lung health and disease in early life and to identify opportunities for scientific advancement. They identified that future investigations will need not only to examine abnormal lung development, but also to use developing technology and resources to better define normal and/or enhanced lung health. Birth cohort studies offer key opportunities to capture the important influence of preconception and obstetric risk factors on lung health, development, and disease. These studies should include well-characterized obstetrical data and comprehensive plans for prospective follow-up. The importance of continued basic science, translational, and animal studies for providing mechanisms to explain causality using new methods cannot be overemphasized. Multidisciplinary approaches involving obstetricians, neonatologists, pediatric and adult pulmonologists, and basic scientists should be encouraged to design and conduct comprehensive and impactful research on the early stages of normal and abnormal human lung growth that influence adult outcome.

  10. Genetics Home Reference: lung cancer

    Science.gov (United States)

    ... and a history of lung disease such as tuberculosis, emphysema, or chronic bronchitis. A history of lung ... Cancer Society: Cancer Facts & Figures 2017 (PDF) Byers LA, Rudin CM. Small cell lung cancer: where do ...

  11. Extracellular matrix in lung development, homeostasis and disease.

    Science.gov (United States)

    Zhou, Yong; Horowitz, Jeffrey C; Naba, Alexandra; Ambalavanan, Namasivayam; Atabai, Kamran; Balestrini, Jenna; Bitterman, Peter B; Corley, Richard A; Ding, Bi-Sen; Engler, Adam J; Hansen, Kirk C; Hagood, James S; Kheradmand, Farrah; Lin, Qing S; Neptune, Enid; Niklason, Laura; Ortiz, Luis A; Parks, William C; Tschumperlin, Daniel J; White, Eric S; Chapman, Harold A; Thannickal, Victor J

    2018-03-08

    The lung's unique extracellular matrix (ECM), while providing structural support for cells, is critical in the regulation of developmental organogenesis, homeostasis and injury-repair responses. The ECM, via biochemical or biomechanical cues, regulates diverse cell functions, fate and phenotype. The composition and function of lung ECM become markedly deranged in pathological tissue remodeling. ECM-based therapeutics and bioengineering approaches represent promising novel strategies for regeneration/repair of the lung and treatment of chronic lung diseases. In this review, we assess the current state of lung ECM biology, including fundamental advances in ECM composition, dynamics, topography, and biomechanics; the role of the ECM in normal and aberrant lung development, adult lung diseases and autoimmunity; and ECM in the regulation of the stem cell niche. We identify opportunities to advance the field of lung ECM biology and provide a set recommendations for research priorities to advance knowledge that would inform novel approaches to the pathogenesis, diagnosis, and treatment of chronic lung diseases. Copyright © 2017. Published by Elsevier B.V.

  12. [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.

  13. MRI of the lung

    Energy Technology Data Exchange (ETDEWEB)

    Kauczor, Hans-Ulrich (ed.) [University Clinic Heidelberg (Germany). Diagnostic and Interventional Radiology

    2009-07-01

    For a long time, only chest X-ray and CT were used to image lung structure, while nuclear medicine was employed to assess lung function. During the past decade significant developments have been achieved in the field of magnetic resonance imaging (MRI), enabling MRI to enter the clinical arena of chest imaging. Standard protocols can now be implemented on up-to-date scanners, allowing MRI to be used as a first-line imaging modality for various lung diseases, including cystic fibrosis, pulmonary hypertension and even lung cancer. The diagnostic benefits stem from the ability of MRI to visualize changes in lung structure while simultaneously imaging different aspects of lung function, such as perfusion, respiratory motion, ventilation and gas exchange. On this basis, novel quantitative surrogates for lung function can be obtained. This book provides a comprehensive overview of how to use MRI for imaging of lung disease. Special emphasis is placed on benign diseases requiring regular monitoring, given that it is patients with these diseases who derive the greatest benefit from the avoidance of ionizing radiation. (orig.)

  14. Lung Cancer Indicators Recurrence

    Science.gov (United States)

    This study describes prognostic factors for lung cancer spread and recurrence, as well as subsequent risk of death from the disease. The investigators observed that regardless of cancer stage, grade, or type of lung cancer, patients in the study were more

  15. Screening for lung cancer

    DEFF Research Database (Denmark)

    Infante, Maurizio V; Pedersen, Jesper H

    2010-01-01

    In lung cancer screening with low-dose spiral computed tomography (LDCT), the proportion of stage I disease is 50-85%, and the survival rate for resected stage I disease can exceed 90%, but proof of real benefit in terms of lung cancer mortality reduction must come from the several randomized...

  16. Study of lung perfusion in colagenosis

    International Nuclear Information System (INIS)

    Macedo de Carvalho, A.C.; Calegaro, J.U.M.

    1982-01-01

    The lung involvement in the various types of colagenosis has been widely described in the literature. However, the study of lung perfusion utilizing radionuclides has been only mentioned in a few papers. With the intention of ascertaining the importance of the lung perfusion scanning in colagenosis, ten cases were studied, seven of which were females and three males, with the following pathologies: 4 rheumatoid arthritis, 4 systemic lupus eritematosous, 1 scleroderma and 1 scleroderma plus dermatomyositis. The ages of the patients varied from 20 to 73 years, and the duration of the disease from 1 month to 39 years. The lung scanning showed perfusion defects in 100% of the cases, not related with the type of colagenosis, duration of the disease, sex or age. On the other hand, the X rays study showed alterations in only 2 patients (20% of the cases). The ventilatory and respiratory functions were tested on 7 patients showing alteration (mixed pattern with predominance of the restrictive factor) in only one (14.3%), while the other patients were normal (85.7%). The importance of the lung perfusion scanning study in all patients with collagen vascular diseases is emphasized. (author) [es

  17. Understanding the mechanisms of lung mechanical stress

    Directory of Open Access Journals (Sweden)

    C.S.N.B. Garcia

    2006-06-01

    Full Text Available Physical forces affect both the function and phenotype of cells in the lung. Bronchial, alveolar, and other parenchymal cells, as well as fibroblasts and macrophages, are normally subjected to a variety of passive and active mechanical forces associated with lung inflation and vascular perfusion as a result of the dynamic nature of lung function. These forces include changes in stress (force per unit area or strain (any forced change in length in relation to the initial length and shear stress (the stress component parallel to a given surface. The responses of cells to mechanical forces are the result of the cell's ability to sense and transduce these stimuli into intracellular signaling pathways able to communicate the information to its interior. This review will focus on the modulation of intracellular pathways by lung mechanical forces and the intercellular signaling. A better understanding of the mechanisms by which lung cells transduce physical forces into biochemical and biological signals is of key importance for identifying targets for the treatment and prevention of physical force-related disorders.

  18. Study of lung perfusion in colagenosis

    Energy Technology Data Exchange (ETDEWEB)

    Macedo de Carvalho, A.C.; Calegaro, J.U.M. (Fundacao Hospitalar do Distrito Federal, Distrito Federal (Brazil). Unidade de Medicina Nuclear)

    1982-07-01

    The lung involvement in the various types of colagenosis has been widely described in the literature. However, the study of lung perfusion utilizing radionuclides has been only mentioned in a few papers. With the intention of ascertaining the importance of the lung perfusion scanning in colagenosis, ten cases were studied, seven of which were females and three males, with the following pathologies: 4 rheumatoid arthritis, 4 systemic lupus eritematosous, 1 scleroderma and 1 scleroderma plus dermatomyositis. The ages of the patients varied from 20 to 73 years, and the duration of the disease from 1 month to 39 years. The lung scanning showed perfusion defects in 100% of the cases, not related with the type of colagenosis, duration of the disease, sex or age. On the other hand, the X rays study showed alterations in only 2 patients (20% of the cases). The ventilatory and respiratory functions were tested on 7 patients showing alteration (mixed pattern with predominance of the restrictive factor) in only one (14.3%), while the other patients were normal (85.7%). The importance of the lung perfusion scanning study in all patients with collagen vascular diseases is emphasized.

  19. Relationship between regional lung compliance and ventilation homogeneity in the supine and prone position.

    Science.gov (United States)

    Tang, R; Huang, Y; Chen, Q; Hui, X; Li, Y; Yu, Q; Zhao, H; Yang, Y; Qiu, H

    2012-10-01

    The prone position (PP) improves ventilation homogeneity in acute respiratory distress syndrome. The aim of this study was to investigate whether the alleviation of ventilation inhomogeneity in PP was due to changes in regional lung compliance. Ten lung-lavaged piglets were mechanically ventilated in supine position (SP) and in PP. In each position, positive end-expiratory pressure (PEEP) was reduced from 20 to 6 cmH(2)O in steps of 2 cmH(2)O every 10 min after full lung recruitment. Respiratory mechanics, blood gas, haemodynamic data and whole-lung computed tomography scans were recorded at each PEEP. The compliances of normally aerated (C(normal)) and newly recruited (C(recruited)) lung regions were calculated. Open lung PEEP (OL-PEEP) was defined as the lowest PEEP to maintain full lung recruitment. At OL-PEEP, PP significantly increased normally aerated lung regions, decreased poorly aerated and hyperinflated lung regions and decreased tidal recruitment and hyperinflation. C(normal) was significantly reduced in PP compared with SP (12.8 ± 4.2 ml/cmH(2)O vs. 20.1 ± 6.2 ml/cmH(2)O, P cmH(2)O vs. 9.4 ± 2.4 ml/cmH(2)O, P < 0.001). C(normal) was correlated with hyperinflated lung regions at end-expiration (rho = 0.67) and end-inspiration (rho = 0.56) at OL-PEEP. C(recruited) was correlated with normally (r(2) = 0.36) and poorly aerated lung regions (rho = -0.58) at OL-PEEP. This surfactant-depleted model shows that the improvement of ventilation homogeneity in PP is related to an increase in C(recruited) and a decrease in C(normal). © 2012 The Authors. Acta Anaesthesiologica Scandinavica © 2012 The Acta Anaesthesiologica Scandinavica Foundation.

  20. Your Lung Operation: After Your Operation

    Medline Plus

    Full Text Available ... Surgeons Education Patients and Family Skills Programs Your Lung Operation Your Lung Operation DVD After Your Operation Back to Your Lung Operation Your Lung Operation DVD Welcome Your Lung ...

  1. Lung cancer - non-small cell

    Science.gov (United States)

    Cancer - lung - non-small cell; Non-small cell lung cancer; NSCLC; Adenocarcinoma - lung; Squamous cell carcinoma - lung ... Smoking causes most cases (around 90%) of lung cancer. The risk depends on the number of cigarettes ...

  2. Perfusion lung scintigraphy in primary pulmonary hypertension

    International Nuclear Information System (INIS)

    Ogawa, Y.; Hayashida, K.; Uehara, T.; Shimonagata, T.; Nishimura, T.; Osaka Univ., Suita

    1993-01-01

    15 cases of primary pulmonary hypertension were classified into two groups by patterns of perfusion lung scintigraphy. Perfusion scintigrams showed multiple, small, ill-defined defects (mottled + ve) pattern in eight cases, and the remaining seven cases had a normal (mottled - ve) pattern. The mean pulmonary arterial pressure in patients with a mottled pattern (54 ± 10 mmHg) was higher than in those with a normal pattern (42 ± 9 mmHg, p < 0.05). There were no significant differences between the two groups in right ventricular ejection fraction, partial pressures of oxygen in the arterial blood or alveolo-arterial oxygen difference. All the patients with a mottled pattern died within 2 years following the lung scintigraphy. There was a significant difference in the survival curves between the two groups. (author)

  3. Noninvasive quantification of heterogeneous lung growth following extensive lung resection by high-resolution computed tomography.

    Science.gov (United States)

    Yilmaz, Cuneyt; Ravikumar, Priya; Dane, D Merrill; Bellotto, Dennis J; Johnson, Robert L; Hsia, Connie C W

    2009-11-01

    To quantify the in vivo magnitude and distribution of regional compensatory lung growth following extensive lung resection, we performed high-resolution computed tomography at 15- and 30-cmH(2)O transpulmonary pressures and measured air and tissue (including microvascular blood) volumes within and among lobes in six adult male foxhounds, before and after balanced 65% lung resection ( approximately 32% removed from each side). Each lobe was identified from lobar fissures. Intralobar gradients in air and tissue volumes were expressed along standardized x,y,z-coordinate axes. Fractional tissue volume (FTV) was calculated as the volume ratio of tissue/(tissue + air). Following resection compared with before, lobar air and tissue volumes increased 1.8- to 3.5-fold, and whole lung air and tissue volumes were 67 and 90% of normal, respectively. Lobar-specific compliance doubled post-resection, and whole lung-specific compliance normalized. These results are consistent with vigorous compensatory growth in all remaining lobes. Compared with pre-resection, post-resection interlobar heterogeneity of FTV, assessed from the coefficient of variation, decreased at submaximal inflation, but was unchanged at maximal inflation. The coefficient of variation of intralobar FTV gradients changed variably due to the patchy development of thickened pleura and alveolar septa, with elevated alveolar septal density and connective tissue content in posterior-caudal and peripheral regions of the remaining lobes; these areas likely experienced disproportional mechanical stress. We conclude that HRCT can noninvasively and quantitatively assess the magnitude and spatial distribution of compensatory lung growth. Following extensive resection, heterogeneous regional mechanical lung strain may exceed the level that could be sustained solely by existing connective tissue elements.

  4. Immunosuppression in lung transplantation.

    Science.gov (United States)

    Scheffert, Jenna L; Raza, Kashif

    2014-08-01

    Lung transplantation can be a life-saving procedure for those with end-stage lung diseases. Unfortunately, long term graft and patient survival are limited by both acute and chronic allograft rejection, with a median survival of just over 6 years. Immunosuppressive regimens are employed to reduce the rate of rejection, and while protocols vary from center to center, conventional maintenance therapy consists of triple drug therapy with a calcineurin inhibitor (cyclosporine or tacrolimus), antiproliferative agents [azathioprine (AZA), mycophenolate, sirolimus (srl), everolimus (evl)], and corticosteroids (CS). Roughly 50% of lung transplant centers also utilize induction therapy, with polyclonal antibody preparations [equine or rabbit anti-thymocyte globulin (ATG)], interleukin 2 receptor antagonists (IL2RAs) (daclizumab or basiliximab), or alemtuzumab. This review summarizes these agents and the data surrounding their use in lung transplantation, as well as additional common and novel therapies in lung transplantation. Despite the progression of the management of lung transplant recipients, they continue to be at high risk of treatment-related complications, and poor graft and patient survival. Randomized clinical trials are needed to allow for the development of better agents, regimens and techniques to address above mentioned issues and reduce morbidity and mortality among lung transplant recipients.

  5. Corners of normal matrices

    Indian Academy of Sciences (India)

    The structure of general normal matrices is far more complicated than that of two special kinds — hermitian and unitary. There are many interesting theorems for hermitian and unitary matrices whose extensions to arbitrary normal matrices have proved to be extremely recalcitrant (see e.g., [1]). The problem whose study we ...

  6. Normalized medical information visualization.

    Science.gov (United States)

    Sánchez-de-Madariaga, Ricardo; Muñoz, Adolfo; Somolinos, Roberto; Castro, Antonio; Velázquez, Iker; Moreno, Oscar; García-Pacheco, José L; Pascual, Mario; Salvador, Carlos H

    2015-01-01

    A new mark-up programming language is introduced in order to facilitate and improve the visualization of ISO/EN 13606 dual model-based normalized medical information. This is the first time that visualization of normalized medical information is addressed and the programming language is intended to be used by medical non-IT professionals.

  7. Baby Poop: What's Normal?

    Science.gov (United States)

    ... I'm breast-feeding my newborn and her bowel movements are yellow and mushy. Is this normal for baby poop? Answers from Jay L. Hoecker, M.D. Yellow, mushy bowel movements are perfectly normal for breast-fed babies. Still, ...

  8. Incidental Transient Cortical Blindness after Lung Resection

    Science.gov (United States)

    Oncel, Murat; Sunam, Guven Sadi; Varoglu, Asuman Orhan; Karabagli, Hakan; Yildiran, Huseyin

    2016-01-01

    Transient vision loss after major surgical procedures is a rare clinical complication. The most common etiologies are cardiac, spinal, head, and neck surgeries. There has been no report on vision loss after lung resection. A 65-year-old man was admitted to our clinic with lung cancer. Resection was performed using right upper lobectomy with no complications. Cortical blindness developed 12 hours later in the postoperative period. Results from magnetic resonance imaging and diffusion-weighted investigations were normal. The neurologic examination was normal. The blood glucose level was 92 mg/dL and blood gas analysis showed a PO 2 of 82 mm Hg. After 24 hours, the patient began to see and could count fingers, and his vision was fully restored within 72 hours after this point. Autonomic dysfunction due to impaired microvascular structures in diabetes mellitus may induce posterior circulation dysfunction, even when the hemodynamic state is normal in the perioperative period. The physician must keep in mind that vision loss may occur after lung resection due to autonomic dysfunction, especially in older patients with diabetes mellitus. PMID:28824977

  9. The lung communication network.

    Science.gov (United States)

    Losa, Davide; Chanson, Marc

    2015-08-01

    The different types of cells in the lung, from the conducting airway epithelium to the alveolar epithelium and the pulmonary vasculature, are interconnected by gap junctions. The specific profile of gap junction proteins, the connexins, expressed in these different cell types forms compartments of intercellular communication that can be further shaped by the release of extracellular nucleotides via pannexin1 channels. In this review, we focus on the physiology of connexins and pannexins and describe how this lung communication network modulates lung function and host defenses in conductive and respiratory airways.

  10. Insulin and the Lung

    DEFF Research Database (Denmark)

    Singh, Suchita; Prakash, Y S; Linneberg, Allan

    2013-01-01

    , molecular understanding is necessary. Insulin resistance is a strong, independent risk factor for asthma development, but it is unknown whether a direct effect of insulin on the lung is involved. This review summarizes current knowledge regarding the effect of insulin on cellular components of the lung...... and highlights the molecular consequences of insulin-related metabolic signaling cascades that could adversely affect lung structure and function. Examples include airway smooth muscle proliferation and contractility and regulatory signaling networks that are associated with asthma. These aspects of insulin...

  11. 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

  12. The Danish Lung Cancer Registry

    DEFF Research Database (Denmark)

    Jakobsen, Erik; Rasmussen, Torben Riis

    2016-01-01

    AIM OF DATABASE: The Danish Lung Cancer Registry (DLCR) was established by the Danish Lung Cancer Group. The primary and first goal of the DLCR was to improve survival and the overall clinical management of Danish lung cancer patients. STUDY POPULATION: All Danish primary lung cancer patients since...... 2000 are included into the registry and the database today contains information on more than 50,000 cases of lung cancer. MAIN VARIABLES: The database contains information on patient characteristics such as age, sex, diagnostic procedures, histology, tumor stage, lung function, performance...... as a source for research regarding lung cancer in Denmark and in comparisons with other countries....

  13. Making nuclear 'normal'

    International Nuclear Information System (INIS)

    Haehlen, Peter; Elmiger, Bruno

    2000-01-01

    The mechanics of the Swiss NPPs' 'come and see' programme 1995-1999 were illustrated in our contributions to all PIME workshops since 1996. Now, after four annual 'waves', all the country has been covered by the NPPs' invitation to dialogue. This makes PIME 2000 the right time to shed some light on one particular objective of this initiative: making nuclear 'normal'. The principal aim of the 'come and see' programme, namely to give the Swiss NPPs 'a voice of their own' by the end of the nuclear moratorium 1990-2000, has clearly been attained and was commented on during earlier PIMEs. It is, however, equally important that Swiss nuclear energy not only made progress in terms of public 'presence', but also in terms of being perceived as a normal part of industry, as a normal branch of the economy. The message that Swiss nuclear energy is nothing but a normal business involving normal people, was stressed by several components of the multi-prong campaign: - The speakers in the TV ads were real - 'normal' - visitors' guides and not actors; - The testimonials in the print ads were all real NPP visitors - 'normal' people - and not models; - The mailings inviting a very large number of associations to 'come and see' activated a typical channel of 'normal' Swiss social life; - Spending money on ads (a new activity for Swiss NPPs) appears to have resulted in being perceived by the media as a normal branch of the economy. Today we feel that the 'normality' message has well been received by the media. In the controversy dealing with antinuclear arguments brought forward by environmental organisations journalists nowadays as a rule give nuclear energy a voice - a normal right to be heard. As in a 'normal' controversy, the media again actively ask themselves questions about specific antinuclear claims, much more than before 1990 when the moratorium started. The result is that in many cases such arguments are discarded by journalists, because they are, e.g., found to be

  14. Significance of the microbiome in obstructive lung disease.

    Science.gov (United States)

    Han, Meilan K; Huang, Yvonne J; Lipuma, John J; Boushey, Homer A; Boucher, Richard C; Cookson, William O; Curtis, Jeffrey L; Erb-Downward, John; Lynch, Susan V; Sethi, Sanjay; Toews, Galen B; Young, Vincent B; Wolfgang, Matthew C; Huffnagle, Gary B; Martinez, Fernando J

    2012-05-01

    The composition of the lung microbiome contributes to both health and disease, including obstructive lung disease. Because it has been estimated that over 70% of the bacterial species on body surfaces cannot be cultured by currently available techniques, traditional culture techniques are no longer the gold standard for microbial investigation. Advanced techniques that identify bacterial sequences, including the 16S ribosomal RNA gene, have provided new insights into the depth and breadth of microbiota present both in the diseased and normal lung. In asthma, the composition of the microbiome of the lung and gut during early childhood development may play a key role in the development of asthma, while specific airway microbiota are associated with chronic asthma in adults. Early bacterial stimulation appears to reduce asthma susceptibility by helping the immune system develop lifelong tolerance to innocuous antigens. By contrast, perturbations in the microbiome from antibiotic use may increase the risk for asthma development. In chronic obstructive pulmonary disease, bacterial colonisation has been associated with a chronic bronchitic phenotype, increased risk of exacerbations, and accelerated loss of lung function. In cystic fibrosis, studies utilising culture-independent methods have identified associations between decreased bacterial community diversity and reduced lung function; colonisation with Pseudomonas aeruginosa has been associated with the presence of certain CFTR mutations. Genomic analysis of the lung microbiome is a young field, but has the potential to define the relationship between lung microbiome composition and disease course. Whether we can manipulate bacterial communities to improve clinical outcomes remains to be seen.

  15. Localization and stretch-dependence of lung elastase activity in development and compensatory growth.

    Science.gov (United States)

    Young, Sarah Marie; Liu, Sheng; Joshi, Rashika; Batie, Matthew R; Kofron, Matthew; Guo, Jinbang; Woods, Jason C; Varisco, Brian Michael

    2015-04-01

    Synthesis and remodeling of the lung matrix is necessary for primary and compensatory lung growth. Because cyclic negative force is applied to developing lung tissue during the respiratory cycle, we hypothesized that stretch is a critical regulator of lung matrix remodeling. By using quantitative image analysis of whole-lung and whole-lobe elastin in situ zymography images, we demonstrated that elastase activity increased twofold during the alveolar stage of postnatal lung morphogenesis in the mouse. Remodeling was restricted to alveolar walls and ducts and was nearly absent in dense elastin band structures. In the mouse pneumonectomy model of compensatory lung growth, elastase activity increased threefold, peaking at 14 days postpneumonectomy and was higher in the accessory lobe compared with other lobes. Remodeling during normal development and during compensatory lung growth was different with increased major airway and pulmonary arterial remodeling during development but not regeneration, and with homogenous remodeling throughout the parenchyma during development, but increased remodeling only in subpleural regions during compensatory lung growth. Left lung wax plombage prevented increased lung elastin during compensatory lung growth. To test whether the adult lung retains an innate capacity to remodel elastin, we developed a confocal microscope-compatible stretching device. In ex vivo adult mouse lung sections, lung elastase activity increased exponentially with strain and in peripheral regions of lung more than in central regions. Our study demonstrates that lung elastase activity is stretch-dependent and supports a model in which externally applied forces influence the composition, structure, and function of the matrix during periods of alveolar septation. Copyright © 2015 the American Physiological Society.

  16. The Schneeberg lung cancer cases

    International Nuclear Information System (INIS)

    Kalthoff, J.

    1982-01-01

    47 cases of ''Schneeberg lung cancer'' are reported which received financial compensation in West Germany after 1945 after being officially acknowledged as occupational disease. With two exceptions, all patients had been occupied in the Saxonian and Bohemian uranium mines (or their extensions after World War II). The geotechnical fundamentals, industrial hygiene measures taken, the radiobiological situation and its effects are presented. Most patients had small-cell carcinomas or epitheliomas. Accompanying silicosis, usually in a mild form, was found in 35 cases. The mean exposure time was 10.3 years (in 11 cases, less than five years), the mean latency time 22 years (minimum: 8 years). The mean age at the time of death was 58.2 years, i.e. 10 years less than in a normal control group. (orig.) [de

  17. Childhood Interstitial Lung Disease

    Science.gov (United States)

    ... process. Overview Researchers have only begun to study, define, and understand chILD in the last decade. Currently, ... This term refers to inhaling substances—such as food, liquid, or vomit—into the lungs. Inhaling these ...

  18. Eosinophilic Lung Disorders

    Science.gov (United States)

    ... in eosinophil number in the lung tissue. Treatment Treatment of acute eosinophilic pneumonia may require hospitalization. It may be necessary to support the person with assistance from a breathing machine. Treatment with intravenous (IV) steroids or other medications which ...

  19. Open lung biopsy

    Science.gov (United States)

    ... cancerous) tumors Cancer Certain infections (bacterial, viral, or fungal) Lung diseases (fibrosis) The procedure may help diagnose a number ... 20th ed. Philadelphia, PA: Elsevier; 2017:chap 57. Review Date 11/11/2016 Updated by: Mary C. ...

  20. Lung surgery - discharge

    Science.gov (United States)

    ... Lung biopsy - discharge; Thoracoscopy - discharge; Video-assisted thoracoscopic surgery - discharge; VATS - discharge ... milk) for 2 weeks after video-assisted thoracoscopic surgery and 6 to 8 weeks after open surgery. ...

  1. Diffuse cavitary lung lesions

    International Nuclear Information System (INIS)

    Grunzke, Mindy; Garrington, Timothy; Hayes, Kari; Bourland, Wendy

    2010-01-01

    An 11-year-old girl presented with a 2-month history of progressively worsening cough, daily fevers, and weight loss. A chest radiograph revealed multiple cystic cavitary lung lesions. An extensive infectious work-up was negative. Chest CT verified multiple cavitary lung lesions bilaterally, and [F-18]2-fluoro-2-deoxy-D-glucose ( 18 F-FDG) positron emission tomography with CT (PET/CT) showed increased uptake in the lung lesions as well as regional lymph nodes. Subsequent biopsy of an involved lymph node confirmed classical Hodgkin lymphoma, nodular sclerosis type. This case represents an unusual presentation for a child with Hodgkin lymphoma and demonstrates a role for 18 F-FDG PET/CT in evaluating a child with cavitary lung lesions. (orig.)

  2. Lung cancer imaging

    CERN Document Server

    Ravenel, James G

    2013-01-01

    This book provides a guide to the diagnosis, staging and overview of the management of lung cancer relevant to practicing radiologists so that they can better understand the decision making issues and provide more useful communication to treating physicians.

  3. [Interstitial lung diseases].

    Science.gov (United States)

    Junker, K; Brasch, F

    2008-11-01

    Interstitial lung diseases comprise a heterogeneous group of about 200 entities. In the classification of these diseases, diffuse parenchymal lung diseases with known cause, granulomatous diseases, and other specific interstitial lung diseases are separated from the important group of idiopathic interstitial pneumonias, which are classified according to the 2002 ATS/ERS consensus classification. Concerning the histological pattern, this classification differentiates between "usual interstitial pneumonia" (UIP), "nonspecific interstitial pneumonia" (NSIP), "organising pneumonia" (COP), "diffuse alveolar damage" (DAD), "respiratory bronchiolitis" (RB), "desquamative interstitial pneumonia" (DIP), "lymphocytic interstitial pneumonia" (LIP) and "unclassifiable interstitial pneumonias". A key message of this classification is that the pathologist will give the diagnosis of a histological pattern, whereas the final clinicopathologic diagnosis can be made only by the clinical pulmonologist after careful correlation with the clinical and radiologic features, which is essential in the diagnosis of interstitial lung diseases.

  4. Lungs in TSC

    Science.gov (United States)

    ... or pulmonary hypertension (high blood pressure in the arteries that supply the lungs). There have been only ... www.thoracic.org The LAM Foundation 4520 Cooper Road, Suite 300, Cincinnati, OH 45242 Phone: 513-777- ...

  5. Quantification of pulmonary thallium-201 activity after upright exercise in normal persons: importance of peak heart rate and propranolol usage in defining normal values

    International Nuclear Information System (INIS)

    Brown, K.A.; Boucher, C.A.; Okada, R.D.; Strauss, H.W.; Pohost, G.M.

    1984-01-01

    Fifty-nine normal patients (34 angiographically normal and 25 clinically normal by Bayesian analysis) underwent thallium-201 imaging after maximal upright exercise. Lung activity was quantitated relative to myocardial activity and a lung/myocardial activity ratio was determined for each patient. Stepwise regression analysis was then used to examine the influence of patient clinical characteristics and exercise variables on the lung/myocardium ratio. Peak heart rate during exercise and propranolol usage both showed significant negative regression coefficients (p less than 0.001). No other patient data showed a significant relation. Using the regression equation and the estimated variance, a 95% confidence level upper limit of normal could be determined for a give peak heart rate and propranolol status. Sixty-one other patients were studied to validate the predicted upper limits of normal based on this model. None of the 27 patients without coronary artery disease had an elevated lung/myocardial ratio, compared with 1 of 8 with 1-vessel disease (difference not significant), 6 of 14 with 2-vessel disease (p less than 0.005), and 6 of 12 with 3-vessel disease (p less than 0.0001). Thus, lung activity on upright exercise thallium-201 studies can be quantitated relative to myocardial activity, and is inversely related to peak heart rate and propranolol use. Use of a regression analysis allows determination of a 95% confidence upper limit of normal to be anticipated in an individual patient

  6. 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

  7. Multiple cystic lung disease

    Directory of Open Access Journals (Sweden)

    Flavia Angélica Ferreira Francisco

    2015-12-01

    Full Text Available Multiple cystic lung disease represents a diverse group of uncommon disorders that can present a diagnostic challenge due to the increasing number of diseases associated with this presentation. High-resolution computed tomography of the chest helps to define the morphological aspects and distribution of lung cysts, as well as associated findings. The combination of appearance upon imaging and clinical features, together with extrapulmonary manifestations, when present, permits confident and accurate diagnosis of the majority of these diseases without recourse to open-lung biopsy. The main diseases in this group that are discussed in this review are lymphangioleiomyomatosis, pulmonary Langerhans cell histiocytosis and folliculin gene-associated syndrome (Birt–Hogg–Dubé; other rare causes of cystic lung disease, including cystic metastasis of sarcoma, are also discussed. Disease progression is unpredictable, and understanding of the complications of cystic lung disease and their appearance during evolution of the disease are essential for management. Correlation of disease evolution and clinical context with chest imaging findings provides important clues for defining the underlying nature of cystic lung disease, and guides diagnostic evaluation and management.

  8. Normality in Analytical Psychology

    Science.gov (United States)

    Myers, Steve

    2013-01-01

    Although C.G. Jung’s interest in normality wavered throughout his career, it was one of the areas he identified in later life as worthy of further research. He began his career using a definition of normality which would have been the target of Foucault’s criticism, had Foucault chosen to review Jung’s work. However, Jung then evolved his thinking to a standpoint that was more aligned to Foucault’s own. Thereafter, the post Jungian concept of normality has remained relatively undeveloped by comparison with psychoanalysis and mainstream psychology. Jung’s disjecta membra on the subject suggest that, in contemporary analytical psychology, too much focus is placed on the process of individuation to the neglect of applications that consider collective processes. Also, there is potential for useful research and development into the nature of conflict between individuals and societies, and how normal people typically develop in relation to the spectrum between individuation and collectivity. PMID:25379262

  9. Normal Female Reproductive Anatomy

    Science.gov (United States)

    ... an inner lining called the endometrium. Normal female reproductive system anatomy. Topics/Categories: Anatomy -- Gynecologic Type: Color, Medical Illustration Source: National Cancer Institute Creator: Terese Winslow (Illustrator) AV Number: CDR609921 Date Created: November 17, 2014 Date Added: ...

  10. Normal growth and development

    Science.gov (United States)

    A child's growth and development can be divided into four periods: Infancy Preschool years Middle childhood years Adolescence Soon after birth, an infant normally loses about 5% to 10% of their birth weight. By about age ...

  11. Normal pressure hydrocephalus

    Science.gov (United States)

    Hydrocephalus - occult; Hydrocephalus - idiopathic; Hydrocephalus - adult; Hydrocephalus - communicating; Dementia - hydrocephalus; NPH ... Ferri FF. Normal pressure hydrocephalus. In: Ferri FF, ed. ... Elsevier; 2016:chap 648. Rosenberg GA. Brain edema and disorders ...

  12. Normal Functioning Family

    Science.gov (United States)

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Español Text Size Email Print Share Normal Functioning Family Page Content Article Body Is there any way ...

  13. Normal Pressure Hydrocephalus

    Science.gov (United States)

    ... improves the chance of a good recovery. Without treatment, symptoms may worsen and cause death. What research is being done? The NINDS conducts and supports research on neurological disorders, including normal pressure hydrocephalus. Research on disorders such ...

  14. Sex Differences and Sex Steroids in Lung Health and Disease

    Science.gov (United States)

    Townsend, Elizabeth A.; Miller, Virginia M.

    2012-01-01

    Sex differences in the biology of different organ systems and the influence of sex hormones in modulating health and disease are increasingly relevant in clinical and research areas. Although work has focused on sex differences and sex hormones in cardiovascular, musculoskeletal, and neuronal systems, there is now increasing clinical evidence for sex differences in incidence, morbidity, and mortality of lung diseases including allergic diseases (such as asthma), chronic obstructive pulmonary disease, pulmonary fibrosis, lung cancer, as well as pulmonary hypertension. Whether such differences are inherent and/or whether sex steroids play a role in modulating these differences is currently under investigation. The purpose of this review is to define sex differences in lung structure/function under normal and specific disease states, with exploration of whether and how sex hormone signaling mechanisms may explain these clinical observations. Focusing on adult age groups, the review addresses the following: 1) inherent sex differences in lung anatomy and physiology; 2) the importance of certain time points in life such as puberty, pregnancy, menopause, and aging; 3) expression and signaling of sex steroid receptors under normal vs. disease states; 4) potential interplay between different sex steroids; 5) the question of whether sex steroids are beneficial or detrimental to the lung; and 6) the potential use of sex steroid signaling as biomarkers and therapeutic avenues in lung diseases. The importance of focusing on sex differences and sex steroids in the lung lies in the increasing incidence of lung diseases in women and the need to address lung diseases across the life span. PMID:22240244

  15. HOXC13 promotes proliferation of lung adenocarcinoma via modulation of CCND1 and CCNE1

    OpenAIRE

    Yao, Yu; Luo, Jing; Sun, Qi; Xu, Ting; Sun, Siqing; Chen, Meili; Lin, Xin; Qian, Qiuping; Zhang, Yu; Cao, Lin; Zhang, Po; Lin, Yong

    2017-01-01

    In this study, we confirmed that HOXC13 might be a potential oncogene in lung adenocarcinoma through an analysis of The Cancer Genome Atlas (TCGA) datasets. Further analysis revealed that the expression of HOXC13 was significantly higher in lung adenocarcinoma tissues than in adjacent normal tissues; importantly, its expression correlated with poor clinical characteristics and worse prognosis. In vitro experiments showed that HOXC13 expression generally increased in lung adenocarcinoma cell l...

  16. LINKING LUNG AIRWAY STRUCTURE TO PULMONARY FUNCTION VIA COMPOSITE BRIDGE REGRESSION.

    Science.gov (United States)

    Chen, Kun; Hoffman, Eric A; Seetharaman, Indu; Jiao, Feiran; Lin, Ching-Long; Chan, Kung-Sik

    2016-12-01

    The human lung airway is a complex inverted tree-like structure. Detailed airway measurements can be extracted from MDCT-scanned lung images, such as segmental wall thickness, airway diameter, parent-child branch angles, etc. The wealth of lung airway data provides a unique opportunity for advancing our understanding of the fundamental structure-function relationships within the lung. An important problem is to construct and identify important lung airway features in normal subjects and connect these to standardized pulmonary function test results such as FEV1%. Among other things, the problem is complicated by the fact that a particular airway feature may be an important (relevant) predictor only when it pertains to segments of certain generations. Thus, the key is an efficient, consistent method for simultaneously conducting group selection (lung airway feature types) and within-group variable selection (airway generations), i.e., bi-level selection. Here we streamline a comprehensive procedure to process the lung airway data via imputation, normalization, transformation and groupwise principal component analysis, and then adopt a new composite penalized regression approach for conducting bi-level feature selection. As a prototype of composite penalization, the proposed composite bridge regression method is shown to admit an efficient algorithm, enjoy bi-level oracle properties, and outperform several existing methods. We analyze the MDCT lung image data from a cohort of 132 subjects with normal lung function. Our results show that, lung function in terms of FEV1% is promoted by having a less dense and more homogeneous lung comprising an airway whose segments enjoy more heterogeneity in wall thicknesses, larger mean diameters, lumen areas and branch angles. These data hold the potential of defining more accurately the "normal" subject population with borderline atypical lung functions that are clearly influenced by many genetic and environmental factors.

  17. Neurotrophins expression is decreased in lungs of human infants with congenital diaphragmatic hernia

    Directory of Open Access Journals (Sweden)

    O'Hanlon LD

    2014-02-01

    Full Text Available Lynn D O'Hanlon, Sherry M Mabry, Ikechukwu I EkekezieChildren's Mercy Hospitals/University of Missouri-Kansas City School of Medicine, Department of Pediatrics, Section of Neonatal-Perinatal Medicine, Kansas City, MO, USAObjectives: To evaluate neurotrophin (NT (nerve growth factor [NGF], NT-3, and brain-derived neurotrophic factor [BDNF] expression in autopsy lung tissues of human congenital diaphragmatic hernia (CDH infants versus that of infants that expired with: 1 "normal" lungs (controls; 2 chronic lung disease (CLD; and 3 pulmonary hypertension (PPHN.Hypothesis: NT expression will be significantly altered in CDH lung tissue compared with normal lung tissue and other neonatal lung diseases.Study design: Immunohistochemical studies for NT proteins NGF, BDNF, and NT-3 were applied to human autopsy neonatal lung tissue samples.Subject selection: The samples included a control group of 18 samples ranging from 23-week gestational age to term, a CDH group of 15 samples, a PPHN group of six samples, and a CLD group of 12 samples.Methodology: The tissue samples were studied, and four representative slide fields of alveoli/saccules and four of bronchioles were recorded from each sample. These slide fields were then graded (from 0 to 3 by three blinded observers for intensity of staining.Results: BDNF, NGF, and NT-3 immunostaining intensity scores were significantly decreased in the CDH lung tissue (n=15 compared with normal neonatal lung tissue (n=18 (P<0.001. The other neonatal pulmonary diseases that were studied, CLD and PPHN, were much less likely to be affected and were much more variable in their neurotrophin expression.Conclusion: NT expression is decreased in CDH lungs. The decreased expression of NT in CDH lung tissue may suggest they contribute to the abnormality in this condition.Keywords: nerve growth factor, NGF, brain-derived neurotrophic factor, BDNF, neurotrophin-3, NT-3, chronic lung disease, persistent pulmonary hypertension, lung

  18. The aging lung

    Directory of Open Access Journals (Sweden)

    Lowery EM

    2013-11-01

    Full Text Available Erin M Lowery,1 Aleah L Brubaker,2 Erica Kuhlmann,1 Elizabeth J Kovacs31Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine at Loyola University Medical Center, 2Loyola University Stritch School of Medicine, 3Department of Surgery, Loyola University Medical Center, Maywood, IL, USAAbstract: There are many age-associated changes in the respiratory and pulmonary immune system. These changes include decreases in the volume of the thoracic cavity, reduced lung volumes, and alterations in the muscles that aid respiration. Muscle function on a cellular level in the aging population is less efficient. The elderly population has less pulmonary reserve, and cough strength is decreased in the elderly population due to anatomic changes and muscle atrophy. Clearance of particles from the lung through the mucociliary elevator is decreased and associated with ciliary dysfunction. Many complex changes in immunity with aging contribute to increased susceptibility to infections including a less robust immune response from both the innate and adaptive immune systems. Considering all of these age-related changes to the lungs, pulmonary disease has significant consequences for the aging population. Chronic lower respiratory tract disease is the third leading cause of death in people aged 65 years and older. With a large and growing aging population, it is critical to understand how the body changes with age and how this impacts the entire respiratory system. Understanding the aging process in the lung is necessary in order to provide optimal care to our aging population. This review focuses on the nonpathologic aging process in the lung, including structural changes, changes in muscle function, and pulmonary immunologic function, with special consideration of obstructive lung disease in the elderly.Keywords: aging, lung, pulmonary immunology, COPD

  19. Elastin in lung development and disease pathogenesis.

    Science.gov (United States)

    Mecham, Robert P

    2018-01-11

    Elastin is expressed in most tissues that require elastic recoil. The protein first appeared coincident with the closed circulatory system, and was critical for the evolutionary success of the vertebrate lineage. Elastin is expressed by multiple cell types in the lung, including mesothelial cells in the pleura, smooth muscle cells in airways and blood vessels, endothelial cells, and interstitial fibroblasts. This highly crosslinked protein associates with fibrillin-containing microfibrils to form the elastic fiber, which is the physiological structure that functions in the extracellular matrix. Elastic fibers can be woven into many different shapes depending on the mechanical needs of the tissue. In large pulmonary vessels, for example, elastin forms continuous sheets, or lamellae, that separate smooth muscle layers. Outside of the vasculature, elastic fibers form an extensive fiber network that originates in the central bronchi and inserts into the distal airspaces and visceral pleura. The fibrous cables form a looping system that encircle the alveolar ducts and terminal air spaces and ensures that applied force is transmitted equally to all parts of the lung. Normal lung function depends on proper secretion and assembly of elastin, and either inhibition of elastin fiber assembly or degradation of existing elastin results in lung dysfunction and disease. Copyright © 2018 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

  20. Protein misfolding and obstructive lung disease.

    LENUS (Irish Health Repository)

    Greene, Catherine M

    2010-11-01

    The endoplasmic reticulum has evolved a number of mechanisms to manage the accumulation of incorrectly folded proteins. This results in loss of function of these proteins, but occasionally, in conditions such as α-1 antitrpysin (A1AT) deficiency, the misfolded protein can acquire a toxic gain of function promoting exaggerated ER stress responses and inflammation. Mutations leading to deficiency in a second serine proteinase inhibitor, α-1 antichymotrpysin (ACT), can induce potentially similar consequences. A1AT and ACT deficiencies are associated with chronic obstructive lung disease. Until recently, it was thought that the lung diseases associated with these conditions were entirely due to loss of antiprotease protection in the lung (i.e., loss of function), whereas gain of function was the major cause of the liver disease associated with A1AT deficiency. This paradigm is being increasingly challenged because ER stress is being recognized in bronchial epithelial cells and inflammatory cells normally resident in the lung, giving rise to an inflammatory phenotype that adds to the proteolytic burden associated with these conditions. In this article, we describe the cellular mechanisms that are activated to cope with an increasing burden of misfolded proteins within the ER in A1AT and ACT deficiency, show how these events are linked to inflammation, and outline the therapeutic strategies that can potentially interfere with production of misfolded proteins.

  1. Case-based lung image categorization and retrieval for interstitial lung diseases: clinical workflows.

    Science.gov (United States)

    Depeursinge, Adrien; Vargas, Alejandro; Gaillard, Frédéric; Platon, Alexandra; Geissbuhler, Antoine; Poletti, Pierre-Alexandre; Müller, Henning

    2012-01-01

    Clinical workflows and user interfaces of image-based computer-aided diagnosis (CAD) for interstitial lung diseases in high-resolution computed tomography are introduced and discussed. Three use cases are implemented to assist students, radiologists, and physicians in the diagnosis workup of interstitial lung diseases. In a first step, the proposed system shows a three-dimensional map of categorized lung tissue patterns with quantification of the diseases based on texture analysis of the lung parenchyma. Then, based on the proportions of abnormal and normal lung tissue as well as clinical data of the patients, retrieval of similar cases is enabled using a multimodal distance aggregating content-based image retrieval (CBIR) and text-based information search. The global system leads to a hybrid detection-CBIR-based CAD, where detection-based and CBIR-based CAD show to be complementary both on the user's side and on the algorithmic side. The proposed approach is in accordance with the classical workflow of clinicians searching for similar cases in textbooks and personal collections. The developed system enables objective and customizable inter-case similarity assessment, and the performance measures obtained with a leave-one-patient-out cross-validation (LOPO CV) are representative of a clinical usage of the system.

  2. Quantitative assessment of irradiated lung volume and lung mass in breast cancer patients treated with tangential fields in combination with deep inspiration breath hold (DIBH)

    International Nuclear Information System (INIS)

    Kapp, Karin Sigrid; Zurl, Brigitte; Stranzl, Heidi; Winkler, Peter

    2010-01-01

    Purpose: Comparison of the amount of irradiated lung tissue volume and mass in patients with breast cancer treated with an optimized tangential-field technique with and without a deep inspiration breath-hold (DIBH) technique and its impact on the normal-tissue complication probability (NTCP). Material and Methods: Computed tomography datasets of 60 patients in normal breathing (NB) and subsequently in DIBH were compared. With a Real-Time Position Management Respiratory Gating System (RPM), anteroposterior movement of the chest wall was monitored and a lower and upper threshold were defined. Ipsilateral lung and a restricted tangential region of the lung were delineated and the mean and maximum doses calculated. Irradiated lung tissue mass was computed based on density values. NTCP for lung was calculated using a modified Lyman-Kutcher-Burman (LKB) model. Results: Mean dose to the ipsilateral lung in DIBH versus NB was significantly reduced by 15%. Mean lung mass calculation in the restricted area receiving ≤ 20 Gy (M 20 ) was reduced by 17% in DIBH but associated with an increase in volume. NTCP showed an improvement in DIBH of 20%. The correlation of individual breathing amplitude with NTCP proved to be independent. Conclusion: The delineation of a restricted area provides the lung mass calculation in patients treated with tangential fields. DIBH reduces ipsilateral lung dose by inflation so that less tissue remains in the irradiated region and its efficiency is supported by a decrease of NTCP. (orig.)

  3. Pre- and post-bronchodilator lung function as predictors of mortality in the Lung Health Study

    Directory of Open Access Journals (Sweden)

    Diaz-Guzman Enrique

    2011-10-01

    Full Text Available Abstract Background Chronic obstructive pulmonary disease (COPD is supposed to be classified on the basis of post-bronchodilator lung function. Most longitudinal studies of COPD, though, do not have post-bronchodilator lung function available. We used pre-and post bronchodilator lung function data from the Lung Health Study to determine whether these measures differ in their ability to predict mortality. Methods We limited our analysis to subjects who were of black or white race, on whom we had complete data, and who participated at either the 1 year or the 5 year follow-up visit. We classified subjects based on their baseline lung function, according to COPD Classification criteria using both pre- and post-bronchodilator lung function. We conducted a survival analysis and logistic regression predicting death and controlling for age, sex, race, treatment group, smoking status, and measures of lung function (either pre- or post-bronchodilator. We calculated hazard ratios (HR with 95% confidence intervals (CI and also calculated area under the curve for the logistic regression models. Results By year 15 of the study, 721 of the original 5,887 study subjects had died. In the year 1 sample survival models, a higher FEV1 % predicted lower mortality in both the pre-bronchodilator (HR 0.87, 95% CI 0.81, 0.94 per 10% increase and post-bronchodilator (HR 0.84, 95% CI 0.77, 0.90 models. The area under the curve for the respective models was 69.2% and 69.4%. Similarly, using categories, when compared to people with "normal" lung function, subjects with Stage 3 or 4 disease had similar mortality in both the pre- (HR 1.51, 95% CI 0.75, 3.03 and post-bronchodilator (HR 1.45, 95% CI 0.41, 5.15 models. In the year 5 sample, when a larger proportion of subjects had Stage 3 or 4 disease (6.4% in the pre-bronchodilator group, mortality was significantly increased in both the pre- (HR 2.68, 95% CI 1.51, 4.75 and post-bronchodilator (HR 2.46, 95% CI 1.63, 3

  4. Immune and Inflammatory Cell Composition of Human Lung Cancer Stroma.

    Directory of Open Access Journals (Sweden)

    G-Andre Banat

    Full Text Available Recent studies indicate that the abnormal microenvironment of tumors may play a critical role in carcinogenesis, including lung cancer. We comprehensively assessed the number of stromal cells, especially immune/inflammatory cells, in lung cancer and evaluated their infiltration in cancers of different stages, types and metastatic characteristics potential. Immunohistochemical analysis of lung cancer tissue arrays containing normal and lung cancer sections was performed. This analysis was combined with cyto-/histomorphological assessment and quantification of cells to classify/subclassify tumors accurately and to perform a high throughput analysis of stromal cell composition in different types of lung cancer. In human lung cancer sections we observed a significant elevation/infiltration of total-T lymphocytes (CD3+, cytotoxic-T cells (CD8+, T-helper cells (CD4+, B cells (CD20+, macrophages (CD68+, mast cells (CD117+, mononuclear cells (CD11c+, plasma cells, activated-T cells (MUM1+, B cells, myeloid cells (PD1+ and neutrophilic granulocytes (myeloperoxidase+ compared with healthy donor specimens. We observed all of these immune cell markers in different types of lung cancers including squamous cell carcinoma, adenocarcinoma, adenosquamous cell carcinoma, small cell carcinoma, papillary adenocarcinoma, metastatic adenocarcinoma, and bronchioloalveolar carcinoma. The numbers of all tumor-associated immune cells (except MUM1+ cells in stage III cancer specimens was significantly greater than those in stage I samples. We observed substantial stage-dependent immune cell infiltration in human lung tumors suggesting that the tumor microenvironment plays a critical role during lung carcinogenesis. Strategies for therapeutic interference with lung cancer microenvironment should consider the complexity of its immune cell composition.

  5. Changes in expression of injury after irradiation of increasing volumes in rat lung

    NARCIS (Netherlands)

    Novakova-Jiresova, Alena; van Luijk, Peter; van Goor, Harry; Kampinga, Harm H.; Coppes, Robert P.

    2007-01-01

    Purpose: To improve the cure rates of thoracic malignancies by radiation dose escalation, very accurate insight is required in the dose delivery parameters that maximally spare normal lung function. Radiation-induced lung complications are classically divided into an early pneumonitic and a late

  6. The value of lung scintigraphy in the diagnosis of pulmonary embolism

    NARCIS (Netherlands)

    van Beek, E. J.; Tiel-van Buul, M. M.; Büller, H. R.; van Royen, E. A.; ten Cate, J. W.

    1993-01-01

    The role of lung scintigraphy in the diagnostic management of patients with clinically suspected pulmonary embolism is reviewed. Evidence is provided that a normal perfusion scan excludes clinically relevant pulmonary embolism, and that a high probability lung scan, defined as a segmental perfusion

  7. Semaphorin 4A enhances lung fibrosis through activation of Akt via ...

    Indian Academy of Sciences (India)

    Semaphorin 4A plays a regulatory role in immune function and angiogenesis. However, its specific involvement in controlling lung fibrosis, a process that is closely related to angiogenesis and inflammation is still poorly understood. In the present study, we show that treatment of Sema4A on normal lung fibroblasts induces ...

  8. Semaphorin 4A enhances lung fibrosis through activation of Akt via ...

    Indian Academy of Sciences (India)

    In the present study, we show that treatment of Sema4A on normal lung fibroblasts induces expression of proteins that contribute to a contractile phenotype, including a-smooth muscle actin (-SMA), ezrin, moesin, and paxillin. We confirm that Sema4A enhances the ability of lung fibroblasts to contract collagen gel. Sema4A ...

  9. Slow-growing lung cancer as an emerging entity : from screening to clinical management

    NARCIS (Netherlands)

    Infante, Maurizio; Berghmans, Thierry; Heuvelmans, Marjolein A.; Hillerdal, Gunnar; Oudkerk, Matthijs

    2013-01-01

    The current paradigm is that untreated lung cancer is invariably and rapidly fatal, therefore the medical community normally dismisses the idea that a patient could live with such a disease for years without any therapy. Yet evidence from lung cancer screening research and from recent clinical

  10. Multislice spiral computed tomography to determine the effects of a recruitment maneuver in experimental lung injury

    Energy Technology Data Exchange (ETDEWEB)

    Henzler, Dietrich; Rossaint, Rolf [University Hospital, RWTH Aachen, Anesthesiology Department, Aachen (Germany); Mahnken, Andreas H.; Wildberger, Joachim E.; Guenther, Rolf W. [University Hospital of the RWTH Aachen, Clinic of Diagnostic Radiology, Aachen (Germany); Kuhlen, Ralf [University Hospital of the RWTH Aachen, Operative Intensive Care Department, Aachen (Germany)

    2006-06-15

    Although recruitment of atelectatic lung is a common aim in acute respiratory distress syndrome (ARDS), the effects of a recruitment maneuver have not been assessed quantitatively. By multislice spiral CT (MSCT), we analyzed the changes in lung volumes calculated from the changes in the CT values of hyperinflated (V{sub HYP}), normally (V{sub NORM}), poorly (V{sub POOR}) and nonaerated (V{sub NON}) lung in eight mechanically ventilated pigs with saline lavage-induced acute lung injury before and after a recruitment maneuver. This was compared to single slice analysis near the diaphragm. The increase in aerated lung was mainly for V{sub POOR} and the less in V{sub NORM}. Total lung volume and intrathoracic gas increased. No differences were found for tidal volumes measured by spirometry or determined by CT. The inspiratory-expiratory volume differences were not different after the recruitment maneuver in V{sub NON} (from 62{+-}18 ml to 43{+-}26 ml, P=0.114), and in V{sub NORM} (from 216{+-}51 ml to 251{+-}37 ml, P=0.102). Single slice analysis significantly underestimated the increase in normally and poorly aerated lung. Quantitative analysis of lung volumes by whole lung MSCT revealed the increase of poorly aerated lung as the main mechanism of a standard recruitment maneuver. MSCT can provide additional information as compared to single slice CT. (orig.)

  11. Contribution of Fetal, but Not Adult, Pulmonary Mesothelium to Mesenchymal Lineages in Lung Homeostasis and Fibrosis.

    Science.gov (United States)

    von Gise, Alexander; Stevens, Sean M; Honor, Leah B; Oh, Jin Hee; Gao, Chi; Zhou, Bin; Pu, William T

    2016-02-01

    The lung is enveloped by a layer of specialized epithelium, the pulmonary mesothelium. In other organs, mesothelial cells undergo epithelial-mesenchymal transition and contribute to organ stromal cells. The contribution of pulmonary mesothelial cells (PMCs) to the developing lung has been evaluated with differing conclusions. PMCs have also been indirectly implicated in lung fibrosis in the progressive, fatal lung disease idiopathic pulmonary fibrosis. We used fetal or postnatal genetic pulse labeling of PMCs to assess their fate in murine development, normal lung homeostasis, and models of pulmonary fibrosis. We found that most fetal PMC-derived mesenchymal cells (PMCDCs) expressed markers of pericytes and fibroblasts, only a small minority expressed smooth muscle markers, and none expressed endothelial cell markers. Postnatal PMCs did not contribute to lung mesenchyme during normal lung homeostasis or in models of lung fibrosis. However, fetal PMCDCs were abundant and actively proliferating within fibrotic regions in lung fibrosis models, suggesting that they actively participate in the fibrotic process. These data clarify the role of fetal and postnatal PMCDCs in lung development and disease.

  12. Radionuclide-determined changes in pulmonary blood volume and thallium lung uptake in patients with coronary artery disease

    International Nuclear Information System (INIS)

    Wilson, R.A.; Okada, R.D.; Boucher, C.A.; Strauss, H.W.; Pohost, G.M.

    1983-01-01

    Exercise-induced increases in radionuclide-determined pulmonary blood volume (PBV) and thallium lung uptake have been described in patients with coronary artery disease (CAD) and have been shown to correlate with transient exercise-induced left ventricular dysfunction. To compare these 2 techniques in the same patients, 74 patients (59 with and 15 without significant CAD) underwent supine bicycle exercise twice on the same day--first for thallium myocardial and lung imaging and then for technetium-99m gated blood pool imaging for the PBV ratio determination. Thallium activity of lung and myocardium was determined to calculate thallium lung/heart ratio. Relative changes in PBV from rest to exercise were expressed as a ratio of pulmonary counts (exercise/rest). Previously reported normal ranges for thallium lung/heart ratio and PBV ratio were used. The PBV ratio and thallium lung/heart ratio were abnormal in 71 and 36%, respectively, of patients with CAD (p less than 0.01). Both ratios were normal in all patients without CAD. Although the resting ejection fractions did not differ significantly in patients with normal versus those with abnormal PBV ratios or thallium lung/heart ratios, abnormal PBV ratios and thallium lung/heart ratios were associated with an exercise-induced decrease in ejection fraction. Propranolol use was significantly higher in patients with abnormal than in those with normal thallium lung/heart ratios (p less than 0.01). No significant difference in propranolol use was present in patients with abnormal or normal PBV ratios. In conclusion: (1) the prevalence of an abnormal thallium lung/heart ratio is less than that of the PBV ratio in patients with CAD; (2) both tests are normal in normal control subjects; (3) propranolol does not cause abnormal results in normal control subjects; however, propranolol may influence lung thallium uptake in patients with CAD; and (4) when both tests are abnormal, there is a high likelihood of multivessel disease

  13. Recent lung imaging studies

    International Nuclear Information System (INIS)

    Taplin, G.V.; Chopra, S.K.

    1976-01-01

    Radionuclide lung imaging procedures have been available for 11 years but only the perfusion examination has been used extensively and mainly for the diagnosis of pulmonary embolism (P.E.). Its ability to reveal localized ischemia makes it a valuable test of regional lung function as well as a useful diagnostic aid in P.E. Although it had been recognized for several years that chronic obstructive pulmonary disease (COPD) can cause lung perfusion defects which may simulate pulmonary embolism, relatively little use has been made of either the radioxenon or the radioaerosol inhalation lung imaging procedures until the last few years as a means of distinguishing P.E. from COPD. In this review emphasis is placed on our recent experience with both of these inhalation procedures in comparison with pulmonary function tests and roentgenography for the early detection of COPD in population studies. Equal emphasis is given to simultaneous aerosol ventilation-perfusion (V/P) imaging for a functional diagnosis of P.E. Two new developments in regional lung diffusion imaging, performed after the inhalation of radioactive gases and/or rapidly absorbed radioaerosols are described. The experimental basis for their potential clinical application in pulmonary embolism detection is presented

  14. Lung cancer screening: Update

    International Nuclear Information System (INIS)

    Kim, Hyea Young

    2015-01-01

    Lung cancer is the leading cause of cancer deaths worldwide as well as in Korea. A recent National Lung Screening Trial in U.S. revealed that low-dose CT (LDCT) screening reduced lung cancer specific mortality by 20% in high risk individuals as compared to chest radiograph screening. Based on this evidence, several expert societies in U.S. and Korean multisociety collaborative committee developed guidelines for recommendation of lung cancer screening using annual LDCT in high risk populations. In most of the societies high risk groups are defined as persons aged 55 to 74 years, who are current smokers with history of smoking of more than 30 packs per year or ex-smokers, who quit smoking up to 15 or more years ago. The benefits of LDCT screening are modestly higher than the harms in high risk individuals. The harms included a high rate of false-positive findings, over-diagnosis and radiation-related deaths. Invasive diagnostic procedure due to false positive findings may lead to complications. LDCT should be performed in qualified hospitals and interpreted by expert radiologists. Recently, the American College of Radiology released the current version of Lung cancer CT screening Reporting and Data Systems. Education and actions to stop smoking must be offered to current smokers

  15. Mechanisms of lung aging.

    Science.gov (United States)

    Brandenberger, Christina; Mühlfeld, Christian

    2017-03-01

    Lung aging is associated with structural remodeling, a decline of respiratory function and a higher susceptibility to acute and chronic lung diseases. Individual factors that modulate pulmonary aging include basic genetic configuration, environmental exposure, life-style and biography of systemic diseases. However, the actual aging of the lung takes place in pulmonary resident cells and is closely linked to aging of the immune system (immunosenescence). Therefore, this article reviews the current knowledge about the impact of aging on pulmonary cells and the immune system, without analyzing those factors that may accelerate the aging process in depth. Hallmarks of aging include alterations at molecular, cellular and cell-cell interaction levels. Because of the great variety of cell types in the lung, the consequences of aging display a broad spectrum of phenotypes. For example, aging is associated with more collagen and less elastin production by fibroblasts, thus increasing pulmonary stiffness and lowering compliance. Decreased sympathetic airway innervation may increase the constriction status of airway smooth muscle cells. Aging of resident and systemic immune cells leads to a pro-inflammatory milieu and reduced capacity of fighting infectious diseases. The current review provides an overview of cellular changes occurring with advancing age in general and in several cell types of the lung as well as of the immune system. Thereby, this survey not only aims at providing a better understanding of the mechanisms of pulmonary aging but also to identify gaps in knowledge that warrant further investigations.

  16. Monitoring the normal body

    DEFF Research Database (Denmark)

    Nissen, Nina Konstantin; Holm, Lotte; Baarts, Charlotte

    2015-01-01

    provides us with knowledge about how to prevent future overweight or obesity. This paper investigates body size ideals and monitoring practices among normal-weight and moderately overweight people. Methods : The study is based on in-depth interviews combined with observations. 24 participants were...... recruited by strategic sampling based on self-reported BMI 18.5-29.9 kg/m2 and socio-demographic factors. Inductive analysis was conducted. Results : Normal-weight and moderately overweight people have clear ideals for their body size. Despite being normal weight or close to this, they construct a variety...... of practices for monitoring their bodies based on different kinds of calculations of weight and body size, observations of body shape, and measurements of bodily firmness. Biometric measurements are familiar to them as are health authorities' recommendations. Despite not belonging to an extreme BMI category...

  17. Efecto Zeeman Normal

    OpenAIRE

    Calderón Chamochumbi, Carlos

    2015-01-01

    Se describe el Efecto Zeeman Normal y se presenta una derivación general del torque experimentado por un dipolo magnético debido a su interacción con un campo magnético externo. Los cálculos correspondientes al elemento diferencial de energía potencial magnética y de la energía potencial magnética convencional son estándares. ABSTRACT: The Normal Zeeman Effect is described and a general derivation of the torque undergone by a magnetic dipole due to its interactio...

  18. The normal holonomy group

    International Nuclear Information System (INIS)

    Olmos, C.

    1990-05-01

    The restricted holonomy group of a Riemannian manifold is a compact Lie group and its representation on the tangent space is a product of irreducible representations and a trivial one. Each one of the non-trivial factors is either an orthogonal representation of a connected compact Lie group which acts transitively on the unit sphere or it is the isotropy representation of a single Riemannian symmetric space of rank ≥ 2. We prove that, all these properties are also true for the representation on the normal space of the restricted normal holonomy group of any submanifold of a space of constant curvature. 4 refs

  19. Normal modified stable processes

    DEFF Research Database (Denmark)

    Barndorff-Nielsen, Ole Eiler; Shephard, N.

    2002-01-01

    This paper discusses two classes of distributions, and stochastic processes derived from them: modified stable (MS) laws and normal modified stable (NMS) laws. This extends corresponding results for the generalised inverse Gaussian (GIG) and generalised hyperbolic (GH) or normal generalised inverse...... Gaussian (NGIG) laws. The wider framework thus established provides, in particular, for added flexibility in the modelling of the dynamics of financial time series, of importance especially as regards OU based stochastic volatility models for equities. In the special case of the tempered stable OU process...

  20. Medically-enhanced normality

    DEFF Research Database (Denmark)

    Møldrup, Claus; Traulsen, Janine Morgall; Almarsdóttir, Anna Birna

    2003-01-01

    Objective: To consider public perspectives on the use of medicines for non-medical purposes, a usage called medically-enhanced normality (MEN). Method: Examples from the literature were combined with empirical data derived from two Danish research projects: a Delphi internet study and a Telebus......, to optimise economic, working and family conditions. The term "doping" does not cover or explain the use of medicines as enhancement among healthy non-athletes. Conclusion: We recommend wider use of the term medically-enhanced normality as a conceptual framework for understanding and analysing perceptions...... of what is considered rational medicine use in contemporary society....

  1. Normal MR imaging of fetal organs

    Energy Technology Data Exchange (ETDEWEB)

    Kawabata, Ichiro; Tamaya, Teruhiko (Gifu Univ. (Japan). Faculty of Medicine)

    1990-12-01

    MR imaging has recently been used in medical scene, especially in obstetrics. The definite prenatal diagnosis of fetal anomaly using MR imaging has proved to be useful. But MR imaging of normal fetal organs remains to be understood. There have been not complete systemical research works about normal fetus by MR imaging, up to date. MR imaging on 25 pregnant cases were carried out to get the definite diagnosis of the possible fetal anomalies. MR imaging in fetus is usually disturbed by fetal movement. Generally, diazepam to mother or muscle relaxants to fetus have been used in given cases in order to obtain good quality of imaging. Mothers were requested to walk around the lobby in hospital before examination and fetal movement was decreased, resulting in 85% good imaging. The understanding of normal findings of fetal organs by MR imagings is important for diagnosis of the fetal anomalies. For example, brain and bowel showed high signals in T{sub 1} weighted images. Lung showed high signal in T{sub 2} weighted images. Liver was demonstrated clearly in T{sub 1} weighted images and proton density images. Heart and vessels showed low signals because of flow void phenomenon. Thus, it is necessary to detect and diagnose fetal anomalies after understanding the normal findings of fetal organs in MR imaging. (author).

  2. Unexpandable lung from pleural disease.

    Science.gov (United States)

    Huggins, John T; Maldonado, Fabien; Chopra, Amit; Rahman, Najib; Light, Richard

    2018-02-01

    Unexpandable lung is a common complication of malignant pleural effusions and inflammatory pleural diseases, such as pleural infection (e.g. empyema and complicated parapneumonic effusion) and noninfectious fibrinous pleuritis. Unexpandable lung due to pleural disease may be because of an active pleural process, and is referred to as malignant or inflammatory lung entrapment. An unexpandable lung may also be encountered in the setting of remote pleural inflammation resulting in a mature fibrous membrane overlying the visceral pleura preventing full expansion of the lung. This condition is termed trapped lung and may be understood as a form of defective healing of the pleural space. Trapped lung typically presents as a chronic, stable pleural effusion without evidence of active pleural disease. An unexpandable lung most often manifests itself as an inability of fully expanding the lung with pleural space drainage. Patients will either develop chest pain preventing complete drainage of the pleural space or develop a post-procedure pneumothorax. Pleural manometry and radiological imaging are useful in the assessment of an unexpandable lung. Pleural manometry can demonstrate abnormal lung expansion during drainage and imaging will demonstrate abnormal visceral pleural thickening found in trapped lung or malignant and inflammatory lung entrapment. © 2017 Asian Pacific Society of Respirology.

  3. Lung Ultrasound Has Limited Diagnostic Value in Rare Cystic Lung Diseases

    DEFF Research Database (Denmark)

    Davidsen, Jesper Rømhild; Bendstrup, Elisabeth; Henriksen, Daniel P

    2017-01-01

    findings. IS could not be found in any patients despite GGO presentation on HRCT among 75% of the patients with a Belmaati in the highest category of 0.76-1.00. Pleural thickening on LUS was present in three patients, but with inconsistent findings. Conclusion: This study indicates that LUS has limited...... value as a diagnostic tool in patients with LAM, PLCH, and BHDS as normal LUS findings did not rule out severe cystic lung disease....

  4. Lung boundary detection in pediatric chest x-rays

    Science.gov (United States)

    Candemir, Sema; Antani, Sameer; Jaeger, Stefan; Browning, Renee; Thoma, George R.

    2015-03-01

    Tuberculosis (TB) is a major public health problem worldwide, and highly prevalent in developing countries. According to the World Health Organization (WHO), over 95% of TB deaths occur in low- and middle- income countries that often have under-resourced health care systems. In an effort to aid population screening in such resource challenged settings, the U.S. National Library of Medicine has developed a chest X-ray (CXR) screening system that provides a pre-decision on pulmonary abnormalities. When the system is presented with a digital CXR image from the Picture Archive and Communication Systems (PACS) or an imaging source, it automatically identifies the lung regions in the image, extracts image features, and classifies the image as normal or abnormal using trained machine-learning algorithms. The system has been trained on adult CXR images, and this article presents enhancements toward including pediatric CXR images. Our adult lung boundary detection algorithm is model-based. We note the lung shape differences during pediatric developmental stages, and adulthood, and propose building new lung models suitable for pediatric developmental stages. In this study, we quantify changes in lung shape from infancy to adulthood toward enhancing our lung segmentation algorithm. Our initial findings suggest pediatric age groupings of 0 - 23 months, 2 - 10 years, and 11 - 18 years. We present justification for our groupings. We report on the quality of boundary detection algorithm with the pediatric lung models.

  5. Novel nanoparticulate systems for lung cancer therapy: an updated review.

    Science.gov (United States)

    Madni, Asadullah; Batool, Amna; Noreen, Sobia; Maqbool, Irsah; Rehman, Faizza; Kashif, Prince Muhammad; Tahir, Nayab; Raza, Ahmad

    2017-07-01

    Lung cancer is the leading cause of cancer-related deaths in the world. Conventional therapy for lung cancer is associated with lack of specificity and access to the normal cells resulting in cytotoxicity, reduced cellular uptake, drug resistance and rapid drug clearance from the body. The emergence of nanotechnology has revolutionized the treatment of lung cancer. The focus of nanotechnology is to target tumor cells with improved bioavailability and reduced toxicity. In the recent years, nanoparticulate systems have extensively been exploited in order to overcome the obstacles in treatment of lung cancer. Nanoparticulate systems have shown much potential for lung cancer therapy by gaining selective access to the tumor cells due to surface modifiability and smaller size. In this review, various novel nanoparticles (NPs) based formulations have been discussed in the treatment of lung cancer. Nanotechnology is expected to grow fast in future, and it will provide new avenues for the improved treatment of lung cancer. This review article also highlights the characteristics, recent advances in the designing of NPs and therapeutic outcomes.

  6. Radiofrequency Ablation of Lung Malignancies: Where Do We Stand?

    International Nuclear Information System (INIS)

    Lencioni, Riccardo; Crocetti, Laura; Cioni, Roberto; Mussi, Alfredo; Fontanini, Gabriella; Ambrogi, Marcello; Franchini, Chiara; Cioni, Dania; Fanucchi, Olivia; Gemignani, Raffaello; Baldassarri, Rubia; Angeletti, Carlo Alberto; Bartolozzi, Carlo

    2004-01-01

    Percutaneous radiofrequency (RF) ablation is a minimally invasive technique used to treat solid tumors. Because of its ability to produce large volumes of coagulation necrosis in a controlled fashion, this technique has gained acceptance as a viable therapeutic option for unresectable liver malignancies. Recently, investigation has been focused on the clinical application of RF ablation in the treatment of lung malignancies. In theory, lung tumors are well suited to RF ablation because the surrounding air in adjacent normal parenchyma provides an insulating effect, thus facilitating energy concentration within the tumor tissue. Experimental studies in rabbits have confirmed that lung RF ablation can be safely and effectively performed via a percutaneous, transthoracic approach, and have prompted the start of clinical investigation. Pilot clinical studies have shown that RF ablation enables successful treatment of relatively small lung malignancies with a high rate of complete response and acceptable morbidity, and have suggested that the technique could represent a viable alternate or complementary treatment method for patients with non-small cell lung cancer or lung metastases of favorable histotypes who are not candidates for surgical resection. This article gives an overview of lung RF ablation, discussing experimental animal findings, rationale for clinical application, technique and methodology, clinical results, and complications

  7. Utility of Lung Ultrasound in Near-Drowning Victims

    DEFF Research Database (Denmark)

    Laursen, Christian Borbjerg; Rømhild Davidsen, Jesper; Madsen, Poul Henning

    2013-01-01

    ultrasound may have a potential role in the evaluation of drowning or near-drowning victims. In this case report the authors describe a 71-year-old man who was brought to hospital with acute respiratory failure after a near-drowning accident. Lung ultrasound showed multiple B-lines on the anterior......Drowning and near-drowning are common causes of accidental death worldwide and respiratory complications such as non-cardiogenic pulmonary oedema, acute respiratory distress syndrome and pneumonia are often seen. In other settings lung ultrasound can accurately diagnose these conditions; hence lung...... and lateral surfaces of both lungs, consistent with pulmonary oedema. Focus assessed transthoracic echocardiography showed no pericardial effusion and a normal global left ventricular function. Based on these fi ndings the patient was diagnosed as having non-cardiogenic pulmonary oedema. Subsequent chest x...

  8. Lung pair phantom

    Science.gov (United States)

    Olsen, Peter C.; Gordon, N. Ross; Simmons, Kevin L.

    1993-01-01

    The present invention is a material and method of making the material that exhibits improved radiation attenuation simulation of real lungs, i.e., an "authentic lung tissue" or ALT phantom. Specifically, the ALT phantom is a two-part polyurethane medium density foam mixed with calcium carbonate, potassium carbonate if needed for K-40 background, lanthanum nitrate, acetone, and a nitrate or chloride form of a radionuclide. This formulation is found to closely match chemical composition and linear attenuation of real lungs. The ALT phantom material is made according to established procedures but without adding foaming agents or preparing thixotropic concentrate and with a modification for ensuring uniformity of density of the ALT phantom that is necessary for accurate simulation. The modification is that the polyurethane chemicals are mixed at a low temperature prior to pouring the polyurethane mixture into the mold.

  9. Lung mass, right upper lung - chest x-ray (image)

    Science.gov (United States)

    This picture is a chest x-ray of a person with a lung mass. This is a front view, where the lungs are the two dark areas and ... visible in the middle of the chest. The x-ray shows a mass in the right upper lung, ...

  10. Corners of normal matrices

    Indian Academy of Sciences (India)

    ∗Department of Mathematics, University of Toronto, Toronto M5S 2E4, Canada. E-mail: rbh@isid.ac.in; choi@math.toronto.edu. To Kalyan Sinha on his sixtieth birthday. Abstract. We study various conditions on matrices B and C under which they can be the off-diagonal blocks of a partitioned normal matrix. Keywords.

  11. Normality in Analytical Psychology

    Directory of Open Access Journals (Sweden)

    Steve Myers

    2013-11-01

    Full Text Available Although C.G. Jung’s interest in normality wavered throughout his career, it was one of the areas he identified in later life as worthy of further research. He began his career using a definition of normality which would have been the target of Foucault’s criticism, had Foucault chosen to review Jung’s work. However, Jung then evolved his thinking to a standpoint that was more aligned to Foucault’s own. Thereafter, the post Jungian concept of normality has remained relatively undeveloped by comparison with psychoanalysis and mainstream psychology. Jung’s disjecta membra on the subject suggest that, in contemporary analytical psychology, too much focus is placed on the process of individuation to the neglect of applications that consider collective processes. Also, there is potential for useful research and development into the nature of conflict between individuals and societies, and how normal people typically develop in relation to the spectrum between individuation and collectivity.

  12. Normalized information distance

    NARCIS (Netherlands)

    Vitányi, P.M.B.; Balbach, F.J.; Cilibrasi, R.L.; Li, M.; Emmert-Streib, F.; Dehmer, M.

    2009-01-01

    The normalized information distance is a universal distance measure for objects of all kinds. It is based on Kolmogorov complexity and thus uncomputable, but there are ways to utilize it. First, compression algorithms can be used to approximate the Kolmogorov complexity if the objects have a string

  13. Differential Effect of Soy Isoflavones in Enhancing High Intensity Radiotherapy and Protecting Lung Tissue in a Pre-Clinical Model of Lung Carcinoma

    Science.gov (United States)

    Hillman, Gilda G.; Singh-Gupta, Vinita; Hoogstra, David J.; Abernathy, Lisa; Rakowski, Joseph; Yunker, Christopher K.; Rothstein, Shoshana E.; Sarkar, Fazlul H.; Gadgeel, Shirish; Konski, Andre A.; Lonardo, Fulvio; Joiner, Michael C.

    2013-01-01

    Background Radiotherapy of locally-advanced non-small cell lung cancer is limited by radiation-induced pneumonitis and fibrosis. We have further investigated the role of soy isoflavones to improve the effect of a high intensity radiation and reduce lung damage in a pre-clinical lung tumor model. Methods Human A549 NSCLC cells were injected i.v. in nude mice to generate a large tumor burden in the lungs. Mice were treated with lung irradiation at 10 Gy and with oral soy. The therapy effect on the tumor cells and surrounding lung tissue was analyzed on lung sections stained with H&E, Ki-67 and Masson’s Trichrome. Pneumonitis and vascular damage were evaluated by measurements of alveolar septa and immunofluorescent staining of vessel walls. Results Combined soy and radiation caused a significantly stronger inhibition of tumor progression compared to each modality alone in contrast to large invasive tumor nodules seen in control mice. At the same time, soy reduced radiation injury in lung tissue by decreasing pneumonitis, fibrosis and protecting alveolar septa, bronchioles and vessels. Conclusions These studies demonstrate a differential effect of soy isoflavones on augmenting tumor destruction induced by radiation while radioprotecting normal lung tissue and support using soy to alleviate radiotoxicity in lung cancer. PMID:24021346

  14. An experimental study of the recovery of injured porcine lungs with prolonged normothermic cellular ex vivo lung perfusion following donation after circulatory death.

    Science.gov (United States)

    Spratt, John R; Mattison, Lars M; Iaizzo, Paul A; Brown, Roland Z; Helms, Haylie; Iles, Tinen L; Howard, Brian; Panoskaltsis-Mortari, Angela; Loor, Gabriel

    2017-09-01

    Donation after circulatory death (DCD) is an underused source of donor lungs. Normothermic cellular ex vivo lung perfusion (EVLP) is effective in preserving standard donor lungs but may also be useful in the preservation and assessment of DCD lungs. Using a model of DCD and prolonged EVLP, the effects of donor warm ischemia and postmortem ventilation on graft recovery were evaluated. Adult male swine underwent general anesthesia and heparinization. In the control group (n = 4), cardioplegic arrest was induced and the lungs were procured immediately. In the four treatment groups, a period of agonal hypoxia was followed by either 1 h of warm ischemia with (n = 4) or without (n = 4) ventilation or 2 h of warm ischemia with (n = 4) or without (n = 4) ventilation. All lungs were studied on an EVLP platform for 24 h. Hemodynamic measures, compliance, and oxygenation on EVLP were worse in all DCD lungs compared with controls. Hemodynamics and compliance normalized in all lungs after 24 h of EVLP, but DCD lungs demonstrated impaired oxygenation. Normothermic cellular EVLP is effective in preserving and monitoring of DCD lungs. Early donor postmortem ventilation and timely procurement lead to improved graft function. © 2017 Steunstichting ESOT.

  15. Lung Cancer Precision Medicine Trials

    Science.gov (United States)

    Patients with lung cancer are benefiting from the boom in targeted and immune-based therapies. With a series of precision medicine trials, NCI is keeping pace with the rapidly changing treatment landscape for lung cancer.

  16. Modeling of lung cancer risk due to radon exhalation of granite stone in dwelling houses

    Directory of Open Access Journals (Sweden)

    Akbar Abbasi

    2017-01-01

    Conclusions: The estimated numbers of lung cancer deaths attributable to indoor radon due to granite stones in 2013 were 145 (3.33% and 103 (2.37% for poor and normal ventilation systems, respectively. According to our estimations, the values of 3.33% and 2.37% of lung cancer deaths in 2013 are attributed to radon exhalation of granite stones with poor and normal ventilation systems, respectively.

  17. Reversible ventilation and perfusion abnormalities in unilateral obstructed lung

    International Nuclear Information System (INIS)

    Ward, H.E.; Jones, R.L.; King, E.G.; Sproule, B.J.; Fortune, R.L.

    1982-01-01

    An intraluminal carcinoid tumor obstructing the left mainstem bronchus produced hypoxemia through alteration in ventilation/perfusion matching. Studies of regional lung function using 133-xenon (/sup 133/Xe) and a multiprobe computerized instrumentation system documented a reduction of perfusion to 22 percent and ventilation to 6 percent of the total. There was negligible washout of intravenously injected /sup 133/Xe from the left lung consistent with air trapping. Four days after left mainstem bronchial sleeve resection, perfusion, ventilation and washout of injected xenon had significantly improved and by four months postresection, all measurements were virtually normal, although complete restoration of perfusion in relation to ventilation was delayed. Regional lung function studied with a multiprobe system in this patient provided a clinical model for the study of ventilation and perfusion inter-relationships in large airway obstruction and demonstrated that a prolonged time may be required for return of perfusion to normal

  18. High prevalence of emphysema and its association with BMI: a study of smokers with normal spirometry.

    Science.gov (United States)

    Stratelis, Georgios; Fransson, Sven-Göran; Schmekel, Birgitta; Jakobsson, Per; Mölstad, Sigvard

    2008-01-01

    To evaluate to what extent emphysema was evident, as identified by High Resolution Computed Tomography (HRCT), in smokers with normal lung function and to relate age, gender, smoking history, and body mass index (BMI) to the HRCT results. A secondary aim was to study to what extent emphysema was present in smokers with lower normal values of lung function defined as FEV(1)/FVC ratio percentage of predicted value (89-93% of predicted value for males and 90-93% for females) or FEF(50) smokers without this definition. Fifty-nine smokers, with a mean age of 53 years and with normal lung function, were examined with HRCT. Emphysema evidenced visually by HRCT was present in 43% of the subjects. Using a 0-5 grade scale (0=normal finding; 5=emphysema in most slices), the degree of emphysema was almost exclusively 3-4. The type of emphysema was distributed as centrilobular emphysema predominant in 43.5%, paraseptal emphysema predominant in 43.5%, and as an equal mixture of these types in 13%. The presence of emphysema did not differ between the group of smokers with lower normal values of lung function and the rest of the smokers. Smokers with emphysema had significantly lower BMI than those devoid of emphysema, 24 and 27 respectively (psmokers with normal lung function. The densitometric quantitative analysis method is inadequate for detecting mild emphysema. High prevalence of emphysema was associated with low BMI.

  19. Risk for COPD with Obstruction of Active Smokers with Normal Spirometry and Reduced Diffusion Capacity

    Science.gov (United States)

    Kaner, Robert J.; Sanders, Abraham; Vincent, Thomas L.; Mezey, Jason G.; Crystal, Ronald G.

    2016-01-01

    Background Smokers are assessed for COPD using spirometry, with COPD defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) as airflow limitation not fully reversible with bronchodilators. There is a subset of smokers with normal spirometry (by GOLD criteria), who have a low diffusion capacity (DLCO), a parameter linked to emphysema and small airway disease. The natural history of these “normal spirometry/low DLCO” smokers is unknown. Methods From a cohort of 1570 smokers in the New York City metropolitian area, all of whom had normal spirometry, two groups were randomly selected for lung function follow-up: smokers with normal spirometry/normal DLCO (n=59) and smokers with normal spirometry/low DLCO (n=46). All had normal history, physical examination, CBC, urinalysis, HIV status, α1-antitrypsin level, chest X-ray, FEV1, FVC, FEV1/FVC ratio and total lung capacity (TLC). Throughout the study, all continued to be active smokers. Findings In the normal spirometry/normal DLCO group assessed over 45 ± 20 months, 3% developed GOLD-defined COPD. In contrast, in the normal spirometry/low DLCO group, followed over 41 ± 31 months, 22% developed GOLD-defined COPD. Interpretation Despite appearing “normal” by GOLD, smokers with normal spirometry but low DLCO are at significant risk for developing COPD with obstruction to airflow. PMID:26541521

  20. Genomic Alteration During Metastasis of Lung Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Qiang Tan

    2016-02-01

    Full Text Available Background/Aims: Recurrent gene mutation has been identified by the analysis of exonic DNA from lung adenocarcinoma, but its progression has not been extensively profiled. The investigation of the mutational landscape of tumors provides new insights into cancer genome evolution and further discovers the interplay of somatic mutation, adaptation of clones to their environment and natural selection. Cancer development involves cycles of genomic damage, epigenetic deregulation, and increased cellular proliferation that eventually culminate in the carcinoma phenotype. Methods: Comparative whole exome sequencing of both primary and metastatic tumor tissues from four patients of stage IV lung adenocarcinoma patients with chest wall metastasis was performed. Both primary and metastatic tumors were diagnosed through biopsy followed by surgical resection. All tumor specimens were cut into several pieces to assess potential heterogenic clones within the tumor tissue. Adjacent normal lung tissue was also obtained to provide germline mutation background. Results: By modeling and analyzing progression of the cancer metastasis based on non-synonymous variants, we defined the extent of heterogeneity of cancer genomes and identified similar cancer evolution pattern in the four patients: metastasis was an early event occurring right after the primary cancer formation and evolution in the metastatic tumor was continuously and simultaneously in progression with that in the primary tumor. By characterizing the clonal hierarchy of genetic lesions, we further charted a pathway of oncogenic events along which genes may drive lung adenocarcinoma metastasis, such as TAS2R31 and UMODL1, involving in G-protein coupled receptor protein signaling pathway. Conclusion: The candidate genes identified in this study may become targets for the treatment of lung adenocarcinoma metastasis.

  1. 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.

  2. AUTOTRANSPLANTATION OF THE LUNG: EXPERIMENTAL ...

    African Journals Online (AJOL)

    undertaken to investigate the technique of lung trans- plantation in subhuman primates, and to determine lung ..... Perfect intimal approximation seems to be an important aspect of this problem. The value of ... systemic heparinization supplemented by temporary local heparinization of the lung, feeling it offered a measure.

  3. Radiodiagnosis of lung picture changes

    International Nuclear Information System (INIS)

    Kamenetskij, M.S.; Lezova, T.F.

    1988-01-01

    The roentgenological picture of changes of the lung picture in the case of different pathological states in the lungs and the heart, is described. A developed diagnostic algorithm for the syndrome of lung picture change and the rules of its application are given. 5 refs.; 9 figs

  4. Your Lungs and Respiratory System

    Science.gov (United States)

    ... your vocal cords when you're not ready. Love Your Lungs Your lungs are amazing. They allow you to breathe, talk to your friend, shout at a game, sing, laugh, cry, and more! And speaking of a game, your lungs even work with your brain to help you inhale and exhale a larger ...

  5. P53 MUTATIONS IN HUMAN LUNG-TUMORS

    NARCIS (Netherlands)

    MILLER, CW; ASLO, A; KOK, K; YOKOTA, J; BUYS, CHCM; TERADA, M; KOEFFLER, HP; Simon, K.

    1992-01-01

    Mutation of one p53 allele and loss of the normal p53 allele [loss of heterozygosity (LOH)] occur in many tumors including lung cancers. These alterations apparently contribute to development of cancer by interfering with the tumor suppressor activity of p53. We directly sequenced amplified DNA in

  6. Normal Weight Dyslipidemia

    DEFF Research Database (Denmark)

    Ipsen, David Hojland; Tveden-Nyborg, Pernille; Lykkesfeldt, Jens

    2016-01-01

    Objective: The liver coordinates lipid metabolism and may play a vital role in the development of dyslipidemia, even in the absence of obesity. Normal weight dyslipidemia (NWD) and patients with nonalcoholic fatty liver disease (NAFLD) who do not have obesity constitute a unique subset...... of individuals characterized by dyslipidemia and metabolic deterioration. This review examined the available literature on the role of the liver in dyslipidemia and the metabolic characteristics of patients with NAFLD who do not have obesity. Methods: PubMed was searched using the following keywords: nonobese......, dyslipidemia, NAFLD, NWD, liver, and metabolically obese/unhealthy normal weight. Additionally, article bibliographies were screened, and relevant citations were retrieved. Studies were excluded if they had not measured relevant biomarkers of dyslipidemia. Results: NWD and NAFLD without obesity share a similar...

  7. Idiopathic Normal Pressure Hydrocephalus

    Directory of Open Access Journals (Sweden)

    Basant R. Nassar BS

    2016-04-01

    Full Text Available Idiopathic normal pressure hydrocephalus (iNPH is a potentially reversible neurodegenerative disease commonly characterized by a triad of dementia, gait, and urinary disturbance. Advancements in diagnosis and treatment have aided in properly identifying and improving symptoms in patients. However, a large proportion of iNPH patients remain either undiagnosed or misdiagnosed. Using PubMed search engine of keywords “normal pressure hydrocephalus,” “diagnosis,” “shunt treatment,” “biomarkers,” “gait disturbances,” “cognitive function,” “neuropsychology,” “imaging,” and “pathogenesis,” articles were obtained for this review. The majority of the articles were retrieved from the past 10 years. The purpose of this review article is to aid general practitioners in further understanding current findings on the pathogenesis, diagnosis, and treatment of iNPH.

  8. small Cell Lung Cancer

    African Journals Online (AJOL)

    Hospital of Qiqihar Medical University Hospital. Inclusion criteria for the current study was histologically and cytologically confirmed NSCLC patients, patients with either lung cancer stage. IIIA, IIIB or IV, chemotherapy naïve, patients having evaluable and measureable disease,. WHO performance status (PS): 0 – 2, no active.

  9. Pediatric acute lung injury

    NARCIS (Netherlands)

    Dahlem, P.; van Aalderen, W. M. C.; Bos, A. P.

    2007-01-01

    Among ventilated children, the incidence of acute lung injury (ALI) was 9%; of that latter group 80% developed the acute respiratory distress syndrome (ARDS). The population-based prevalence of pediatric ARDS was 5.5 cases/100.000 inhabitants. Underlying diseases in children were septic shock (34%),

  10. Tuberculosis mimicking lung cancer

    Directory of Open Access Journals (Sweden)

    I. Hammen

    2015-01-01

    Our case report presents two patients, who were referred to the Thorax diagnostic centre at the Department of Respiratory Medicine, Odense University Hospital, with presumptive diagnosis of neoplasm and had proved lung TB with no evidence of malignancy instead. In the first case diagnosis was confirmed after thoracotomy, in the second case after bronchoscopy.

  11. Chemoprevention of Lung Cancer

    Science.gov (United States)

    Szabo, Eva; Mao, Jenny T.; Lam, Stephen; Reid, Mary E.

    2013-01-01

    Background: Lung cancer is the most common cause of cancer death in men and women in the United States. Cigarette smoking is the main risk factor. Former smokers are at a substantially increased risk of developing lung cancer compared with lifetime never smokers. Chemoprevention refers to the use of specific agents to reverse, suppress, or prevent the process of carcinogenesis. This article reviews the major agents that have been studied for chemoprevention. Methods: Articles of primary, secondary, and tertiary prevention trials were reviewed and summarized to obtain recommendations. Results: None of the phase 3 trials with the agents β-carotene, retinol, 13-cis-retinoic acid, α-tocopherol, N-acetylcysteine, acetylsalicylic acid, or selenium has demonstrated beneficial and reproducible results. To facilitate the evaluation of promising agents and to lessen the need for a large sample size, extensive time commitment, and expense, surrogate end point biomarker trials are being conducted to assist in identifying the most promising agents for later-stage chemoprevention trials. With the understanding of important cellular signaling pathways and the expansion of potentially important targets, agents (many of which target inflammation and the arachidonic acid pathway) are being developed and tested which may prevent or reverse lung carcinogenesis. Conclusions: By integrating biologic knowledge, additional early-phase trials can be performed in a reasonable time frame. The future of lung cancer chemoprevention should entail the evaluation of single agents or combinations that target various pathways while working toward identification and validation of intermediate end points. PMID:23649449

  12. Lung Cancer Survivorship

    Centers for Disease Control (CDC) Podcasts

    2016-10-20

    A lung cancer survivor shares her story about diagnosis, treatment, and community support. She also gives advice for other cancer survivors.  Created: 10/20/2016 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 10/20/2016.

  13. Lung Cancer Prevention

    Science.gov (United States)

    ... a radioactive gas that comes from the breakdown of uranium in rocks and soil. It seeps up through the ground, and leaks ... show that living in areas with higher levels of air pollution increases the risk of lung cancer. Beta carotene ...

  14. Lung Cancer: Management.

    Science.gov (United States)

    Mott, Timothy F

    2018-01-01

    Lung cancer management that is individualized for age, comorbidities, cancer type, cancer stage, and patient preference has long been a cornerstone of management. New to this realm of individualized management are the emerging biologic therapies, immunotherapies, and targeted therapies for non-small-cell lung cancer provided by advances in genetics and molecular medicine. These techniques have led to a new field of precision medicine based on the unique molecular characteristics of a specific patient and the specific cancer. However, standard management including surgery, chemotherapy, and radiation therapy remains the most common management options for stage I through III lung cancers. Advancements in precision medicine are most relevant to patients with stage IV (ie, metastatic) lung cancers. Functional patient assessment and pulmonary function testing are keys to preoperative assessment. Early palliative care and a minimally invasive approach to surgery should be considered in patients who can tolerate surgery. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

  15. Predicting occupational lung diseases

    NARCIS (Netherlands)

    Suarthana, E.

    2008-01-01

    This thesis aims at demonstrating the development, validation, and application of prediction models for occupational lung diseases. Prediction models are developed to estimate an individual’s probability of the presence or future likelihood of occurrence of an outcome (i.e. disease of interest or

  16. Lung Size and the Risk of Radiation Pneumonitis

    Energy Technology Data Exchange (ETDEWEB)

    Briere, Tina Marie, E-mail: tmbriere@mdanderson.org [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Krafft, Shane [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liao, Zhongxing [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Martel, Mary K. [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2016-02-01

    Purpose: The purpose of this study was to identify patient populations treated for non-small cell lung cancer (NSCLC) who may be more at risk of radiation pneumonitis. Methods and Materials: A total of 579 patients receiving fractionated 3D conformal or intensity modulated radiation therapy (IMRT) for NSCLC were included in the study. Statistical analysis was performed to search for cohorts of patients with higher incidences of radiation pneumonitis. In addition to conventional risk factors, total and spared lung volumes were analyzed. The Lyman-Kutcher-Burman (LKB) and cure models were then used to fit the incidence of radiation pneumonitis as a function of lung dose and other factors. Results: Total lung volumes with a sparing of less than 1854 cc at 40 Gy were associated with a significantly higher incidence of radiation pneumonitis at 6 months (38% vs 12% for patients with larger volumes, P<.001). This patient cohort was overwhelmingly female and represented 22% of the total female population of patients and nearly 30% of the cases of radiation pneumonitis. An LKB fit to normal tissue complication probability (NTCP) including volume as a dose modifying factor resulted in a dose that results in a 50% probability of complication for the smaller spared volume cohort that was 9 Gy lower than the fit to all mean lung dose data and improved the ability to predict radiation pneumonitis (P<.001). Using an effective dose parameter of n=0.42 instead of mean lung dose further improved the LKB fit. Fits to the data using the cure model produced similar results. Conclusions: Spared lung volume should be considered when treating NSCLC patients. Separate dose constraints based on smaller spared lung volume should be considered. Smaller spared lung volume patients should be followed closely for signs of radiation pneumonitis.

  17. Neuroethics beyond Normal.

    Science.gov (United States)

    Shook, John R; Giordano, James

    2016-01-01

    An integrated and principled neuroethics offers ethical guidelines able to transcend conventional and medical reliance on normality standards. Elsewhere we have proposed four principles for wise guidance on human transformations. Principles like these are already urgently needed, as bio- and cyberenhancements are rapidly emerging. Context matters. Neither "treatments" nor "enhancements" are objectively identifiable apart from performance expectations, social contexts, and civic orders. Lessons learned from disability studies about enablement and inclusion suggest a fresh way to categorize modifications to the body and its performance. The term "enhancement" should be broken apart to permit recognition of enablements and augmentations, and kinds of radical augmentation for specialized performance. Augmentations affecting the self, self-worth, and self-identity of persons require heightened ethical scrutiny. Reversibility becomes the core problem, not the easy answer, as augmented persons may not cooperate with either decommissioning or displacement into unaccommodating societies. We conclude by indicating how our four principles of self-creativity, nonobsolescence, empowerment, and citizenship establish a neuroethics beyond normal that is better prepared for a future in which humans and their societies are going so far beyond normal.

  18. Ethics and "normal birth".

    Science.gov (United States)

    Lyerly, Anne Drapkin

    2012-12-01

    The concept of "normal birth" has been promoted as ideal by several international organizations, although debate about its meaning is ongoing. In this article, I examine the concept of normalcy to explore its ethical implications and raise a trio of concerns. First, in its emphasis on nonuse of technology as a goal, the concept of normalcy may marginalize women for whom medical intervention is necessary or beneficial. Second, in its emphasis on birth as a socially meaningful event, the mantra of normalcy may unintentionally avert attention to meaning in medically complicated births. Third, the emphasis on birth as a normal and healthy event may be a contributor to the long-standing tolerance for the dearth of evidence guiding the treatment of illness during pregnancy and the failure to responsibly and productively engage pregnant women in health research. Given these concerns, it is worth debating not just what "normal birth" means, but whether the term as an ideal earns its keep. © 2012, Copyright the Authors Journal compilation © 2012, Wiley Periodicals, Inc.

  19. Clinical Utility of Additional Measurement of Total Lung Capacity in Diagnosing Obstructive Lung Disease in Subjects With Restrictive Pattern of Spirometry.

    Science.gov (United States)

    Lee, Hyun; Chang, Boksoon; Kim, Kyunga; Song, Won Jun; Chon, Hae Ri; Kang, Hyung Koo; Kim, Jung Soo; Jeong, Byeong-Ho; Oh, Yeon-Mok; Koh, Won-Jung; Park, Hye Yun

    2016-04-01

    Total lung capacity (TLC), forced expiratory flow between 25 and 75% (FEF25-75%), peak expiratory flow (PEF), or post-bronchodilator volume response is recommended to detect obstructive abnormalities in the lung. The present study was performed to evaluate the usefulness of these pulmonary function test (PFT) parameters to diagnose obstructive lung disease in subjects with a restrictive pattern of spirometry. A retrospective study was conducted in 64 subjects with a restrictive pattern of spirometry (normal FEV1/FVC and low FVC) out of 3,030 patients who underwent all pre- and post-bronchodilator spirometry and lung volume measurement between April 2008 and December 2010. After subjects were clinically classified into those with obstructive lung disease, restrictive lung disease, and mixed lung disease, the agreements between the clinical diagnosis and PFT classification according to TLC, FEF(25-75%), PEF, and post-bronchodilator response criteria were compared. Of 64 subjects, 18 (28.1%) were classified with obstructive lung disease, 39 (60.9%) had restrictive lung disease, 1 (1.6%) had mixed lung disease, and 6 (9.4%) had no clinical lung disease. Among the 58 subjects with clinical lung disease, 22 (37.9%), 37 (63.8%), 33 (56.9%), and 3 (5.2%) were classified as having obstructive pattern based on TLC, FEF25-75%, PEF, and post-bronchodilator response criteria, respectively. The kappa coefficients for the agreement between the clinical classification and PFT classification using TLC, FEF25-75%, PEF, and post-bronchodilator response criteria in 58 subjects were 0.59, 0.18, 0.17, and spirometry, when obstructive lung disease is clinically suspected. Copyright © 2016 by Daedalus Enterprises.

  20. Quantitation of postexercise lung thallium-201 uptake during single photon emission computed tomography

    International Nuclear Information System (INIS)

    Kahn, J.K.; Carry, M.M.; McGhie, I.; Pippin, J.J.; Akers, M.S.; Corbett, J.R.

    1989-01-01

    To test the hypothesis that analysis of lung thallium uptake measured during single photon emission computed tomography (SPECT) yields supplementary clinical information as reported for planar imaging, quantitative analysis of lung thallium uptake following maximal exercise was performed in 40 clinically normal subjects (Group 1) and 15 angiographically normal subjects (Group 2). Lung thallium uptake was measured from anterior projection images using a ratio of heart-to-lung activities. Seventy subjects with coronary artery disease (CAD) (Group 3) determined by angiography (greater than or equal to 70% luminal stenosis) underwent thallium perfusion SPECT. Thirty-nine percent of these subjects had multivessel and 61% had single vessel CAD. Lung thallium uptake was elevated in 47 of 70 (67%) Group 3 subjects. Group 3 subjects with elevated lung thallium uptake did not differ from Group 3 subjects with normal lung thallium uptake with respect to extent or distribution of coronary artery disease, left ventricular function, or severity of myocardial ischemia as determined by exercise and redistribution thallium SPECT. Thus, the measurement of thallium lung uptake from anterior projection images obtained during SPECT frequently identifies patients with CAD, but it may not provide supplementary information regarding the extent of myocardial ischemia or ventricular dysfunction

  1. Phenotype of normal spirometry in an aging population.

    Science.gov (United States)

    Vaz Fragoso, Carlos A; McAvay, Gail; Van Ness, Peter H; Casaburi, Richard; Jensen, Robert L; MacIntyre, Neil; Gill, Thomas M; Yaggi, H Klar; Concato, John

    2015-10-01

    In aging populations, the commonly used Global Initiative for Chronic Obstructive Lung Disease (GOLD) may misclassify normal spirometry as respiratory impairment (airflow obstruction and restrictive pattern), including the presumption of respiratory disease (chronic obstructive pulmonary disease [COPD]). To evaluate the phenotype of normal spirometry as defined by a new approach from the Global Lung Initiative (GLI), overall and across GOLD spirometric categories. Using data from COPDGene (n = 10,131; ages 45-81; smoking history, ≥10 pack-years), we evaluated spirometry and multiple phenotypes, including dyspnea severity (Modified Medical Research Council grade 0-4), health-related quality of life (St. George's Respiratory Questionnaire total score), 6-minute-walk distance, bronchodilator reversibility (FEV1 % change), computed tomography-measured percentage of lung with emphysema (% emphysema) and gas trapping (% gas trapping), and small airway dimensions (square root of the wall area for a standardized airway with an internal perimeter of 10 mm). Among 5,100 participants with GLI-defined normal spirometry, GOLD identified respiratory impairment in 1,146 (22.5%), including a restrictive pattern in 464 (9.1%), mild COPD in 380 (7.5%), moderate COPD in 302 (5.9%), and severe COPD in none. Overall, the phenotype of GLI-defined normal spirometry included normal adjusted mean values for dyspnea grade (0.8), St. George's Respiratory Questionnaire (15.9), 6-minute-walk distance (1,424 ft [434 m]), bronchodilator reversibility (2.7%), % emphysema (0.9%), % gas trapping (10.7%), and square root of the wall area for a standardized airway with an internal perimeter of 10 mm (3.65 mm); corresponding 95% confidence intervals were similarly normal. These phenotypes remained normal for GLI-defined normal spirometry across GOLD spirometric categories. GLI-defined normal spirometry, even when classified as respiratory impairment by GOLD, included adjusted mean values in the

  2. Effects of therapeutic irradiation delivered in early childhood upon subsequent lung function

    International Nuclear Information System (INIS)

    Wohl, M.E.B.; Griscom, N.T.; Graggis, D.G.; Jaffe, N.

    1975-01-01

    To determine the long-term effects of therapeutic pulmonary irradiation and treatment with actinomycin D during a period of lung growth, 12 patients treated for Wilms' tumor metastatic to the lung and 8 patients treated for Wilms' tumor with no evidence of pulmonary metastases were studied 7 to 14 years after their initial tumor therapy. All patients had received irradiation to the tumor bed and treatment with actinomycin D. Group 1 had received a single course of bilateral pulmonary irradiation; group 2 had received additional pulmonary irradiation and/or thoracic surgery; group 3 had received no therapeutic irradiation directed primarily to the chest. Total lung capacity (TLC) averaged 71 percent of predicted value in group 1, 58 percent in group 2, and 94 percent in group 3. Diffusing capacity in groups 1 and 2 was reduced to the same extent as lung volume. Quasi-static pressure-volume relationships, studied in three of six patients in group 1, were within the normal range when lung volume was expressed as percentage of observed TLC. Airway resistance, evaluated by spirometry, maximum expiratory flow-volume curves, and resistance of the total respiratory system, was normal or reduced. The data support the hypothesis that therapeutic irradiation during a period of lung growth primarily affects the lung parenchyma and produces a decrease in subsequent size of both the lung and chest wall. No effect of actinomycin D alone upon the lung could be demonstrated

  3. Histogram analysis for age change of human lung with computed tomography

    International Nuclear Information System (INIS)

    Shirabe, Ichiju

    1990-01-01

    In order to evaluate physiological changes of normal lung with aging by computed tomography (CT), the peak position (PP) and full width half maximum (FWHM) of CT-histogram were studied in 77 normal human lung. Above 30 years old, PP tended to be seen in the lower attenuation value with advancing ages, with the result that the follow equation was obtained. CT attenuation value of PP=-0.87 x age -815. The peak position shifted to the range of higher CT attenuation in 30's. FWHM did not change with advancing ages. There were no differences of peak value and FWHM among the upper, middle and lower lung field. In this study, physiological changes of lung were evaluated quantitatively. Furthermore, this study was considered to be useful for diagnosis and treatment in lung diseases. (author)

  4. Motivating smokers in the hospital pulmonary function laboratory to quit smoking by use of the lung age concept.

    Science.gov (United States)

    Kaminsky, David A; Marcy, Theodore; Dorwaldt, Anne; Pinckney, Richard; DeSarno, Michael; Solomon, Laura; Hughes, John R

    2011-11-01

    The purpose of this study was to investigate the use of lung age to motivate a quit attempt among smokers presenting to a hospital pulmonary function testing (PFT) laboratory. Participants were randomized to receive a lung age-based motivational strategy (intervention group) versus standard care (control group). At 1 month, all participants were interviewed by telephone to determine whether they made a quit attempt. A total of 67 participants were enrolled, and 51 completed the study. Baseline mean data included age = 52 years, 70% women, 40 pack-years of smoking, FEV(1) = 69% predicted, and lung age = 83 years. The quit attempt rates were not different between the intervention and control groups (32% vs. 24%, respectively, p = .59). There was a near significant interaction between lung age and intervention strategy (p = .089), with quit attempt rates among those with normal lung age of 18% in the intervention group versus 33% in the control group and among those with high (worse) lung age of 39% in the intervention group versus 17% in the control group; p = .38. Using lung age to motivate smokers presenting to the PFT laboratory to quit may succeed in patients with high lung age but may undermine motivation in smokers with normal lung age. Further work is needed to refine the approach to smokers with normal lung age.

  5. Rapid diagnosis and intraoperative margin assessment of human lung cancer with fluorescence lifetime imaging microscopy

    Directory of Open Access Journals (Sweden)

    Mengyan Wang

    2017-12-01

    Full Text Available A method of rapidly differentiating lung tumor from healthy tissue is extraordinarily needed for both the diagnosis and the intraoperative margin assessment. We assessed the ability of fluorescence lifetime imaging microscopy (FLIM for differentiating human lung cancer and normal tissues with the autofluorescence, and also elucidated the mechanism in tissue studies and cell studies. A 15-patient testing group was used to compare FLIM results with traditional histopathology diagnosis. Based on the endogenous fluorescence lifetimes of the testing group, a criterion line was proposed to distinguish normal and cancerous tissues. Then by blinded examined 41 sections from the validation group of other 16 patients, the sensitivity and specificity of FLIM were determined. The cellular metabolism was studied with specific perturbations of oxidative phosphorylation and glycolysis in cell studies. The fluorescence lifetime of cancerous lung tissues is consistently lower than normal tissues, and this is due to the both decrease of reduced nicotinamide adenine dinucleotide (NADH and flavin adenine dinucleotide (FAD lifetimes. A criterion line of lifetime at 1920 ps can be given for differentiating human lung cancer and normal tissues.The sensitivity and specificity of FLIM for lung cancer diagnosis were determined as 92.9% and 92.3%. These findings suggest that NADH and FAD can be used to rapidly diagnose lung cancer. FLIM is a rapid, accurate and highly sensitive technique in the judgment during lung cancer surgery and it can be potential in earlier cancer detection.

  6. 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

  7. Lysyl oxidase promotes bleomycin-induced lung fibrosis through modulating inflammation.

    Science.gov (United States)

    Cheng, Tao; Liu, Qingbo; Zhang, Rui; Zhang, Ying; Chen, Jianfeng; Yu, Ronghuan; Ge, Gaoxiang

    2014-12-01

    Enzymes involved in collagen biosynthesis, including lysyl oxidase (LOX), have been proposed as potential therapeutic targets for idiopathic pulmonary fibrosis. LOX expression is significantly upregulated in bleomycin (BLM)-induced lung fibrosis, and knockdown of LOX expression or inhibition of LOX activity alleviates the lung fibrosis. Unexpectedly, treatment of the mice with LOX inhibitor at the inflammatory stage, but not the fibrogenic stage, efficiently reduces collagen deposition and normalizes lung architecture. Inhibition of LOX impairs inflammatory cell infiltration, TGF-β signaling, and myofibroblast accumulation. Furthermore, ectopic expression of LOX sensitizes the fibrosis-resistant Balb/c mice to BLM-induced inflammation and lung fibrosis. These results suggest that LOX is indispensable for the progression of BLM-induced experimental lung fibrosis by aggravating the inflammatory response and subsequent fibrosis process after lung injury. © The Author (2014). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.

  8. Non-invasive determination of absolute lung resistivity in adults using electrical impedance tomography

    International Nuclear Information System (INIS)

    Zhang, Jie; Patterson, Robert

    2010-01-01

    Lung resistivity is a physiological parameter that describes the electrical characteristics of the lungs. Lung composition changes due to changes in the lung tissues, fluid and air volume. Various diseases that can cause a change in lung composition may be monitored by measuring lung resistivity. Currently, there is no accepted non-invasive method to measure lung resistivity. In this study, we presented a method and framework to non-invasively determine lung resistivity using electrical impedance tomography (EIT). By comparing actual measurements from subjects with data from a 3D human thorax model, an EIT image can be reconstructed to show a resistivity difference between the model and the subject. By adjusting the lung resistivity in the model, the resistivity difference in the lung regions can be reduced to near zero. This resistivity value then is the estimation of the lung resistivity of the subject. Using the proposed method, the lung resistivities of four normal adult males (43 ± 13 years, 78 ± 10 kg) in the supine position at air volumes starting at functional residual capacity (FRC—end expiration) and increasing in 0.5 l steps to 1.5 l were studied. The averaged lung resistivity changes 12.59%, from 1406 Ω cm to 1583 Ω cm, following the inspiration of 1.5 l air from FRC. The coefficients of variation (CV) of precision for the four subjects are less than 10%. The experiment was repeated five times at each air volume on a subject to test the reproducibility. The CVs are less than 3%. The results show that it is feasible to determine absolute lung resistivity using an EIT-based method

  9. The Effect of Compartmental Asymmetry on the Monitoring of Pulmonary Mechanics and Lung Volumes.

    Science.gov (United States)

    Keenan, Joseph C; Cortes-Puentes, Gustavo A; Adams, Alexander B; Dries, David J; Marini, John J

    2016-11-01

    Esophageal pressure measurement for computation of transpulmonary pressure (P tp ) has begun to be incorporated into clinical use for evaluating forces across the lungs. Gaps exist in our understanding of how esophageal pressure (and therefore P tp ), a value measured at a single site, responds when respiratory system compartments are asymmetrically affected by whole-lung atelectasis or unilateral injury as well as changes in chest wall compliance. We reasoned that P tp would track with aerated volume changes as estimated by functional residual capacity (FRC) and tidal volume. We examined this hypothesis in the setting of asymmetric lungs and changes in intra-abdominal pressure. This study was conducted in the animal laboratory of a university-affiliated hospital. Models of unilateral atelectasis and unilateral and bilateral lung injury exposed to intra-abdominal hypertension (IAH) in 10 deeply sedated mechanically ventilated swine. Atelectasis was created by balloon occlusion of the left main bronchus. Unilateral lung injury was induced by saline lavage of isolated right lung. Diffuse lung injury was induced by saline lavage of both lungs. The peritoneum was insufflated with air to create a model of pressure-regulated IAH. We measured esophageal pressures, airway pressures, FRC by gas dilution, and oxygenation. FRC was reduced by IAH in normal lungs (P lung pathologies (P lung injury (P = .003) as well as unilateral atelectasis (P = .019). In the setting of both lung injury models, end-expiratory P tp showed a moderate correlation in tracking with FRC. P tp tracks with aerated lung volume in the setting of thoracic asymmetry and changes in intra-abdominal pressure. However, used alone, it cannot distinguish the relative contributions of air-space distention and recruitment of lung units. Copyright © 2016 by Daedalus Enterprises.

  10. Differential epigenetic regulation of TOX subfamily high mobility group box genes in lung and breast cancers.

    Directory of Open Access Journals (Sweden)

    Mathewos Tessema

    Full Text Available Aberrant cytosine methylation affects regulation of hundreds of genes during cancer development. In this study, a novel aberrantly hypermethylated CpG island in cancer was discovered within the TOX2 promoter. TOX2 was unmethylated in normal cells but 28% lung (n = 190 and 23% breast (n = 80 tumors were methylated. Expression of two novel TOX2 transcripts identified was significantly reduced in primary lung tumors than distant normal lung (p<0.05. These transcripts were silenced in methylated lung and breast cancer cells and 5-Aza-2-deoxycytidine treatment re-expressed both. Extension of these assays to TOX, TOX3, and TOX4 genes that share similar genomic structure and protein homology with TOX2 revealed distinct methylation profiles by smoking status, histology, and cancer type. TOX was almost exclusively methylated in breast (43% than lung (5% cancer, whereas TOX3 was frequently methylated in lung (58% than breast (30% tumors. TOX4 was unmethylated in all samples and showed the highest expression in normal lung. Compared to TOX4, expression of TOX, TOX2 and TOX3 in normal lung was 25, 44, and 88% lower, respectively, supporting the premise that reduced promoter activity confers increased susceptibility to methylation during lung carcinogenesis. Genome-wide assays revealed that siRNA-mediated TOX2 knockdown modulated multiple pathways while TOX3 inactivation targeted neuronal development and function. Although these knockdowns did not result in further phenotypic changes of lung cancer cells in vitro, the impact on tissue remodeling, inflammatory response, and cell differentiation pathways suggest a potential role for TOX2 in modulating tumor microenvironment.

  11. Normal radiological findings

    International Nuclear Information System (INIS)

    Moeller, T.B.

    1987-01-01

    This book is intended for learners in radiology, presenting a wealth of normal radiological findings together with a systematic guide for appraisal and interpretation, and for formulation of reports. The text examples and criteria given will help beginners in learning to 'read' a radiograph, and to verify their conclusions by means of checklists and standard reports. The case material covers numerous illustrations from the following sectors: Skeletal radiography, mammography, tomography, contrast radiography, organ examination by intravenous techniques, arthrography and angiography, and specialized radiography, (ECB) With 184 figs [de

  12. Antioxidant macromolecules in the epithelial lining fluid of the normal human lower respiratory tract.

    Science.gov (United States)

    Cantin, A M; Fells, G A; Hubbard, R C; Crystal, R G

    1990-09-01

    We hypothesized that the alveolar structures may contain extracellular macromolecules with antioxidant properties to defend against oxidants. To evaluate this 51Cr-labeled human lung fibroblasts (HFL-1) and cat lung epithelial cells (AKD) were exposed to a H2O2-generating system and alveolar epithelial lining fluid (ELF) from healthy nonsmokers was tested for its ability to protect the lung cells from H2O2-mediated injury. The ELF provided marked antioxidant protection, with most from a H2O-soluble fraction in the 100-300-kD range. Plasma proteins with anti-H2O2 properties were in insufficient concentrations to provide the antioxidant protection observed. However, catalase, a normal intracellular antioxidant, was present in sufficient concentration to account for most of the observed anti-H2O2 properties of ELF. Depletion of ELF with an anticatalase antibody abolished the anti-H2O2 macromolecular defenses of ELF. Since catalase is not normally released by cells, a likely explanation for its presence in high concentrations in normal ELF is that it is released by lung inflammatory and parenchymal cells onto the epithelial surface of the lower respiratory tract during their normal turnover and collects there due to the slow turnover of ELF. It is likely that catalase in the ELF of normal individuals plays a role in protecting lung parenchymal cells against oxidants present in the extracellular milieu.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-08-15

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

  14. Mass Spectrometry–based Proteomic Profiling of Lung Cancer

    Science.gov (United States)

    Ocak, Sebahat; Chaurand, Pierre; Massion, Pierre P.

    2009-01-01

    In an effort to further our understanding of lung cancer biology and to identify new candidate biomarkers to be used in the management of lung cancer, we need to probe these tissues and biological fluids with tools that address the biology of lung cancer directly at the protein level. Proteins are responsible of the function and phenotype of cells. Cancer cells express proteins that distinguish them from normal cells. Proteomics is defined as the study of the proteome, the complete set of proteins produced by a species, using the technologies of large-scale protein separation and identification. As a result, new technologies are being developed to allow the rapid and systematic analysis of thousands of proteins. The analytical advantages of mass spectrometry (MS), including sensitivity and high-throughput, promise to make it a mainstay of novel biomarker discovery to differentiate cancer from normal cells and to predict individuals likely to develop or recur with lung cancer. In this review, we summarize the progress made in clinical proteomics as it applies to the management of lung cancer. We will focus our discussion on how MS approaches may advance the areas of early detection, response to therapy, and prognostic evaluation. PMID:19349484

  15. Three dimensional conformal radiation therapy may improve the therapeutic ratio of radiation therapy after pneumonectomy for lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Trouette, R.; Causse, N.; Elkhadri, M.; Caudry, M.; Maire, J.P.; Houlard, J.P.; Racaldini, L.; Demeaux, H.

    1995-12-01

    Three dimensional conformal radiation therapy would allow to decrease the normal tissue dose while maintaining the same target dose as standard treatment. To evaluate the feasibility of normal tissue dose reduction for ten patients with pneumonectomy for lung cancer, we determined the dose distribution to the normal tissue with 3-dimensional conformal radiation therapy (3-DCRT) and conventional treatment planning (CTP). Dose-volume histograms for target and normal tissue (lung, heart) were used for comparison of the different treatment planning. The mean percentages of lung and heart volumes which received 40 Gy with 3-DCRT were respectively 63% and 37% of the mean percentage of lung and volumes which received the same dose with CTP. These preliminary results suggest that conformal therapy may improve the therapeutic ratio by reducing risk to normal tissue.

  16. 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.

  17. Risk of COPD with obstruction in active smokers with normal spirometry and reduced diffusion capacity.

    Science.gov (United States)

    Harvey, Ben-Gary; Strulovici-Barel, Yael; Kaner, Robert J; Sanders, Abraham; Vincent, Thomas L; Mezey, Jason G; Crystal, Ronald G

    2015-12-01

    Smokers are assessed for chronic obstructive pulmonary disease (COPD) using spirometry, with COPD defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) as airflow limitation that is not fully reversible with bronchodilators. There is a subset of smokers with normal spirometry (by GOLD criteria), who have a low diffusing capacity of the lung for carbon monoxide (DLCO), a parameter linked to emphysema and small airway disease. The natural history of these "normal spirometry/low DLCO" smokers is unknown.From a cohort of 1570 smokers in the New York City metropolitian area, all of whom had normal spirometry, two groups were randomly selected for lung function follow-up: smokers with normal spirometry/normal DLCO (n=59) and smokers with normal spirometry/low DLCO (n=46). All had normal history, physical examination, complete blood count, urinalysis, HIV status, α1-antitrypsin level, chest radiography, forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC ratio and total lung capacity. Throughout the study, all continued to be active smokers.In the normal spirometry/normal DLCO group assessed over 45±20 months, 3% developed GOLD-defined COPD. In contrast, in the normal spirometry/low DLCO group, followed over 41±31 months, 22% developed GOLD-defined COPD.Despite appearing "normal" according to GOLD, smokers with normal spirometry but low DLCO are at significant risk of developing COPD with obstruction to airflow. Copyright ©ERS 2015.

  18. Lung density as measured by computerized tomography: implications for radiotherapy

    International Nuclear Information System (INIS)

    Van Dyk, J.; Keane, T.J.; Rider, W.D.

    1982-01-01

    Accurate dose calculations for radiotherapy planning require a detailed knowledge of the internal anatomy of the patient both in terms of geometry and density. Computed tomography (CT) is presently the best means of providing these data. Fifty-eight patients who had scans of the thorax for radiotherapy planning were studied. The CT numbers were converted to relative electron densities and average lung densities were obtained for every patient. A linear correlation of lung density with age was found with the mean lung density of 0.35 at an age 5 years and 0.19 at an age of 80. The effect of scanning the patient under full inspiration, full expiration or normal shallow breathing conditions was analyzed. At the age of 5 years the expiration and inspiration average lung densities were 0.36 and 0.20, while at the age of 80 years they were 0.22 and 0.16, respectively. Respiratory volume changes were linearly correlated with changes in relative electron density. Differences in lung density between expiration and inspiration scans were found to demonstrate a similar trend with age as the relationship between vital capacity and age. The dosimetric and the possible clinical implications of lung density measurements for radiotherapy are considered. In particular, dose calculations were performed using scans taken under a number of different respiratory conditions. Doses calculated for a single cobalt-60 beam can differ by more than 25% when comparing a full inspiration scan to a normal breathing scan. A similar comparison for a parallel pair distribution on the lung yields a difference of about 3% while a typical three field technique for treating cancer of the esophagus shows a difference of nearly 10%

  19. Biomarker Identification and Pathway Analysis by Serum Metabolomics of Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yingrong Chen

    2015-01-01

    Full Text Available Lung cancer is one of the most common causes of cancer death, for which no validated tumor biomarker is sufficiently accurate to be useful for diagnosis. Additionally, the metabolic alterations associated with the disease are unclear. In this study, we investigated the construction, interaction, and pathways of potential lung cancer biomarkers using metabolomics pathway analysis based on the Kyoto Encyclopedia of Genes and Genomes database and the Human Metabolome Database to identify the top altered pathways for analysis and visualization. We constructed a diagnostic model using potential serum biomarkers from patients with lung cancer. We assessed their specificity and sensitivity according to the area under the curve of the receiver operator characteristic (ROC curves, which could be used to distinguish patients with lung cancer from normal subjects. The pathway analysis indicated that sphingolipid metabolism was the top altered pathway in lung cancer. ROC curve analysis indicated that glycerophospho-N-arachidonoyl ethanolamine (GpAEA and sphingosine were potential sensitive and specific biomarkers for lung cancer diagnosis and prognosis. Compared with the traditional lung cancer diagnostic biomarkers carcinoembryonic antigen and cytokeratin 19 fragment, GpAEA and sphingosine were as good or more appropriate for detecting lung cancer. We report our identification of potential metabolic diagnostic and prognostic biomarkers of lung cancer and clarify the metabolic alterations in lung cancer.

  20. Glucocorticoids decrease Treg cell numbers in lungs of allergic mice.

    Science.gov (United States)

    Olsen, P C; Kitoko, J Z; Ferreira, T P; de-Azevedo, C T; Arantes, A C; Martins, Μ A

    2015-01-15

    Glucocorticoids have been the hallmark anti-inflammatory drug used to treat asthma. It has been shown that glucocorticoids ameliorate asthma by increasing numbers and activity of Tregs, in contrast recent data show that glucocorticoid might have an opposite effect on Treg cells from normal mice. Since Tregs are target cells that act on the resolution of asthma, the aim of this study was to elucidate the effect of glucocorticoid treatment on lung Tregs in mouse models of asthma. Allergen challenged mice were treated with either oral dexamethasone or nebulized budesonide. Broncoalveolar lavage and airway hyperresponsiveness were evaluated after allergenic challenge. Lung, thymic and lymph node cells were phenotyped on Treg through flow cytometry. Lung cytokine secretion was detected by ELISA. Although dexamethasone inhibited airway inflammation and hyperresponsiveness, improving resolution, we have found that both dexamethasone and budesonide induce a reduction of Treg numbers on lungs and lymphoid organs of allergen challenged mice. The reduction of lung Treg levels was independent of mice strain or type of allergen challenge. Our study also indicates that both glucocorticoids do not increase Treg activity through production of IL-10. Glucocorticoid systemic or localized treatment induced thymic atrophy. Taken together, our results demonstrate that glucocorticoids decrease Treg numbers and activity in different asthma mouse models, probably by reducing thymic production of T cells. Therefore, it is possible that glucocorticoids do not have beneficial effects on lung populations of Treg cells from asthmatic patients. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Integrin αβ3-Targeted Imaging of Lung Cancer

    Directory of Open Access Journals (Sweden)

    Xiaoyuan Chen

    2005-03-01

    Full Text Available A series of radiolabeled cyclic arginine-glycineaspartic acid (RGD peptide ligands for cell adhesion molecule integrin αβ3-targeted tumor angiogenesis targeting are being developed in our laboratory. In this study, this effort continues by applying a positron emitter 64Cu-labeled PEGylated dimeric RGD peptide radiotracer 64Cu-DOTA-PEG-E[c(RGDyK]2 for lung cancer imaging. The PEGylated RGD peptide indicated integrin αβ3 avidity, but the PEGylation reduced the receptor binding affinity of this ligand compared to the unmodified RGD dimer. The radiotracer revealed rapid blood clearance and predominant renal clearance route. The minimum nonspecific activity accumulation in normal lung tissue and heart rendered high-quality orthotopic lung cancer tumor images, enabling clear demarcation of both the primary tumor at the upper lobe of the left lung, as well as metastases in the mediastinum, contralateral lung, diaphragm. As a comparison, fluorodeoxyglucose (FDG scans on the same mice were only able to identify the primary tumor, with the metastatic lesions masked by intense cardiac uptake and high lung background. 64Cu-DOTA-PEGE[c(RGDyK]2 is an excellent positron emission tomography (PET tracer for integrin-positive tumor imaging. Further studies to improve the receptor binding affinity of the tracer and subsequently to increase the magnitude of tumor uptake without comprising the favorable in vivo kinetics are currently in progress.

  2. Development of Antisense Therapeutic and Imaging Agents to Detect and Suppress Inducible Nitric Oxide Synthase (iNOS) Expression in Acute Lung Injury (ALI)

    Science.gov (United States)

    Shen, Yuefei

    This dissertation focuses on the development and investigation of antisense imaging and therapeutic agents, combined with nanotechnology, to detect and suppress inducible nitric oxide synthase (iNOS) expression for the diagnosis and treatment of acute lung injury (ALI). To achieve this goal, several efforts were made. The first effort was the identification and characterization of high binding affinity antisense peptide nucleic acids (PNAs) and shell-crosslinked knedel-like nanoparticle (SCK)-PNA conjugates to the iNOS mRNA. Antisense binding sites on the iNOS mRNA were first mapped by a procedure for rapidly generating a library of antisense accessible sites on native mRNAs (MASL) which involves reverse transcription of whole cell mRNA extracts with a random oligodeoxynucleotide primer followed by mRNA-specific PCR. Antisense PNAs against the antisense accessible sites were accordingly synthesized and characterized. The second effort was the investigation of cationic shell crosslinked knedel-like nanoparticle (cSCK)-mediated siRNA delivery to suppress iNOS expression for the treatment of ALI. siRNA with its unique gene-specific properties could serve as a promising therapeutic agent, however success in this area has been challenged by a lack of efficient biocompatible transfection agents. cSCK with its nanometer size and positive charge previously showed efficient cellular delivery of phosphorothioate ODNs (oligodeoxynucleotides), plasmid DNA and PNA. Herein, cSCK showed good siRNA binding and facilitated efficient siRNA transfection in HeLa, a mouse macrophage cell line and other human cell lines. cSCK led to greater silencing efficiency than Lipofectamine 2000 in HeLa cells as determined by the viability following transfection with cytotoxic and non-cytotoxic siRNAs, as well in 293T and HEK cells, and was comparable in BEAS-2B and MCF10a cells. The third effort was the preparation of an iNOS imaging probe through electrostatic complexation between a radiolabeled

  3. Diffuse parenchymal lung disease

    Directory of Open Access Journals (Sweden)

    Sara Tomassetti

    2017-04-01

    Full Text Available Between September 2015 and August 2016 there were >1500 publications in the field of diffuse parenchymal lung diseases (DPLDs. For the Clinical Year in Review session at the European Respiratory Society Congress that was held in London, UK, in September 2016, we selected only five articles. This selection, made from the enormous number of published papers, does not include all the relevant studies that will significantly impact our knowledge in the field of DPLDs in the near future. This review article provides our personal view on the following topics: early diagnosis of idiopathic pulmonary fibrosis, current knowledge on the multidisciplinary team diagnosis of DPLDs and the diagnostic role of transbronchial cryobiopsy in this diagnostic setting, insights on the new entity of interstitial pneumonia with autoimmune features, and new therapeutic approaches for scleroderma-related interstitial lung disease.

  4. Human models of acute lung injury

    Directory of Open Access Journals (Sweden)

    Alastair G. Proudfoot

    2011-03-01

    Full Text Available Acute lung injury (ALI is a syndrome that is characterised by acute inflammation and tissue injury that affects normal gas exchange in the lungs. Hallmarks of ALI include dysfunction of the alveolar-capillary membrane resulting in increased vascular permeability, an influx of inflammatory cells into the lung and a local pro-coagulant state. Patients with ALI present with severe hypoxaemia and radiological evidence of bilateral pulmonary oedema. The syndrome has a mortality rate of approximately 35% and usually requires invasive mechanical ventilation. ALI can follow direct pulmonary insults, such as pneumonia, or occur indirectly as a result of blood-borne insults, commonly severe bacterial sepsis. Although animal models of ALI have been developed, none of them fully recapitulate the human disease. The differences between the human syndrome and the phenotype observed in animal models might, in part, explain why interventions that are successful in models have failed to translate into novel therapies. Improved animal models and the development of human in vivo and ex vivo models are therefore required. In this article, we consider the clinical features of ALI, discuss the limitations of current animal models and highlight how emerging human models of ALI might help to answer outstanding questions about this syndrome.

  5. CT densitometry of lung mass: the effect of reconstruction algorithm

    International Nuclear Information System (INIS)

    Kim, Jun Ho; Park, Kyung Joo; Kang, Hae Jin; Lee, Yi Hyung; Suh, Jung Ho

    2000-01-01

    To evaluate the effect of reconstruction algorithms on the CT measurement of mean lung mass density and normal thoracic structures. Forty-six patients with a 2-9 cm-sized lung mass underwent thoracic CT examinations with intravenous contrast enhancement and using a CT HiSpeed Advantage scanner (GE Medical Systems). In each examination, the axial image of the lung mass was reconstructed using soft, standard, detail, and bone algorithms. The mean value and standard deviation of mass density in Hounsfield Units (HU) were measured using ROIs of three different sizes (50 mm 2 , and 350 mm 2 or more), and the same method was used to measure the density of normal lung, muscle, bone, and vessels. In 21 patients, mass density was also measured on unenhanced and delayed enhanced images and the degree of enhancement was calculated. The average maximum difference in mean mass density in the images of the four different algorithms was less than 1 (range, 0.1-1.9) HU (ROI size, 350 mm 2 or more), 0-4.2 HU (200 mm 2 ), and 0.1-3.6 HU (50 mm 2 ). The average maximum difference in the degree of lung mass enhancement was 0.5-1.2 (range, 0-1.6) HU (ROI size, 350 mm 2 or more)> The mean density of the four normal thoracic structures was highest in images reconstructed with the bone algorithm, though there was no significant difference between the four different algorithms (p=1.000). The measured mean CT density of a lung mass larger than 2 cm does not significantly change according to the reconstruction algorithm used. When using a small ROI, however, the density difference may increase

  6. Angiosarcoma of the lung

    Energy Technology Data Exchange (ETDEWEB)

    Grafino, Monica; Alves, Paula; Almeida, Margarida Mendes de; Garrido, Patricia; Hasmucrai, Direndra; Teixeira, Encarnacao; Sotto-Mayor, Renato, E-mail: mgrafino@gmail.com [Centro Hospitalar Lisboa Norte, EPE, Lisboa (Portugal)

    2016-06-01

    Angiosarcoma is a rare malignant vascular tumor. Pulmonary involvement is usually attributable to metastasis from other primary sites, primary pulmonary angiosarcoma therefore being quite uncommon. We report a case of angiosarcoma with pulmonary involvement, probably primary to the lung, which had gone untreated for more than two years. We describe this rare neoplasm and its growth, as well as the extensive local invasion and hematogenous metastasis at presentation. We also discuss its poor prognosis. (author)

  7. Frequent loss of Fas expression and function in human lung tumours with overexpression of FasL in small cell lung carcinoma.

    Science.gov (United States)

    Viard-Leveugle, Isabelle; Veyr